美国的护理人数高达310万人，是健康照护专业人员最多的国家。在照护团队中，护士作为患者与家属之间的沟通枢纽，负责护理、协调与整合工作。医学研究所（Institute of Medicine）的研究报告显示：医护差错及医疗护理质量的差异性已被...美国的护理人数高达310万人，是健康照护专业人员最多的国家。在照护团队中，护士作为患者与家属之间的沟通枢纽，负责护理、协调与整合工作。医学研究所（Institute of Medicine）的研究报告显示：医护差错及医疗护理质量的差异性已被广泛认可。展开更多
Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.
Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy r...Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced展开更多
Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv inf...Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv infection-associated oxidative stress and reactive oxygen species(ROS)production.Here,we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells,and expedites adenovirus production.By stably overexpressing GAPDH in HEK293(293G)and 293pTP(293GP)cells,respectively,we demonstrated that rAdV-induced RoS production and cell apoptosis were significantly suppressed in 293G and 293GP cells.Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells.Similarly,Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells.We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells.293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells,indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production.These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production.Therefore,the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.展开更多
Cervical cancer(CC)is one of the most common gynecological cancers,ranking fourth in incidence and mortality rates among women worldwide and second in China[1].Approximately 15%-61%of patients with CC develop recurren...Cervical cancer(CC)is one of the most common gynecological cancers,ranking fourth in incidence and mortality rates among women worldwide and second in China[1].Approximately 15%-61%of patients with CC develop recurrent or metastatic(r/m)disease in the first two years after initial therapy completion,with a 5-year survival rate of 17%[2].Platinum-based chemotherapy is the first-line treatment for r/mCC.展开更多
Background:Understanding willingness to undergo pulmonary function tests(PFTs)and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary...Background:Understanding willingness to undergo pulmonary function tests(PFTs)and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease(COPD).This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods:We collected data from participants in the"Happy Breathing Program"in China.Participants who did not follow physicians’recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs.We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs.We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results:A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study.Out of these participants,7660(90.4%)were willing to undergo PFTs.Among those who were willing to undergo PFTs but actually did not,the main reasons for not doing so were geographical inaccessibility(n=3304,43.1%)and a lack of trust in primary healthcare institutions(n=2809,36.7%).Among the 815 participants who were unwilling to undergo PFTs,over half(n=447,54.8%)believed that they did not have health problems and would only consider PFTs when they felt unwell.In the multivariable regression,individuals who were≤54 years old,residing in rural townships,with a secondary educational level,with medical reimbursement,still working,with occupational exposure to dust,and aware of the abbreviation"COPD"were more willing to undergo PFTs.Conclusions:Willingness to undergo PFTs was high among high-risk populations.Policymakers may consider implementing strategies such as providing financial incentives,promoting education,and establishing community-based pro展开更多
BACKGROUND Although cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)offer the potential for long-term survival in peritoneal carcinomatosis,outcomes following CRS/HIPEC vary significantly...BACKGROUND Although cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)offer the potential for long-term survival in peritoneal carcinomatosis,outcomes following CRS/HIPEC vary significantly.AIM To identify the clinical factors associated with progression-free survival(PFS)after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal,ovarian,and gastric cancers.METHODS We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival(OS)in patients recruited between 2015 and 2020.Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year.Kaplan–Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS.RESULTS Of the 80 enrolled patients,39 had an unfavorable PFS(<1 year)and 41 had a favorable PFS(≥1 year).Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0(CC-0)or length of CRS≤6 h had a favorable PFS[odds ratio(OR)=0.141,P=0.004;and OR=0.361,P=0.027,respectively].In multiple logistic regression,achieving CC-0 was the strongest prognostic factor for a favorable PFS(OR=0.131,P=0.005).A peritoneal cancer index score>12 was associated with a lower rate of achieving CC-0(P=0.027).The favorable PFS group had a significantly longer OS(median 81.7 mo vs 17.0 mo,P<0.001).CONCLUSION Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival.This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.展开更多
Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of pr...Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.展开更多
Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been...Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.展开更多
Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatme...Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.展开更多
Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with ...Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.展开更多
AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature sea...AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios(OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen(HBs Ag) positive] were included. The comparison group consisted of HBs Agnegative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of Der Simonian and Laird. The protocol for this metaanalysis is registered with PROSPERO(International Prospective Register of Systematic Reviews; no. CRD42017080657).RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBs Ag-negative recipients, HBs Ag-positive status was significantly associated with increased risk of mortality after kidney transplantation(pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBs Ag-positive recipients and year of study(slopes =-0.062, P = 0.001). HBs Agpositive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46(95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure(slopes =-0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBs Ag-positive recipients, respectively.CONCLUSION Among kidney transplant patients, there are significant as展开更多
Objective: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome(PMS) and dysmenorrhea. Methods: A randomized, triple-blind, placebocontrolled trial ...Objective: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome(PMS) and dysmenorrhea. Methods: A randomized, triple-blind, placebocontrolled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days(7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. Results: Administration of curcumin was associated with a significant increase in memory score(P=0.002), inhibitory control and selective attention(P=0.020), and total cognitive ability task(P=0.024). In addition, significant increments were found in scores of memory(3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively;P=0.035), inhibitory control and selective attention(3.0±3.7 vs. 0.4±3.7;P=0.027) and total cognitive abilities(8.3±12.3 vs. 2.2±12.4;P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. Conclusion: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention.(Registration No. IRCT20191112045424N1, available at: https://www.irct.ir)展开更多
Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investiga...Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.展开更多
AIM To assess prevalence of pre-existing atrial fibrillation(AF) and/or incidence of AF following liver transplantation, and the trends of patient's outcomes overtime; to evaluate impact of pre-existing AF and pos...AIM To assess prevalence of pre-existing atrial fibrillation(AF) and/or incidence of AF following liver transplantation, and the trends of patient's outcomes overtime; to evaluate impact of pre-existing AF and post-operative AF on patient outcomes following liver transplantation. METHODS A literature search was conducted utilizing MEDLINE, EMBASE and Cochrane Database from inception throughMarch 2018. We included studies that reported:(1) prevalence of pre-existing AF or incidence of AF following liver transplantation; or(2) outcomes of liver transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing randomeffect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO(International Prospective Register of Systematic Reviews, No. CRD42018093644). RESULTS Twelve observational studies with a total of 38586 liver transplant patients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing liver transplantation was 5.4%(95%CI: 4.9%-5.9%) and pooled estimated incidence of AF following liver transplantation was 8.5%(95%CI: 5.2%-13.6%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF(P = 0.08) or post-operative AF after liver transplantation(P = 0.54). The pooled OR of mortality among liver transplant recipients with pre-existing AF was 2.34(2 studies; 95%CI: 1.10-5.00). In addition, pre-existing AF is associated with postoperative cardiovascular complications among liver transplant recipients(3 studies; OR: 5.15, 95%CI: 2.67-9.92, I2 = 64%). With limited studies, two studies suggested significant association between new-onset AF and poor clinical outcomes including mortality, cerebrovascular events, post-transplant acute kidney injury, and increased risk of graft failure among liver transplant recipients(P < 0.05).CONCLUSION The overall estimated prevalence of pre-exist展开更多
Objective Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions;less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic...Objective Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions;less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic stroke.Methods Medical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year 2007.Haematocrit values within 24 hours of admission were classified as≤27%,28%-32%,33%-37%,38%-42%,43%-47% or≥48%.Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital,30-day,6-month and 1-year mortality,adjusting for age,medical comorbidities,modified Acute Physiology and Chronic Health Evaluation-III and stroke severity.Impact factors were calculated to standardise comparisons between haematocrit tier and other covariates.results Among n=3750 patients included in the analysis,the haematocrit values were≤27%in 2.1%(n=78),28%-32% in 6.2%(n=234),33%-37%in 17.9%(n=670),38%-42% in 36.4%(n=1366),43%-47% in 28.2%(n=1059)and≥48% in 9.1%(n=343).Patients with haematocrit≤27%,compared with patients in the 38%-42% range,were more likely to have died across all follow-up intervals,with statistically significant adjusted ORs(aORs)ranging from 2.5 to 3.5.Patients with polycythaemia(ie,haematocrit≥48%)were at increased risk of in-hospital mortality(aOR=2.9;95%CI 1.4 to 6.0),compared with patients with mid-range admission haematocrits.Pronounced differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity analysis.Impact factors in the 1-year mortality model were 0.46(severe anaemia),0.06(cancer)and 0.018(heart disease).Conclusions Anaemia is independently associated with an increased risk of death throughout the first year post stroke;high haematocrit is associated with early poststroke mortality.Severe anaemia is associated with 1-year mortality to a greater degree than cancer or heart disease.These data cannot address the qu展开更多
Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromi...Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.展开更多
On December 31,2019,the World Health Organization(WHO)China Country Office,was informed of pneumonia cases of unknown etiology detected in Wuhan,a city of Hubei Province in China.
