Objective To analyze the clinical features,therapeutic management and risk factors for mortality of patients with severe novel A(H1N1)influenza in Shanghai,China.Methods All patients were diagnosed by influenza A(H1N1...Objective To analyze the clinical features,therapeutic management and risk factors for mortality of patients with severe novel A(H1N1)influenza in Shanghai,China.Methods All patients were diagnosed by influenza A(H1N1)virus mRNA detection.Chest CT scan,routine blood,hepatic function,humoral and cellular immunity,sputum smears,and sputum cultures were performed.Logistic analysis was applied to identify risk factors for mortality.Results Total of 68 patients were enrolled in this study,the primary clinical symptoms including cough(66,97.1%),expectoration(41,60.3%),and polypnea(41,60.3%).Altogether,37(54.4%)and 11(16.2%)patients were infected with bacterial and fungal,respectively.CT scan demonstrated that 67(98.6%)patients had pneumonia.Oxygen therapy,oseltamivir,antibiotic and antifungal drugs were performed in 68(100%),66(97.1%),39(57.4%),and 11(16.2%)patients,respectively.Finally,4 of 68 patients died.Logistic analysis demonstrated that there was a significant correlation between the percentage of neutrophils and mortality before therapy and direct bilirubin content and mortality after therapy,respectively.Conclusions Patients with severe H1N1 influenza were susceptible to bacterial and/or fungal infection.The risk factors for mortality may be associated with pre-therapeutic neutrophil percentage and post-therapeutic direct bilirubin content.展开更多
BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,comme...BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,China.AIM To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.METHODS This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III trial.The participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 wk.Starting from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week.In this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion rates.RESULTS For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B(4.46 vs 4.70 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA(87.23%vs 94.12%in Group A vs Group B,respectively;P>0.05).Finally,similar percentages of CHB patients(HBeAg-positive or HBeAg-negative)in the two groups exhibited normalization of ALT(80.14%vs 84.57%in Group A vs Group B,respectively;P>0.05),and similar incidences of adverse events were observed(106 vs 104 in Group A vs Group B,respectively;P>0.05).CONCLUSION Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.展开更多
AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute ...AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P < 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.展开更多
AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the study.The third-g...AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the study.The third-generation Elecsys Anti-HCV assay(Roche Diagnostics GmbH,Sandhofer Strasse 116,D-68305,Mannheim,Germany)was used to screen for antibodies against HCV.The RIBA strip,a supplemental antiHCV test with high specificity,was performed on all of the samples that tested positive during the initial screening.All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer(Roche Diagnostics)for direct detection of HCV RNA.All of the HCV RNA-positive samples were sequenced for genotype determination.RESULTS:The preliminary screening identified 262(60.6%)subjects who were seropositive for HCV.Of the 62 females and 200 males seropositive subjects,16(16.7%)and 65(19.3%),respectively,were confirmed by RIBA,yielding an overall HCV seropositive rate of18.8%.Four female(6.5%)and 14 male(7.0%)subjects tested positive for HCV RNA,indicating an active infection rate of 4.2%for the entire study population.The 18 HCV RNA-positive serum samples were genotyped.Seven individuals were genotype 1b,and four were genotype 1a.One individual each was infected with genotypes 2a,2b and 3a.Four subjects were coinfected with multiple strains:two with genotypes 1a and 2a,and two with genotypes 1b and 2a.The active infection rate among HCV-seropositive individuals was22.2%,which was significantly lower than most estimates.CONCLUSION:The prevalence of HCV is relatively low among IDUs in Shanghai,with a spontaneous recovery rate much higher than previous estimates.展开更多
Hepatitis E virus(HEV)is the most common cause of acute liver failure(LF)and one of the most common factors causing acute injury in acute-on-chronic LF(ACLF).When HEV-related LF occurs,a series of changes take place i...Hepatitis E virus(HEV)is the most common cause of acute liver failure(LF)and one of the most common factors causing acute injury in acute-on-chronic LF(ACLF).When HEV-related LF occurs,a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment.The changed types and distribution of immune cells(infiltrating macrophages and increased lymphocytes)in liver tissue,as well the increased proinflammatory cytokines and chemokines in the blood,indicate that the occurrence and progression of HEVrelated LF are closely related to immune imbalance.The clinical features and immune reaction in the body during HEV-related acute LF(ALF)and ACLF are complicated.This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.展开更多
