OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

To mine tacrolimus-related adverse event signals affecting the cardiovascular system based on an international authoritative database, aiming to provide a reference for clinical safe drug use.

Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

ObjectiveTo study the characteristics of the five tones of Parkinson's disease （PD） patients based on the theory of "five-viscera phonology"， and provide references for the syndrome differentiation and treatment of PD. MethodsA total of 272 cases of PD patients were collected as the PD group， and 240 individuals， including patient family members and hospital staff， were recruited as the control group. The 25-tone analyzer was used to collect the five-tone characteristics of both PD patients and control group participants. The participants were then stratified into three age groups， 41~55， 56~70， and 71~85 years old， and categorized by gender （male and female） for analysis. The frequency and composition ratio of the five tones were analyzed for both groups across the different age ranges and genders. Additionally， the average voice frequency of each participant was calculated to compare differences between groups， stratified by age range and gender. ResultsIn the 41~55 and 56~70 age groups， male participants in the PD group and the control group exhibited the highest frequency of Yu （羽） tone， with the PD group showing a significantly higher composition ratio of Yu tone compared to the control group （P＜0.05）； for males in the 56~70 age group， the composition ratios of Shang （商） and Zhi （徵） tone in the PD group were lower than those in the control group （P＜0.05）. For males in the 71~85 age group， both the PD group and the control group had the highest frequency of Yu tone， but there was no statistically significant difference in the composition ratios of the five tones between groups （P＞0.05）. For female participants in the PD group across all age groups， Yu tone was the most frequent， whereas for the control group， Jue （角） tone was the most frequent in all age groups， and the composition ratio of Yu tone in the PD group was significantly higher than that in the control group across all age groups （P＜0.05）； in the 56~70 age group， the composition ratio of Jue tone was lower in the PD group compared to that in the control group （P＜0.05）. Regarding voice frequency， males in the PD group aged 41~55 and 56~70 had higher voice frequency than those in the control group of the same age range， and similarly， females in the PD group aged 56~70 and 71~85 had higher voice frequency than their counterparts in the control group （P＜0.05）. ConclusionPD patients have a voice with a higher frequency and an increased proportion of Yu tone in their five-tone distribution. According to the theory of five-viscera phonology， PD patients may have disease mechanism of kidney essence deficiency.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

Objective To understand the equity and influencing factors of maternal health service utilization in Changning District, Shanghai. Methods A convenience sampling method was used to conduct a questionnaire survey among mothers of children aged 1 to 1.5 years old who received health services from the child health care clinics and EPI clinics of 10 community health service centers in Changning District, Shanghai from March to April 2022. Count data was expressed by frequency and percentage. Chi-square analysis, binomial logistic regression analysis, and multivariate logistic regression analysis were used to analyze fairness-related factors. Rate difference, rate ratio and concentration index were used to represent fairness. Results A total of 696 subjects were investigated, with an average age of (33.35±4.76) years. There were statistically significant differences in service utilization among women with different household registrations only in early pregnancy registration (χ²=11.026, P=0.001) and postpartum visits (χ²=4.989, P=0.026). Women with a career showed differently in folic acid supplement (χ²=6.247, P=0.012), early pregnancy registration (χ²=12.989, P=0.002), physical examination in 42 days postpartum (χ²=4.446, P=0.035) and postpartum contraception (χ²=4.061, P=0.044), and the differences were statistically significant. Women with different monthly family income had a statistically significant difference in pre-pregnancy examination (χ²=8.977, P=0.030) and postpartum visit (χ²=16.114, P=0.001). There was a statistically significant difference between women with maternity insurance or not in the early pregnancy registration (χ²=10.576, P=0.001) and physical examination in 42 days postpartum (χ²=8.166, P=0.004). The results of the multivariate analysis showed that occupation (OR=2.616, 95% CI: 1.142-5.990) and maternity insurance (OR=4.490, 95% CI: 1.992~10.120) affected the utilization of service in early pregnancy registration. The monthly household income (OR=0.278, 95% CI: 0.124-0.625) affected the utilization of services in postpartum visit. At the same time, the monthly household income (10,000-19,999: OR=0.286, 95% CI: 0.090-0.907; ≥30,000: OR=0.180, 95% CI: 0.041-0.801) also affected the utilization of service in physical examination in 42 days postpartum. Conclusion The equity of maternal health care service utilization overall is good in central area in Shanghai, but there is still room for improvement. It is necessary to strengthen community mobilization, propagandize maternal health services, and expand the coverage of maternity insurance to improve the equity of maternal health service utilization and provide equal access to maternity health services.