Background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European countries.If and to what extent these trends affect the trends in overall survival(O...Background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European countries.If and to what extent these trends affect the trends in overall survival(OS)of patients with non-metastatic GaC at the population level remain unclear.This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC.Methods:Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands,Belgium,Sweden,Norway,and Slovenia,and the US Surveillance,Epidemiology,and End Results database.We analyzed data for each country separately.Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables,with and without including resection and chemotherapy as potential explanatory variables.Results:A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed,with an accumulated follow-up of 172,357 person-years.Without adjustment for resection,OS was improved only slightly in the US[hazard ratio(HR)_(per year)=0.99;HR_(≥vs.<2010)=0.96],and no improvement was observed in the investigated European countries,with OS even worsening in Sweden(HR_(per year)=1.03;HR_(≥vs.<2010)=1.17).After adjusting for resection,the increasing OS trend became stronger in the US(HR_(per year)=0.98;HR_(≥vs.<2010)=0.88),and the temporal trend became insignificant in Sweden.In Slovenia(HR_(per year)=0.99;HR_(≥vs.<2010)=0.92)and Norway(HR_(per year)=0.97;HR_(≥vs.<2010)=0.86),improved OS over time emerged after resection adjustment.Improved OS in patients undergoing resection was observed in the US,the Netherlands,and Norway.Adjustment for chemotherapy did not alter the observed associations.Stratified analyses by tumor location showedmostly similar resultswith the findings展开更多
基金This research was supported in part by the Japan Agency for Medical Research and Development(AMED)(JP15ck0106096 to TK)Japan Science and Tech-nology Agency(JST)Core Research for Evolutionary Science and Technology(JPMJCR1689 to RH)+5 种基金Artifi-cial Intelligence,Big Data,IoT,Cyber Security Integration Project of the Public/Private R&D Investment Strategic Expansion Program(JPMJCR18Y4 to RH)the Japan Soci-ety for the Promotion of Science(JSPS)Grant-in-Aid for Scientific Research(S)(17H06162 to HN),Grant-in-Aid for Scientific Research(B)(20H03695 to KS),Grants-in-Aid for the Tailor-Made Medical Treatment Program(BioBank Japan Project)from the Japanese Ministry of Education,Culture,Sports,ScienceandTechnology(MEXT),Princess Takamatsu Cancer Research Fund,and National Cancer Center Research and Development Fund(NCC Biobank and NCC Core Facility).The J-MICC study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer(No.17015018 to KW)Innovative Areas(No.221S0001 to KW)from MEXTby JSPS Grant-in-Aid for Scientific Research Grant(No.16H06277[CoBiA])The JPHC Study was supported by National Cancer Center Research and Development Fund since 2011(latest grant number:2020-J4)and a Grant-in-Aid for Cancer Research from the Ministry of Health,Labor and Welfare of Japan(1989-2010).ToMMoissupportedinpartbyMEXT-JSTand AMED(most recent grant numbers:JP20km0105001 and JP20km0105002)Iwate Tohoku Medical Megabank Orga-nization(Iwate Medical University)is supported in part by MEXT-JST and AMED(most recent grant numbers:JP20km0105003 and JP20km0105004).