Objective:This study aims to evaluate the effects of a symptom management intervention(SMI)based on symptom management group sessions combined with a mobile health(mHealth)application(app)on the knowledge of symptom m...Objective:This study aims to evaluate the effects of a symptom management intervention(SMI)based on symptom management group sessions combined with a mobile health(mHealth)application(app)on the knowledge of symptom management,the certainty of symptom self-management,symptom severity,symptom distress,medication adherence,social support,and quality of life among persons living with HIV(PLWH)in China.Methods:A parallel randomized controlled trial with 61 PLWH was conducted in Shanghai,China.The participants in the control group(n¼30)downloaded the Symptom Management(SM)app according to their needs and preferences,and received routine follow-ups.The participants in the intervention group(n¼31)were guided to download and use the SM app,and received four tailored weekly group sessions at routine follow-ups.Each group session lasted for approximately 2 h and targeted one of the major modules of the SM app.All the outcomes were assessed at baseline and post-intervention.The study was registered with the Chinese Clinical Trial Registry(ChiCTR1900024821).Results:The symptom management knowledge and certainty of symptom self-management were significantly improved after the intervention(all P<0.01).Compared with the control group,the scores of symptoms reasons knowledge score improved 11.47 points(95%CI:3.41,19.53)and scores of symptoms self-management knowledge score improved 12.80 points(95%CI:4.55,21.05)in the intervention group after controlling for covariates.However,other outcomes did not show statistically significant differences between the intervention group and the control group(P>0.05).Conclusion:The SMI could improve PLWH’s symptom management knowledge and certainty of symptom self-management.Multi-center studies with larger sample sizes and longer follow-ups are needed to further understand the effects of SM app on ameliorating symptom severity and symptom distress.More innovative strategies are also needed to promote and maintain the sustainability of the SM app.展开更多
Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,an...Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,and nurses owing to their advantages of convenient carrying,a long maintenance period,low complications,and a high quality of life for patients.Currently,medical personnel that handle TIAP implantation and management in China are from different areas of healthcare,including surgery,internal medicine,radiology,nurse anesthesia,vascular access,etc.,and many only handle TIAP as a part of their duties.Therefore,the operating procedures and steps for the diagnosis and treatment of complications of TIAP vary from person to person,resulting in different incidence and treatment methods for complications in the implantation and use of TIAP in different medical units.Based on this,we have updated the Shanghai expert consensus on TIAPs from 2015 and explored the diagnosis and treatment procedures of related complications while continuing to emphasize standardized implantation and maintenance.展开更多
BACKGROUND Management of retroperitoneal sarcoma(RPS)involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team(MDT)members during surgical treatment.AIM To summarize the cl...BACKGROUND Management of retroperitoneal sarcoma(RPS)involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team(MDT)members during surgical treatment.AIM To summarize the clinicopathologic features of RPS involving the iliac artery and our retroperitoneal soft tissue tumor MDT surgical experience.METHODS In this retrospective study,15 patients with RPS involving the iliac artery who underwent surgery at our retroperitoneal soft tissue tumor center from July 2004 to June 2020 were analyzed.Statistical analyses were performed by Student’s ttest with SPSS 16.0.RESULTS Complete tumor resection(R0/R1)and iliac artery reconstruction were achieved in all 15 patients.All the operations were successful,with no serious complications or perioperative death.Resection with bilateral iliac artery reconstruction required a higher intraoperative blood transfusion volume than resection with unilateral iliac artery reconstruction.Recurrent cases were more likely to bleed and required a higher blood transfusion volume than primary cases.As of January 2021,11 patients were alive,and 4 had died.Local recurrence occurred in two patients,one of whom developed liver metastasis.CONCLUSION Resection of RPS involving iliac vessels is feasible and effective when performed by MDT members.Iliac artery oncovascular resection and reconstruction are key to a successful operation.Adequate blood preparation is important for successful completion of surgery.展开更多
The authors regret that the clinical trial registration number appear incorrectly due to their unintentional mistake,which matched another of their clinical trial project.The correct registration number is(ChiCTR20000...The authors regret that the clinical trial registration number appear incorrectly due to their unintentional mistake,which matched another of their clinical trial project.The correct registration number is(ChiCTR2000039097).The authors would like to apologise for any inconvenience caused.展开更多
Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil?, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase l...Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil?, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in patients with viral hepatitis (VH). However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The main objective of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil?) treatment in reducing the serum TBil by 50%. Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected. Results The safety set (SS) included 834 patients and the full analysis set included 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased≥ 50%versus baseline after 14 days treatment in 288 (37.7%) patients (95%CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the drug. Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with signiifcant reduction of TBil levels in more than 30%of patients 14 days after treatment initiation.展开更多
Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissue...Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.展开更多
Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Hea...Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.展开更多
