OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.
Male ; Humans ; Carcinoma, Squamous Cell/drug therapy* ; Diosgenin/metabolism* ; Mouth Neoplasms/drug therapy* ; Apoptosis ; Prostatic Neoplasms/drug therapy*

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

We have identified anti-inflammatory quality markers (Q-markers) of Jiangzhenxiang. The chemical components of Jiangzhenxiang were identified by mass spectrometry and the substances that contribute to its anti-inflammatory activity, their targets and signaling pathways were analyzed by network pharmacology to identify potential Q-markers of the anti-inflammatory action of Jiangzhenxiang. The potential Q-markers were verified by high performance liquid chromatography, and in vitro experiments verified the anti-inflammatory activity and the target of the potential Q-markers. The experimental scheme was approved the Guangxi University of Chinese Medicine Institutional Animal Ethical and Welfare Committee. The results show that 31 chemical components were identified by mass spectrometry from the Jiangzhenxiang extract. Through network pharmacological screening, 727 component targets, 422 disease targets and 110 targets including prostaglandin G/H synthase 2 (PTGS2) were obtained. These targets were mainly enriched in 498 biological processes including inflammatory response and response to lipopolysaccharide, with 101 pathways that included the TNF signaling pathway, toll-like receptor signaling pathway and others. Isorhamnetin, formononetin, naringenin, glycitein, ursolic acid and oleanolic acid were detected by high performance liquid chromatography. Jiangzhenxiang medicated serum and 6 components thereof could significantly reduce the content of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α in RAW264.7 cells induced by lipopolysaccharide (P < 0.01 or P < 0.05). These six components are regarded as the potential anti-inflammatory Q-markers of Jiangzhenxiang. Isorhamnetin was screened and verified from the 6 potential Q-markers as an inhibitor of PTGS2 by molecular docking and in vitro cyclooxygenase 2 (COX-2) activity assay. The half-inhibitory concentration of isorhamnetin was 9.55 μmol·L^-1. In summary, extracts of Jiangzhenxiang showed significant in vitro anti-inflammatory actions. The anti-inflammatory mechanism of Jiangzhenxiang appears to be related to regulation of TNF signaling pathway and Toll-like receptor signaling pathway meditated by IL-6, RAC alpha serine/threonine protein kinase, PTGS2 and other targets. Isorhamnetin, formononetin, naringenin, glycitein, ursolic acid and oleanolic acid could be regarded as the Q-markers of Jiangzhenxiang. Isorhamnetin appears to act as a COX-2 inhibitor.

Objective To investigate the recognition status and attitudes of general practice medical professional for rural-oriented clinical medical (general practice direction) students, and provide effective basis for teaching reform. Methods Using cluster sampling method, a questionnaire survey was conducted among 305 rural-oriented medical students in Hubei Medical University who belonged to four different grades. The questionnaire effective recovery was 98.07%, SPSS 17.0 software was used to analyze data, pro-portion (%) were used for statistical descriptive, chi-square test and nonparametric test were used for statis-tical inference. Results 16% (49) students believed that it was not necessary for local medical colleges and universities to set up general practice professional, The rates of students who understood this professional training objectives, employment channel, the future work and professional developments were 82.3% (251 students ), 64.5% (197 students ), 69.2% (211 students) and 66.9% (204 students ), respectively. 27.5%(84) of the students still didn't understand this professional curriculum, and lower cognitive learning public health curriculum. Only 31.1%(105) of students were satisfied with the current general medicine education.52.5% (160) students thought that the professional curriculum system had problems, mainly for the course content overlap and course setting time being not reasonable. Different grades of students had different de-gree of satisfaction in the professional knowledge, the general practice of professional learning attitude, teaching arrangement . Conclusion We should strengthen rural-oriented medical students' ! professional education thought and their cognition of general medicine as soon as possible and integrate and optimize the curriculum system, adjust the teaching content and set up reasonable curriculum opening time.

OBJECTIVETo study the alkaloids of Macleaya cordata and their anti-tumor activities.

