1.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
2.Analysis of serum bile acid profiles in patients with hepatitis B virus infection complicated with liver cirrhosis
Wang ZHANG ; Jia LIU ; Aixia LIU ; Jie SUN ; Lifang XIA ; Bo LI ; Boan LI
Chinese Journal of Experimental and Clinical Virology 2025;39(4):419-426
Objective:By analyzing the concentration distribution and hydrophilic/hydrophobic proportion differences of 15 bile acid subtypes in the serum of patients with hepatitis B virus(HBV)infection complicated with liver cirrhosis and primary biliary cholangitis(PBC)complicated with liver cirrhosis,this study aims to explore the potential associations between bile acid metabolism and these diseases,providing a reference basis for identifying disease-specific metabolic fingerprints in the diagnosis,treatment,and prognosis of liver diseases. Furthermore,building on the pharmacological mechanisms of ursodeoxycholic acid(UDCA)in the treatment of PBC,this research investigates potential therapeutic applications of bile acid drugs in HBV infection.Methods:A retrospective analysis method was adopted. We enrolled 27 HBV infection complicated with liver cirrhosis patients and 59 PBC complicated with liver cirrhosis patients who received outpatient or inpatient treatment at the Fifth Medical Center of PLA General Hospital from November 2024 to April 2025. The general data and routine clinical laboratory data of the two groups of patients were collected and analyzed. Using the ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UHPLC-QqQ-MS/MS)platform,precise quantification and differential analysis of 15 bile acid subtypes were performed in serum samples. Partial least squares discriminant analysis(PLS-DA)was employed to perform discriminant analysis on serum bile acid profiles data between the two groups,and variable importance in projection(VIP)values were calculated to identify key bile acid subtypes that could differentiate the two diseases. Box plots were constructed to analyze proportion differences in serum hydrophilic and hydrophobic bile acids between the two groups,aiming to explore potential associations between bile acid metabolism and the diseases.Results:The HBV infection group and the PBC group exhibited similar impairment of routine liver function parameters. The HBV infection group had higher serum concentrations of cholic acid(CA),chenodeoxycholic acid(CDCA)and deoxycholic acid(DCA),but lower concentrations of UDCA,glycoursodeoxycholic acid(GUDCA)and tauroursodeoxycholic acid(TUDCA). The score plot generated by the PLS-DA model demonstrated significant differences in bile acid profile characteristics between the two diseases,with VIP values for UDCA,CDCA,GUDCA,TUDCA,and DCA all greater than 1. Box plots demonstrated a higher proportion of hydrophobic bile acids in the bile acid profile of the HBV infection group compared to the PBC group.Conclusion:This study found significant differences in serum bile acid profile characteristics between patients with HBV infection complicated with liver cirrhosis and those with PBC complicated with liver cirrhosis,specific bile acid subtypes such as CDCA and DCA have the potential to become specific metabolic fingerprints for these two diseases. HBV infection group exhibited higher proportion of hydrophobic bile acids in their bile acid profiles compared to PBC group. The characteristic changes in bile acid profiles can reflect the pathological characteristics of liver diseases,and their differences in hydrophilic/hydrophobic bile acids proportion represents a novel dimension independent of traditional liver function indicators,with potential value for disease prognosis assessment. UDCA or its derivatives may hold therapeutic potential for HBV infection patients with liver cirrhosis who exhibit accumulation of hydrophobic bile acids.
3.Laboratory study for an outbreak of foodborne diseases caused by Salmonella Java
Yuwei LIU ; Wei DING ; Shuang ZHANG ; Yu ZHAO ; Shoufei LI ; Aixia YAN ; Ying LI ; Bo PANG ; Xuerong SUN ; Zhenpeng LI
Chinese Journal of Zoonoses 2025;41(9):960-966
The aim of this study was to identify the Salmonella strains isolated from an outbreak of foodborne illness in a seafood buffet restaurant and analyze their pathogenic characteristics.Epidemiological data,fecal samples from patients and chefs,and food/environmental samples from the restaurant were analyzed.Research methods included bacterial culture,serotyping,quadruple fluo-rescence PCR identification,whole-genome sequencing and antibiotic susceptibility testing.The results showed that 4 S.Java strains(serotype 1,4,12∶b∶1,2;ST42)were isolated from two outbreak cases and two sporadic cases.All isolates exhibited similar genomic features,harboring 9 virulence islands and 98 virulence genes.Antimicrobial resistance profiling revealed streptomycin monoresis-tance,mediated by aac(6′)-Iy and aac(6′)-Iaa genes.In conclusion,this event was the first reported outbreak of foodborne illness caused by S.Java in China,indicating that S.Java may be prevalent in the surveyed district.The catering industry should optimize food handling and processing procedures and enhance the surveillance of high risk pathogens.Meanwhile,further studies should ad-dress differential diagnosis and pathogenic mechanism differences between S.Java and S.paratyphi B,which will facilitate evidence-based monitoring in China.