AIM: To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). METHODS: A total of 137 consecutive ...AIM: To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). METHODS: A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase (ALT) level. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio (LR) of aminotransferase/platelet ratio index (APRI) ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid (HA) cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis (fibrosis stages 2 and 4) and no to mild fibrosis/cirrhosis (fibrosis stages 0 and 1). RESULTS: The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis (stages 2-4) in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION: The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis (stages 2-4) in Crib patients.展开更多
AIM: To optimize the viral persistence rate in a hydrodynamic injection(HI) based hepatitis B virus(HBV) transfection mouse model.METHODS:(1) 5-6-wk-old male C3H/He N and C57BL/6 mice were hydrodynamically injected wi...AIM: To optimize the viral persistence rate in a hydrodynamic injection(HI) based hepatitis B virus(HBV) transfection mouse model.METHODS:(1) 5-6-wk-old male C3H/He N and C57BL/6 mice were hydrodynamically injected with 10 μg endotoxin-free p AAV/HBV1.2 plasmid DNA via the tail vein. Hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag) and HBV DNA, both in the serum and liver, were detected at different time points post HI by ELISA, immunohistochemical staining or quantitative polymerase chain reaction(PCR);(2) male C3H/He N and C57BL/6 mice, either hydrodynamically injected mice at 10 wk post HI or na?ve mice, were all immunized subcutaneously with 5 μg HBs Ag formulated in complete Freund's adjuvant three times at a 2-wk interval. Two weeks after the final immunization, splenocytes were isolated for T cell function analysis by ELISPOT assay; and(3) five weeks post HI, C3H/He N mice were intragastrically administered 0.1 mg/kg entecavir once a day for 14 d, or were intraperitoneally injected with 1 mg/kg interferon(IFN)-α twice a week for 2 wk, or were treated with PBS as controls. The sera were collected and assayed for HBV DNA on days 0, 7 and 14 after drug treatment. RESULTS:(1) Approximately 90%(22/25) of the injected C3H/He N mice were still HBs Ag-positive at 46 wk post HI, whereas HBs Ag in C57BL/6 mice were completely cleared at 24 wk. Serum levels of HBe Ag in C3H/He N mice were higher than those in C57BL/6 mice from 4 wk to 46 wk. HBV DNA levels in the hydrodynamically injected C3H/He N mice were higher than those in the C57BL/6 mice, both in the serum(from 4 wk to 46 wk) and in the liver(detected at 8 wk and 46 wk post HI). Histology showed that hepatitis B core antigen and HBs Ag were expressed longer in the liver of C3H/He N mice than in C57BL/6;(2) HBs Ag specific T cell responses after HBs Ag vaccination in hydrodynamically injected C3H/He N and C57BL/6 mice, or naive control mice were detected by ELISPOT assay. After stimulation with HBs Ag, the frequencies of IFN-γ producing splenocytes in the hydrodynamically injected C3H/He N mice were significantly lower than those in hydrodynamically injected C57BL/6 mice, control C3H/He N and control C57BL/6 mice, which were 0, 17 ± 7, 18 ± 10, and 41 ± 10 SFCs/106 splenocytes, respectively, and the mean spot sizes showed the same pattern. Even just stimulated with PMA and ionomysin, T-cell responses elicited in the vaccinated control C3H/He N were much higher than those in hydrodynamically injected C3H/He N mice; and(3) For drug treatment experiments on the hydrodynamically injected C3H/He N mice, serum HBV DNA levels in the entecavir treatment group declined(131.2 folds, P < 0.01) on day 7 after treatment and kept going down. In the group of IFN-α treatment, serum HBV DNA levels declined to a lowest point(6.42 folds, P < 0.05) on 7 d after treatment and then rebounded.CONCLUSION: We have developed a novel HI-based HBV transfection model using C3H/He N mice, which had a higher HBV persistence rate than the classic C57BL/6 mouse model.展开更多
Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In thi...Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In this re- port, we describe the first case of acquired immune de- ficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with am- photericin B for 3 mo, while receiving concomitant ther- apy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 too. R marneffei should be considered in the differential di- agnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with R marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.展开更多
Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus(HIV).However,little is known about the treatment options and survival rate of lymphoma in the Chinese peop...Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus(HIV).However,little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV(PLHIV).Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide,prednisone,vincristine,cyclophosphamide,doxorubicin,and rituximab(DA-EPOCH-R)with standard cyclophosphamide,doxorubicin,vincristine,prednisone and rituximab(R-CHOP)as front line therapy for PLHIV with diffuse large B-cell lymphoma(DLBCL)receiving modern combined antiretroviral therapy(cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019.The demographic and clinical data were collected,and overall survival(OS)and progression-free survival(PFS)analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis.Additionally,a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months(interquartile range[IQR]:8-29 months).The proportion of high international prognostic index(IPI)patients was much larger in the DA-EPOCH-R group(n=29)than that in the R-CHOP group(n=25).The CD4 cell counts and HIV RNA levels were not significantly different between the two groups.The 2-year OS for all patients was 73%.However,OS was not significantly different between the two groups,with a 2-year OS rate of 78%for the DA-EPOCH-R group and 66%for the R-CHOP group.Only an IPI greater than 3 was associated with a decrease in OS,with a hazard ratio of 5.0.The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy.No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.展开更多
