OBJECTIVE: To analyze the acupoint selection patterns and core prescriptions of acupuncture for polycystic ovary syndrome (PCOS) using data mining, and to explore the molecular mechanisms of core acupoints through network acupuncture medicine. METHODS: The randomized controlled trials (RCTs) on acupuncture for PCOS published from January 1, 2004 to July 21, 2024 were retrieved from CNKI, VIP, Wanfang, PubMed, and Web of Science databases. R software (version 4.4.0) was used for acupoint frequency and association rule analysis to identify core acupoint prescriptions. Potential targets were predicted via the STITCH and Swiss Target Prediction databases, and a "core prescription-active compounds-targets- PCOS" network was constructed. Cytoscape 3.7.1 was applied to build protein-protein interaction (PPI) networks of potential targets of core acupoint prescriptions. Key therapeutic targets were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses using the DAVID and Microbioinformatics platforms. RESULTS: A total of 176 RCTs were included, covering 208 prescriptions and 89 acupoints. The five most frequently used acupoints were Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1), Zusanli (ST36) and Zhongji (CV3). Association rule analysis yielded 13 core acupoint combinations, with Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1) and Zusanli (ST36) as the core prescription. Twenty-seven active compounds were involved, with 852 potential therapeutic targets, among which 208 targets overlapped with PCOS-related targets. Network acupuncture medicine analysis suggested that the core prescription may act through targets such as estrogen receptor 1 (ESR1), proto-oncogene tyrosine-protein kinase Src (SRC), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferator-activated receptor gamma (PPARG), and RAC-alpha serine/threonine-protein kinase (AKT1). GO and KEGG analyses indicated that the main pathways included the hypoxia-inducible factor 1 (HIF-1) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, involving processes such as signal transduction, receptor complex formation, and cytokine activity. CONCLUSION The core acupoint prescription for PCOS might exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for mechanistic research on acupoint prescriptions.
Humans ; Acupuncture Therapy ; Data Mining ; Acupuncture Points ; Polycystic Ovary Syndrome/metabolism* ; Female ; Protein Interaction Maps ; Randomized Controlled Trials as Topic

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

Proteolysis-targeting chimeras (PROTACs) represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can, potentially revolutionizing drug discovery and treatment strategies. However, the links between in vitro and in vivo data are poorly understood, hindering a comprehensive understanding of the absorption, distribution, metabolism, and excretion (ADME) of PROTACs. In this work, ¹⁴C-labeled vepdegestrant (ARV-471), which is currently in phase III clinical trials for breast cancer, was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics (PK) by establishing a physiologically based pharmacokinetics (PBPK) model. For in vitro-in vivo extrapolation (IVIVE), hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did. PBPK models, which were initially developed and validated in rats, accurately simulate ARV-471's PK across fed and fasted states, with parameters within 1.75-fold of the observed values. Human models, informed by in vitro ADME data, closely mirrored postoral dose plasma profiles at 30 mg. Furthermore, no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans. This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Objectives:To investigate the relationship between the improvement of lumbar symptoms and imaging parameters in patients with tandem spinal stenosis(TSS)primarily manifesting as cervical spondylotic myelopathy(CSM)after initial cervical decompression surgery,and to explore related imaging predictive factors.Methods:A retrospective analysis was conducted on 69 TSS patients who underwent primary cervical decom-pression surgery,with an average age of 64.3±10.5 years(ranging from 41 to 86 years old)and a follow-up period of 33.8±5.5 months(ranging from 24 to 48 months).Preoperative symptoms and signs,Nurick gait clas-sification,and preoperative and final follow-up Japanese Orthopaedic Association(JOA)scores for both the cer-vical and lumbar spine were recorded and analyzed.The patients were divided into an improvement group(n=37)and a non-improvement group(n=32)based on the improvement conditions of lumbar spine JOA scores at the final follow-up.Imaging parameters were measured including spinal cord compression ratio,cross-sectional area of the dural sac at the narrowest point of the cervical spinal cord,the ratio of the vertebral canal to the vertebral body and the actual spinal canal width from C3 to C7,and the actual width of the vertebral canal from L1 to L5.The conditions of spinal canal stenosis were evaluated according to the grading system of spinal canal stenosis of cervical and lumbar spine proposed by Lee et al,and the number of cervical verte-brae with a stenosis score ≥1,score at the narrowest part of cervical spinal canal,and the total score of cervical stenosis,as well as the number of lumbar vertebrae with a stenosis score ≥1,score at the narrowest part of lumbar spinal canal,and the total score of lumbar stenosis were calculated.Intergroup comparisons were performed using t tests,chi-square tests,and Mann-Whitney U tests.For the statistic data with statisti-cal differences between the two groups,receiver operating characteristic(ROC)curve was used to determine op-timal thresholds for each parameter,and the area under the ROC curve(AUC)and its corresponding 95％ con-fidence interval(CI)were calculated.Multivariate logistic regression analysis was conducted to identify radiolog-ical predictive factors for non-improvement of lumbar symptoms in TSS patients.Results:The non-improvement group was significantly higher than the improvement group in the total score of lumbar stenosis(5.00±1.68 vs 2.68±1.23,P＜0.001),the number of lumbar vertebrae with a stenosis score≥1(2.47±0.84 vs 1.86±0.95,P=0.004),and the prevalence of redundant nerve roots(14/18 vs 6/13,P=0.017).The AUC of the total lumbar stenosis score was 0.864(P＜0.001,95％CI 0.779-0.950),with an optimal threshold of 3.5(sensitivity:81.3％;specificity:75.7％).The AUC of the number of lumbar vertebrae with a stenosis score ≥1 was 0.691(P=0.007;95％CI 0.565-0.817),with an optimal threshold of 1.5(sensitivity:87.5％;specificity:56.8％).Multivariate logistic regression showed that the number of lumbar spinal stenosis＞1.5(OR=1.493;95％CI 0.392-5.686;P=0.557)and presence of redundant nerve roots(OR=2.815;95％CI 0.740-10.711;P=0.129)had no significant relationship with improvement of lumbar symptoms.The total lumbar stenosis score＞3.5 was significantly related with improvement of lumbar symptoms(OR=10.983;95％CI 3.261-36.994;P＜0.001),which was an independent risk factor for non-improvement in lumbar symtoms after initial cervical decompression in TSS patients.Conclusions:When the total score of lumbar spinal stenosis exceeds 3.5 in TSS patients,the possibility of improvement in lumbar symptoms after initial cervical decompression is small.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

