ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

Objective: To analyze the disease burden and trends of oral diseases among China’s elderly population (1990-2021) and provide evidence for developing targeted intervention strategies Methods : Using data from the Global Burden of Disease (GBD) 2021 study, we extracted prevalence, incidence, and disability-adjusted life years (DALYs) for oral conditions (permanent dental caries, edentulism, periodontal diseases, and other oral disorders) in individuals aged ≥60 years in China. Due to data limitations, other oral diseases only included DALYs and prevalence. Age-standardized rates (ASR)—including age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized DALYs rate (ASDR)--were calculated. Trends were assessed via Joinpoint regression using average annual percentage change (AAPC), stratified by sex and age groups (60-64, 65-69, 70-74, 75-79, 80-84, 85-89, 90-94, 95+ years). Results: From 1990 to 2021, China’s elderly population exhibited distinct trends in oral disease burden. Overall oral diseases showed declining ASDR and ASPR, yet ASIR slightly increased. Permanent dental caries demonstrated significant rises across ASDR, ASIR, and ASPR. Edentulism showed declining ASDR and ASPR alongside stable ASIR. 95+ age group saw rising rates. Periodontal diseases remained largely stable in ASDR and ASPR but experienced a slight ASIR decline. Other oral disorders showed mild ASDR decline and stable ASPR. Notably, sex and age disparities persisted. Women consistently bore higher burdens for overall oral diseases, caries, edentulism, and other oral diseases but lower periodontal disease rates compared to men. 85-89, 90-95, 95+ age group faced rising DALYs and prevalence for overall oral diseases, while all other age groups demonstrated declining trends in both DALYs and prevalence; for permanent caries, the 60-64 age group showed the largest increases in DALY rate, incidence, and prevalence; edentulism demonstrated the most pronounced and sustained rises in DALY rate and prevalence in the 95+ group, while declining most rapidly in the 60-64 age group; for periodontal disease, both DALY rates and prevalence declined in the 90-94 and 95+ age groups, but increased across all measures (DALY rate, incidence, and prevalence) in the 70-74 and 75-79 age group; other oral conditions exhibited relatively stable burden distributions or minor changes, with no significant age-specific shifting trends observed. Conclusion From 1990 to 2021, China’s elderly oral disease burden declined overall, but caries surged, edentulism improved, periodontal diseases stabilized, and other oral diseases slightly declined. Prioritizing older women and the adults aged 85+ is critical to addressing evolving oral health needs.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

Objective To investigate the effect of quercetin on HCE-2 injury of human corneal epithelial cells induced by high osmotic pressure and its mechanism.Methods HCE-2 cells were randomly divided into control group(normal osmotic pressure),model group(high osmotic pressure),experimental-L group(high osmotic pressure+31.25 pg·mL-1 quercetin),experimental-M group(high osmotic pressure+62.50 μg·mL-1 quercetin),experimental-H group(high osmotic pressure+125.00 μg·mL-1 quercetin),erastin group(high osmotic pressure+125.00 μg·mL-1 quercetin+30.00 μmol·L-1 iron death inducer erastin).Cell survival rate was detected by cell counting kit 8;reactive oxygen species(ROS)levels was detected by C11-BODIPY 581/591 probe staining;glutathione(GSH)and malondialdehyde(MDA)levels were determined by kit method;the expression levels of glutathione peroxidase 4(GPX4),dihydrolactate dehydrogenase(DHODH)and ferroptosis suppressor protein 1(FSP1)were detected by real-time quantitative polymerase chain reaction and Western blot.Results The cell survival rates of control group,model group,experimental-H group and erastin group were(100.00±3.97)％,(50.05±5.83)％,(86.35±7.35)％and(58.32±4.66)％,respectively;ROS levels were 1.00±0.09,2.45±0.16,1.19±0.05 and 2.09±0.30,respectively;GPX4 protein levels were 1.09±0.11,0.34±0.03,0.91±0.12 and 0.30±0.04,respectively;FSP1 protein levels were 0.92±0.06,0.25±0.03,0.89±0.07 and 0.39±0.07,respectively;DHODH protein levels were 0.89±0.11,0.31±0.04,0.86±0.11,0.41±0.04,respectively.Compared with model group,the above indexes in control group were statistically significant(all P＜0.05);the differences between experimental-H group and model group were statistically significant(all P＜0.05);the above indexes in erastin group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Quercetin can ameliorate HCE-2 cell damage induced by high osmotic pressure by inhibiting iron death pathway.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To investigate the mechanism that Rubescensine A reduces the podocyte damage induced by high glucose(HG)through the autophagy pathway mediated by AMP activated protein kinase/silent information regulator 1(AMPK/SIRT1)pathway.Methods Human glomerular podocytes were cultured in vitro,and randomly divided into Control group(Con),HG group,hydroxychloroquine(HCQ)group,and Rapamycin(RAP)group.CCK-8 was used to detect cell viability.Western blotting was used to detect cell apoptosis and podocyte injury related protein expression in each group.The podocyte model induced by high glucose(HG)was treated with Rubescensine A(Rub A)at different concentrations and the optimal concentration was selected.Then,human glomerular podocytes were randomly divided into Con group,HG group,Rub A group,Compound C group,and Rub A+Compound C group.The expression of autophagy,AMPK/SIRT1 pathway related proteins were detected in each group.Results Compared with Con group,the podocyte viability and the protein expressions of Synaptopodin and Bcl-2 was significantly reduced(P<0.05),while the protein expressions of Desmin and Bax were significantly increased in HG group(P<0.05).Compared with the HG group,all indicators were relieved in RAP group.However,the levels of all indicators were worsened in HCQ group.Compared with Con group,the expression levels of Desminand Bax proteins in podocytes were significantly increased(P<0.05),and the podocyte viability,number of autophagosomes,the expression levels of Synaptopodin,Bcl-2,microtubule associated protein light chain 3(LC3)II/I,Beclin-1,p-AMPK/AMPK and SIRT1 proteins were significantly reduced in HG group(P<0.05).Compared with HG group and Rub A+Compound C group,the above indicators were improved in Rub A group.Compound C group reversed the protective effect of Rub A.Conclusion Rubescensine A can promote autophagy by activating AMPK/SIRT1 pathway,thereby reduce podocyte damage induced by high glucose.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

