ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.