METHODAlcohol and liquid-liquid extraction were used methods were used to extract the alkaloids constituents, and silica gel, reverse-phase octadecylsilyl (ODS), sephadex LH-20 chromatographic methods and HPLC were applied to isolate and purify compounds. MS, NMR spectroscopic methods were used to determine their structures. Furthermore, the cytotoxicity of these chemical components for MCF-7 and SF-268 cell lines was measured by MTT method.

RESULTTwelve alkaloids were isolated from the fruits of M. cordata, and their structures were identified as: maclekarpine E (1), 6-acetonyldihyrochelerythrine (2), cavidilinine (3), 6-acetonyldihyrosanguinnarine (4), O-methylzanthoxyline (5), 6-methoxy-dihydrosanguinarine (6), spallidamine (7), 6-hydroxyldihydrochelerythrine (8), arnotianamida (9), dihydrosanguinarine (10), protopine (11), and cryptopine (12).

CONCLUSIONCompounds 1, 3, 7-9 were isolated from M. cordata for the first time, and compound 5 is a new natural product. The results of cytotoxic assay indicated that compound 6 showed strong cytotoxicity against MCF-7 and SF-268 cell lines with IC50 values of 0.61 μmol · L(-1) and 0.54 μmol · L(-1), respectively.

Alkaloids ; isolation & purification ; pharmacology ; Antineoplastic Agents, Phytogenic ; isolation & purification ; Cell Line, Tumor ; Humans ; Papaveraceae ; chemistry

Objective To study the distribution of ameloblastin(AMBN) gene polymorphism in coal-fire caused fluorosis (CFCF) in Chongqing municipality and the relationship between AMBN gene polymorphism and the susceptibility to dental fluorosis.Methods Under a case-control study,100 children aged 8-12 and 30 adults with dental fluorosis were enrolled in Wushan and Fengjie counties of Chongqing from December 2010 to February 2011.Another 100 children aged 8-12 and 30 adults with non-dental fluorosis were chosen as internal control groups together with 50 childrenand 30 adults without dental fluorosis were selected as external control groups in the non-epidemic area of Yubei district.DNA was extracted from peripheral blood sample of these people.Genotype of AMBN gene 7 extron 538_540delGGA,10 extron 657A＞G and 13 extron 986C＞T loci were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique.Results The rates of 7 extron 538_540delGGA loci among case,internal and external control groups were as follows:GGA/GGA-/-61.2％ (74/121),78.5％ (102/130),74.3％ (52/70) ;GGA/-:24.0％ (29/121),15.4％ (20/130),22.9％ (16/70) ;-/-:14.8％ (18/121),6.1％ (8/130),2.8％ (2/70),the difference was statistically significant (x2=14.353,P＜0.05).The AA appeared to be 86.8％(105/121),93.1％(121/130),91.4％(64/70) and AG were 13.2％(16/121),6.9％(9/130),8.6％ (6/70),with difference not statistically significant (x2=2.972,P＞0.05).CC appeared as 81.0％ (98/121),90.0％(117/130),87.1％(61/70) while CT as 19.0％(23/121),10.0％(13/130),12.9％(9/70),with difference not statistically significant (x2=4.319,P＞0.05).In comparing with the two control groups,the frequency of GGA/GGA was decreasing (x2 values were 8.957,3.405,respectively,P＜0.05) while the frequency of-/-was increasing (x2 values were 5.134,6.833,respectively,P＜0.05).Results from the univariate analysis showed that the individuals who were carrying-/-genotype had an increased risk of suffering from fluorosis (OR values were 2.7,5.9,respectively,P＜0.05).When compared with the internal control group,the CT genotype of case group showed an increase (x2=4.139,P＜0.05) while individuals that carrying CT genotype had an increased risk of suffering from fluorosis (OR=2.1,P＜0.05),in epidemic-area.Conclusion Our results showed that the 7 extron 538_540delGGA and the 13 extron 986C＞T loci polymorphism in AMBN gene might serve as the susceptibility factors causing the coal-fired fluorosis.