Background:There are remarkable genetic differences between animal major histocompatibility complex(MHC)systems and the human leukocyte antigen(HLA)system.HLA transgenic humanized mouse model systems offer a much bett...Background:There are remarkable genetic differences between animal major histocompatibility complex(MHC)systems and the human leukocyte antigen(HLA)system.HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-Arestricted responses against infection in human.Methods:A recombinant gene encoding the chimeric HLA-A30 monochain was constructed.This HHD molecule contains the following:α1-α2 domains of HLA-A30,α3 and cytoplasmic domains of H-2D~b,linked at its N-terminus to the C-terminus of humanβ2m by a 15-amino-acid peptide linker.The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome(BAC)CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination.Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes.This humanized mouse model was further used to assess the immune responses against influenza A virus(H1N1)pdm09 clinically isolated from human patients.Immune cell population,cytokine production,and histopathology in the lung were analyzed.Results:We describe a novel humanβ2m-HLA-A30(α1α2)-H-2D~b(α3 transmembrane cytoplasmic)(HHD)monochain transgenic mouse strain,which contains the intact HLA-A01 gene locus including 49 kb 5’-UTR and 74 kb 3’-UTR of HLA-A01*01.Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained,and the robust expression of exogenous transgene was detected in various tissues from A30-18#and A30-19#lines encompassing the intact flanking sequences.Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice.Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice,and induced the rapid increase of cytokines,including IFN-γ,TNF-α,and IL-6,in both HLA-A30 humanized Tg mice and wild-type mice.The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9#line at 3 days post-infection(dpi).Conclusions:We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse,which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development,and support the study of HLA-A-restricted responses against infection in humans.展开更多
In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degree...In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.展开更多
AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphthe...AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.展开更多
Objective:The overarching objective of this study was to examine the effectiveness of HIV symptom management guidelines in China in reducing the incidence and severity of symptoms and improving patients'quality of...Objective:The overarching objective of this study was to examine the effectiveness of HIV symptom management guidelines in China in reducing the incidence and severity of symptoms and improving patients'quality of life.Methods:We conducted a controlled,pre-and post-implementation design in the HIV/AIDS inpatient unit in Shanghai.Patients recruited from November 2014 to February 2015 were in the intervention group and those from October 2013 to February 2014 were in the control group.There were 74 patients in each group.Participants in the intervention group received interventions based on the HIV symptom management guidelines.Overall symptom severity,depression,and quality of life were measured in two groups at baseline,week 4,and week 8.Results:Totally 126 patients completed the research,65 in the intervention group and 61 in the control group.The total symptom severity scores showed a statistically significant difference between groups across time(P<0.05).It showed that frequencies of fatigue(36.9%vs.44.3%),fever(6.2%vs.11.5%),loss in weight(9.2%vs.16.4%),mouth ulcers(12.3%vs.16.4%),headaches(9.2%vs.19.7%)and depression(F=1.09,P>0.05)in the intervention group were lower than those in the control group in week 8 without statistical significance.The multilevel growth mixture model indicated a greater increase in the total score of quality of life for the group treated according to the symptom management guidelines(P=0.04).Conclusion:The evidence-based HIV symptom management guidelines can improve a patient's quality of life and relieve negative symptoms.The guidelines can be applied in a similar context to other HIV/AIDS units or clinics.展开更多
基金supported by a grant-in-aid from the state administration of Traditional Chinese Medicine of China for the infectious disease prophylaxis and treatment through grant number 200907001-2
文摘Objective To analyze the clinical features,therapeutic management and risk factors for mortality of patients with severe novel A(H1N1)influenza in Shanghai,China.Methods All patients were diagnosed by influenza A(H1N1)virus mRNA detection.Chest CT scan,routine blood,hepatic function,humoral and cellular immunity,sputum smears,and sputum cultures were performed.Logistic analysis was applied to identify risk factors for mortality.Results Total of 68 patients were enrolled in this study,the primary clinical symptoms including cough(66,97.1%),expectoration(41,60.3%),and polypnea(41,60.3%).Altogether,37(54.4%)and 11(16.2%)patients were infected with bacterial and fungal,respectively.CT scan demonstrated that 67(98.6%)patients had pneumonia.Oxygen therapy,oseltamivir,antibiotic and antifungal drugs were performed in 68(100%),66(97.1%),39(57.4%),and 11(16.2%)patients,respectively.Finally,4 of 68 patients died.Logistic analysis demonstrated that there was a significant correlation between the percentage of neutrophils and mortality before therapy and direct bilirubin content and mortality after therapy,respectively.Conclusions Patients with severe H1N1 influenza were susceptible to bacterial and/or fungal infection.The risk factors for mortality may be associated with pre-therapeutic neutrophil percentage and post-therapeutic direct bilirubin content.
