1.A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years.
Bo YU ; Haiyu WANG ; Guangming LI ; Junyi SUN ; Hong LUO ; Mengzhao YANG ; Yanyang ZHANG ; Ruihan LIU ; Ming CHENG ; Shixi ZHANG ; Guotao LI ; Ling WANG ; Guowu QIAN ; Donghua ZHANG ; Silin LI ; Quancheng KAN ; Jiandong JIANG ; Zhigang REN
Acta Pharmaceutica Sinica B 2025;15(3):1333-1343
Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.
2.Clinical characteristics and risk factors of delayed viral clearance in 562 Chikungunya fever patients in Shunde region, Guangdong Province, 2025
Zuning REN ; Guotao LYU ; Qun LIN ; Zhifeng HONG ; Shuichun WAN ; Feng KANG ; Yanling OUYANG ; Chunhua TU ; Guo RAO ; Hua LIANG ; Yawei LIU ; Yan ZHU ; Jie PENG ; Jie SHEN ; Hong LI
Chinese Journal of Infectious Diseases 2025;43(8):449-456
Objective:To analyze the clinical characteristics of the Chikungunya fever outbreak in Shunde District, Foshan City, Guangdong Province in July 2025 and the risk factors associated with delayed viral RNA clearance.Methods:A total of 562 patients with Chikungunya fever admitted to three designated hospitals in Shunde District from July 10 to 30, 2025 were enrolled. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into four age groups including minors (<18 years), young adults (18 to 39 years), middle-aged adults (40 to 64 years) and elderly adults (≥65 years). The differences of clinical characteristics among these age groups were analyzed. Intergroup comparisons were performed using chi-square test, one-way analysis of variance, or Kruskal-Wallis H test. Pairwise comparisons between groups were conducted using the Bonferroni or Games-Howell or Dunn method. Binary logistic regression was employed to analyze risk factors associated with delayed viral RNA clearance (>7 days). Results:The mean age of the 562 enrolled Chikungunya fever patients was (44.8±21.3) years. Fever, arthralgia and rash were the three core symptoms, with incidence rates of 87.5% (492/562), 88.4%(497/562) and 69.6%(391/562), respectively. At discharge, only 54.1%(304/562) of patients achieved complete symptom resolution, while 26.5%(149/562) still had arthralgia and 36.1%(203/562) had residual rash. Significant differences were observed among age groups in the incidence of fever ( χ2=9.43, P=0.024), peak body temperature ( F=6.54, P<0.001), incidence of arthralgia ( χ2=26.89, P<0.001), duration of arthralgia ( F=12.68, P=0.001), incidence of rash ( χ2=68.99, P<0.001), rate of residual rash at discharge ( χ2=32.37, P<0.001), lymphocyte count ( F=12.94, P<0.001), platelet count ( F=14.95, P<0.001), and C-reactive protein levels (CRP) ( H=94.18, P<0.001). Further pairwise comparisons revealed that compared to the middle-aged and elderly groups, the minor group had a higher incidence of fever and a lower incidence of arthralgia, and the duration of arthralgia was shorter than the elderly group (all P<0.008 3). Compared with the other three groups, the elderly group had lower incidence and residual rate of rash, and lower platelet counts (all P<0.008 3), and higher levels of CRP (all P<0.05). The elderly group had lower lymphocyte counts compared to the minor and young adult groups (both P<0.05). Significant differences were found among age groups in the time to viral RNA clearance ( F=5.77, P=0.003) and length of hospital stay ( F=11.64, P<0.001), with the elderly group having significantly longer duration for both compared to the other three groups (all P<0.05). Multivariate analysis showed that advanced age (odds ratio ( OR)=1.049, 95% confidence interval ( CI) 1.015 to 1.083), longer duration of fever ( OR=1.529, 95% CI 1.086 to 2.155) and longer duration of arthralgia ( OR=1.927, 95% CI 1.318 to 2.817) were independent risk factors for delayed viral RNA clearance (all P<0.05). Conclusions:Patients with Chikungunya fever in Shunde District primarily present with fever, arthralgia and rash. The incidence and characteristics of these three core symptoms show age-related variations. Elderly patients and those with longer durations of fever or arthralgia are more likely to experience delayed viral clearance.
