Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives. METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480. RESULTS These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

Objective To investigate the influences of Lycium barbarum polysaccharide on apoptosis of corneal epithelial cells induced by hypertonicity through regulating adenosine monophosphate activated protein kinase(AMPK)/uncoordinated 51-like kinase 1(ULK1)autophagy pathway.Methods The ophthalmoxerosis cell model was established by osmotic pressure of 500 mOsm·L-1 on corneal epithelial cells.They were divided into model group,positive control group(0.3％sodium hyaluronate eye drops),inhibitor group(1 mg·mL-1 Lycium barbarum polysaccharide+10 μmol·L-1compound C),experimental-L,-H groups(0.5,1.0 mg·mL 1 Lycium barbarum polysaccharide),and normal cultured CRL-11135 cells were taken as blank group(no treatment was performed).Cell apoptosis was detected by flow cytometry.Autophagy was detected by MDC staining.Western blot was used to detect the expressions of p-AMPK/AMPK and p-ULK1/ULK1.Results The apoptosis rates of experimental-L,experimental-H,positive control,inhibitor,model and blank groups were(26.47±2.13)％,(13.68±2.21)％,(12.54±2.16)％,(18.73±2.12)％,(37.56±3.25)％and(6.35±2.14)％;the relative contents of autophagosomes were(59.63±8.14)％,(89.89±9.04)％,(90.31±9.13)％,(62.75±7.26)％,(43.11±6.45)％and(100.00±0.00)％;p-AMPK/AMPK were 0.45±0.07,0.64±0.08,0.66±0.06,0.53±0.04,0.34±0.05 and 0.87±0.06;p-ULKl/ULKl were 0.54±0.06,0.75±0.05,0.77±0.03,0.65±0.04,0.46±0.04 and 0.92±0.08,respectively.The above indexes in experimental-L,-H groups and positive control group were significantly different from those in model group(all P＜0.05);the above indexes in inhibitor group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Lycium barbarum polysaccharide can inhibit the apoptosis of corneal epithelial cells induced by hypertonicity by activating the AMPK/ULK1 autophagy pathway.

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB)integrity through PI3K/Akt pathway after cerebral ischemia.Methods A permanent middle cerebral artery occlusion(MCAO)model was established in SPF adult male SD rats.Totally 48 rats were randomly divided into sham group(n=12),model group(n=12),MCAO+miR-199a-5p group(n=12),and MCAO+miR-199a-5p negative control group(n=12).The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats;The integrity of the BBB after ischemia stroke was detected through Evans blue staining;Immunofluorescent staining was used to determine apoptosis after cerebral ischemia;Western blotting technology was used to detect the protein expression of claudin-5,phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2),p-Akt,Akt,and vascular endothelial growth factor(VEGF)-A;Real-time PCR was used to investigate the expression levels of miR-199a-5p,claudin-5,and VEGF-A in the ischemic penumbra and infarcted area of the brain.Results The result showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats.MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke,activated the Akt signaling pathway,and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra.In addition,miR-199a-5p alleviated inflammation after cerebral ischemia.MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia.Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke,activate the Akt signaling pathway,reduce the expression of inflammatory cytokines,and alleviate the damage to the blood-brain barrier.

Objective To analyze the efficacy and safety of double-ring sandwich procedure in the treatment of acute A-type aortic dissection root.Methods The clinical data of 103 patients with acute A-type aortic dissection treated by double-ring sandwich procedure in our center from October 2020 to May 2023 were retrospectively analyzed to investigate the surgical effect,short-term cardiac structural changes and short-term postoperative complications.Results Needle hemostasis was applied in 11.65％of all patients.The amount of red blood cell transfusion during the perioperative period was(2.95±1.97)U,plasma was(543.68±208.48)ml,and blood platelet was(0.08±0.30)U.The residual aortic regurgitation,cardiac function and pericardial effusion were significantly improved at 2 weeks after operation(P＜0.05).The proportion of residual false lumen in the aortic root was significantly reduced after operation(P＜0.05).The length of hospital stay,duration of intubation,and drainage within 24 hours after surgery were less.The incidence of postoperative short-term complications such as secondary thoracotomy,cerebral infarction,cerebral hemorrhage,hemofiltration,tracheal incision and death was low.Conclusions Double-ring sandwich procedure in the treatment of acute A-type aortic dissection can effectively block the false lumen of aortic root dissection,reduce the risk of aortic intimal avulsion,and the operation is safe and effective.

