Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a re...Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.Methods Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method,the serum creatinine （Scr） levels were also measured to reduce the bias caused by possible differences in renal excretion function.The disease progression was scored by Hoehn and Yahr （H＆Y） scales and disease durations; PD group was divided into 3 subgroups according to H＆Y scales.Independent-samples ttest was performed to analyze the differences between PD group and control group.Multiple analysis of covariance was performed to analyze the differences between PD subgroups.Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.Results PD patients were found to have significantly lower levels of serum UA than controls （（243.38±78.91） vs.（282.97±90.80） pmol/L,P〈0.01）.As the disease progression,the serum UA levels were gradually reduced.There was a significantly inverse correlation of UA levels with H＆Y scales （Rs=-0.429,P 〈0.01） and disease duration （Rs=-0.284,P 〈0.01） in PD patients of both females and males.No significant difference of the Scr level between PD patients and controls was found （（70.01±14.70） vs.（69.84±16.46） μmol/L）,and the Scr level was not involved in disease progression.Conclusion Lower serum UA levels may possess a higher risk of PD,which may be a potential useful biomarker to indicate the progression of PD.展开更多
Diabetes mellitus, together with its complications, has been increasing in prevalence worldwide. Its complications include cardiovascular disease(e.g., myocardial infarction, stroke), neuropathy, nephropathy, and eye ...Diabetes mellitus, together with its complications, has been increasing in prevalence worldwide. Its complications include cardiovascular disease(e.g., myocardial infarction, stroke), neuropathy, nephropathy, and eye complications(e.g., glaucoma, cataracts, retinopathy, and macular edema). In patients with either type 1 or type 2 diabetes mellitus, diabetic retinopathy is the leading cause of visual impairment or blindness. It is characterized by progressive changes in the retinal microvasculature. The progression from nonproliferative diabetic retinopathy to a more advanced stage of moderate to severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy occurs very quickly after diagnosis of mild nonproliferative diabetic retinopathy. The etiology of diabetic retinopathy is unclear, and present treatments have limited effectiveness. Currently diabetic retinopathy can only be diagnosed by a trained specialist, which reduces the population that can be examined. A screening biomarker of diabetic retinopathy with high sensitivity and specificity would aid considerably in identifying those individuals in need of clinical assessment and treatment. The majority of the studies reviewed identified specific microRNAs in blood serum/plasma able to distinguish diabetic patients with retinopathy from those without retinopathy and for the progresion of the disease from nonproliferative diabetic retinopathy to proliferative diabetic retinopathy. In addition,certain microRNAs in vitreous humor were dysregulated in proliferative diabetic retinopathy compared to controls. A very high percentage of patients with diabetic retinopathy develop Alzheimer’s disease. Thus, identifying diabetic retinopathy by measurement of suitable biomarkers would also enable better screening and treatment of those individuals at risk of Alzheimer’s disease.展开更多
The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It h...The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings;however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively.展开更多
Background Glioblastoma multiforme （GBM） is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecula...Background Glioblastoma multiforme （GBM） is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. Methods A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients＇ progression free survival （PFS） time and overall survival （OS） time. Results Age, preoperative Karnofsky Performance Scale （KPS） score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors （P 〈0.05） for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age 〈50 years, preoperative KPS score 〉80, KPS score change after operation 〉0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors （P 〈0.05） for patients＇ clinical outcomes. Conclusions Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.展开更多
Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been es...Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurren展开更多
Background Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 （HIV-1） infection i...Background Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 （HIV-1） infection in China. It is important to characterize HIV-l-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development. Methods A cross-sectional study was performed on HIV-l-infected former blood donors （FBDs） and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4^＋ T-cell counts with other characteristics. Results Two hundred and ninety-four HIV-l-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade （10.8 --12.8 years） ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus （HCV, 89.5%）, hepatitis B virus （HBV） co-infection was observed in only 11 HIV＋participants （3.7%）. Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4^＋ T-cell counts. The decrease of total lymphocyte counts （P〈0.001） and hemoglobin levels （P〈0.001） and the appearance of dermatosis （P=0.03） were observed in parallel with the decrease of CD4^＋ T-cell counts whereas viral loads （P〈0.001） and CD8^＋ T-cell counts （P=0.01） were inversely associated with CD4^＋ T-cell counts.Conclusions Co-infection with HCV but not HBV is highly prevalent among HIV-l-infected FBDs. CD4^＋ T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatos展开更多
Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years...Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years;however,it can occur in young children and much older adults.Factors identified in the distribution of MS include age,gender,genetics,environment,and ethnic background.Multiple sclerosis is usually associated with progressive degrees of disability.The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy.Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms,physical examination,and various tests such as magnetic resonance imaging,cerebrospinal fluid and blood tests,and electrophysiology.The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice.Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment.The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood,serum,exosomes isolated from serum,and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other.Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.展开更多
Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of ST...Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.展开更多
Multiple sclerosis （MS） is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, m...Multiple sclerosis （MS） is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.展开更多
Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neur...Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have dif- ferent rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.展开更多
AIM: To investigate the relationship between higher- order aberration (HOA) and myopic progression in schoolchildren. ·METHODS: Between April 23 2011 and August 29, 2011 in the children’s myopia outpatient clini...AIM: To investigate the relationship between higher- order aberration (HOA) and myopic progression in schoolchildren. ·METHODS: Between April 23 2011 and August 29, 2011 in the children’s myopia outpatient clinic of the West China Hospital of Sichuan University, 148 eyes of 74 schoolchildren were reviewed. HOAs for a 6 -mm pupil were measured with an aberrometer. Myopic progression rate was defined according to the change in spherical equivalent refraction (SER) divided by the time span (years). Subjects with myopic progression rate of ≥0.50 diopters (D) were classified as the ’fast’group and the subjects with myopic progression rate of 【0.50D were classified as the’slow’group. A retrospective study was conducted to compare HOA between the two groups, using root mean square (RMS) values and Zernike coefficients. ·RESULTS: The RMS values of HOA (t =2.316, P =0.02), HOA without Z 4 0 (t =2.224, P =0.03),third-order aberrations (t’ =2.62, P =0.01), and coma (t’ =2.49, P =0.01) were significantly higher in the fast group than those in the slow group. The individual Zernike coefficients of Z 3 -1 (t = -2.072, P =0.04) and Z 5 1 (Z =-2.627, P =0.01) displayed statistically significant differences between the two groups. Significant correlations were found between the RMS values of HOA (r =0.193, P =0.019), RMS values of HOA without Z 4 0 (r =0.23, P =0.005), RMS values of coma(r =0.235,P =0.004),RMS values of third-order aberrations (r =0.243, P =0.003), and the progression rate. · CONCLUSION: Our results provide evidence of a relationship between HOA and myopic progression. In a future prospective longitudinal study, we aim to verify whether HOA is a risk factor for myopic progression.展开更多
The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injec...The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.展开更多
基金This work was supported by grants from the National High Technology Research and Development Program of China （No.2007AA022460）,the State Key Development Program for Basic Research of China （No.2011CB510000）,and the National Natural Science Foundation of China （No.81071032）.
文摘Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.Methods Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method,the serum creatinine （Scr） levels were also measured to reduce the bias caused by possible differences in renal excretion function.The disease progression was scored by Hoehn and Yahr （H＆Y） scales and disease durations; PD group was divided into 3 subgroups according to H＆Y scales.Independent-samples ttest was performed to analyze the differences between PD group and control group.Multiple analysis of covariance was performed to analyze the differences between PD subgroups.Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.Results PD patients were found to have significantly lower levels of serum UA than controls （（243.38±78.91） vs.（282.97±90.80） pmol/L,P〈0.01）.As the disease progression,the serum UA levels were gradually reduced.There was a significantly inverse correlation of UA levels with H＆Y scales （Rs=-0.429,P 〈0.01） and disease duration （Rs=-0.284,P 〈0.01） in PD patients of both females and males.No significant difference of the Scr level between PD patients and controls was found （（70.01±14.70） vs.（69.84±16.46） μmol/L）,and the Scr level was not involved in disease progression.Conclusion Lower serum UA levels may possess a higher risk of PD,which may be a potential useful biomarker to indicate the progression of PD.
文摘Diabetes mellitus, together with its complications, has been increasing in prevalence worldwide. Its complications include cardiovascular disease(e.g., myocardial infarction, stroke), neuropathy, nephropathy, and eye complications(e.g., glaucoma, cataracts, retinopathy, and macular edema). In patients with either type 1 or type 2 diabetes mellitus, diabetic retinopathy is the leading cause of visual impairment or blindness. It is characterized by progressive changes in the retinal microvasculature. The progression from nonproliferative diabetic retinopathy to a more advanced stage of moderate to severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy occurs very quickly after diagnosis of mild nonproliferative diabetic retinopathy. The etiology of diabetic retinopathy is unclear, and present treatments have limited effectiveness. Currently diabetic retinopathy can only be diagnosed by a trained specialist, which reduces the population that can be examined. A screening biomarker of diabetic retinopathy with high sensitivity and specificity would aid considerably in identifying those individuals in need of clinical assessment and treatment. The majority of the studies reviewed identified specific microRNAs in blood serum/plasma able to distinguish diabetic patients with retinopathy from those without retinopathy and for the progresion of the disease from nonproliferative diabetic retinopathy to proliferative diabetic retinopathy. In addition,certain microRNAs in vitreous humor were dysregulated in proliferative diabetic retinopathy compared to controls. A very high percentage of patients with diabetic retinopathy develop Alzheimer’s disease. Thus, identifying diabetic retinopathy by measurement of suitable biomarkers would also enable better screening and treatment of those individuals at risk of Alzheimer’s disease.
