1.Effect and mechanism of transplantation of human umbilical cord mesenchymal stem cells with overexpression of the Numb gene in treatment of cholestatic liver fibrosis
Shihao ZHANG ; Changqing ZHAO ; Mingyan YANG ; Feifei XING ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(1):80-89
ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell (hUC-MSC) with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis (CLF). MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC (hUC-MSCNumb-OE), and hUC-MSC transfected with empty vector (hUC-MSCOE-EV) was used as negative control. Bile duct ligation (BDL) was performed to establish a rat model of CLF, and then the rats were randomly divided into BDL group, hUC-MSC group, hUC-MSCOE-EV group, and hUC-MSCNumb-OE group, while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL, and samples were collected at the end of week 4. Related indicators were measured, including serum biochemistry, liver histopathology, the content of hydroxyproline (Hyp) in the liver, hepatic stellate cell activation, ductular reaction, liver regeneration, and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group, the hUC-MSC group and the hUC-MSCOE-EV group had significant reductions in the levels of serum biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, total bile acid, total bilirubin, and direct bilirubin), liver fibrosis markers (the content of Hyp and the expression levels of alpha-smooth muscle actin, tumor necrosis factor-α, and transforming growth factor-beta 1), and ductular reaction markers (the expression levels of CK7 and CK19) (all P <0.05), and compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significantly greater improvements in the above indicators (all P <0.05). In addition, compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significant improvements in the expression levels of liver regeneration-related markers (albumin and hepatocyte nuclear factor 4α) and the molecules associated with the Numb-p53 signaling axis (Numb, pNumb, Mdm2, and p53) (all P <0.05). ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF, possibly by activating the Numb-PTBL-p53-HNF4α axis, promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.
2.Influencing factors for recompensation and its impact on the prognosis in patients with decompensated liver cirrhosis
Danqing XU ; Haiwen LI ; Huan MU ; Yingyuan ZHANG ; Caifen SA ; Li LIU ; Yongrui YANG
Journal of Clinical Hepatology 2026;42(1):90-100
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated liver cirrhosis, as well as the impact of recompensation on the prognosis of such patients, and to provide a basis for early identification of high-risk patients in clinical practice. MethodsA retrospective analysis was performed for the clinical data of patients who attended The Third People’s Hospital of Kunming from January 2016 to December 2022 and were diagnosed with decompensated liver cirrhosis due to hepatitis B, hepatitis C, alcoholic hepatitis, and autoimmune hepatitis, and they were divided into recompensation group and persistent decompensation group. To control for confounding factors, whether recompensation occurred was used as the rouping variable,and BMI, alcohol consumption history, HIV infection history, TG, CHOL, LDL, and HDL were used as covariates. The propensity score was calculated, and 1:1 nearest neighbor matching was performed with a caliper value of 0.1. After propensity score matching, the recompensation group and the persistent decompensation group with relatively balanced covariates were obtained. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for recompensation; the “rms” package was used to establish a nomogram; the receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC); the Hosmer-Lemeshow test was used to assess the goodness of fit of the model; the “Calibration Curves” package was used to plot calibration curves for model assessment. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival curves. ResultsAmong the 863 patients with decompensated liver cirrhosis, 305 experienced recompensation, resulting in an incidence rate of 35.3%. After PSM, 610 cases were successfully matched, with 305 cases in each group. The univariate and multivariate Cox regression analyses showed that etiology (hepatitis C: hazard ratio[HR]=0.288, P=0.002); male(HR=0.701, P=0.016), age(HR=0.988, P=0.047), hemoglobin (HGB)(HR=1.006, P=0.017), and CD4 T cell(HR=1.001,P=0.047), TIPS procedure (HR=1.808,P=0.042) were independent influencing factors for recompensation in patients with decompensated liver cirrhosis. During follow-up, 116 patients died of liver disease-related causes, with 27 patients (8.85%) in the recompensation group and 89 (15.95%) in the persistent decompensation group; 109 patients developed HCC, with 23 patients (7.54%) in the recompensation group and 86 (15.41%) in the persistent decompensation group. The Kaplan-Meier survival curves showed significant separation between the patients with different states of compensation in terms of liver disease-related mortality rate and the incidence rate of HCC, and the Log-rank test showed that there were significant differences between the two groups in liver disease-related mortality rate (χ2=9.023, P=0.003) and the incidence rate of HCC (χ2=10.526, P=0.001). ConclusionEtiology,sex,age,TIPS,HGB,and CD4 T cell are independent influencing factors for recompensation in patients with decompensated liver cirrhosis. There is a significant difference in the incidence rate of recompensation between decompensated liver cirrhosis patients with different etiologies, and female patients and patients with a younger age,a history of TIPS, a higher HGB level, and a higher CD4 lymphocyte count are more likely to experience recompensation. Recompensation is the key to improving the long-term prognosis of patients and can significantly reduce long-term liver disease-related mortality rate and the incidence rate of HCC.