OBJECTIVE To explore the impact of Shaoyao decoction on the intestinal microecology of rats with damp-heat diarrhea. METHODS Male SD rats were randomly divided into physiological group， model group， and Shaoyao decoction low-， medium- and high-dose groups （single dose of 5.62， 28.10 and 56.20 g/kg， by raw drugs）， with 7 rats in each group. Except for the physiological group， the remaining groups were all fed with high-sugar and high-fat diet， raised in a high-temperature and high- humidity environment， and administered white liquor and Escherichia coli suspension by gavage to establish a rat model of damp- heat diarrhea. On the second day after modeling， rats in each dosage group of Shaoyao decoction were administered the corresponding solution by gavage， once in the morning and once in the evening， for 3 consecutive days. After the last administration， fecal metagenomic sequencing analysis and biological information analysis were performed to detect the activities of intestinal cytochrome P450 （CYP） enzymes and intestinal flora metabolic enzymes. RESULTS There was no significant difference in the α diversity indexes of intestinal flora among the groups （P＞0.05）. The main phyla of rats in each group included Firmicutes， Actinobacteriota and Verrucomicrobiota， and the core dominant genera included Dubosiella， Lactobacillus and Romboutsia； low- ， medium- and high-dose of Shaoyao decoction could reverse the decrease in the relative abundance of Firmicutes， Romboutsia， Bifidobacterium and Monoglobus， as well as the increase in the relative abundance of Proteobacteria， Verrucomicrobiota， Escherichia-Shigella and Corynebacterium （P＜0.05）. Rats in each dosage group of Shaoyao decoction showed higher relative abundance of intestinal flora involved in carbon metabolism and cofactor biosynthesis pathways. Compared with the model group， the elimination rates of aminophenol and midazolam， as well as the concentration （except for the low-dose group） and metabolic rate of p-nitrophenol in rats of each dose group of Shaoyao decoction were significantly increased （P＜0.05）. CONCLUSIONS Shaoyao decoction can correct intestinal flora disorder in rats with damp-heat diarrhea， promote the recovery of intestinal CYP metabolic enzymes and intestinal flora metabolic enzymes， and thereby comprehensively improve intestinal microecology. Δ 基金项目 国家自然科学基金青年科学基金项目 （No. 82104726）；河南省软科学研究项目（No.252400410455）

Objective: To investigate the mechanism of action of curcumol on mitochondrial autophagy in hepatic stellate cells and its molecular mechanism against liver fibrosis. Methods : Hepatic stellate cells were divided into blank group, model group(lipopolysaccharide 5 mg/L), and low, medium and high curcumol group(12.5, 25 and 50 mg/L); Thiazolyland(MTT) was used to detect the effects of curcumol on the viability of hepatic stellate cells; flow cytometry was used to detect the effects of curcumol on apoptosis of hepatic stellate cells; 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide(JC-1) was used to detect the mitochondrial membrane potential; effects of curcumol on mitochondrial morphology and autophagosome were detected by transmission electron microscopy; effect of curcumol on mitochondrial localisation were detected by fluorescent probe; Immunoblotting assay was performed to detect the effects of curcumin on PTEN-induced putative kinase 1(PINK1), Parkinson's disease protein(Parkin), microtubule-associated protein light chain 3(LC3), autophagy-associated protein(Beclin1), mitochondrial inner membrane translocase 23(Timm23), mitochondrial outer membrane translocase 20(Tomm20), Bcl-2 associated X protein(Bax), B lymphocytoma-2(Bcl2), cleaved-cysteine protease 3(Caspase3), α-smooth muscle actin(ɑ-SMA), collagen type Ⅰ(Collagen Ⅰ), and collagen type Ⅲ(Collagen Ⅲ) protein expression. Results : Compared with the blank control group, cell proliferation rate, Caspase3, Bcl2, LC3Ⅱ, Beclin1, PINK1, Parkin, ɑ-SMA, CollagenⅠ, CollagenⅢ proteins significantly increased in the model group(P<0.01), co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01), while Timm23 and Tomm20 proteins, mitochondrial membrane potential decreased significantly(P<0.01), apoptosis rate decreased, and Bax protein expression decreased. Compared with the model group, after curcumol intervention, cell proliferation rate, Bcl2, Timm23, Tomm20, α-SMA, CollagenⅠ and CollagenⅢ protein expression significantly decreased in the curcumol low-, medium-and high-concentration groups(P<0.01), and the mitochondrial membrane potential significantly decreased(P<0.01), whereas apoptosis rate, Caspase3, Bax, LC3Ⅱ, Beclin1, PINK1 and Parkin proteins significantly increased(P<0.05), the co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01). Conclusion Curcumol exerts ameliorative effects on hepatic fibrosis by modulating mitochondrial hyperautophagy mediated by the PINK1/Parkin signaling pathway, and promoting hepatic stellate cell apoptosis.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.