1.Chronic active EB virus infection in a child with the onset of IgA nephropathy
Shuying FAN ; Xin WANG ; Ning WEI ; Qiumei ZHOU ; Wenhong WANG
Chinese Journal of Nephrology 2024;40(2):137-140
Chronic active Epstein-Barr virus (CAEBV) infection with renal involvement is not common. The paper reported a child of multisystem-compromised CAEBV infection with the onset of IgA nephropathy (IgAN). The child presented with intermittent gross hematuria, and renal biopsy showed focal proliferative IgAN, administered methylprednisolone pulse followed by oral prednisolone treatment. Intermittent increase of blood Epstein-Barr virus (EBV) load and abnormal EBV antibody, pneumonia caused by EBV and Staphylococcus aureus-mixed infection, periappendiceal abscess, and pancytopenia occurred during treatment follow-up. The CAEBV infection was considered. Echocardiography suggested pulmonary hypertension. Head CT presented multiple calcifications in the bilateral basal ganglia. Bone marrow biopsy showed bone marrow EBV-DNA 6.5×10 3 copies per liter. Immunohistochemistry of renal biopsy showed about 50 CD8 + (scattered +) cells per high power field (HPF), about 40 CD4 + (focal +) cells per HPF (local), CD68 + (-), latent membrane protein 1 (-), EBV-encoded small RNA (scattered +) approximately 25 cells per HPF. The lymphocyte subsets infected with EBV showed CD4 + T cells EBV-DNA 3.4×10 4 copies per 1 million cells, CD8 + T cells EBV-DNA 3.3×10 5 copies per 1 million cells, B cells EBV-DNA 1.25×10 4 copies per 1 million cells, NK cells/NK T cells EBV-DNA 2.3×10 4 copies per 1 million cells. The clinical diagnosis was CAEBV infection and EBV-associated IgAN. The patient currently receives oral prednisone treatment, and it is recommended to undergo hematopoietic stem cell transplantation and treatment is under follow up.
2.Analysis of Biomechanical Characteristics of Lower Limbs During Stair Descent in Patients with Hemiplegia
Luxing ZHOU ; Qinghua MENG ; Wenhong LIU ; Nan ZHANG ; Shuaiqi CUI ; Jiao LIU
Journal of Medical Biomechanics 2024;39(1):125-131
Objective To conduct a comparative analysis of the biomechanical characteristics of the lower limbs during stair descent in patients with hemiplegia using different method to provide theoretical references for reducing fall risk during stair descent.Methods Ten healthy subjects and 20 patients with hemiplegia were selected,and their kinematic and dynamic data during stair descent were collected using the Qualisys Motion capture system and the Kistler three-dimensional dynamometer.Their biomechanical characteristics and fall risks were also analyzed.Results Compared with that of healthy subjects and patients that step on the healthy side(SHS),the range of motion(ROM)of the affected side in the lower-limb joints of patients that step on the affected side(SAS)was smaller.SHS reduced the flexion and extension ranges of the healthy side of the knee joint,and the ROM of the affected side in the lower-limb joints of SHS patients was greater than that of SAS patients.The ground reaction force(GRF)curve changes of SAS patients in left and right directions during stair descent were relatively consistent with those of normal subjects.The maximum vertical GRF of the affected side in SAS patients at the moment of landing was 1.05 times the body weight,whereas that of the healthy side was 1.25 times the body weight,which was lower than that of normal subjects(1.5 times the body weight).The maximum vertical GRF of the healthy side in SHS patients at the moment of landing was 1.85 times the body weight,which was higher than that of SAS patients and normal subjects.Conclusions Compared with that of SAS patients,the affected limb side of SHS patients has a greater ROM and vertical GRF at the moment of landing during stair descent,making SHS difficult to master.SAS is most consistent with the biomechanical characteristics during stair descent of patients with hemiplegia.
3.Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway
Wu JIABIN ; Li KE ; Zhou MUGE ; Gao HAOYANG ; Wang WENHONG ; Xiao WEIHUA
Journal of Pharmaceutical Analysis 2024;14(8):1125-1139
Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Toll-like receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or vi-ruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.
4.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
5.Value of prophylactic anticoagulation therapy in the 28-day prognosis of severe COVID-19 patients
Linlin CAO ; Yanmei ZHANG ; Wanjie ZHA ; Yuan ZHOU ; Qitian OU ; Qiwen HUANG ; Junde LI ; Miaoyun WEN ; Wenhong ZHONG
The Journal of Practical Medicine 2023;39(21):2730-2735
Objective To explore the value of prophylactic anticoagulation in the 28-day prognosis of patients with severe COVID-19.Methods The clinical data of COVID-19 patients admitted to Guangdong Provincial People's Hospital from December 2022 to January 2023 were collected,including age,gender,past medical history,routine blood test,liver and renal function,procalcitonin,coagulation function,Padua prediction score,antiviral therapy,hormonotherapy,immunotherapy and anticoagulation therapy.The patients were divided into an anticoagula-tion group and a non-anticoagulation group.The differences in various indicators were compared between the two groups.Cox regression was performed to assess the independent risk factors for 28-day mortality and the anticoagula-tion efficacy between the subgroups.Results Among 158 patients,128 received anticoagulation;There were significant differences between the two groups in case number of hypertension and critical condition,lymphocyte count,prothrombin time,D-dimer,and case number of immunotherapy.COX logistic regression showed that antico-agulation(HR = 2.25,95%CI:1.01~5.01,P = 0.048)was an independent risk factor for all-cause mortality of COVID-19 patients within 28 days.Subgroup analysis showed that anticoagulation therapy led to an increase in the 28-day mortality as level of procalcitonin of≥0.5 pg/mL(HR = 2.72,95%CI:1.05~7.04)or D-dimer of<2 000 ng/mL(HR = 9.16,95%CI:1.63~51.48).Conclusions Prophylactic anticoagulation did not reduce all-cause mortality of COVID-19 within 28 days.