The descriptive cross sectional surveys were carried out among the outstanding clinical physicians in the field of acupuncture and moxibustion by using the survey sampling. The fuzzy comprehensive evaluation techniques was applied to evaluate the opinions of clinical experts in the field of acupuncture and moxibustion in order to classify the spectrum of diseases related to the musculoskeletal and connective tissue. After the statistical analysis on sixty-four diseases with 104 subtypes, the spectrum of diseases were determined as grade I spectrum of diseases with 13 subtypes of diseases, grade II spectrum of diseases with 51 subtypes of diseases, grade III spectrum of diseases with 10 subtypes of diseases, and grade IV spectrum of diseases with 30 subtypes of diseases. The outcomes reveal that acupuncture and moxibustion therapy have been applied widely for musculoskeletal diseases and connective tissue related diseases.
Acupuncture Therapy ; methods ; Bone Diseases ; therapy ; Connective Tissue Diseases ; therapy ; Cross-Sectional Studies ; Humans ; Moxibustion ; methods ; Muscular Diseases ; therapy ; Surveys and Questionnaires

OBJECTIVETo study the expression levels of ANXA1 and ANXA2 and elucidate their clinicopathological significance in adenocarcinoma, peritumoral tissues, adenomatous polyp and chronic cholecystitis of gallbladder.

METHODSEnVision(TM) immunohistochemical staining was used to detect the expression of ANXA1 and ANXA2 in paraffin-embedded tissue sections from resected specimens of adenocarcinoma (n = 108), peritumoral tissue (n = 46), adenomatous polyp (n = 15) and chronic cholecystitis (n = 35).

RESULTSThe positive rates and scores of ANXA1 and ANXA2 were significantly higher in adenocarcinoma (59.3%, 56.5%; 3.2 ± 0.9, 3.4 ± 0.8) than those in peritumoral tissues (34.8%, 1.1 ± 0.8, P < 0.01; 30.4%, 1.0 ± 0.8, P < 0.01), adenomatous polyp (26.7%, 0.9 ± 0.7, P < 0.05 or P < 0.01; 26.7%, 0.9 ± 0.8, P < 0.05 or P < 0.01) and chronic cholecystitis (17.1%, 0.7 ± 0.9, P < 0.01; 20.0%, 0.8 ± 0.8, P < 0.01). The benign lesions with positive ANXA1 and/or ANXA2 expression showed mild to severe atypical hyperplasia of the gallbladder epithelium. The positive rates of ANXA1 and/or ANXA2 were significantly lower in the well-differentiated adenocarcinoma, in a maximal diameter of < 2 cm, with no metastasis to lymph nodes and no invasion to surrounding tissues than those in the moderately or poorly-differentiated adenocarcinoma, in a maximal diameter of ≥ 2 cm, with metastasis to lymph nodes and invasion in surrounding tissues (P < 0.05 or P < 0.01). A high consistence was found between the expression levels of ANXA1 and ANXA2 (χ(2) = 67.84, P < 0.01), and a close positive correlation between the scores of ANXA1 and ANXA2 (r = 0.78, P < 0.01) in gallbladder adenocarcinoma. Kaplan-Meier analysis and multivariate Cox regression analysis showed that ANXA1 or ANXA2 was not an independent prognostic predictor in gallbladder adenocarcinoma.

CONCLUSIONThe expression levels of ANXA1 and/or ANXA2 may be important biological markers in the carcinogenesis, progression and biological behaviors of gallbladder adenocarcinoma.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; surgery ; Adenomatous Polyps ; metabolism ; pathology ; Adult ; Aged ; Annexin A1 ; metabolism ; Annexin A2 ; metabolism ; Cholecystectomy ; methods ; Cholecystitis ; metabolism ; pathology ; Female ; Gallbladder ; metabolism ; pathology ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Proportional Hazards Models ; Survival Rate