基金Supported by The 13th Five-year Science and Technology Major Project of China,on the Prevention and Treatment of Major Infectious Diseases,No.2017ZX10202202.
文摘BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,China.AIM To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.METHODS This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III trial.The participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 wk.Starting from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week.In this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion rates.RESULTS For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B(4.46 vs 4.70 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA(87.23%vs 94.12%in Group A vs Group B,respectively;P>0.05).Finally,similar percentages of CHB patients(HBeAg-positive or HBeAg-negative)in the two groups exhibited normalization of ALT(80.14%vs 84.57%in Group A vs Group B,respectively;P>0.05),and similar incidences of adverse events were observed(106 vs 104 in Group A vs Group B,respectively;P>0.05).CONCLUSION Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.
基金Supported by National Program on Key Basic Research Project(973 Program),No.2015CB554300(to Zhang SY)the Joint Research Program for Emerging Frontier Technology in the Municipal Hospital of Shanghai,China,No.SHDC12015129
文摘AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P < 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.
基金Supported by Science and Technology Commission Xuhui District and Xuhui Health Bureau of ShanghaiNo.SHXH201226
文摘AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the study.The third-generation Elecsys Anti-HCV assay(Roche Diagnostics GmbH,Sandhofer Strasse 116,D-68305,Mannheim,Germany)was used to screen for antibodies against HCV.The RIBA strip,a supplemental antiHCV test with high specificity,was performed on all of the samples that tested positive during the initial screening.All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer(Roche Diagnostics)for direct detection of HCV RNA.All of the HCV RNA-positive samples were sequenced for genotype determination.RESULTS:The preliminary screening identified 262(60.6%)subjects who were seropositive for HCV.Of the 62 females and 200 males seropositive subjects,16(16.7%)and 65(19.3%),respectively,were confirmed by RIBA,yielding an overall HCV seropositive rate of18.8%.Four female(6.5%)and 14 male(7.0%)subjects tested positive for HCV RNA,indicating an active infection rate of 4.2%for the entire study population.The 18 HCV RNA-positive serum samples were genotyped.Seven individuals were genotype 1b,and four were genotype 1a.One individual each was infected with genotypes 2a,2b and 3a.Four subjects were coinfected with multiple strains:two with genotypes 1a and 2a,and two with genotypes 1b and 2a.The active infection rate among HCV-seropositive individuals was22.2%,which was significantly lower than most estimates.CONCLUSION:The prevalence of HCV is relatively low among IDUs in Shanghai,with a spontaneous recovery rate much higher than previous estimates.
基金Shanghai Shenkang Hospital Development Center,No.SHDC12020109Shanghai Association for Science and Technology,No.21S11905600Plan of the Research Project Funded by Shanghai Public Health Clinical Centre,No.KY-GW-2022-22.
文摘Hepatitis E virus(HEV)is the most common cause of acute liver failure(LF)and one of the most common factors causing acute injury in acute-on-chronic LF(ACLF).When HEV-related LF occurs,a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment.The changed types and distribution of immune cells(infiltrating macrophages and increased lymphocytes)in liver tissue,as well the increased proinflammatory cytokines and chemokines in the blood,indicate that the occurrence and progression of HEVrelated LF are closely related to immune imbalance.The clinical features and immune reaction in the body during HEV-related acute LF(ALF)and ACLF are complicated.This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.
基金This paper is part of a project funded by the National Natural Science Foundation of China(Grant Number 71673057)the China Scholarship Council(No.201906100135).