6.Effects of ICMT gene silencing on the invasion and migration of human salivary adenoid cystic carcinoma cells in vitro
LU Zhou ; GONG Wenhong ; XU Xiao ; CHEN Zhenggang
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(6):400-407
Objective :
To investigate the effect of isoprene cysteine carboxymethyltransferase (ICMT) gene on the migration and invasion of salivary adenoid cystic cancer cells (SACC) and the related mechanism, to provide experimental evidence for molecular targeted therapy of SACC.
Methods:
Adenoid cystic cancer cells SACC-LM and SACC-83 were cultured in vitro, and siRNA was transfected into human SACC-LM and SACC-83 cells (experimental group) by transient transfection of a liposome vector. A blank control group and negative control group were set up respectively (transfected NC-siRNA). qRT-PCR was peformed to measure the mRNA expression of ICMT and RhoA in each group after transfection and to determine the silencing efficiency. The expression of ICMT, membrane RhoA, total RhoA, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and Rho associated with coiled helical binding protein kinase 1 (ROCK1) in each group was detected by Western blot. The proliferation abilityies of SACC cells was detected by CCK-8 assay. The migration and invasion ability of SACC cells were detected by comparing the relative healing area of cell scratch assay and the number of Transwell assay cells.
Results:
After transfection of ICMT-siRNA into SACC-LM and SACC-83 cells, the expression of ICMT gene and protein in the experimental group was significantly decreased compared with the negative control group and blank control group (P<0.05), but there were no significant differences in the expression of RhoA gene and total protein among all groups (P>0.05). The expression of RhoA membrane proteins, ROCK1, MMP-2, MMP-9 in the experimental group was significantly decreased compared with that in the negative control group and blank control group (P<0.05). Cell proliferation ability was significantly decreased (P<0.05). The migration and invasion abilities were significantly decreased (P<0.05).
Conclusion
In vitro silencing of ICMT gene can effectively inhibit the migration and invasion of human SACC-LM and SACC-83 cells, and the mechanism may be related to RhoA-ROCK signaling pathway.
7.Study on influencing factors associated with the analysis of 226Ra gamma spectra
Qiang ZHOU ; Jing ZHANG ; Baolu YANG ; Wenhong LI ; Zeshu LI ; Fei TUO
Chinese Journal of Radiological Medicine and Protection 2023;43(2):112-117
Objective:To measure the influencing factors associated with the analysis of 226Ra gamma spectra in order to obtain more acurate and precise measuring result on a basis of further optimizing the gamma spectrometry method for 226Ra activity. Methods:A laboratory-based HPGe gamma spectrometer was used to carry out the studies on tracking measurement of sample sealing time, measurement of background fluctuation with lead shielding, analytical method, and selection of characteristic gamma ray energy peak of its daughter nuclides in 226Ra measurement. Results:After the sample was sealed for 12 d, the decay products of 226Ra- 222Rn basically reached equilibrium. The day and night fluctuations of 222Rn in the shielded lead room were obvious but had no obvious regularity. The way of filling nitrogen into the shielded lead room could reduce or avoid the influence of background fluctuations. For 31 soil samples measured after 23 days of sealing, the result of using the efficiency curve method showed that the 226Ra result calculated from the 351.9 keV energy peak were generally higher than the 609.3 keV energy peak, and the higher ratio ranged from 8.0% to 20.7%. The result of relative comparison method showed that the deviation ratio of the two peaks ranged from -4.1 % to 10.3 %. Conclusions:It is recommended to consider the uncertainty attributed from decay equilibrium about 4 % of measured at 12 d after the sample is sealed. When filling nitrogen through the shielded lead chamber to avoid background fluctuations, attention must be paid to the matching relationship between the volume of the lead chamber and the nitrogen filling flow. When the efficiency curve method is used to analyze the activity of 226Ra, the 214Bi ( 609.3 keV ) energy peak has the effect of cascade coincidence addition, so 214Bi(609.3 keV) energy peak should be avoided. When the relative comparison method is used to analyze the activity of 226Ra, both two energy peaks of 214Pb ( 351.9 keV ) and 214Bi ( 609.3 keV ) can be used.