文摘Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.
文摘Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced
基金supported in part by research grants from the Natural Science Foundation of China (No.82000744 to ZT,and 82102696 to J.F.)the Chongqing Bayu Young Scholar Award (China) (to J.F.)+5 种基金the 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau of China) (No.298 to J.F.)the National Institutes of Health (No.CA226303 to T.C.H.,DE030480 to R.R.R.)supported by the Medical Scientist Training Program of the National Institutes of Health (USA) (No.T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant (No.P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through grant number 2UL1TR002389-06 that funds the Institute for Translational Medicine (ITM)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.
文摘Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv infection-associated oxidative stress and reactive oxygen species(ROS)production.Here,we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells,and expedites adenovirus production.By stably overexpressing GAPDH in HEK293(293G)and 293pTP(293GP)cells,respectively,we demonstrated that rAdV-induced RoS production and cell apoptosis were significantly suppressed in 293G and 293GP cells.Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells.Similarly,Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells.We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells.293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells,indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production.These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production.Therefore,the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.
基金supported by the CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.,Ltd.
文摘Cervical cancer(CC)is one of the most common gynecological cancers,ranking fourth in incidence and mortality rates among women worldwide and second in China[1].Approximately 15%-61%of patients with CC develop recurrent or metastatic(r/m)disease in the first two years after initial therapy completion,with a 5-year survival rate of 17%[2].Platinum-based chemotherapy is the first-line treatment for r/mCC.
基金funding from the Strategic Research and Consulting Project of the Chinese Academy of Engineering(No.2022-XBZD-14)funding from the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-049).
文摘Background:Understanding willingness to undergo pulmonary function tests(PFTs)and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease(COPD).This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods:We collected data from participants in the"Happy Breathing Program"in China.Participants who did not follow physicians’recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs.We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs.We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results:A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study.Out of these participants,7660(90.4%)were willing to undergo PFTs.Among those who were willing to undergo PFTs but actually did not,the main reasons for not doing so were geographical inaccessibility(n=3304,43.1%)and a lack of trust in primary healthcare institutions(n=2809,36.7%).Among the 815 participants who were unwilling to undergo PFTs,over half(n=447,54.8%)believed that they did not have health problems and would only consider PFTs when they felt unwell.In the multivariable regression,individuals who were≤54 years old,residing in rural townships,with a secondary educational level,with medical reimbursement,still working,with occupational exposure to dust,and aware of the abbreviation"COPD"were more willing to undergo PFTs.Conclusions:Willingness to undergo PFTs was high among high-risk populations.Policymakers may consider implementing strategies such as providing financial incentives,promoting education,and establishing community-based pro
基金the Chang Gung Medical Foundation,No.CMRPG6L0091,No.CMRPG6L0092,and No.CMRPG6L0093.
文摘BACKGROUND Although cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)offer the potential for long-term survival in peritoneal carcinomatosis,outcomes following CRS/HIPEC vary significantly.AIM To identify the clinical factors associated with progression-free survival(PFS)after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal,ovarian,and gastric cancers.METHODS We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival(OS)in patients recruited between 2015 and 2020.Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year.Kaplan–Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS.RESULTS Of the 80 enrolled patients,39 had an unfavorable PFS(<1 year)and 41 had a favorable PFS(≥1 year).Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0(CC-0)or length of CRS≤6 h had a favorable PFS[odds ratio(OR)=0.141,P=0.004;and OR=0.361,P=0.027,respectively].In multiple logistic regression,achieving CC-0 was the strongest prognostic factor for a favorable PFS(OR=0.131,P=0.005).A peritoneal cancer index score>12 was associated with a lower rate of achieving CC-0(P=0.027).The favorable PFS group had a significantly longer OS(median 81.7 mo vs 17.0 mo,P<0.001).CONCLUSION Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival.This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.