3.Analysis of clinical factors related to complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Hui YANG ; Xiaofeng MU ; Linan SONG ; Wenjie NI ; Lei DING
Chinese Journal of Radiological Health 2026;35(1):6-11
Objective To explore the clinical factors influencing complete response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods Clinical data of LARC patients treated in the Department of Radiation Oncology at Beijing Shijitan Hospital between January 2013 and December 2024 were retrospectively collected. All patients received nCRT, after which surgery or a watch-and-wait approach was adopted based on treatment response. Univariable and multivariable logistic regression analyses were performed to identify prognostic factors influencing complete response. A clinical prediction model was constructed based on the multivariable analysis results, and its predictive performance was evaluated using the receiver operating characteristic curve. Results A total of 113 eligible patients were included. After nCRT, 19 patients (16.8%) achieved complete response, including 3 with clinical complete response and 16 with pathological complete response. Univariable analysis indicated that pretreatment clinical N stage, extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen were associated with complete response after nCRT (P<0.05). Multivariable logistic regression analysis identified pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen as independent influencing factors for complete response (P<0.05). A prediction model incorporating these independent factors yielded an area under the receiver operating characteristic curve of 0.813 (95% confidence interval: 0.713-0.913), with a sensitivity of 89.5% and a specificity of 60.6%, demonstrating good predictive performance. Conclusion Pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen are independent factors influencing complete response after nCRT in LARC patients. The prediction model combining these factors may assist in evaluating treatment efficacy following nCRT in LARC patients.
4.Comparison of dosimetry and radiobiology between volumetric modulated arc therapy and helical tomotherapy for craniospinal irradiation
Yongqing GE ; Xiunan WANG ; Hui YANG ; Xiaofeng MU
Chinese Journal of Radiological Health 2026;35(1):113-119
Objective To compare the dosimetric and radiobiological differences of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in craniospinal irradiation. Methods The CT images of 15 patients who received craniospinal irradiation in our hospital were selected. The target volumes and organs at risk (OARs) were contoured, and HT and VMAT plans were designed. The dosimetric parameters of the two plans were compared. A Matlab program based on equivalent uniform dose was developed to calculate the normal tissue complication probability (NTCP). The NTCP values of the two plans were compared. Results The homogeneity index of the target volume in the HT group was better than that in the VMAT group, with values of 0.06 ± 0.01 and 0.08 ± 0.24, respectively, and the difference was statistically significant (P=0.03). However, there was no significant difference in the conformity index of the target volume (P>0.05). There were significant differences in key indicators (Dmean, V5, Dmax) of the lungs, liver, lens, and eyeballs between the two groups (P<0.05). Regarding OARs, the NTCP values of the lens, optic chiasm, lungs, and liver in the HT and VMAT groups were as follows: 0.04 ± 0.03 vs. 0.1 ± 0.06 in the left lens, 0.04 ± 0.06 vs. 0.1 ± 0.07 in the right lens, 0.16 (0.14-0.17) vs. 0.21 (0.18-0.24) in the optic chiasm, 3.89 × 10−4 (2.45 × 10−4-7.3 × 10−4) vs. 8.95 × 10−4 (5.19 × 10−4-1.75 × 10−3) in the lungs, and 3.45 × 10−8 (6.0 × 10−9-1.036 × 10−7) vs. 9.54 × 10−8 (1.70 × 10−8-2.056 × 10−7) in the liver; the HT group was superior to the VMAT group, and all differences were statistically significant (P<0.05). The NTCP values of the heart in the two groups were 1.35 × 10−8 (6.34 × 10−9-2.06 × 10−9) vs. 5.06 × 10−9 (2.29 × 10−9-7.9 × 10−9), significantly lower in the VMAT group than in the HT group (P<0.05). Conclusion HT has high homogeneity and consistency. The two plans have their own advantages in OAR protection. For OARs with no significant differences in physical dosimetry, NTCP results can be used as a reference. Therefore, comparing the dosimetric parameters and OAR NTCP of HT and VMAT plans can help select the optimal clinical treatment strategy.