4.Laboratory study for an outbreak of foodborne diseases caused by Salmonella Java
Yuwei LIU ; Wei DING ; Shuang ZHANG ; Yu ZHAO ; Shoufei LI ; Aixia YAN ; Ying LI ; Bo PANG ; Xuerong SUN ; Zhenpeng LI
Chinese Journal of Zoonoses 2025;41(9):960-966
The aim of this study was to identify the Salmonella strains isolated from an outbreak of foodborne illness in a seafood buffet restaurant and analyze their pathogenic characteristics.Epidemiological data,fecal samples from patients and chefs,and food/environmental samples from the restaurant were analyzed.Research methods included bacterial culture,serotyping,quadruple fluo-rescence PCR identification,whole-genome sequencing and antibiotic susceptibility testing.The results showed that 4 S.Java strains(serotype 1,4,12∶b∶1,2;ST42)were isolated from two outbreak cases and two sporadic cases.All isolates exhibited similar genomic features,harboring 9 virulence islands and 98 virulence genes.Antimicrobial resistance profiling revealed streptomycin monoresis-tance,mediated by aac(6′)-Iy and aac(6′)-Iaa genes.In conclusion,this event was the first reported outbreak of foodborne illness caused by S.Java in China,indicating that S.Java may be prevalent in the surveyed district.The catering industry should optimize food handling and processing procedures and enhance the surveillance of high risk pathogens.Meanwhile,further studies should ad-dress differential diagnosis and pathogenic mechanism differences between S.Java and S.paratyphi B,which will facilitate evidence-based monitoring in China.
5.Analysis of serum bile acid profiles in patients with hepatitis B virus infection complicated with liver cirrhosis
Wang ZHANG ; Jia LIU ; Aixia LIU ; Jie SUN ; Lifang XIA ; Bo LI ; Boan LI
Chinese Journal of Experimental and Clinical Virology 2025;39(4):419-426
Objective:By analyzing the concentration distribution and hydrophilic/hydrophobic proportion differences of 15 bile acid subtypes in the serum of patients with hepatitis B virus(HBV)infection complicated with liver cirrhosis and primary biliary cholangitis(PBC)complicated with liver cirrhosis,this study aims to explore the potential associations between bile acid metabolism and these diseases,providing a reference basis for identifying disease-specific metabolic fingerprints in the diagnosis,treatment,and prognosis of liver diseases. Furthermore,building on the pharmacological mechanisms of ursodeoxycholic acid(UDCA)in the treatment of PBC,this research investigates potential therapeutic applications of bile acid drugs in HBV infection.Methods:A retrospective analysis method was adopted. We enrolled 27 HBV infection complicated with liver cirrhosis patients and 59 PBC complicated with liver cirrhosis patients who received outpatient or inpatient treatment at the Fifth Medical Center of PLA General Hospital from November 2024 to April 2025. The general data and routine clinical laboratory data of the two groups of patients were collected and analyzed. Using the ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UHPLC-QqQ-MS/MS)platform,precise quantification and differential analysis of 15 bile acid subtypes were performed in serum samples. Partial least squares discriminant analysis(PLS-DA)was employed to perform discriminant analysis on serum bile acid profiles data between the two groups,and variable importance in projection(VIP)values were calculated to identify key bile acid subtypes that could differentiate the two diseases. Box plots were constructed to analyze proportion differences in serum hydrophilic and hydrophobic bile acids between the two groups,aiming to explore potential associations between bile acid metabolism and the diseases.Results:The HBV infection group and the PBC group exhibited similar impairment of routine liver function parameters. The HBV infection group had higher serum concentrations of cholic acid(CA),chenodeoxycholic acid(CDCA)and deoxycholic acid(DCA),but lower concentrations of UDCA,glycoursodeoxycholic acid(GUDCA)and tauroursodeoxycholic acid(TUDCA). The score plot generated by the PLS-DA model demonstrated significant differences in bile acid profile characteristics between the two diseases,with VIP values for UDCA,CDCA,GUDCA,TUDCA,and DCA all greater than 1. Box plots demonstrated a higher proportion of hydrophobic bile acids in the bile acid profile of the HBV infection group compared to the PBC group.Conclusion:This study found significant differences in serum bile acid profile characteristics between patients with HBV infection complicated with liver cirrhosis and those with PBC complicated with liver cirrhosis,specific bile acid subtypes such as CDCA and DCA have the potential to become specific metabolic fingerprints for these two diseases. HBV infection group exhibited higher proportion of hydrophobic bile acids in their bile acid profiles compared to PBC group. The characteristic changes in bile acid profiles can reflect the pathological characteristics of liver diseases,and their differences in hydrophilic/hydrophobic bile acids proportion represents a novel dimension independent of traditional liver function indicators,with potential value for disease prognosis assessment. UDCA or its derivatives may hold therapeutic potential for HBV infection patients with liver cirrhosis who exhibit accumulation of hydrophobic bile acids.
