In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a n...In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.展开更多
Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the d...Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.展开更多
Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an imp...Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.展开更多
Background Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the...Background Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China. Methods Through a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 （1775 on hemodialysis （HD） and 613 on peritoneal dialysis （PD）） patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records. Results In this cohort, 1313 （55.0%） were male. The mean age was 54 years old. The median time for dialysis was 26 months （12-51 months）. Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients. Conclusions This observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.展开更多
Background:A patient’s infectivity is determined by the presence of the virus in different body fluids,secretions,and excreta.The persistence and clearance of viral RNA from different specimens of patients with 2019 ...Background:A patient’s infectivity is determined by the presence of the virus in different body fluids,secretions,and excreta.The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease(COVID-19)remain unclear.This study analyzed the clearance time and factors influencing 2019 novel coronavirus(2019-nCoV)RNA in different samples from patients with COVID-19,providing further evidence to improve the management of patients during convalescence.Methods:The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20,2020 to February 10,2020 were collected retrospectively.The reverse transcription polymerase chain reaction(RT-PCR)results for patients’oropharyngeal swab,stool,urine,and serum samples were collected and analyzed.Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive(minimum 24 h sampling interval)negative RT-PCR results for viral RNA from oropharyngeal swabs.The effects of cluster of differentiation 4(CD4)+T lymphocytes,inflammatory indicators,and glucocorticoid treatment on viral nucleic acid clearance were analyzed.Results:In the 292 confirmed cases,66 patients recovered after treatment and were included in our study.In total,28(42.4%)women and 38 men(57.6%)with a median age of 44.0(34.0-62.0)years were analyzed.After in-hospital treatment,patients’inflammatory indicators decreased with improved clinical condition.The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5(6.0-11.0)days.By February 10,2020,11 convalescent patients(16.7%)still tested positive for viral RNA from stool specimens and the other 55 patients’stool specimens were negative for 2019-nCoV following a median duration of 11.0(9.0-16.0)days after symptom onset.Among these 55 patients,43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs,with 展开更多
The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regul...The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.展开更多
The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ...The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.展开更多
AIM: To compare endoscopic submucosal dissection(ESD) and endoscopic mucosal resection(EMR) for early gastric cancer(EGC).METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Scho...AIM: To compare endoscopic submucosal dissection(ESD) and endoscopic mucosal resection(EMR) for early gastric cancer(EGC).METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Schol-ar and Cochrane library databases. Quality of each included study was assessed according to current Co-chrane guidelines. Primary endpoints were en bloc re-section rate and histologically complete resection rate. Secondary endpoints were length of procedure, post-treatment bleeding, post-procedural perforation and re-currence rate. Comparisons between the two treatment groups across all the included studies were performed by using Mantel-Haenszel test for fixed-effects mod-els(in case of low heterogeneity) or DerSimonian and Laird test for random-effects models(in case of high heterogeneity).RESULTS: Ten retrospective studies(8 full text and 2 abstracts) were included in the meta-analysis. Overall data on 4328 lesions, 1916 in the ESD and 2412 in the EMR group were pooled and analyzed. The mean operation time was longer for ESD than for EMR(stan-dardized mean difference 1.73, 95%CI: 0.52-2.95, P =0.005) and the "en bloc " and histological complete re-section rates were significantly higher in the ESD group [OR = 9.69(95%CI: 7.74-12.13), P < 0.001 and OR = 5.66,(95%CI: 2.92-10.96), P < 0.001, respectively]. As a consequence of its greater radicality, ESD provided lower recurrence rate [OR = 0.09,(95%CI: 0.05-0.17), P < 0.001]. Among complications, perforation rate was significantly higher after ESD [OR = 4.67,(95%CI, 2.77-7.87), P < 0.001] whereas the bleeding incidences did not differ between the two techniques [OR = 1.49(0.6-3.71), P = 0.39].CONCLUSION: In the endoscopic therapy of EGC, ESD showed a superior efficacy but higher complication rate with respect to EMR.展开更多
Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct ...Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones (CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and cost-effectiveness of imaging techniques used to identify CBDS increase together in a parallel way, the concept of “risk of carrying CBDS” has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of “under-studying” by poor diagnostic work up or “over-studying” by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. “Low risk” patients do not require further examination before laparoscopic cholecystectomy. Two main “philosophical approaches” face each other for patients with an “intermediate to high risk” of carrying CBDS: on one hand, the “laparoscopy-first” approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the “endoscopy-first” attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have si展开更多
Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver trans...Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver transplantation is considered the best option,but the lack of liver donors represents a major limitation.Therefore,surgical resection,offering a 5-year-survival rate of over 50%,is considered the first-choice treatment for patients with early stage HCC,whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery.However,in the recent years some trials showed that percutaneous radiofrequency ablation(RFA) can be as effective as surgical resection in terms of overall survival and recurrencefree survival rates in patients with small HCC,and a retrospective comparative study reported 1-,3-,and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection.RFA is less expensive,less invasive,with lower complication rate and shorter hospital stay than surgical resection,and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC.However,RFA is size-dependent,so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection.The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion.In this regard,the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation,which could become the ablation technique of choice in the next future.展开更多
BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that inte...BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the ex展开更多
Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic ba...Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.展开更多
Lower limb rehabilitation exoskeleton robots integrate sensing, control, and other technologies and exhibit the characteristics of bionics, robotics, information and control science, medicine, and other interdisciplin...Lower limb rehabilitation exoskeleton robots integrate sensing, control, and other technologies and exhibit the characteristics of bionics, robotics, information and control science, medicine, and other interdisciplinary areas. In this review, the typical products and prototypes of lower limb exoskeleton rehabilitation robots are introduced and stateof-the-art techniques are analyzed and summarized. Because the goal of rehabilitation training is to recover patients’ sporting ability to the normal level, studying the human gait is the foundation of lower limb exoskeleton rehabilitation robot research. Therefore, this review critically evaluates research progress in human gait analysis and systematically summarizes developments in the mechanical design and control of lower limb rehabilitation exoskeleton robots. From the performance of typical prototypes, it can be deduced that these robots can be connected to human limbs as wearable forms;further, it is possible to control robot movement at each joint to simulate normal gait and drive the patient’s limb to realize robot-assisted rehabilitation training. Therefore human–robot integration is one of the most important research directions, and in this context, rigid-flexible-soft hybrid structure design, customized personalized gait generation, and multimodal information fusion are three key technologies.展开更多
Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immu...Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.展开更多
Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide....Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders(for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.展开更多
status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay （LOS） and the in-patient cost were also compared between these two groups. Results： A...status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay （LOS） and the in-patient cost were also compared between these two groups. Results： At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin （ALB）, transferrin, and ALB parameters （P = 0.001, 0.000, and 0.000, respectively）. The complication incidences, including bone marrow suppression （20% vs. 48%, P = 0.037） and complications related infections （ 12% vs. 44%, P = 0.012）, in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy （96% vs. 76%, P - 0.103）. Furthemlore, the average LOS was decreased by 4.5 days （P = 0.001 ） and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times （P 〉 0.05） in the NST group. Conelusions： A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.展开更多
MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various s...MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 （BMP-6） has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition （EMT） through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter （miPPR-21）, we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3＇UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.展开更多
基金supported(in part)by the Entrusted Project of National Center for Medical Service Administration,National Health and Family Planning Commission China(No.[2019]099)the First Level Funding of the Second Medical Leading Talent Project in Hubei Provincethe Special Project for Emergency of the Ministry of Science and Technology(2020YFC0841300)。
文摘In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
基金supported by NIH grants AR055915 and AR054465 to DC
文摘Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.
文摘Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.
基金This work was supported by the grants from the National 973 Program （No. 2012CB517703 and No. 2011CB504005）, the National Natural Science Foundation of China （No. U0932002）, and the Public Welfare and Health Sector Research Project （No. 201002010）.
文摘Background Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China. Methods Through a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 （1775 on hemodialysis （HD） and 613 on peritoneal dialysis （PD）） patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records. Results In this cohort, 1313 （55.0%） were male. The mean age was 54 years old. The median time for dialysis was 26 months （12-51 months）. Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients. Conclusions This observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.
基金The work was supported by grants from the First-class university and first-class discipline building project of the Fudan University(No.IDF162005)the Scientific research for special subjects on 2019 novel coronavirus(No.2019-nCoV)the Shanghai Public Health Clinical Center(No.2020YJKY01)。
文摘Background:A patient’s infectivity is determined by the presence of the virus in different body fluids,secretions,and excreta.The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease(COVID-19)remain unclear.This study analyzed the clearance time and factors influencing 2019 novel coronavirus(2019-nCoV)RNA in different samples from patients with COVID-19,providing further evidence to improve the management of patients during convalescence.Methods:The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20,2020 to February 10,2020 were collected retrospectively.The reverse transcription polymerase chain reaction(RT-PCR)results for patients’oropharyngeal swab,stool,urine,and serum samples were collected and analyzed.Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive(minimum 24 h sampling interval)negative RT-PCR results for viral RNA from oropharyngeal swabs.The effects of cluster of differentiation 4(CD4)+T lymphocytes,inflammatory indicators,and glucocorticoid treatment on viral nucleic acid clearance were analyzed.Results:In the 292 confirmed cases,66 patients recovered after treatment and were included in our study.In total,28(42.4%)women and 38 men(57.6%)with a median age of 44.0(34.0-62.0)years were analyzed.After in-hospital treatment,patients’inflammatory indicators decreased with improved clinical condition.The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5(6.0-11.0)days.By February 10,2020,11 convalescent patients(16.7%)still tested positive for viral RNA from stool specimens and the other 55 patients’stool specimens were negative for 2019-nCoV following a median duration of 11.0(9.0-16.0)days after symptom onset.Among these 55 patients,43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs,with
基金Supported by A Grant from Agenzia Italiana del Farmaco(AIFA) grant code FARM6FJ728
文摘The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.
基金Supported by(in part)FARB-ex 60%2012 of the University of Salerno grant to Vajro P
文摘The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.