5.The effect of body mass index and inferior pulmonary ligament division on the residual lung expansion after right upper lobectomy: A retrospective cohort study in a single center
Guang MU ; Wenhao ZHANG ; Hongchang WANG ; Yan GU ; Chenghao FU ; Wentao XUE ; Shiyuan XIE ; Tong WANG ; Ke WEI ; Yang XIA ; Liang CHEN ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):261-266
Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2<BMI≤23 kg/m2), a group B (23 kg/m2<BMI≤29 kg/m2) and a group C (BMI>29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.
6.Tangbikang Granules Improve Diabetic Peripheral Neuropathy by Inhibiting Ferroptosis via AMPK/Nrf2 Signaling Pathway
Zehong YANG ; Tonghua LIU ; Xiaohong MU ; Yaqi ZHANG ; Huizhong BAI ; Lingling QIN ; Xiaolei JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):52-60
ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty (ZDF) rats. After successful modeling, the rats were divided into a normal group, a model group, high-, medium-, and low-dose Tangbikang granules groups, and a metformin hydrochloride group. The high-, medium-, and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5, 1.25, 0.625 g·kg-1, respectively. The metformin hydrochloride group received 0.135 g·kg-1 by gavage, while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration, and at 4, 8, 12 weeks. Following the 12-week intervention, the thermal pain threshold and the sciatic nerve conduction velocity (SNCV) were measured. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and adenosine triphosphate (ATP) in the sciatic nerve were measured using enzyme-linked immunosorbent assay (ELISA). Morphological changes in the sciatic nerve were observed using hematoxylin and eosin (HE) staining, and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 (GPx4) were detected using immunofluorescence (IF) assay. The protein expression levels of p-AMPK, Nrf2, GPx4, and acyl-CoA synthetase long-chain family member 4 (ACSL4) were detected using Western blot. ResultsCompared with the normal group, the model group had significantly higher blood glucose levels after administration and at weeks 4, 8 and 12 (P<0.01). The thermal pain threshold was significantly prolonged (P<0.01), and the SNCV was significantly slowed down (P<0.01). The SOD and ATP levels significantly decreased (P<0.01), while the MDA levels significantly increased (P<0.01). Pathologically, the sciatic nerve fibers in the model group showed a dispersed structure, disordered and sparse arrangement, axonal atrophy, irregular myelin sheath halo, increased and swollen Schwann cell nuclei, obvious endoneurial fibrosis, and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 (P<0.01). Western blot analysis showed significantly decreased protein expression levels of p-AMPK, Nrf2, and GPx4 (P<0.01), and significantly increased expression of ACSL4 (P<0.01) in the model group. Compared with the model group, fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 (P<0.05). The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups (P<0.01). The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups (P<0.01). The SOD levels were significantly elevated in the high-dose Tangbikang granules group (P<0.01). The MDA levels significantly decreased in all Tangbikang granules groups (P<0.01). Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups (P<0.01). The protein expression levels of p-AMPK, Nrf2, and GPx4 were significantly increased (P<0.01), while ACSL4 protein expression significantly decreased (P<0.01). ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.