文摘Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.
基金the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32000667)+5 种基金the Shanghai Science and Technology Innovation Action(21ZR1470600)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022264)the National Natural Science Foundation of China(81771465 and 81930033)the Science and Technology Project of the Department of Education of Jiangxi Province(GJJ211248)the Division of Intramural Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health(grant 1ZIA-Al-001169)the US-China Biomedical Collaborative Research Program(grant Al-129775).
文摘Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.
文摘Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.
基金This work was supported by the Natural Science Foundation of China[grant number 81974255]Science and Technology Research Program of Chongqing Municipal Education Commission,China[grant number KJZD-M201800401].
文摘Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.
文摘AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios(OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen(HBs Ag) positive] were included. The comparison group consisted of HBs Agnegative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of Der Simonian and Laird. The protocol for this metaanalysis is registered with PROSPERO(International Prospective Register of Systematic Reviews; no. CRD42017080657).RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBs Ag-negative recipients, HBs Ag-positive status was significantly associated with increased risk of mortality after kidney transplantation(pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBs Ag-positive recipients and year of study(slopes =-0.062, P = 0.001). HBs Agpositive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46(95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure(slopes =-0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBs Ag-positive recipients, respectively.CONCLUSION Among kidney transplant patients, there are significant as
基金Supported by Grants from Birjand University of Medical Sciences,Birjand,Iran (No.5109)。
文摘Objective: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome(PMS) and dysmenorrhea. Methods: A randomized, triple-blind, placebocontrolled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days(7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. Results: Administration of curcumin was associated with a significant increase in memory score(P=0.002), inhibitory control and selective attention(P=0.020), and total cognitive ability task(P=0.024). In addition, significant increments were found in scores of memory(3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively;P=0.035), inhibitory control and selective attention(3.0±3.7 vs. 0.4±3.7;P=0.027) and total cognitive abilities(8.3±12.3 vs. 2.2±12.4;P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. Conclusion: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention.(Registration No. IRCT20191112045424N1, available at: https://www.irct.ir)
基金supported by the Heart Association of Thailand under the Royal Patronage of H.M. the Kingthe National Research Council of Thailand
文摘Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.
文摘AIM To assess prevalence of pre-existing atrial fibrillation(AF) and/or incidence of AF following liver transplantation, and the trends of patient's outcomes overtime; to evaluate impact of pre-existing AF and post-operative AF on patient outcomes following liver transplantation. METHODS A literature search was conducted utilizing MEDLINE, EMBASE and Cochrane Database from inception throughMarch 2018. We included studies that reported:(1) prevalence of pre-existing AF or incidence of AF following liver transplantation; or(2) outcomes of liver transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing randomeffect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO(International Prospective Register of Systematic Reviews, No. CRD42018093644). RESULTS Twelve observational studies with a total of 38586 liver transplant patients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing liver transplantation was 5.4%(95%CI: 4.9%-5.9%) and pooled estimated incidence of AF following liver transplantation was 8.5%(95%CI: 5.2%-13.6%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF(P = 0.08) or post-operative AF after liver transplantation(P = 0.54). The pooled OR of mortality among liver transplant recipients with pre-existing AF was 2.34(2 studies; 95%CI: 1.10-5.00). In addition, pre-existing AF is associated with postoperative cardiovascular complications among liver transplant recipients(3 studies; OR: 5.15, 95%CI: 2.67-9.92, I2 = 64%). With limited studies, two studies suggested significant association between new-onset AF and poor clinical outcomes including mortality, cerebrovascular events, post-transplant acute kidney injury, and increased risk of graft failure among liver transplant recipients(P < 0.05).CONCLUSION The overall estimated prevalence of pre-exist
基金This work was supported by the Department of Veterans Affairs,VHA,Office of Quality and Performance,and Health Services Research&Development Service Quality Enhancement Research Initiative Service Directed Project 12-178 and Career Development Award 11-262,and the Department of Veterans Affairs,Health Services Research&Development,Stroke Quality Enhancement Research Initiative(QUERI)Rapid Response Project 09-184.The views expressed in this article are those of the authors and do not necessarily represent the view of the Department of Veterans Affairs.
