ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Mesenchymal stem cells(MSCs)play a crucial role in tissue repair and regeneration,and the extracellular vesicle(EV)released by them holds great promise for applications in clinical biomarkers,vaccines,and drug delivery.However,MSCs-derived EV(MSCs-EV)face challenges such as low pro-duction yield,poor retention,and targeted delivery issues.There-fore,engineering MSCs-EV to enhance their performance and en-able visual research has become a hot topic.Curcumin(CUR),an active component in traditional chinese medicine,exhibits pharmacological effects but has limited bioavailability.Using MSCs-EV as a carrier for CUR delivery can address its solubility and bioavailability challenges.This article reviews the drug loading methods,engineering strategies of MSCs-EV,and their important applications in the delivery and treatment of CUR for cartilage injury diseases.It provides a basis for the clinical ap-plication of engineered MSCs-EV in CUR delivery for cartilage repair,offering potential solutions to the challenges in cartilage tissue repair.

Previous studies have shown that the diversity and composition of intestinal microbiota are related to the effect of tumor immunotherapy,but the mechanism of intestinal microbiota affecting tumor immunotherapy resistance has rarely been sum-marized.This article not only expounds the current clinical sta-tus of tumor immunotherapy resistance,but also summarizes the correlation and regulatory mechanism between the composition and homeostasis of intestinal microbiota and drug resistance to different types of tumor immunotherapy,so as to provide a refer-ence for the study of potential targets for improving tumor immu-notherapy resistance based on intestinal microbiota.

United Nations(UN)agencies are key actors in global procurement of health products,with the United Nations Children's Fund(UNICEF)currently accounting for the largest share of UN procurement expenditures.This study developed a conceptual framework to analyze the processes of UN's global procurement for health products.Based on this framework,the study analyzed the mechanisms and key characteristics of UN procurement practices,identified potential challenges faced by Chinese products and suppliers seeking to engage with the UN's global procurement.The findings indicate a steady increase in the volume of Chinese products procured and their alignment with the UN's sustainable procurement policies.However,Chinese suppliers still face notable barriers,including gaps in technical standards,bidding and contracting capacities,and price competitiveness.In addition,the strategic compliance capabilities of Chinese suppliers and products,such as the ability to offer strategically valuable products and build long-term partnership,remains limited.Based on this,the study recommends that China enhance its participation and influence in the UN health procurements by stabilizing the production capacity,promoting knowledge-sharing among suppliers to enhance their engagement capabilities,and improving the long-term strategic competitiveness of Chinese enterprises in the global market.

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

OBJECTIVE To explore the value of preoperative serum laboratory indicators in the diagnosis of postop-erative abdominal infection in patients with perihilar cholangiocarcinoma.METHODS We retrospectively collected 444 patients who underwent radical resection of perihilar cholangiocarcinoma at the First Medical Center of the People's Liberation Army General Hospital from Jan.2021 to Apr.2023.According to whether postoperative ab-dominal cavity infection occurred,patients were divided into an infection group(52 cases)and a no-infection group(392 cases).The general clinical data,intraoperative and postoperative conditions of the two patient groups were compared.Multivariate logistic regression analysis was employed to investigate the predictive value of preoperative laboratory indicators in the diagnosis of postoperative abdominal infections.RESULTS The abdominal cavity infec-tion rate was 11.71％in patients undergoing radical resection of perihilar cholangiocarcinoma.Compared with the non-infection group,the infection group had significantly higher intraoperative red blood cell transfusion vol-umes,higher incidence rates of postoperative biliary fistula and a longer postoperative hospital stay(P＜0.05).Preoperative serum total protein,C-reactive protein(CRP),carcinoembryonic antigen(CEA),carbohy-drate antigen(CA)125,CA15-3,and CA72-4 were independent risk factors in predicting postoperative abdominal cavity infection in patients with perihilar cholangiocarcinoma(P＜0.05).The receiver operating characteristic(ROC)analysis results showed that the area under the curve(AUC)value of the combination of these six indica-tors for diagnosing postoperative abdominal cavity infection in perihilar cholangiocarcinoma was 0.873(95％CI:0.818-0.929),with a sensitivity of 73.1％(95％CI:0.590-0.844)and a specificity of 87.0％(95％CI:0.833-0.902).CONCLUSION Preoperative peripheral blood CRP,total protein and tumor markers of patients with peri-hilar cholangiocarcinoma have high diagnostic values for postoperative abdominal cavity infection.