文摘AIM: To compare endoscopic submucosal dissection(ESD) and endoscopic mucosal resection(EMR) for early gastric cancer(EGC).METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Schol-ar and Cochrane library databases. Quality of each included study was assessed according to current Co-chrane guidelines. Primary endpoints were en bloc re-section rate and histologically complete resection rate. Secondary endpoints were length of procedure, post-treatment bleeding, post-procedural perforation and re-currence rate. Comparisons between the two treatment groups across all the included studies were performed by using Mantel-Haenszel test for fixed-effects mod-els(in case of low heterogeneity) or DerSimonian and Laird test for random-effects models(in case of high heterogeneity).RESULTS: Ten retrospective studies(8 full text and 2 abstracts) were included in the meta-analysis. Overall data on 4328 lesions, 1916 in the ESD and 2412 in the EMR group were pooled and analyzed. The mean operation time was longer for ESD than for EMR(stan-dardized mean difference 1.73, 95%CI: 0.52-2.95, P =0.005) and the "en bloc " and histological complete re-section rates were significantly higher in the ESD group [OR = 9.69(95%CI: 7.74-12.13), P < 0.001 and OR = 5.66,(95%CI: 2.92-10.96), P < 0.001, respectively]. As a consequence of its greater radicality, ESD provided lower recurrence rate [OR = 0.09,(95%CI: 0.05-0.17), P < 0.001]. Among complications, perforation rate was significantly higher after ESD [OR = 4.67,(95%CI, 2.77-7.87), P < 0.001] whereas the bleeding incidences did not differ between the two techniques [OR = 1.49(0.6-3.71), P = 0.39].CONCLUSION: In the endoscopic therapy of EGC, ESD showed a superior efficacy but higher complication rate with respect to EMR.
文摘Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones (CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and cost-effectiveness of imaging techniques used to identify CBDS increase together in a parallel way, the concept of “risk of carrying CBDS” has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of “under-studying” by poor diagnostic work up or “over-studying” by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. “Low risk” patients do not require further examination before laparoscopic cholecystectomy. Two main “philosophical approaches” face each other for patients with an “intermediate to high risk” of carrying CBDS: on one hand, the “laparoscopy-first” approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the “endoscopy-first” attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have si
文摘Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver transplantation is considered the best option,but the lack of liver donors represents a major limitation.Therefore,surgical resection,offering a 5-year-survival rate of over 50%,is considered the first-choice treatment for patients with early stage HCC,whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery.However,in the recent years some trials showed that percutaneous radiofrequency ablation(RFA) can be as effective as surgical resection in terms of overall survival and recurrencefree survival rates in patients with small HCC,and a retrospective comparative study reported 1-,3-,and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection.RFA is less expensive,less invasive,with lower complication rate and shorter hospital stay than surgical resection,and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC.However,RFA is size-dependent,so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection.The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion.In this regard,the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation,which could become the ablation technique of choice in the next future.
基金Supported by the National Natural Science Foundation of China,No.81503656the National Key Basic Research Program of China(973 Program),No.2015CB554501 and No.2009CB522900
文摘BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the ex
文摘Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.
基金Supported by National Key R&D Program of China(Grant No.2016YFE0105000)National Natural Science Foundation of China(Grant No.91848104)
文摘Lower limb rehabilitation exoskeleton robots integrate sensing, control, and other technologies and exhibit the characteristics of bionics, robotics, information and control science, medicine, and other interdisciplinary areas. In this review, the typical products and prototypes of lower limb exoskeleton rehabilitation robots are introduced and stateof-the-art techniques are analyzed and summarized. Because the goal of rehabilitation training is to recover patients’ sporting ability to the normal level, studying the human gait is the foundation of lower limb exoskeleton rehabilitation robot research. Therefore, this review critically evaluates research progress in human gait analysis and systematically summarizes developments in the mechanical design and control of lower limb rehabilitation exoskeleton robots. From the performance of typical prototypes, it can be deduced that these robots can be connected to human limbs as wearable forms;further, it is possible to control robot movement at each joint to simulate normal gait and drive the patient’s limb to realize robot-assisted rehabilitation training. Therefore human–robot integration is one of the most important research directions, and in this context, rigid-flexible-soft hybrid structure design, customized personalized gait generation, and multimodal information fusion are three key technologies.
文摘Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.
基金FESR P.O.Apulia Region 2007-2013-Action 1.2.4,No.3Q5AX31
文摘Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders(for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.
文摘status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay （LOS） and the in-patient cost were also compared between these two groups. Results： At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin （ALB）, transferrin, and ALB parameters （P = 0.001, 0.000, and 0.000, respectively）. The complication incidences, including bone marrow suppression （20% vs. 48%, P = 0.037） and complications related infections （ 12% vs. 44%, P = 0.012）, in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy （96% vs. 76%, P - 0.103）. Furthemlore, the average LOS was decreased by 4.5 days （P = 0.001 ） and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times （P 〉 0.05） in the NST group. Conelusions： A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.
文摘MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 （BMP-6） has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition （EMT） through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter （miPPR-21）, we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3＇UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.
