OBJECTIVES: To analyze the distribution of Y chromosome azoospermia factor (AZF) microdeletions and their association with testicular development in male pediatric patients with congenital reproductive system disorders, including hypospadias, cryptorchidism, and disorders of sex development (DSD). METHODS: A prospective cohort study was conducted on pediatric patients admitted to the Department of Urology of Shanghai Children's Hospital from November 2021 to December 2023. The observation group included boys with hypospadias, cryptorchidism, or DSD, while the control group comprised boys with phimosis, indirect inguinal hernia, or hydrocele. Blood samples were collected for AZF microdeletion analysis using multiplex PCR to detect 15 sequence-tagged sites. Testicular ultrasound was performed to record testicular position and volume. Propensity score matching (PSM) was used to balance the groups. After matching, testicular volume differences were assessed. Stratified analyses compared testicular volume among children with AZF microdeletions, the control group, and children without micro-deletions in observation group. RESULTS: A total of 493 children were enrolled (observation group: 463; control group: 30). No Y chromosome microdeletions were detected in the control group. Four boys in the observation group had AZF microdeletions: one with cryptorchidism (AZFc+AZFd), one with isolated hypospadias (AZFc), and two with DSD (one with AZFb+AZFc+AZFd and one with AZFa). Ultrasonography measured 888 testicles. After PSM, testicular volume was significantly smaller in the observation group than in the control group (P<0.01). Stratified analysis revealed that among children under 9 years, those with AZF microdeletions tended to be older but had smaller testicular volumes compared to the control group and those without microdeletions in the observation group, although differences were not statistically significant (all P>0.05). Among children over 9 years, ages were comparable, but children with AZF microdeletions had smaller testicular volumes than the other two groups (statistical analysis was not performed due to small sample size). CONCLUSIONS The prevalence of Y chromosome microdeletions is higher in male children with congenital reproductive system disorders compared to the general population, particularly in those with DSD. Hypospadias, cryptorchidism, DSD, and AZF microdeletions may be associated with delayed testicular development in these children.

This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name， origin， harvesting and processing， quality and others by consulting ancient and modern literature， in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application， and it derives its name from its distinctive growth pattern， featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus， leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research， it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu， and throughout history， Baidu has been recognized as its official name， though it also bears alternative names such as Baibing， Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia， S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia）. Additionally， Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China， exhibiting a wide distribution. Historically， wild harvesting was predominant， but cultivation is now established. In ancient times， the harvesting time was mostly in the second， third， and eighth lunar months， when roots were harvested and dried. Nowadays， it is more common to pick and excavate in the spring and autumn seasons. After excavation， the roots are washed， fibrous roots removed， briefly blanched in boiling water or steamed until no white core remains， and then sun-dried or oven-dried. In ancient times， the processing of Stemonae Radix primarily involved roasting（stir-frying）， wine roasting， or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials， ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick， robust stems with firm texture". Evaluating quality with authenticity， since the Song dynasty， it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin， reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history， including relieving coughs， eliminating phlegm and parasites. Based on the research results， it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix， the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas， and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.

This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name， origin， harvesting and processing， quality and others by consulting ancient and modern literature， in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application， and it derives its name from its distinctive growth pattern， featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus， leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research， it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu， and throughout history， Baidu has been recognized as its official name， though it also bears alternative names such as Baibing， Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia， S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia）. Additionally， Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China， exhibiting a wide distribution. Historically， wild harvesting was predominant， but cultivation is now established. In ancient times， the harvesting time was mostly in the second， third， and eighth lunar months， when roots were harvested and dried. Nowadays， it is more common to pick and excavate in the spring and autumn seasons. After excavation， the roots are washed， fibrous roots removed， briefly blanched in boiling water or steamed until no white core remains， and then sun-dried or oven-dried. In ancient times， the processing of Stemonae Radix primarily involved roasting（stir-frying）， wine roasting， or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials， ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick， robust stems with firm texture". Evaluating quality with authenticity， since the Song dynasty， it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin， reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history， including relieving coughs， eliminating phlegm and parasites. Based on the research results， it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix， the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas， and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.

Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, providing novel insights and approaches for managing related conditions.Methods:Using the pQTL data from large-scale proteomics studies, a two-sample Mendelian randomization (TwoSampleMR) was conducted to preliminarily identify potential drug therapeutic targets. Subsequently, sensitivity analysis was performed to evaluate potential confounding factors such as heterogeneity and horizontal pleiotropy, and a leave-one-out sensitivity analysis was conducted by eliminating each single nucleotide polymorphism (SNP) one by one. Finally, co-localization analysis was carried out to explore whether there are shared genetic variants between the identified plasma proteins and traits.Results:The proteomic data used in this study included 4, 907 pQTLs, while the genetic data related to hair pigmentation and shaft abnormalities comprised 124 cases and 432, 686 controls. After Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. Leave-one-out sensitivity analysis indicated that no single SNP significantly influenced the overall result. Notably, HOMER2 was supported by colocalization analysis with strong evidence, suggesting its potential role in regulating genetic mechanisms underlying hair pigmentation and shaft health.Conclusions:This study identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 showing stronger evidence. These findings provide novel directions for the treatment of hair color and hair shaft abnormalities.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Objective To investigate the expression of leukocyte cell-derived chemotaxin 2(LECT2)and complement C3 in the serum of patients with autoimmune hepatitis(AIH),and their correlation with liver function grading and prognosis.Methods A total of 109 AIH patients admitted to our hospital from January 2022 to February 2024 were included as the observation group.According to the disease activity upon admission,they were grouped into the active group(59 cases)and the remission group(50 cases).According to the Child-Pugh grading,they were assigned into the grade A group(47 cases),the grade B group(40 cases),and the grade C group(22 cases).According to the prognosis,they were assigned into a poor prognosis group(35 cases)and a good prognosis group(74 cases),with 110 healthy volunteers who underwent physical checkup in our hospital as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum LECT2 level.Immunoturbidimetry was applied to detect serum complement C3 level.The correlation between LECT2,complement C3 and clinical indexes was analyzed by Pearson correlation analysis.Spearman correlation analysis was applied to analyze the relationship between serum LECT2,complement C3,and Child-Pugh grading.Receiver operating characteristic(ROC)curves were established to evaluate the predictive value of LECT2 and complement C3 levels for poor prognosis in AIH patients.Results The serum level of LECT2 in the observation group was higher than that in the control group,and the level of complement C3 was lower than that in the control group(P＜0.05).The expression level of ELECT2 in the grade C group was prominently higher than that in the grade B group and grade A group,while the expression level of complement C3 was prominently lower than that in the grade B group and grade A group(P＜0.05).The level of serum LECT2 in poor prognosis group was higher than that in good prognosis group,and the level of serum complement C3 was lower than that in good prognosis group(P＜0.05).Pearson correlation analysis showed that LECT2 was positively correlated with IgG,IL-6,TNF-α and Th17/Treg,and negatively correlated with TGF-β,while complement C3 was negatively correlated(all P＜0.05);Spearman correlation analysis showed that LECT2 level was positively correlated with Child-Pugh grading,while complement C3 level was negatively correlated with Child-Pugh grading(rs=0.803,-0.875,both P＜0.05).ROC curve reveled that the AUC of serum LECT2 and complement C3 levels in predicting poor prognosis of AIH patients was 0.802 and 0.805,respectively,the AUC of their combined detection was 0.905,which was higher than that of single indicator detection(P＜0.05).Conclusion Serum LECT2 level is elevated and complement C3 level is reduced in AIH patients,and they are correlated with liver function grading and disease severity.The combined detection of the two can serve as serological indicators for evaluating liver function and predicting prognosis.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective To investigate the expression of leukocyte cell-derived chemotaxin 2(LECT2)and complement C3 in the serum of patients with autoimmune hepatitis(AIH),and their correlation with liver function grading and prognosis.Methods A total of 109 AIH patients admitted to our hospital from January 2022 to February 2024 were included as the observation group.According to the disease activity upon admission,they were grouped into the active group(59 cases)and the remission group(50 cases).According to the Child-Pugh grading,they were assigned into the grade A group(47 cases),the grade B group(40 cases),and the grade C group(22 cases).According to the prognosis,they were assigned into a poor prognosis group(35 cases)and a good prognosis group(74 cases),with 110 healthy volunteers who underwent physical checkup in our hospital as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum LECT2 level.Immunoturbidimetry was applied to detect serum complement C3 level.The correlation between LECT2,complement C3 and clinical indexes was analyzed by Pearson correlation analysis.Spearman correlation analysis was applied to analyze the relationship between serum LECT2,complement C3,and Child-Pugh grading.Receiver operating characteristic(ROC)curves were established to evaluate the predictive value of LECT2 and complement C3 levels for poor prognosis in AIH patients.Results The serum level of LECT2 in the observation group was higher than that in the control group,and the level of complement C3 was lower than that in the control group(P＜0.05).The expression level of ELECT2 in the grade C group was prominently higher than that in the grade B group and grade A group,while the expression level of complement C3 was prominently lower than that in the grade B group and grade A group(P＜0.05).The level of serum LECT2 in poor prognosis group was higher than that in good prognosis group,and the level of serum complement C3 was lower than that in good prognosis group(P＜0.05).Pearson correlation analysis showed that LECT2 was positively correlated with IgG,IL-6,TNF-α and Th17/Treg,and negatively correlated with TGF-β,while complement C3 was negatively correlated(all P＜0.05);Spearman correlation analysis showed that LECT2 level was positively correlated with Child-Pugh grading,while complement C3 level was negatively correlated with Child-Pugh grading(rs=0.803,-0.875,both P＜0.05).ROC curve reveled that the AUC of serum LECT2 and complement C3 levels in predicting poor prognosis of AIH patients was 0.802 and 0.805,respectively,the AUC of their combined detection was 0.905,which was higher than that of single indicator detection(P＜0.05).Conclusion Serum LECT2 level is elevated and complement C3 level is reduced in AIH patients,and they are correlated with liver function grading and disease severity.The combined detection of the two can serve as serological indicators for evaluating liver function and predicting prognosis.