文摘Objective:This study aims to evaluate the effects of a symptom management intervention(SMI)based on symptom management group sessions combined with a mobile health(mHealth)application(app)on the knowledge of symptom management,the certainty of symptom self-management,symptom severity,symptom distress,medication adherence,social support,and quality of life among persons living with HIV(PLWH)in China.Methods:A parallel randomized controlled trial with 61 PLWH was conducted in Shanghai,China.The participants in the control group(n¼30)downloaded the Symptom Management(SM)app according to their needs and preferences,and received routine follow-ups.The participants in the intervention group(n¼31)were guided to download and use the SM app,and received four tailored weekly group sessions at routine follow-ups.Each group session lasted for approximately 2 h and targeted one of the major modules of the SM app.All the outcomes were assessed at baseline and post-intervention.The study was registered with the Chinese Clinical Trial Registry(ChiCTR1900024821).Results:The symptom management knowledge and certainty of symptom self-management were significantly improved after the intervention(all P<0.01).Compared with the control group,the scores of symptoms reasons knowledge score improved 11.47 points(95%CI:3.41,19.53)and scores of symptoms self-management knowledge score improved 12.80 points(95%CI:4.55,21.05)in the intervention group after controlling for covariates.However,other outcomes did not show statistically significant differences between the intervention group and the control group(P>0.05).Conclusion:The SMI could improve PLWH’s symptom management knowledge and certainty of symptom self-management.Multi-center studies with larger sample sizes and longer follow-ups are needed to further understand the effects of SM app on ameliorating symptom severity and symptom distress.More innovative strategies are also needed to promote and maintain the sustainability of the SM app.
文摘Totally implantable access ports(TIAPs)are used for patients with poor peripheral vascular support requiring central venous access.In recent years,TIAPs have been gradually accepted and promoted by patients,doctors,and nurses owing to their advantages of convenient carrying,a long maintenance period,low complications,and a high quality of life for patients.Currently,medical personnel that handle TIAP implantation and management in China are from different areas of healthcare,including surgery,internal medicine,radiology,nurse anesthesia,vascular access,etc.,and many only handle TIAP as a part of their duties.Therefore,the operating procedures and steps for the diagnosis and treatment of complications of TIAP vary from person to person,resulting in different incidence and treatment methods for complications in the implantation and use of TIAP in different medical units.Based on this,we have updated the Shanghai expert consensus on TIAPs from 2015 and explored the diagnosis and treatment procedures of related complications while continuing to emphasize standardized implantation and maintenance.
文摘BACKGROUND Management of retroperitoneal sarcoma(RPS)involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team(MDT)members during surgical treatment.AIM To summarize the clinicopathologic features of RPS involving the iliac artery and our retroperitoneal soft tissue tumor MDT surgical experience.METHODS In this retrospective study,15 patients with RPS involving the iliac artery who underwent surgery at our retroperitoneal soft tissue tumor center from July 2004 to June 2020 were analyzed.Statistical analyses were performed by Student’s ttest with SPSS 16.0.RESULTS Complete tumor resection(R0/R1)and iliac artery reconstruction were achieved in all 15 patients.All the operations were successful,with no serious complications or perioperative death.Resection with bilateral iliac artery reconstruction required a higher intraoperative blood transfusion volume than resection with unilateral iliac artery reconstruction.Recurrent cases were more likely to bleed and required a higher blood transfusion volume than primary cases.As of January 2021,11 patients were alive,and 4 had died.Local recurrence occurred in two patients,one of whom developed liver metastasis.CONCLUSION Resection of RPS involving iliac vessels is feasible and effective when performed by MDT members.Iliac artery oncovascular resection and reconstruction are key to a successful operation.Adequate blood preparation is important for successful completion of surgery.
文摘The authors regret that the clinical trial registration number appear incorrectly due to their unintentional mistake,which matched another of their clinical trial project.The correct registration number is(ChiCTR2000039097).The authors would like to apologise for any inconvenience caused.
文摘Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil?, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in patients with viral hepatitis (VH). However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The main objective of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil?) treatment in reducing the serum TBil by 50%. Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected. Results The safety set (SS) included 834 patients and the full analysis set included 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased≥ 50%versus baseline after 14 days treatment in 288 (37.7%) patients (95%CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the drug. Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with signiifcant reduction of TBil levels in more than 30%of patients 14 days after treatment initiation.
基金Shanghai Science and Technology Commission“R&D Public Service Platform and Institutional Capacity Improvement Project”,Grant/Award Number:21DZ2291300National Science and Technology Major Project,Grant/Award Number:2017ZX10304402-001-006 and 2017ZX10304402-001-012Start-on Funding from Shanghai Public Health Clinical Center,Grant/Award Number:KY-GW-2019-11,KYGW-2019-19 and KY-GW-2021-39。
文摘Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.