Objective:To explore the effect and mechanism of Andrias davidianus skin mucopolysaccharides (ASMP) on full-thickness skin defect wound healing in diabetic mice. Methods:This study was an experimental study. The ASMP with polysaccharide content of (70.0±0.3)% was prepared; the proliferation activity of human umbilical vein endothelial cells (HUVECs) was detected by cell counting kit-8, showing that the optimal concentration of ASMP was 0.05 mg/mL. The HUVECs were taken and divided into blank control group, vascular endothelial growth factor (VEGF) group, and ASMP group according to the random number table method (the same grouping method below), which were cultured with conventional medium and the media containing 50 ng/mL VEGF and 0.05 mg/mL ASMP, respectively, and then cultured under hypoxic (with volume fraction of oxygen being 5%) and normal-oxygen conditions for 12 hours, and the length of tube formation was observed. Human monocytic leukemia cells were induced with phorbol ester to differentiate into M0 macrophages. These cells were then divided into blank control group, lipopolysaccharide (LPS) group, and ASMP group, which were cultured respectively using conventional medium, LPS-containing medium followed by conventional medium, and LPS-containing medium followed by 0.05 mg/mL ASMP-containing medium. After 48 hours of culture, the expressions of CD86 and CD206 proteins (expressed as relative fluorescence intensity, the same below) were measured by immunofluorescence, and the mRNA expression levels of arginase-1 (Arg1) and CD206 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Eighteen male C57 mice aged 8-10 weeks were used, and diabetic model was successfully established using streptozotocin combined with a high-fat and high-sugar diet. Full-thickness skin defect wounds were created on the backs of the mice, and the mice were divided into blank control group, alginate dressing group, and ASMP group (with 6 mice in each group), which were treated with physiological saline, alginate dressing, and ASMP, respectively. Wound healing was observed on post injury day (PID) 3, 7, 10, and 14, and the wound healing rates of mice were calculated. On PID 7, the expressions of CD31 and CD206 proteins in the wound tissue of mice were observed by immunofluorescence. On PID 14, the thickness of granulation tissue in wounds of mice was observed by hematoxylin-eosin staining. The sample size for all experiments was 3.Results:After 12 hours of culture in normal-oxygen condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 10.08 and 16.91, respectively, P<0.05). After 12 hours of culture in hypoxic condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 11.61 and 16.91, respectively, P<0.05); compared with that in VEGF group, the tube formation length of HUVECs in ASMP group was significantly increased ( q=5.30, P<0.05). After 48 hours of culture, the relative fluorescence intensity of CD206 protein in M0 macrophages in ASMP group was 31.90±1.76, significantly higher than 1.00±0.25 in blank control group and 2.21±0.42 in LPS group (with q values of 50.75 and 48.75, respectively, both P values <0.05); the relative fluorescence intensity of CD86 protein was 5.82±0.63, significantly lower than 53.73±4.61 in LPS group ( q=30.90, P<0.05). After 48 hours of culture, the mRNA expressions of Arg1 and CD206 in M0 macrophages in ASMP group were significantly higher than those in blank control group (with q values of 35.02 and 13.09, respectively, P<0.05) and LPS group (with q values of 32.24 and 11.24, respectively, P<0.05). On PID 3, there was no statistically significant difference in intercomparison in the wound healing rate of mice among the blank control, alginate dressing, and ASMP groups ( P>0.05). Compared with those in blank control group, the wound healing rates of mice in alginate dressing group on PID 10 and 14 were significantly increased (with q values of 11.76 and 12.50, respectively, P<0.05), and the wound healing rates of mice in ASMP group on PID 7, 10, and 14 were significantly increased (with q values of 5.84, 15.90, and 14.96, respectively, P<0.05); compared with those in alginate dressing group, the wound healing rates of mice in ASMP group on PID 7 and 10 were significantly increased (with q values of 4.77 and 4.14, respectively, P<0.05). On PID 7, the relative fluorescence intensity of CD31 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 7.63 and 16.85, respectively, P<0.05); the relative fluorescence intensity of CD31 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group ( q=9.22, P<0.05). On PID 7, the relative fluorescence intensity of CD206 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 8.76 and 29.36, respectively, P<0.05), and the relative fluorescence intensity of CD206 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group ( q=20.61, P<0.05). On PID 14, the wound granulation tissue of mice in ASMP group was thicker compared with that in blank control group and alginate dressing group. Conclusions:ASMP can significantly enhance the ability of new blood vessel formation and optimize the immune microenvironment by promoting HUVEC tube formation as well as inducing macrophages to polarize toward the M2 type, thereby accelerating full-thickness skin defect wound healing in diabetic mice.