7.Influencing factors on the prevalence of depressive symptoms among middle school students in Yunnan Province in 2023
Xiaodong MU ; Hong LIU ; Fan YANG ; Tunan LI ; Junyu NI ; Yunjuan YANG
Shanghai Journal of Preventive Medicine 2026;38(2):108-115
ObjectiveTo investigate the epidemiological characteristics and influencing factors of depressive symptoms among middle school (junior, senior, and vocational high school) students in Yunnan Province, China, and to inform evidence-based intervention strategies for adolescent mental health. MethodsA cross-sectional survey was conducted between October and November 2023 using stratified random cluster sampling. Students from eight counties (districts) across four prefectures (cities) in Yunnan Province were included. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate logistic regression analysis was performed to examine factors associated with depressive symptoms, with stratified analyses conducted by gender, educational stage, and ethnicity. ResultsA total of 4 672 questionnaires were distributed, with 4 670 valid questionnaires retrieved, yielding a valid response rate of 99.96%. The surveyed participants were predominantly female students (50.81%), junior high school students (49.13%), ethnic minorities (52.78%), and urban residents (79.29%). The mean CES-D score for middle school students in Yunnan Province was (15.31±10.83). Female students had a significantly higher mean score (16.63±11.41) than male students (13.95±10.02) (P<0.001). Senior high school students had a significantly higher mean score (16.61±10.61) compared to both junior high school students (14.74±11.45) and vocational high school students (13.10±7.71) (all pairwise comparisons P<0.001). The prevalence of depressive symptoms among middle school students in Yunnan Province was 28.18%. The prevalence was significantly higher in females (34.09%) than in males (22.07%). By school type, the detection rate was highest among senior high school students (33.39%), followed by junior high school students (26.29%) and vocational high school students (17.27%) (P<0.05). Multivariate logistic regression analysis showed that female gender (OR=2.16, 95%CI: 1.86‒2.50), being in junior high school (OR=2.43, 95%CI: 1.84‒3.20) or senior high school (OR=2.27, 95%CI: 1.73‒2.98), not living with parents (OR=1.24, 95%CI: 1.07‒1.44), irregular breakfast consumption (OR=1.52, 95%CI: 1.33‒1.75), lack of moderate-to-vigorous physical activity (MVPA) (OR=1.69, 95%CI: 1.37‒2.09), sleep duration ≤5 h per night (OR=2.52, 95%CI: 2.02‒3.14) or 6‒7 h per night (OR=1.47, 95%CI: 1.25‒1.73), smoking (OR=1.86, 95%CI: 1.56‒2.23), and alcohol consumption (OR=1.81, 95%CI: 1.54‒2.13) were positively associated with depressive symptoms. In contrast, screen time ≤1 h (OR=0.71, 95%CI: 0.59‒0.86) was negatively associated with depressive symptoms. Stratified analyses showed that female students not living with parents (OR=1.29, 95%CI: 1.06‒1.58), senior high school students (OR=1.51, 95%CI: 1.21‒1.88), and Han Chinese students (OR=1.37, 95%CI: 1.11‒1.69) were more likely to experience depressive symptoms. Han Chinese students who smoked were also more likely to have depressive symptoms (OR=1.72, 95%CI: 1.34‒2.21). In contrast, male students with screen time ≤1 h (OR=0.71, 95%CI: 0.53‒0.95) and ethnic minority students (OR=0.74, 95%CI: 0.58‒0.95) were less likely to experience depressive symptoms. Regardless of gender, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, smoking, and alcohol consumption were all positively associated with depressive symptoms (P<0.05). Among both junior and senior high school students, irregular breakfast consumption, lack of MVPA, smoking, and alcohol consumption were positively associated with depressive symptoms (all P<0.05), while screen time ≤1 h was negatively associated with depressive symptoms (all P<0.05). For junior high school students, engaging in 1‒2 days of MVPA per week, screen time more than 2 h per day, and sleep duration 6‒7 h per night were all positively associated with depressive symptoms (all P<0.05). Among junior high, senior high, and vocational high school students, sleep duration ≤5 h per night was positively associated with depressive symptoms (P<0.05). For both Han Chinese and ethnic minority students, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, and alcohol consumption were all positively associated with depressive symptoms (all P<0.05). ConclusionThe prevalence of depressive symptoms among middle school students in Yunnan Province is comparable to that in central China and higher than that in northern regions. Prevention and control efforts should prioritize female students and those in junior and senior high school stages. Universal improvements in lifestyle behaviors among middle school students, such as regular breakfast consumption, MVPA, sufficient sleep (≥8 h), and abstinence from smoking and alcohol. Particular attention should be given to limiting excessive screen time among junior high school students and addressing the mental health needs of females not living with their parents, senior high school students, and Han Chinese students.