Objective To investigate the effect and potential mechanism of Desmodium renifolium(Linn.)Schindl on ovariectomized osteoporosis rat model.Methods Sixty 3-month-old female SD rats were randomly divided into Sham group,model group,Xianlin Gubao group(0.24 g·kg-1),Desmodium renifolium low-dose group(1.35 g·kg-1,medium-dose group(2.7 g·kg-1)and high-dose group(5.4 g·kg-1).Osteoporosis was induced by performing double ovariectomy in rats.After 14 weeks treatment,the contents of osteocalcin(BGP),osteoprotectin(OPG)and alkaline phosphatase(ALP)in serum were determined.Hematoxylin-eosin(HE)staining was used to observe the changes of bone trabeculae.The osteoclast progenitor-cell line RAW264.7 was divided into negative control group,Receptor activator of nuclear factor-κB ligand(RANKL)group,Xianlin Gubao group,Desmodium renifolium low-dose,medium-dose and high-dose drug groups.The RANKL group and drug groups were induced with 50 ng·mL-1 RANKL.Meanwhile,Xianlin Gubao group and different concentrations of drug-containing serum of Desmodium renifolium,were added for intervention.Tartrate-resistant acid phosphatase(TRAP)staining was performed 10 days after intervention to observe the differentiation of osteoclasts,and quantitative real-time PCR(qPCR)was used to determine the mRNA expression.Results Compared with Sham group,the contents of OPG in serum of model group were significantly decreased(P<0.01),while ALP and BGP were significantly increased(P<0.01),bone trabeculae were significantly reduced,broken,sparsely arranged,and the space between bone trabeculae was large,the OPG mRNA expression in model group were significantly decreased(P<0.01),and the mRNA expression of receptor activator of nuclear factor-κB ligand(RANKL),TNF receptor associated factor 6(TRAF6),nuclear factor of activated t-cells,cytoplasmic 1(NFATC1),cathepsin K(CTK)and calcitonin receptor(CALCR)in model group were significantly increased(P<0.01),all these aspects showed remarkable improvement after Desmodium renifolium intervention.After 10 days of RAW264.7 culture,no osteoclasts were found in the Control group.Compared with the negative control group,osteoclasts in RANKL group were significantly increased,treatment with Desmodium renifolium markedly decreased osteoclast number,the result of RANKL/RANK/OPG signaling mRNA expression were consistent with the animal experiments.Conclusion Desmodium renifolium exerts effects on osteoporosis in ovariectomized rats,its mechanism might be realized by inhibiting osteoclast proliferation and differentiation,and regulating OPG/RANKL/RANK signaling pathway.

Objective To investigate clinical features and risk factors of obstructive sleep apnea(OSA)complicated with metabolic associated fatty liver disease(MAFLD),and to construct a prediction model,so as to provide reference for clinical diagnosis and treat-ment.Methods A total of 228 OSA patients admitted to Xiangyang No.1 People's Hospital Affiliate to Hubei University of Medicine from January 2020 to December 2022 were selected.According to whether complicated with MAFLD,the patients were divided into OSA+MAFLD group(n=94)and OSA group(n=134).According to the liver/spleen CT values,OSA+MAFLD group was further di-vided into OSA+mild MAFLD group(n=56)and OSA+moderate-severe MAFLD group(n=38).General clinical data,polysomnog-raphy(PSG),serological examination and other related indicators and parameters of all patients were collected for statistical analysis.Results Univariate analysis showed that there were significant differences between the OSA group and the OSA+MAFLD group in age,hypertension,diabetes,hyperlipidemia,body mass index(BMI),apnea hypopnea index(AHI),oxygen reduction index(ODI),lon-gest apnea time(LAT),snore frequency,lowest saturation oxygen(LSpO2),mean oxygen saturation(MSpO2),CT90％,fasting plasma glucose(FPG),alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyltransferase(GGT)(P＜0.05);and there were significant differences between the OSA+mild MAFLD group and the OSA+moderate-severe MAFLD group in age,hyperlip-idemia,BMI,AHI,ODI,LAT,snore frequency,LSpO2,MSpO2,CT90％and ALT(P＜0.05).Multivariate Logistic regression analy-sis showed that age,BMI,AHI,snore frequency were independent risk factors for OSA and MAFLD(P＜0.05);Age,BMI,AHI and ALT were independent risk factors for OSA with moderate-severe MAFLD(P＜0.05).The Logistic regression model was established:Y1=-13.183+0.083age+0.205BMI+0.039AHI+0.002snore frequency,the area under the receiver operating characteristic curve was 0.915,and the sensitivity and specificity of the regression model were 87.2％and 82.8％.Y2=-44.956+0.146age+0.510BMI+0.056AHI+0.022ALT,the area under the receiver operating characteristic curve was 0.924,and the sensitivity and specificity of the regression model were 78.9％and 91.1％.Conclusion In clinical work,the occurrence of MAFLD should be considered for OSA pa-tients with older age,higher BMI,higher AHI,and more snoring frequency.OSA patients with MAFLD with older age,higher BMI,higher AHI,and higher ALT are more serious.Moreover,the combined prediction model constructed in this study has better diagnostic value,and can provide reference for early diagnosis of OSA complicated with MAFLD.