This study explored the application of traditional and complementary medicine (T&CM) in the WHO eastern Mediterranean region, revealing the progressive emphasis on T&CM and its uneven development in the region. The study identified herbal and indigenous traditional medicine as the most prevalent T&CM therapies in the area, but there are relatively few relevant policies and scientific studies, and national health insurance coverage for T&CM has been weak. In addition, China provides assistance in TCM services to some countries through medical teams and TCM centers, while India provides assistance to specific countries through academic exchanges and educational cooperation, promoting the construction and development of local T&CM. It is recommended to provide management experience to countries in the region to strengthen supervision, actively carry out scientific research cooperation and people-to-people exchanges, promote their expansion of health insurance coverage to promote the high-quality development of T&CM in the region.

Traditional and complementary medicine (T&CM) in WHO Southeast Asian Region has a long history, rich variety, large scale, strong government support and relatively complete institutional construction. Among them, TCM is highly popular in Thailand and Indonesia and the legislation is relatively complete; there is a relative lack of legislation and policy in India, Nepal and Myanmar; development in Sri Lanka, East Timor, Bhutan, Bangladesh, Maldives and Democratic People's Republic of Korea is still in its infancy. India, Japan, Republic of Korea and China have provided T&CM assistance to the WHO Southeast Asia Region through signing memorandums, financial support, teaching and research cooperation, preparation export, personnel training, medical service base construction, and special assistance in TCM, so as to promote the improvement of T&CM services and standardization in the region. At present, some countries lack T&CM development funds, scientific research data and effective information exchange. In the future, it is necessary to strengthen legislative supervision and cooperation in education and scientific research based on the national conditions and cultural backgrounds of various countries, and promote the better integration of T&CM into the global health system. The dissemination and development of TCM in the WHO Southeast Asia Region can learn from the experience of T&CM in India, Japan and the Republic of Korea in terms of organizational guarantee, standard establishment, cultural publicity and brand effect, pay attention to the exchange and integration with local culture, give full play to the advantages of TCM, and enhance the public's sense of trust, so as to enhance the overseas influence of TCM.