BACKGROUND: Research has indicated that the disease burden of alopecia areata (AA) in China exceeds the global average. Therefore, accurate and updated epidemiological information is crucial for policymakers. In this study, we aimed to comprehensively assess the disease burden of AA in China. METHODS: The following four key indicators were utilized: the prevalence of cases; disability-adjusted life-years (DALYs); the age-standardized prevalence rate (ASPR); and the age-standardized DALY rate (ASDR) of AA according to the Global Burden of Disease (GBD) study 2021. We analyzed the epidemiological burden of AA in China during 2021, examined changes between 1990 and 2021, and performed a Bayesian age-period-cohort analysis to predict trends over the course of the next decade (2022-2030). Additionally, a Gaussian process regression model was applied to estimate the relationship between the gross domestic product (GDP) and the ASPR and ASDR of AA at the provincial level between 1992 and 2021. RESULTS: In 2021, the estimated number of patients with AA in China was approximately 3.49 million (95% uncertainty interval [UI], 3.37-3.62 million); of these patients, 1.20 million (95% UI, 1.16-1.25 million) were male and 2.29 million (95% UI, 2.20-2.37 million) were female. This large number of patients with AA resulted in a total of 114,431.25 DALYs (95% UI, 74,780.27-160,318.96 DALYs). Additionally, the ASPR and ASDR were 224.61 per 100,000 population (95% UI, 216.73-232.65 per 100,000 population) and 7.41 per 100,000 population (95% UI, 4.85-10.44 per 100,000 population), respectively; both of these rates were higher than the global averages. The most affected demographic groups were young and female individuals 25-39 years of age. Slight regional disparities were observed, with the northern and central regions of China bearing comparatively higher burdens. Between 1990 and 2021, the health loss and disease burden caused by AA in China remained relatively stable. The ASPR and ASDR of AA increased with the GDP when the annual GDP was less than 2 trillion Chinese yuan; however, a downward trend was observed as the GDP surpassed 2 trillion Chinese yuan. A slight upward trend in the disease burden of AA in China is predicted to occur over the next decade. CONCLUSIONS AA continues to be a public health concern in China that shows no signs of declining. Targeted efforts for young individuals and females are necessary because they experience a disproportionately high burden of AA.
Humans ; China/epidemiology* ; Alopecia Areata/epidemiology* ; Global Burden of Disease ; Female ; Male ; Adult ; Disability-Adjusted Life Years ; Middle Aged ; Prevalence ; Adolescent ; Young Adult ; Bayes Theorem ; Child ; Quality-Adjusted Life Years ; Child, Preschool

Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry* ; Plant Proteins/chemistry* ; Multigene Family ; Sesquiterpenes, Germacrane/metabolism* ; Alkyl and Aryl Transferases/chemistry* ; Phylogeny ; Gene Expression Regulation, Plant

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Objective： To investigate the correlation between pathological features at the positive margins and biochemical recurrence after radical prostatectomy for prostate cancer. Methods： From June 2014 to December 2019, a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching (1∶1). One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study. All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0. BCR-free survival was estimated using the Kaplan-Meier method. An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis (CART). Cox proportional hazards regression model was used to assess the association between variables and BCR-free survival. Results： A total of 200 patients were included in this study, and 177 patients with pT2 stage were pathological after operation. The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months. A total of 28 cases of biochemical recurrence were found through PSA follow-up after surgery, including 6 cases (6.0%) in the negative margin group and 22 cases (22.0%) in the positive margin group. The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group (log rank χ2=9.336, P=0.003). It was found that the length of positive margin ≥1 mm in the positive margin group was positively correlated with postoperative biochemical recurrence. Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of positive ≥1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin. Conclusion：　The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.
Humans ; Male ; Prostatectomy ; Prostatic Neoplasms/pathology* ; Neoplasm Recurrence, Local ; Margins of Excision ; Prostate-Specific Antigen/blood* ; Proportional Hazards Models ; Middle Aged ; Aged ; Neoplasm Staging ; Kaplan-Meier Estimate

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

Background Oral exposure to metals/metalloid elements in drinking water may be harmful to human health. Objective To assess potential health risks of oral exposure to 9 metals/metalloids in drinking water in Zibo City of Shandong Province from 2019 to 2023, and provide reference for the development of local drinking water management policies. Method From 2019 to 2023, a total of 1178 drinking water samples were collected from 261 rural water monitoring sites and 14 urban water monitoring sites in 8 districts and counties of Zibo City. The US Environmental Protection Agency's (EPA) four-step health assessment model was used to evaluate the health risks of oral exposure to 9 metals/metalloids in drinking water for adults. Results A total of 1178 water samples were collected, including 561 urban water samples and 617 rural water samples; 769 samples of tap water and 409 samples of finished water; 634 samples collected in wet season and 544 in dry season. The median carcinogenic risk (CR) of arsenic exposure in drinking water for adults was 3.53×10⁻⁵, and the median hazard quotient (HQ) was 7.85×10⁻². The HQs of arsenic and zinc showed an upward trend in recent years, while the HQ of aluminum showed a downward trend. The stratified analysis results showed that there was no statistically significant difference in the CR of arsenic between males and females or between urban water and rural water. The CR of arsenic in dry season was higher than that in wet season, and the CR of arsenic in tap water was higher than that in finished water (P<0.05). There was no statistically significant difference in the HQs of 9 metals/metalloids in drinking water between males and females. The HQs of aluminum, copper, arsenic, selenium, and cadmium in tap water were higher than those in finished water (P<0.05). In dry season, the HQs of aluminum, manganese, copper, zinc, arsenic, and selenium were higher than those in wet season (P<0.05). The HQs of aluminum, copper, zinc, cadmium, and lead in urban water were higher than those in rural water (P<0.05). Conclusion The overall health risks of 9 metal/metalloid pollutants in drinking water in Zibo City are lower than the maximum acceptable risk recommended by the US EPA, and suggest an acceptable level and no significant harm to adult health. The health risk of arsenic is relatively high and should be given priority by relevant departments in drinking water risk management.

Objective To explore the comparative application of phase and diaphragmatic navigation in three-dimensional magnetic resonance cholangiopancreatography(3D-MRCP)thin-layer scanning in elderly patients.Methods A total of 180 elderly patients were scanned by phase and diaphragmatic navigation via Siemens Aera1.5T superconducting MR scanner.The acquired images were reconstructed by 3D reconstruction.The anatomical structure,image quality and disease diagnosis were compared between the phase and diaphragmatic navigation groups.Results In liver of anatomy,the liver of primary bile duct,the superior,middle and inferior extrahepatic bile duct and the gallbladder could be well displayed,and the difference was not statistically significant between the two groups(P＞0.05).The display of pancreatic duct and the liver of secondary bile duct of diaphragmatic navigation was significantly better than those of phase navigation(P＜0.05).In terms of image quality,the excellent rate of diaphragmatic navigation was significantly higher than that of phase navigation,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the detection rate of pancreatobiliary system diseases,the diagnostic rate of cholelithiasis,common bile duct stones,common bile duct dilatation and pancreatic duct dilatation between the two groups(P＞0.05).Conclusion Diaphragmatic navigation is signifi-cantly better than phase navigation in the display of the anatomical structure of the pancreatic duct,the liver of secondary bile duct,and the excellent rate of image quality.Diaphragmatic navigation is more suitable for thin-layer 3D-MRCP scanning in elderly patients.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131～9.335),P＜0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.