Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: Rhodiolae Crenulatae Radix et Rhizoma (Hongjingtian in Chinese, RCRR), the roots and rhizomes of Rhodiola crenulata and its application in the medicinal market is very chaotic. In this study, DNA barcoding database and identification engine of Rhodiola species were established, decoction pieces from the medicinal market were identified, and the application and challenges of DNA barcoding in the rapid radiation of Rhodiola species were analyzed. This study provides reference for the protection, rational development, and utilization of endangered resources within Rhodiola species. METHODS: A total of 50 original plant samples from 20 species of the genus Rhodiola from Hebei, Xinjiang, Tibet, Jilin, and other major production areas were collected. Theses samples cover the typical distribution area (Qinghai-Tibetan Platea) of Rhodiola species and other scattered alpine regions (Changbai Mountain, Taibai Mountain, Lushan Mountain, etc.), it encompasses all Rhodiola species with thick rhizomes in China. ITS2 and psbA-trnH barcode of Rhodiola database (BORD) were established and an identification engine named Rhodiola-IDE was developed. The stability and accuracy of the standard DNA barcoding database were evaluated using two datasets. Rhodiola-IDE identified 31 decoction pieces of RCRR from the medicinal material market. RESULTS: The BORD containing 1 532 sequences of 88 Rhodiola species has been established, and the identification efficiency results showed good accuracy and stability. According to the Chinese Pharmacopoeia (2020 edition), 23 samples (74.2%) were identified as authentic R. crenulata, while the rest of the marketed varieties were R. kirilowii, R. dumulosa, and R. fastigiata. The product label "Larger flower, Hongjingtian" was identified as R. crenulata. Samples labeled as "Smaller flower, Hongjingtian" were identified as R. crenulata, R. kirilowii, and R. fastigiata. CONCLUSION ITS2 and psbA-trnH barcodes can identify monophyletic groups represented by R. crenulata. However, for non-monophyletic species, it is necessary to collect as many samples as possible and combine them with multiple markers for joint identification. This study discussed the application and challenges of DNA barcodes in Rhodiola under rapid radiation conditions, providing a scientific basis for the rational development and utilization of Rhodiola varieties.

Idiopathic gingival fibromatosis is a rare, benign condition of unknown etiology characterized by extensive gingival overgrowth. This case reports a severe skeletal Class Ⅱ adult female patient with idiopathic gingival fibromatosis. The patient underwent multidisciplinary treatment involving periodontics, orthodontics, and orthognathic surgery, resulting in remarkable crown height elongation, substantial improvements in occlusal function and aesthetics, and stable long-term follow-up outcomes. This case provides a reference for future clinical practice.
Humans ; Female ; Malocclusion, Angle Class II/complications* ; Fibromatosis, Gingival/complications* ; Adult ; Orthodontics, Corrective ; Orthognathic Surgical Procedures

Objective:To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF).Methods:From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score.Results:A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance.Conclusions:Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model′s generalizability, cross-dataset performance, and algorithm optimization.

Objective:The Capital′s Funds for Health Improvement and Research (referred to as ″CFH″), established to address clinical medical issues, have been operating for over a decade. This study aims to comprehensively evaluate the achievements of this fund and provide empirical support and recommendations for optimizing the operational model of the clinical research fund.Methods:An online questionnaire was used to investigate the following aspects of CFH: subject area, the person in charge, derived projects, theses, patents, transformation of results, and popularization and promotion.Results:A total of 745 projects were collected through the online survey, and after rechecking for outliers, 720 completed projects were ultimately included. The top three disciplinary domains, in terms of the number of completed projects, were oncology, cardiovascular diseases, and neurological disorders. The age distribution of project leaders exhibited a left-skewed pattern, with a median age of 45 years. 319 (44%) received support from other related projects subsequently. 95% of the projects resulted in paper publication. 211 (29%) projects applied for patents and copyrights, with 141 projects being granted patent authorization. 78 (11%) projects successfully achieved technology transfer, with transfer and licensing being the most common modes. 156 (22%) projects disseminated their outputs, often targeting secondary hospitals and community health institutions.Conclusions:CFH aligns with local needs, and the outputs are substantial. In the future, consideration can be given to establishing an evaluation mechanism, increasing efforts to promote high-quality outputs, strengthening the organizational model set by the project guidelines, and further improving the rolling support mechanism.

Talents are the core driving force to promote the high-quality development of public hospitals,and the talent team building is an important factor for hospitals to get sustainable development and improve comprehensive competitiveness.In view of the shortage of high-level talents,the imperfect talent reserve system,and the lagging personnel management mechanism of public hospitals and the resulting unreasonable talent team structure and talent gap,public hospitals should take talent team building as the starting point,pay equal attention to the introduction and training of talents,interact with discipline construction and talent construction,vigorously promote the construction of personnel management system and mechanism innovation,form a standardized,scientific,refined and efficient modern hospital management system,so that the effectiveness of talents can be max-imized,and provide intellectual support for the high-quality development of public hospitals.

Objective To investigate the effect of the mediator of DNA damage check point protein 1(MDC1)on proliferation,migration,invasion,cell cycle and cell apoptosis in cholangiocarcinoma(CCA)and the potential molecular mechanism.Methods The small interfering RNA(siRNA)specifically targeting MDC1 was used to transiently knock down MDC1.Recombined plasmid containing MDC1 was transiently transfected into RBE and Huh28 cells for over-expression of MDC1.Real time quantitative PCR(qPCR)and Western blotting were adopted to verify the effectiveness of MDC1 knockdown or overexpression.The proliferation of CCA cells was measured via CCK-8 and cell colony formation assays.Transwell and Invasion assays were used to detect cell migration and invasion while flow cytometry assays were employed to detect cell cycle and apoptosis.Gene set enrichment analysis(GSEA)was conducted to investigate the pathways which were significantly associated with MDC1,and the expression of p53 downstream protein was verified by Western blotting assay.Co-immunoprecipitation(Co-IP)assays were used to verify the interactions between MDC1 and p53.Flow cytometry and Western blotting assays were performed to find out whether MDC1 promoted cell cycle and cell apoptosis through p53 pathway.Based on The Cancer Genome Altas(TCGA)database,the difference in MDC1 expression levels between CCA and normal tissues was analyzed,and the correlations between the MDC1 expression levels and the clinical prognosis of CCA patients were investigated.Results Knockdown of MDC1 in RBE and Huh28 cells significantly inhibited cells proliferation,migration and invasion,significantly decreased the proportion of cells in S phase,and significantly increased the proportion of cells in G0/G1 phase and apoptosis rate while overexpression of MDC1 could significantly promote cell proliferation,migration and invasion,significantly increase the proportion of cells in S phase,and significantly decrease the proportion of cells in G0/G1 phase and apoptosis rate.It was found that MDC1 interacted with p53 in RBE and Huh28 cells,and MDC1 significantly down-regulated the expressions of p53,p-p53(Ser-15),BAX,PUMA and p21,but significantly up-regulated the expression of Bcl-2,which in turn promoted the tumorigenesis of CCA.MDC1 was up-regulated in CCA tissues compared to the normal tissues,and the high expressions of MDC1 were significantly associated with poor clinical outcomes of CCA patients.Conclusion MDC1 promotes the development of CCA by suppressing the p53 pathway,and MDC1 may be a candidate marker for the poor prognosis in CCA.

Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.