Objective:This study utilizes data from the 2021 Chinese Longitudinal Healthy Longevity and Happy Family Survey(CLHLS-HF)to examine the current status of Long-Term Care Insurance(LTCI)implementation and to identify the factors influencing whether disabled elderly individuals receive formal care services.The study aims to provide policy recommendations to enhance the effectiveness and equity of the system.Methods:In this cross-sectional study, a sample of 1 447 older participants with dependency, residing in LTCI pilot areas and meeting the inclusion criteria from the 2021 CLHLS-HF, was selected.Chi-square tests and binary logistic regression analyses were employed to explore the factors influencing the receipt of formal care by dependent older individuals.Results:Among the 1 447 participants, there were 496 males with an average age of 92 years(SD 9)and 951 females with an average age of 95 years(SD 9). Of these, 701 received formal care.The logistic regression analysis revealed that factors influencing the receipt of formal care included urban residence( OR=2.237, 95% CI: 1.675-2.987, P<0.001), residing in the eastern region( OR=2.907, 95% CI: 1.747-4.837, P<0.001), living in the western region( OR=3.132, 95% CI: 1.816-5.501, P<0.001), having no children( OR=2.478, 95% CI: 1.108-5.540, P=0.027), and the degree of disability, with severe disability being more likely to receive care compared to mild( OR=0.497, 95% CI: 0.388-0.637, P<0.001)and moderate disabilities( OR=0.589, 95% CI: 0.433-0.801, P=0.001). Conclusions:Dependent older individuals in the eastern and western regions, particularly those without children or with severe disabilities, are more likely to receive formal care through the LTCI system.However, there are substantial inequities in LTCI coverage among individuals with varying degrees of disability.To enhance the effectiveness of the LTCI system, greater efforts should be directed towards economically disadvantaged regions and older individuals with mild to moderate disabilities, thereby ensuring better protection for the disabled population.

Proteolysis-targeting chimeras(PROTACs)represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can,potentially revolu-tionizing drug discovery and treatment strategies.However,the links between in vitro and in vivo data are poorly understood,hindering a comprehensive understanding of the absorption,distribution,metabolism,and excretion(ADME)of PROTACs.In this work,14C-labeled vepdegestrant(ARV-471),which is currently in phase Ⅲ clinical trials for breast cancer,was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics(PK)by estab-lishing a physiologically based pharmacokinetics(PBPK)model.For in vitro-in vivo extrapolation(IVIVE),hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did.PBPK models,which were initially developed and validated in rats,accurately simulate ARV-471's PK across fed and fasted states,with parameters within 1.75-fold of the observed values.Human models,informed by in vitro ADME data,closely mirrored postoral dose plasma profiles at 30 mg.Furthermore,no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans.This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.