基金funded by the grants from the National Key Research and Development Program of China[2021YFC2301503,2022YFC2302900]the National Natural and Science Foundation of China[82171739,82171815,81873884]。
文摘Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.
文摘AIM: To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). METHODS: A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase (ALT) level. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio (LR) of aminotransferase/platelet ratio index (APRI) ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid (HA) cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis (fibrosis stages 2 and 4) and no to mild fibrosis/cirrhosis (fibrosis stages 0 and 1). RESULTS: The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis (stages 2-4) in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION: The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis (stages 2-4) in Crib patients.
基金Supported by Shanghai Municipal Fund for Science and Technology Development,No.13140902200 and No.12140900300National Key Basic Research Development Program(973 Program),No.2012CB519005
文摘AIM: To optimize the viral persistence rate in a hydrodynamic injection(HI) based hepatitis B virus(HBV) transfection mouse model.METHODS:(1) 5-6-wk-old male C3H/He N and C57BL/6 mice were hydrodynamically injected with 10 μg endotoxin-free p AAV/HBV1.2 plasmid DNA via the tail vein. Hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag) and HBV DNA, both in the serum and liver, were detected at different time points post HI by ELISA, immunohistochemical staining or quantitative polymerase chain reaction(PCR);(2) male C3H/He N and C57BL/6 mice, either hydrodynamically injected mice at 10 wk post HI or na?ve mice, were all immunized subcutaneously with 5 μg HBs Ag formulated in complete Freund's adjuvant three times at a 2-wk interval. Two weeks after the final immunization, splenocytes were isolated for T cell function analysis by ELISPOT assay; and(3) five weeks post HI, C3H/He N mice were intragastrically administered 0.1 mg/kg entecavir once a day for 14 d, or were intraperitoneally injected with 1 mg/kg interferon(IFN)-α twice a week for 2 wk, or were treated with PBS as controls. The sera were collected and assayed for HBV DNA on days 0, 7 and 14 after drug treatment. RESULTS:(1) Approximately 90%(22/25) of the injected C3H/He N mice were still HBs Ag-positive at 46 wk post HI, whereas HBs Ag in C57BL/6 mice were completely cleared at 24 wk. Serum levels of HBe Ag in C3H/He N mice were higher than those in C57BL/6 mice from 4 wk to 46 wk. HBV DNA levels in the hydrodynamically injected C3H/He N mice were higher than those in the C57BL/6 mice, both in the serum(from 4 wk to 46 wk) and in the liver(detected at 8 wk and 46 wk post HI). Histology showed that hepatitis B core antigen and HBs Ag were expressed longer in the liver of C3H/He N mice than in C57BL/6;(2) HBs Ag specific T cell responses after HBs Ag vaccination in hydrodynamically injected C3H/He N and C57BL/6 mice, or naive control mice were detected by ELISPOT assay. After stimulation with HBs Ag, the frequencies of IFN-γ producing splenocytes in the hydrodynamically injected C3H/He N mice were significantly lower than those in hydrodynamically injected C57BL/6 mice, control C3H/He N and control C57BL/6 mice, which were 0, 17 ± 7, 18 ± 10, and 41 ± 10 SFCs/106 splenocytes, respectively, and the mean spot sizes showed the same pattern. Even just stimulated with PMA and ionomysin, T-cell responses elicited in the vaccinated control C3H/He N were much higher than those in hydrodynamically injected C3H/He N mice; and(3) For drug treatment experiments on the hydrodynamically injected C3H/He N mice, serum HBV DNA levels in the entecavir treatment group declined(131.2 folds, P < 0.01) on day 7 after treatment and kept going down. In the group of IFN-α treatment, serum HBV DNA levels declined to a lowest point(6.42 folds, P < 0.05) on 7 d after treatment and then rebounded.CONCLUSION: We have developed a novel HI-based HBV transfection model using C3H/He N mice, which had a higher HBV persistence rate than the classic C57BL/6 mouse model.
文摘Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In this re- port, we describe the first case of acquired immune de- ficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with am- photericin B for 3 mo, while receiving concomitant ther- apy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 too. R marneffei should be considered in the differential di- agnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with R marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.