[Purpose]To analyze the trend of prostate cancer mortality in China from 2011 to 2020,and to predict the prostate cancer mortality trend from 2021 to 2030.[Methods]The data were collected from the National Mortality Surveillance System(NMSS)from 2011 to 2020,the burden of prostate cancer in China from 2011 to 2020 were analyzed by the number of deaths,age-standardized mortality rate(ASMR),years of life lost(YLL)and age-standardized YLL rate.Joinpoint regression model was used to calculate the average annual percentage change(AAPC)to describe the trend of change.The Bayesian age-period-cohort model was used to predict the mor-tality rate of prostate cancer from 2021 to 2030 and estimate the number of deaths of prostate can-cer in the future.Decomposition analysis was carried out to explore the potential drivers of changes of mortality.[Results]The number of prostate cancer deaths in China in 2020 was 30 805 with an ASMR of 5.56/105.The ASMR for prostate cancer in urban and rural areas was 6.56/105 and 4.84/105,respectively.From 2011 to 2020,the number of prostate cancer deaths,ASMR and age-standardized YLL rate of prostate cancer in China showed an upward trend,AAPC was 5.4％(95％CI:4.7％～6.1％),1.5％(95％CI:1.4％～1.6％)and 1.1％(95％CI:1.1％～1.2％),respective-ly.The ASMR of prostate cancer was higher in the eastern region than those in the central and western regions.Prostate cancer deaths increased in both urban and rural areas among people aged 60 years old and above.In 2030,it is predicted the ASMR of prostate cancer would increase to 5.74/105.Population aging,changes in age-specific mortality rates,and natural population growth accounted for 24.75％,2.77％,and 7.45％of the changes in total deaths of prostate can-cer,respectively.[Conclusion]The burden of prostate cancer is increasing in China.Targeted measures should be implemented in high-risk areas and high-risk groups to effectively reduce the disease burden caused by prostate cancer.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Objective To observe the effects of Bushen Antai Mixture on angiogenesis at the maternal fetal interface in recurrent spontaneous abortion(RSA)mice;To explore its mechanism in treating RSA based on the VEGF/Hippo/YAP pathway.Methods RSA mouse model and normal pregnancy mouse were constructed using Clark classic method.RSA model mice were randomly divided into model group,progesterone group,Bushen Antai Mixture low-,medium-and high-dosage groups,and normal pregnant mice were used as normal group,with 10 mice in each group.Starting from the first day of pregnancy,each medication group was given the corresponding medication by gavage for 15 days.The absorption rate of mouse embryos was calculated,the morphology of decidual tissue were observed by HE staining,the mRNA and protein expression of VEGF and Hippo/YAP pathway-related molecules of decidual tissue were detected by RT-qPCR and Western blot.Results Compared with the normal group,the absorption rate of embryos in the model group significantly increased(P<0.01),the arrangement of decidual tissue cells were disordered,edematous and degenerated,some nuclei disappeared,the vascular density decreased,the mRNA expressions of VEGF,Yes associated protein(YAP),large tumor suppressor factor(LATS)1 and LATS2 in decidual tissue significantly decreased(P<0.01),the protein expression of VEGF decreased(P<0.01),and the protein expressions of p-YAP/YAP and p-LATS/LATS significantly increased(P<0.01).Compared with the model group,the absorption rate of embryos in each dosage group of Bushen Antai Mixture was significantly reduced(P<0.05,P<0.01),the cells in the decidual tissue were arranged in an orderly manner,and edema degeneration was reduced,the mRNA expressions of VEGF,YAP,LATS1 and LATS2 in decidual tissue significantly increased(P<0.05,P<0.01),and the protein expression of VEGF significantly increased(P<0.05,P<0.01),the protein expressions of p-YAP/YAP and p-LATS/LATS decreased(P<0.05,P<0.01).Conclusion Bushen Antai Mixture can promote the expressions of VEGF,YAP,LATS by activating VEGF/Hippo/YAP signaling pathway,promote angiogenesis at the maternal-fetal interface,reduce the pregnancy loss rate,and play a therapeutic effect of RSA.