文摘Objective Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions;less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic stroke.Methods Medical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year 2007.Haematocrit values within 24 hours of admission were classified as≤27%,28%-32%,33%-37%,38%-42%,43%-47% or≥48%.Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital,30-day,6-month and 1-year mortality,adjusting for age,medical comorbidities,modified Acute Physiology and Chronic Health Evaluation-III and stroke severity.Impact factors were calculated to standardise comparisons between haematocrit tier and other covariates.results Among n=3750 patients included in the analysis,the haematocrit values were≤27%in 2.1%(n=78),28%-32% in 6.2%(n=234),33%-37%in 17.9%(n=670),38%-42% in 36.4%(n=1366),43%-47% in 28.2%(n=1059)and≥48% in 9.1%(n=343).Patients with haematocrit≤27%,compared with patients in the 38%-42% range,were more likely to have died across all follow-up intervals,with statistically significant adjusted ORs(aORs)ranging from 2.5 to 3.5.Patients with polycythaemia(ie,haematocrit≥48%)were at increased risk of in-hospital mortality(aOR=2.9;95%CI 1.4 to 6.0),compared with patients with mid-range admission haematocrits.Pronounced differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity analysis.Impact factors in the 1-year mortality model were 0.46(severe anaemia),0.06(cancer)and 0.018(heart disease).Conclusions Anaemia is independently associated with an increased risk of death throughout the first year post stroke;high haematocrit is associated with early poststroke mortality.Severe anaemia is associated with 1-year mortality to a greater degree than cancer or heart disease.These data cannot address the qu
基金supported by the grants from the National Key R&D Program of China(2018YFA0801200)the National Natural Science Foundation of China(31970777,31771628,and 31601165)+1 种基金Guangdong Natural Science Fund for Distinguished Young Scholars(2017A030306024)to J.Z.the Deutsche Forschungsgemeinschaft(DFG:GO 1990/1-1)to M.G
文摘Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.
文摘On December 31,2019,the World Health Organization(WHO)China Country Office,was informed of pneumonia cases of unknown etiology detected in Wuhan,a city of Hubei Province in China.
文摘Background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European countries.If and to what extent these trends affect the trends in overall survival(OS)of patients with non-metastatic GaC at the population level remain unclear.This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC.Methods:Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands,Belgium,Sweden,Norway,and Slovenia,and the US Surveillance,Epidemiology,and End Results database.We analyzed data for each country separately.Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables,with and without including resection and chemotherapy as potential explanatory variables.Results:A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed,with an accumulated follow-up of 172,357 person-years.Without adjustment for resection,OS was improved only slightly in the US[hazard ratio(HR)_(per year)=0.99;HR_(≥vs.<2010)=0.96],and no improvement was observed in the investigated European countries,with OS even worsening in Sweden(HR_(per year)=1.03;HR_(≥vs.<2010)=1.17).After adjusting for resection,the increasing OS trend became stronger in the US(HR_(per year)=0.98;HR_(≥vs.<2010)=0.88),and the temporal trend became insignificant in Sweden.In Slovenia(HR_(per year)=0.99;HR_(≥vs.<2010)=0.92)and Norway(HR_(per year)=0.97;HR_(≥vs.<2010)=0.86),improved OS over time emerged after resection adjustment.Improved OS in patients undergoing resection was observed in the US,the Netherlands,and Norway.Adjustment for chemotherapy did not alter the observed associations.Stratified analyses by tumor location showedmostly similar resultswith the findings