基金supported by research grants from the program for Brain/MINDS Beyond program from the Japan Agency for Medical Research and Development(AMED)under Grant Number JP18dm0307024(to KK)MEXT-Supported Program for the Private University Research Branding Project+1 种基金ImPACT Program of Council for Science,Technology and Innovation(Cabinet Office,Government of Japan)JSPS KAKENHI Grant Number JP16K10327(to KK)
文摘The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings;however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively.
基金This study was supported by grants from National Key Project of Science and Technology Supporting Programs of China （No. 2007BAI05B08）, National Natural Science Foundation of China （No. 30772238） and Key Project of National Natural Science Foundation of China （No. 30730035）.
文摘Background Glioblastoma multiforme （GBM） is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. Methods A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients＇ progression free survival （PFS） time and overall survival （OS） time. Results Age, preoperative Karnofsky Performance Scale （KPS） score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors （P 〈0.05） for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age 〈50 years, preoperative KPS score 〉80, KPS score change after operation 〉0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors （P 〈0.05） for patients＇ clinical outcomes. Conclusions Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.
基金This study was supported by the National Key Basic Research Program of China(973 Program No.2015CB553902)
文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurren
基金This research was supported by the China Integrated Programs for Research on AIDS (CIPRA, U19AI51915) and the National Institute of Allergy and Infectious Diseases, National Institute of Health, USA.
文摘Background Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 （HIV-1） infection in China. It is important to characterize HIV-l-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development. Methods A cross-sectional study was performed on HIV-l-infected former blood donors （FBDs） and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4^＋ T-cell counts with other characteristics. Results Two hundred and ninety-four HIV-l-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade （10.8 --12.8 years） ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus （HCV, 89.5%）, hepatitis B virus （HBV） co-infection was observed in only 11 HIV＋participants （3.7%）. Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4^＋ T-cell counts. The decrease of total lymphocyte counts （P〈0.001） and hemoglobin levels （P〈0.001） and the appearance of dermatosis （P=0.03） were observed in parallel with the decrease of CD4^＋ T-cell counts whereas viral loads （P〈0.001） and CD8^＋ T-cell counts （P=0.01） were inversely associated with CD4^＋ T-cell counts.Conclusions Co-infection with HCV but not HBV is highly prevalent among HIV-l-infected FBDs. CD4^＋ T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatos
文摘Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years;however,it can occur in young children and much older adults.Factors identified in the distribution of MS include age,gender,genetics,environment,and ethnic background.Multiple sclerosis is usually associated with progressive degrees of disability.The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy.Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms,physical examination,and various tests such as magnetic resonance imaging,cerebrospinal fluid and blood tests,and electrophysiology.The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice.Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment.The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood,serum,exosomes isolated from serum,and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other.Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.
文摘Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.
文摘Multiple sclerosis （MS） is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.
基金supported by the National Institutes of Health (R15-HD061022 and R15-HD061022-S1)the Faculty Development Fund of the School of Pharmacy and Health Professions,Creighton University in Omaha Nebraska,USA
文摘Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have dif- ferent rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.
基金Sichuan Province Scientific Plan Project,China (No. 2010SZ0087)
文摘AIM: To investigate the relationship between higher- order aberration (HOA) and myopic progression in schoolchildren. ·METHODS: Between April 23 2011 and August 29, 2011 in the children’s myopia outpatient clinic of the West China Hospital of Sichuan University, 148 eyes of 74 schoolchildren were reviewed. HOAs for a 6 -mm pupil were measured with an aberrometer. Myopic progression rate was defined according to the change in spherical equivalent refraction (SER) divided by the time span (years). Subjects with myopic progression rate of ≥0.50 diopters (D) were classified as the ’fast’group and the subjects with myopic progression rate of 【0.50D were classified as the’slow’group. A retrospective study was conducted to compare HOA between the two groups, using root mean square (RMS) values and Zernike coefficients. ·RESULTS: The RMS values of HOA (t =2.316, P =0.02), HOA without Z 4 0 (t =2.224, P =0.03),third-order aberrations (t’ =2.62, P =0.01), and coma (t’ =2.49, P =0.01) were significantly higher in the fast group than those in the slow group. The individual Zernike coefficients of Z 3 -1 (t = -2.072, P =0.04) and Z 5 1 (Z =-2.627, P =0.01) displayed statistically significant differences between the two groups. Significant correlations were found between the RMS values of HOA (r =0.193, P =0.019), RMS values of HOA without Z 4 0 (r =0.23, P =0.005), RMS values of coma(r =0.235,P =0.004),RMS values of third-order aberrations (r =0.243, P =0.003), and the progression rate. · CONCLUSION: Our results provide evidence of a relationship between HOA and myopic progression. In a future prospective longitudinal study, we aim to verify whether HOA is a risk factor for myopic progression.
文摘The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.