6.Study on epidemiological prevalence and serological marker characteristics of hepatitis E infection
Chengrong BIAN ; Xin LIU ; Ruirui HAN ; Lili ZHAO ; Yeli HE ; Lihua YANG ; Weiwei LI ; Lijuan SONG ; Yingwei SONG ; Yongli LI ; Aixia LIU ; Jinli LOU ; Bo′an LI
Chinese Journal of Laboratory Medicine 2024;47(3):245-251
Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.
7.Study on the Lipid-Regulating Mechanism of Zexie Decoction on Hyperlipidemia Model Mice Based on the miR21/PI3K-Akt/SREBP Pathway
Aixia JU ; Shuang SUN ; Ruinan WANG ; Yubo HAN ; Yusheng ZHOU ; Jing CHEN ; Li LIU ; Qiuhong LI
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(9):917-931
OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.
8.Clinical efficacy and influencing factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy
Guohui CAO ; Juan WANG ; Zeyang WANG ; Xiaoli LIU ; Ke XU ; Jinxin ZHAO ; Aixia SUI ; Hongtao ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(1):16-19
Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.
9.Identification of Chinese Herb Pieces Based on YOLOv4
Cong GUO ; Yujia TIAN ; Yang LI ; Yang LIU ; Jun ZHANG ; Jipeng DI ; Aixia YAN ; An LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):133-140
Chinese herbal piece is an important component of the traditional Chinese medicine (TCM) system, and identifying their quality and grading can promote the development and utilization of Chinese herbal pieces. Utilizing deep learning for intelligent identification of Chinese herbal pieces can save time, effort, and cost, while also reasonably avoiding the constraints of human subjectivity, providing a guarantee for efficient identification of Chinese herbal pieces. In this study, a dataset containing 108 kinds of Chinese herbal pieces (14 058 images) was constructed,the basic YOLOv4 algorithm was employed to identify the 108 kinds of Chinese herbal pieces of our database The mean average precision (mAP) of the developed basic YOLOv4 model reached 85.3%. In addition, the receptive field block was introduced into the neck network of YOLOv4 algorithm, and the improved YOLOv4 algorithm was used to identify Chinese herbal pieces. The mAPof the improved YOLOv4 model achieved 88.7%, the average precision of 80 kinds of decoction pieces exceeded 80%, the average precision of 48 kinds of decoction pieces exceeded 90%. These results indicate that adding the receptive field module can help to some extent in the identification of Chinese herbal medicine pieces with different sizes and small volumes. Finally, the average precision of each kind of Chinese herbal medicine piece by the improved YOLOv4 model was further analyzed. Through in-depth analysis of the original images of Chinese herbal medicine pieces with low prediction average precision, it was clarified that the quantity and quality of original images of Chinese herbal medicine pieces are key to performing intelligent object detection. The improved YOLOv4 model constructed in this study can be used for the rapid identification of Chinese herbal pieces, and also provide reference guidance for the manual authentication of Chinese herbal medicine decoction pieces.
10.The role of GPS2 in regulating proliferation,migration and invasion of hepatocellular carcinoma cell line MHCC-97H
Aixia LIU ; Hao ZHANG ; Jie SUN ; Lihua YANG ; Xiaotao ZHAO
Basic & Clinical Medicine 2023;43(12):1784-1791
Objective To explore the role of G protein pathway suppressor 2(GPS2)in regulating proliferation,migration and invasion in hepatocellular carcinoma cell line MHCC-97H.Methods The expression of GPS2 in hepatocellular carcinoma(HCC)cells were detected using quantitative PCR or Western blot;GPS2 was either over-expressed or knocked down in HCC cells using over-expression vectors or short hairpin RNAs(shRNAs)for GPS2,respectively.Clone formation assay,scratch assay and Transwell assay were used to detect the effects of GPS2 on proliferation,migration and invasion of HCC cells.Results In HCC cells,over-expression of GPS2 was found to inhibit the proliferation,migration and invasion of HCC cells MHCC-97H,while knockdown of GPS2 up-regulated proliferation,migration and invasion of MHCC-97H(P<0.05).The over-expression of GPS2 in MHCC-97H cells was found to inhibit the expression of cell proliferation,migration and invasion-related factors such as EGFR,MMP1,MMP3 and MMP9,while knockdown of GPS2 upregulated the expression of these factors(P<0.05).Conclusions GPS2 is a novel HCC regulatory factor that inhibits proliferation,migration and invasion of HCC cells.

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