8.Protective effects and mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice
Xiaoguo WEI ; Shuli MU ; Fan YANG ; Hai’e LI ; Shudan LUO ; Xiaona CHE
China Pharmacy 2026;37(6):752-757
OBJECTIVE To investigate the protective effects and potential mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice. METHODS Fifty male Kunming mice were divided into the blank group, model group, and alisol B 23-acetate low-, medium- and high-dose groups (10, 20, 40 mg/kg), with 10 mice in each group. Each group was given relevant drug solution or normal saline intragastrically, once a day, for 2 consecutive weeks. On the 15th day, mice in the blank group were given normal saline intragastrically, while the other four groups were given 12 mL/kg white wine intragastrically, twice at six-hour intervals, to establish an acute alcoholic liver injury model. On the 16th day of the experiment, the liver indexes of mice in each group were calculated; the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA) and glutathione (GSH) were also determined. The histopathological morphology of their liver tissues was observed and scored. The protein expressions of cytochrome P450 2E1 (CYP2E1), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured in liver tissue. RESULTS Compared with model group, mice in each dosage group of alisol B 23-acetate showed varying degrees of recovery in body weight, along with improvements in pathological changes in liver tissues such as inflammatory cell infiltration and fatty vacu oles. Their liver indexes, histopathological scores of liver tissue, serum levels of ALT, AST, TC, TG and MDA, as well as the protein expressions of CYP2E1 and Keap1 in liver tissue, were all significantly decreased ( P <0.05 or P <0.01). The serum GSH levels and the protein expressions of Nrf2 (except for the alisol B 23-acetate low-dose group) and NQO1 in liver tissue were significantly increased ( P <0.05 or P <0.01), and the changes in the above quantitative indicators showed a dose-dependent pattern. CONCLUSIONS Alisol B 23-acetate can ameliorate acute alcoholic liver injury in mice, and its mechanism may be related to improving antioxidant capacity by regulating the Keap1/Nrf2/NQO1 signaling pathway while simultaneously improving liver lipid metabolism-related indexes.
9.Reinfection of SARS-CoV-2 Variants in Immunocompromised Patients with Prolonged or Relapsed Viral Shedding
Ji Yeun KIM ; Euijin CHANG ; Hyeon Mu JANG ; Jun Ho CHA ; Ju Yeon SON ; Choi Young JANG ; Jeong-Sun YANG ; Joo-Yeon LEE ; Sung-Han KIM
Infection and Chemotherapy 2025;57(1):81-92
Background:
Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance.
Materials and Methods:
From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants.
Results:
Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2.
Conclusion
Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.
10.Compound 3k for osteoarthritis:mechanism of modulating oxidative stress pathway to improve chondrocyte glycolysis
Surong GUO ; Shisheng CAO ; Xingtong MU ; Qing YANG ; Juan ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):363-370
BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

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