ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ （AS-Ⅳ） in vitro and in vivo， as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment， C57BL/6J mice were divided into control group， model group， low-dose AS-Ⅳ （20 mg/kg） group， and high-dose AS-Ⅳ （80 mg/kg） group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis， and since week 3 of injection， the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg， respectively. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured after 4 weeks of administration， as well as the serum levels of hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and collagen type Ⅳ （Col-Ⅳ）. HE staining， picrosirius red staining， and Masson staining were used to observe liver histopathology and collagen deposition； RT-qPCR was used to measure the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue， and Western blot was used to measure the protein expression levels of α-smooth muscle actin （α-SMA）， collagen type Ⅲ （Col-Ⅲ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （pPI3K）， protein kinase B （Akt）， and phosphorylated AKT （p-Akt） in liver tissue； transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment， transforming growth factor-β （TGF-β） was used to induce the activation of LX-2 cells， and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group， model group， AS-Ⅳ group， LY294002 group， and AS-Ⅳ+740 Y-P group， and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K/PI3K， and pAkt/Akt in LX-2 cells were measured， as well as changes in the relative mRNA expression levels of Acta2， Col1a1， and Col3a1. 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. ResultsIn the animal experiment， compared with the model group， the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT， AST， HA， LN， PⅢNP， and Col-Ⅳ （all P<0.01）， the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue （all P<0.05）， and the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） in liver tissue （all P<0.05）. In the cell experiment， compared with the control group， the model group had significant increases in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） after TGF-β induction （all P<0.05）； compared with the model group， the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） （all P<0.05）， and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， Col1a1， and Col3a1 （all P<0.05）. Compared with the AS-Ⅳ group， there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， col1a1， and Col3a1 after 740 Y-P intervention （all P<0.05）. ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis， possibly by inhibiting the PI3K/Akt signaling pathway.

ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Objective The aim of this study is to examine the Chinese version of Visual Prostate Symptom Score(CVPSS)and the International Prostate Symptom Score(IPSS)in the assessment of lower urinary tract symptoms in BPH pa-tients.Methods By using convenient sampling,inpatients in the urology department of a tertiary grade A hospital in Shanghai were selected as the survey subjects from March 2023 to March 2024.The lower urinary tract symptoms of the patients were eval-uated using the self-designed general information questionnaire.And the CVPSS and IPSS with their urine flow rate were meas-ured.A comparative analysis was conducted from aspects such as internal consistency,correlation of item scores,completion time of the scale,and assistance rate.Results A total of 246 patients with BPH were recruited.The total score and life quality score were 13.93±3.55 and 4.23±1.02 by CVPSS.And the total score and life quality by IPSS was 18.33±7.55 and 4.36±1.02,respectively.The Cronbach's α coefficient were 0.761 and 0.787,respectively.The time taken on CVPSS was less than that on IPSS(P＜0.01).And the rate of needing assistance was 23.58％for CVPSS,which was significantly lower than that(65.24％)for IPSS.Conclusion CVPSS is significantly correlated with the corresponding items and total scores of IPSS,as well as the quality of life.Moreover,it takes less time and can be used as a simple and effective self-assessment tool for lower urinary tract symptoms in elderly BPH patients with lower education levels.It reduces the burden of medical staffs as well.

Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.

Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective The aim of this study is to examine the Chinese version of Visual Prostate Symptom Score(CVPSS)and the International Prostate Symptom Score(IPSS)in the assessment of lower urinary tract symptoms in BPH pa-tients.Methods By using convenient sampling,inpatients in the urology department of a tertiary grade A hospital in Shanghai were selected as the survey subjects from March 2023 to March 2024.The lower urinary tract symptoms of the patients were eval-uated using the self-designed general information questionnaire.And the CVPSS and IPSS with their urine flow rate were meas-ured.A comparative analysis was conducted from aspects such as internal consistency,correlation of item scores,completion time of the scale,and assistance rate.Results A total of 246 patients with BPH were recruited.The total score and life quality score were 13.93±3.55 and 4.23±1.02 by CVPSS.And the total score and life quality by IPSS was 18.33±7.55 and 4.36±1.02,respectively.The Cronbach's α coefficient were 0.761 and 0.787,respectively.The time taken on CVPSS was less than that on IPSS(P＜0.01).And the rate of needing assistance was 23.58％for CVPSS,which was significantly lower than that(65.24％)for IPSS.Conclusion CVPSS is significantly correlated with the corresponding items and total scores of IPSS,as well as the quality of life.Moreover,it takes less time and can be used as a simple and effective self-assessment tool for lower urinary tract symptoms in elderly BPH patients with lower education levels.It reduces the burden of medical staffs as well.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective To summarize the clinical characteristics and outcomes of corona virus disease 2019(COVID-19)in patients with adrenal insufficiency(AI),and analyze the risk factors of outcomes.Methods The clinical data of COVID-19 patients with AI in Peking Union Medical College Hospital in December 2022 were ana-lyzed retrospectively and the patients were followed up to collect outcomes of their diseases.Results Among 28 COVID-19 patients with AI,20 cases(71.4%)received basal corticosteroid replacement.Among the 18 patients with community-acquired COVID-19,11 cases(61.1%)increased the corticosteroid dosage proactively at home.The most common symptoms of COVID-19 were fever(96.4%),gastrointestinal symptoms(82.1%)and con-sciousness disturbance(78.6%).Occurrence of severe consciousness disturbance was associated with older age and lower basal corticosteroid replacement dose(P＜0.05). Adrenal crisis(AC)occurred in 20 patients(71.4%),which was associated with lower basal corticosteroid replacement dose,hypochloremia,lower eosinophil,lower platelet,and longer activated partial thromboplastin time(APTT)(P＜0.05). 2 patients died during hospitalization.26.3%(5/19)of surviving patient's recovered consciousness longer than 48 hours.Delayed recovery of conscious-ness was associated with lower systolic pressure,higher blood creatinine,and higher fibrinogen(P＜0.05).Long COVID-19 symptoms such as fatigue and poor appetite occurred in 48.0%(12/25)of patients.Among patients with increased corticosteroid dosage,50.0%(12/24)had their dose reduced to baseline within 3 weeks.Conclusions COVID-19 patients with AI have a high frequency of consciousness disturbance and AC.AI patients are lack of awareness of adjusting corticosteroid dosage proactively in case of infection stress,thus education of"sick day rules"for AI patients should be strengthened in clinical practice.

Objective To investigate the promoting effect of quercetin(QR)on diabetic wound repair and its possible mechanism.Methods HUVEC cell injury model was induced by 33.36 mmol/L high glucose.The cells were divided into normal control group(NG group),mannitol group(MA group),high glucose group(HG group),low dose quercetin+high glucose group(QR 5 μmol/L+HG group),high dose quercetin+high glucose group(QR 20 μmol/L+HG group).Treatment for 24 hours;CCK-8 and Edu were used to measure cell viability.Cell scratch test and Transwell migration assay were used to detect cell migration ability.Matrigel tube formation assay was used to measure the angiogenesis ability.The levels of IL-1β,IL-18 and TNF-α were detected by ELISA.Network pharmacology was used to screen the potential targets of QR on diabetic wounds.Western blot was used to detect the expression of NLRP3 inflammasome,PI3K/Akt/GSK-3β pathway and its phosphorylation.The diabetic wound model of C57 mice was established and divided into STZ group and QR+STZ group.The wound healing rate within 14 days was calculated and analyzed,and the wound tissue was stained with HE and Masson on the 14th day.Results CCK-8 and Edu results showed that a high dose of QR could improve the viability of huvecs induced by high glucose.Scratch test and Transwell migration test showed that high dose of QR could enhance the migration ability of HUVEC cells induced by high glucose.Matrigel tube formation assay showed that high dose of QR could enhance the angiogenesis ability of HUVEC cells induced by high glucose.ELISA results showed that high dose of QR could inhibit the secretion of IL-1β,IL-18 and TNF-α induced by high glucose.Network pharmacology screening results showed that PI3K/Akt/GSK-3β pathway was significantly enriched.Western blot showed that 20 μmol/L QR could increase the phosphorylation level of PI3K/Akt/GSK-3β pathway and inhibit the expression of NLRP3 inflammasome,which could be reversed by the addition of PI3K phosphorylation inhibitor LY294002.Animal experiments have shown that QR can promote diabetic wound healing by enhancing granulation tissue growth,epithelial regeneration,and collagen deposition.Conclusion QR can improve HUVEC injury induced by high glucose and promote wound healing in diabetic mice,and its mechanism may be related to inhibiting NLRP3 expression through PI3K/Akt/GSK-3β pathway.