基金This study was supported by a grant from the National Major Scientific and Technological Special Project(No.2017ZX09304027)。
文摘Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus(HIV).However,little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV(PLHIV).Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide,prednisone,vincristine,cyclophosphamide,doxorubicin,and rituximab(DA-EPOCH-R)with standard cyclophosphamide,doxorubicin,vincristine,prednisone and rituximab(R-CHOP)as front line therapy for PLHIV with diffuse large B-cell lymphoma(DLBCL)receiving modern combined antiretroviral therapy(cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019.The demographic and clinical data were collected,and overall survival(OS)and progression-free survival(PFS)analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis.Additionally,a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months(interquartile range[IQR]:8-29 months).The proportion of high international prognostic index(IPI)patients was much larger in the DA-EPOCH-R group(n=29)than that in the R-CHOP group(n=25).The CD4 cell counts and HIV RNA levels were not significantly different between the two groups.The 2-year OS for all patients was 73%.However,OS was not significantly different between the two groups,with a 2-year OS rate of 78%for the DA-EPOCH-R group and 66%for the R-CHOP group.Only an IPI greater than 3 was associated with a decrease in OS,with a hazard ratio of 5.0.The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy.No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.
基金supported by the followed funds:National Science and Technology Major Project(2017ZX10304402-001-006,2017ZX10304402-001-012,2016YFD0500208)Shanghai Science and Technology Commission“R&D public service platform and institutional capacity improvement project”(21DZ2291300)+1 种基金Shanghai scientific research projects(19140905300)Shanghai Public Health Clinical Center projects(KY-GW-2019-11,KY-GW-2019-19,and KY-GW-2021-39)。
文摘Background:There are remarkable genetic differences between animal major histocompatibility complex(MHC)systems and the human leukocyte antigen(HLA)system.HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-Arestricted responses against infection in human.Methods:A recombinant gene encoding the chimeric HLA-A30 monochain was constructed.This HHD molecule contains the following:α1-α2 domains of HLA-A30,α3 and cytoplasmic domains of H-2D~b,linked at its N-terminus to the C-terminus of humanβ2m by a 15-amino-acid peptide linker.The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome(BAC)CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination.Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes.This humanized mouse model was further used to assess the immune responses against influenza A virus(H1N1)pdm09 clinically isolated from human patients.Immune cell population,cytokine production,and histopathology in the lung were analyzed.Results:We describe a novel humanβ2m-HLA-A30(α1α2)-H-2D~b(α3 transmembrane cytoplasmic)(HHD)monochain transgenic mouse strain,which contains the intact HLA-A01 gene locus including 49 kb 5’-UTR and 74 kb 3’-UTR of HLA-A01*01.Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained,and the robust expression of exogenous transgene was detected in various tissues from A30-18#and A30-19#lines encompassing the intact flanking sequences.Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice.Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice,and induced the rapid increase of cytokines,including IFN-γ,TNF-α,and IL-6,in both HLA-A30 humanized Tg mice and wild-type mice.The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9#line at 3 days post-infection(dpi).Conclusions:We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse,which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development,and support the study of HLA-A-restricted responses against infection in humans.
基金Supported by Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control,No.2020XGZX052.
文摘In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.
基金Supported by Shanghai Science and Technology Development Foundation Project,No.12140900300Shanghai Municipal Commission of Health and Family Planning Project,No.20144Y0073+1 种基金Shanghai Public Health Clinical Center Project,No.2014M08National Science and Technology Major Project,No.2017ZX10304402-001-012
文摘AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.
基金This project was funded by National Natural Science Foundation of China(Grant No.71673057)
文摘Objective:The overarching objective of this study was to examine the effectiveness of HIV symptom management guidelines in China in reducing the incidence and severity of symptoms and improving patients'quality of life.Methods:We conducted a controlled,pre-and post-implementation design in the HIV/AIDS inpatient unit in Shanghai.Patients recruited from November 2014 to February 2015 were in the intervention group and those from October 2013 to February 2014 were in the control group.There were 74 patients in each group.Participants in the intervention group received interventions based on the HIV symptom management guidelines.Overall symptom severity,depression,and quality of life were measured in two groups at baseline,week 4,and week 8.Results:Totally 126 patients completed the research,65 in the intervention group and 61 in the control group.The total symptom severity scores showed a statistically significant difference between groups across time(P<0.05).It showed that frequencies of fatigue(36.9%vs.44.3%),fever(6.2%vs.11.5%),loss in weight(9.2%vs.16.4%),mouth ulcers(12.3%vs.16.4%),headaches(9.2%vs.19.7%)and depression(F=1.09,P>0.05)in the intervention group were lower than those in the control group in week 8 without statistical significance.The multilevel growth mixture model indicated a greater increase in the total score of quality of life for the group treated according to the symptom management guidelines(P=0.04).Conclusion:The evidence-based HIV symptom management guidelines can improve a patient's quality of life and relieve negative symptoms.The guidelines can be applied in a similar context to other HIV/AIDS units or clinics.