3.Research progress on tumors associated with Li-Fraumeni syndrome
Shiqi ZHENG ; Huiru HAN ; Lu JU ; Guotao REN ; Ruifen WANG ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):369-373,379
Li-Fraumeni syndrome(LFS)is a rare autosomal dominant genetic disorder.Patients with LFS tend to develop tumors at a young age and are at risk of multiple types of cancer.The core pathogenic mechanism of LFS is germline mutation of the TP53 gene,which leads to loss of function of the p53 protein and an increase in the risk of tumor development.There are many tumor types closely related to LFS,including soft tissue sarcoma,osteosarcoma,brain tumors,breast cancer,and adrenocortical carcinoma.Although some common mutation sites of the TP53 gene in LFS patients have been identified,there are still differences in mutation sites among different patients,and the type of TP53 gene mutation may affect the clinical manifestations and prognosis of patients.Therefore,genetic testing for LFS patients to determine the specific mutation form of TP53 is of great significance.This article reviews the clinical patho-logical characteristics,treatment methods,and prognosis of LFS-related tumor patients,aiming to provide useful refer-ences for clinical practice.
4.Different Lauren subtypes of gastric cancer exhibit differential expression of fac-tors secreted by cancer-associated fibroblasts
Lu JU ; Guotao REN ; Shiqi ZHENG ; Yeqi SUN ; Lei CAI ; Ruifen WANG ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):324-333
Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio>2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.
5.Research progress of atypical teratoid/rhabdoid tumor of the central nervous system
Huiru HAN ; Lu JU ; Shiqi ZHENG ; Guotao REN ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):380-384
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare,highly malignant central nervous system tumor with a poor prognosis and often occurs in children under 3 years of age.In this article,the clinicopathological features,molecular subtypes,pathogenesis,treatment,prognosis,relevant clinical trials,and existing problems of AT/RT will be reviewed to deepen the understanding of AT/RT.
6.Research progress on tumors associated with Li-Fraumeni syndrome
Shiqi ZHENG ; Huiru HAN ; Lu JU ; Guotao REN ; Ruifen WANG ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):369-373,379
Li-Fraumeni syndrome(LFS)is a rare autosomal dominant genetic disorder.Patients with LFS tend to develop tumors at a young age and are at risk of multiple types of cancer.The core pathogenic mechanism of LFS is germline mutation of the TP53 gene,which leads to loss of function of the p53 protein and an increase in the risk of tumor development.There are many tumor types closely related to LFS,including soft tissue sarcoma,osteosarcoma,brain tumors,breast cancer,and adrenocortical carcinoma.Although some common mutation sites of the TP53 gene in LFS patients have been identified,there are still differences in mutation sites among different patients,and the type of TP53 gene mutation may affect the clinical manifestations and prognosis of patients.Therefore,genetic testing for LFS patients to determine the specific mutation form of TP53 is of great significance.This article reviews the clinical patho-logical characteristics,treatment methods,and prognosis of LFS-related tumor patients,aiming to provide useful refer-ences for clinical practice.
7.Different Lauren subtypes of gastric cancer exhibit differential expression of fac-tors secreted by cancer-associated fibroblasts
Lu JU ; Guotao REN ; Shiqi ZHENG ; Yeqi SUN ; Lei CAI ; Ruifen WANG ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):324-333
Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio>2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.
8.Research progress of atypical teratoid/rhabdoid tumor of the central nervous system
Huiru HAN ; Lu JU ; Shiqi ZHENG ; Guotao REN ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):380-384
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare,highly malignant central nervous system tumor with a poor prognosis and often occurs in children under 3 years of age.In this article,the clinicopathological features,molecular subtypes,pathogenesis,treatment,prognosis,relevant clinical trials,and existing problems of AT/RT will be reviewed to deepen the understanding of AT/RT.