ObjectiveTo simulate the microstructure and mechanical properties of tendon tissue and promote its regeneration and repair, electrospinning technology was used to prepare L-polylactic acid (PLLA) fiber membranes loaded with different nano zinc oxide contents and with oriented structures. Physical and chemical characterization and biological performance evaluation were carried out to explore their effects on tendon cell proliferation and differentiation. MethodsPreparation of PLLA fiber scaffolds and PLLA/ZnO fiber scaffolds containing different mass fractions of nano ZnO was performed using electrospinning technology. The physicochemical properties of the scaffold were characterized by scanning electron microscopy, mechanical stretching, and EDS spectroscopy. The scaffold was co-cultured with mouse tendon cells to detect its biocompatibility and regulatory effects on cell differentiation behavior. ResultsThe fiber scaffolds were arranged in an oriented manner, and zinc elements were uniformly distributed in the fibers. The tensile strength and Young’s modulus of PLLA/0.1%ZnO fiber scaffolds were significantly higher than PLLA fiber scaffolds. The number of cells on the surface of PLLA/0.1%ZnO fiber scaffold was significantly higher than that of the PLLA group, and the activity was better; mouse tendon cells exhibit directional adhesion and growth along the fiber arrangement direction. ConclusionThe oriented PLLA/0.1%ZnO fiber scaffold had excellent physicochemical properties, which can significantly promote the oriented growth, proliferation and differentiation of tendon cells. It is expected to be used for tendon tissue regeneration and repair in the future.

Background Some studies have found that exposure to heavy metals significantly increases the risk of nonalcoholic fatty liver disease (NAFLD), and welding operators in automobile manufacturing enterprises are exposed to heavy metals in the working environment. Objective To analyze the prevalence and related factors of NAFLD in workers of an automobile company in Guangzhou. Methods From January 1 of 2023 to December 31 of 2023, 5463 workers of an automobile company in Guangzhou who participated in the physical examination in the Occupational Health Surveillance Centre of Guangzhou Occupational Disease Prevention and Treatment Hospital were selected as research subjects. The general data, laboratory examinations, B-ultrasound examinations, and other data of the subjects were obtained through the physical examination system. The exposed occupational hazards were identified based on the workplace hazard surveillance report provided by the automotive company. Logistic regression was used to analyze potential influencing factors of NAFLD, and stratified analysis was used to adjust confounding factors according to the stepwise model to evaluate the relationship between exposure to manganese and its inorganic compounds and NAFLD. Results A total of 2129 cases (38.97%) were reported positive NAFLD. The results of logistic regression analysis showed that women had a lower risk of NAFLD (OR=0.40, 95%CI: 0.25, 0.64), while age > 25 years old (OR=1.49, 95%CI: 1.39, 1.60), body mass index (BMI) ≥24 kg·m⁻² (OR=7.54, 95%CI: 6.46, 8.79), and elevated alanine aminotransferase (ALT) (OR=4.87, 95%CI: 3.73, 6.36), γ-glutamyl transpeptidase (γ-GGT) (OR=1.54, 95%CI: 1.17, 2.02), triglyceride (TG) (OR=3.47, 95%CI: 2.92, 4.14), and fasting blood glucose (OR=1.70, 95%CI: 1.32, 2.20) associated with a higher risk of NAFLD. NAFLD was positive in 39.40% of heavy metal exposed workers (701/1779). NAFLD was positive in 45.19% of workers exposed to manganese and its inorganic compounds (169/374), and among workers over 34 years old, exposure to manganese and its inorganic compounds (OR=1.79, 95%CI: 1.07, 2.97) significantly increased the prevalence of NAFLD. Conclusion The association between heavy metal exposure and NAFLD in workers of an automobile enterprise in Guangzhou is not significant, but age and gender are related to the prevalence of NAFLD. BMI, ALT, γ-GGT, TG, and fasting blood glucose are positively correlated with the prevalence of NAFLD. Exposure to manganese and its inorganic compounds in welding workers of the automobile enterprise is associated with elevated risk of the disease, and the prevalence of NAFLD is significantly increased in workers over 34 years old.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.