8.Prevalence and distribution of hepatitis C among high-risk populations in Pudong New Area, Shanghai City
Qiran ZHANG ; Xin XIN ; Chen CHEN ; Jialin JIN ; Shaotan XIAO ; Ping′an WU ; Jing CHEN ; Yixin ZHOU ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2023;41(7):435-439
Objective:To investigate the prevalence of positive hepatitis C virus (HCV) antibody, HCV RNA and genotype distribution of HCV in high-risk populations in Pudong New Area, Shanghai City, so that to provide evidence for making "hepatitis C micro elimination" strategies in Shanghai area.Methods:A survey with proportional sampling method was conducted among the high-risk populations, including people who inject drugs (PWID), voluntarily or compulsorily accepted drug detoxification or methadone treatment, human immunodeficiency virus voluntary counseling and testing (HIV VCT) outpatients, sexually transmitted disease (STD) outpatients, and commercial sex workers, who participated in the routine physical examination activities held by the community health service centers and public hospitals of Pudong New Area from July 2021 to November 2022. The residual plasma samples were collected from medical examinations. HCV antibody was tested in all samples. HCV RNA and HCV genotype were tested in samples with positive HCV antibody results.Results:A total of 1 000 HCV high-risk people were screened, including 453 PWID, 166 human immunodeficiency virus (HIV) infectors, 245 STD outpatients, and 136 commercial sex workers. The positive rates of HCV antibody in the four categories of personnel were 21.85%(99/453), 1.81%(3/166), 1.22%(3/245) and 0(0/136), respectively. The positive rate of HCV RNA was 42.68%(35/82) among HCV antibody positive people in high-risk populations. As much as 74.29%(26/35) of HCV RNA positive people had junior high school education or less, and 77.14%(27/35) of them were not married. Among the 12 samples tested for HCV genotype, five were genotype 3, five were genotype 6, and two were subtype 1b.Conclusions:PWID is the main high-risk HCV infection population, who should be the target of the following "hepatitis C micro elimination" strategies. The proportions of genotype 3 and genotype 6 are high in the high-risk HCV infection populations, and the pan-genotype direct-acting antiviral agent treatment may be more suitable in this situation. HCV infected persons in high-risk groups have low education level and marriage rate, which indicates that education and care in community are needed.
9.Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection.
Jin LI ; Wenhong FAN ; Jianxiong MA ; Wei ZHOU ; Xinxin PANG ; Cungui TIAN ; Guohui YANG ; Yan WANG ; Na ZHAO
Journal of Biomedical Engineering 2023;40(2):320-326
In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.
Radiopharmaceuticals
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Injections
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Hand
10.Clinical characteristics and prognosis of central nervous system tuberculosis in adults
Xian ZHOU ; Ting WANG ; Feng SUN ; Lingyun SHAO ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2022;40(4):217-223
Objective:To investigate the clinical characteristics of central nervous system tuberculosis in adults and the possible factors affecting the mortality and disability of the patients.Methods:The clinical data of patients diagnosed as "tuberculous meningitis" "tuberculous meningoencephalitis" "tuberculous cerebrospinal meningitis" or "tuberculous brain ubscess" in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University in Shanghai from January 1, 2010 to December 31, 2017 were collected, and a retrospective cohort was established. The clinical characteristics were analyzed, Medical Research Council (MRC) grade system was used to assess the severity of meningitis, and the modified Rankin Scale was used to assess the impairment of self-care. Survival rate and disability rate of the cohort were analyzed. Binary logistic regression was used for multivariate analysis. Kaplan-Meier survival curve was used for survival analysis.Results:A total of 161 patients with central nervous system tuberculosis were enrolled. Among the 161 patients, 55 cases (34.2%) were confirmed, 72 cases (44.7%) were highly suspected and 34 cases (21.1%) were suspected diagnosis. There were 56 cases (34.8%) with MRC grade Ⅰ, 76 cases (47.2%) with MRC grade Ⅱ and 29 cases (18.0%) patients with MRC grade Ⅲ before treatment. Up to January 1, 2019, ten (6.2%) patients died, 32 (19.9%) patients lost to follow-up, 119 (73.9%) patients survived. The five-year survival rate was 92.83%. There were 72 patients with no impact on life, 34 patients with moderate impact and 13 patients with severe impact. The disability rate was 39.5% (47/119). Binary logistic regression analysis showed that increasing age (odds ratio ( OR)=1.06, 95%confidence interval ( CI) 1.00 to 1.13, P=0.032) and deterioration of MRC grade during anti-tuberculosis treatment ( OR=89.00, 95% CI4.46 to 1 779.00, P=0.003) were independent risk factors for death. When severe disability and death were used as adverse outcomes, logistic regression analysis showed increasing age ( OR=1.07, 95% CI 1.01 to 1.13, P=0.035) and deterioration of MRC grade during anti-tuberculosis treatment ( OR=77.17, 95% CI4.45 to 1 337.00, P=0.003) were still independent risk factors for adverse outcomes. Conclusions:The mortality of central nervous system tuberculosis in adults in this cohort is relatively low, but the disability rate is still high. Increasing age and deterioration of MRC grade during anti-tuberculosis treatment are independent risk factors for death and disability.


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