9.Clinical characteristics and risk factors of delayed viral clearance in 562 Chikungunya fever patients in Shunde region, Guangdong Province, 2025
Zuning REN ; Guotao LYU ; Qun LIN ; Zhifeng HONG ; Shuichun WAN ; Feng KANG ; Yanling OUYANG ; Chunhua TU ; Guo RAO ; Hua LIANG ; Yawei LIU ; Yan ZHU ; Jie PENG ; Jie SHEN ; Hong LI
Chinese Journal of Infectious Diseases 2025;43(8):449-456
Objective:To analyze the clinical characteristics of the Chikungunya fever outbreak in Shunde District, Foshan City, Guangdong Province in July 2025 and the risk factors associated with delayed viral RNA clearance.Methods:A total of 562 patients with Chikungunya fever admitted to three designated hospitals in Shunde District from July 10 to 30, 2025 were enrolled. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into four age groups including minors (<18 years), young adults (18 to 39 years), middle-aged adults (40 to 64 years) and elderly adults (≥65 years). The differences of clinical characteristics among these age groups were analyzed. Intergroup comparisons were performed using chi-square test, one-way analysis of variance, or Kruskal-Wallis H test. Pairwise comparisons between groups were conducted using the Bonferroni or Games-Howell or Dunn method. Binary logistic regression was employed to analyze risk factors associated with delayed viral RNA clearance (>7 days). Results:The mean age of the 562 enrolled Chikungunya fever patients was (44.8±21.3) years. Fever, arthralgia and rash were the three core symptoms, with incidence rates of 87.5% (492/562), 88.4%(497/562) and 69.6%(391/562), respectively. At discharge, only 54.1%(304/562) of patients achieved complete symptom resolution, while 26.5%(149/562) still had arthralgia and 36.1%(203/562) had residual rash. Significant differences were observed among age groups in the incidence of fever ( χ2=9.43, P=0.024), peak body temperature ( F=6.54, P<0.001), incidence of arthralgia ( χ2=26.89, P<0.001), duration of arthralgia ( F=12.68, P=0.001), incidence of rash ( χ2=68.99, P<0.001), rate of residual rash at discharge ( χ2=32.37, P<0.001), lymphocyte count ( F=12.94, P<0.001), platelet count ( F=14.95, P<0.001), and C-reactive protein levels (CRP) ( H=94.18, P<0.001). Further pairwise comparisons revealed that compared to the middle-aged and elderly groups, the minor group had a higher incidence of fever and a lower incidence of arthralgia, and the duration of arthralgia was shorter than the elderly group (all P<0.008 3). Compared with the other three groups, the elderly group had lower incidence and residual rate of rash, and lower platelet counts (all P<0.008 3), and higher levels of CRP (all P<0.05). The elderly group had lower lymphocyte counts compared to the minor and young adult groups (both P<0.05). Significant differences were found among age groups in the time to viral RNA clearance ( F=5.77, P=0.003) and length of hospital stay ( F=11.64, P<0.001), with the elderly group having significantly longer duration for both compared to the other three groups (all P<0.05). Multivariate analysis showed that advanced age (odds ratio ( OR)=1.049, 95% confidence interval ( CI) 1.015 to 1.083), longer duration of fever ( OR=1.529, 95% CI 1.086 to 2.155) and longer duration of arthralgia ( OR=1.927, 95% CI 1.318 to 2.817) were independent risk factors for delayed viral RNA clearance (all P<0.05). Conclusions:Patients with Chikungunya fever in Shunde District primarily present with fever, arthralgia and rash. The incidence and characteristics of these three core symptoms show age-related variations. Elderly patients and those with longer durations of fever or arthralgia are more likely to experience delayed viral clearance.
10.Marrow mesenchymal stem cell transplantation in treatment of ischemic heart disease in rabbits
Guotao MA ; Hua REN ; Zhaohui ZHU ; Chaoji ZHANG
Basic & Clinical Medicine 2006;0(03):-
Objective To investigate the feasibility of treating ischemic heart disease with transplantation of marrow mesenchymal stem cells.Methods Marrow mesenchymal stem cells were collected from New Zealand rabbit's sternum and cultured.A myocardial infarction model was created by ligation of the distal left anterior descending artery in New Zealand rabbit.MSCs were injected into the region of myocardial infarction.The size of the myocardial infarction area was measured by PET and the cardiac function was assessed by measuring the pressure change of left ventricle(dp/dt).Results The size of the myocardial infarction area diminished and the cardiac function was improved after the transplantation of marrow mesenchymal stem cells.Conclusion Transplantation marrow mesenchymal stem cells may improve cardiac function of ischemic heart disease in animal model of New Zealand rabbit.

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