Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.

Objective To explore the reliability of the reagent burstbead for field blood transfusion compatibility testing by applying it to bloodtype detection,antibody screening and cross matching tests and conduting parallel contrast with the existing arrays.Methods A field treatment shelter was used as the testing site to simulate the scene of emergency blood transfusion for the wounded under the conditions of field blood station,and 1 358 pieces of blood samples sent to some hospital for examination before transfusion were considered as the objects.Parallel contrast tests were carried out between the reagent burstbead method and the tube method for bloodtype detection and between the reagent burstbead method and the manual polybrene method for antibody screening and cross matching.The reagent burstbead method was compared with other methods in terms of the coin-cidence rate of the bloodtype detection results,the detection rate of positive samples for antibody screening and crossmatch incompatibility.Results The reagent burstbead method and the tube method had high consistency when used for bloodtype detection,with the coincidence rate being 100％.During antibody screening and cross matching tests,the reagent burstbead method found 5 cases of antibody-positive samples leading to major crossmatch incompatibility(positive rate being 0.37％),the manual polybrene method detected 2 cases of irregular antibody-positive samples(positive rate being 0.15％),and the two methods both identified 3 cases of minor crossmatch incompatibility.Conclusion The reagent burstbead has high accuracy and reliability when applied to bloodtype detection,antibody screening and cross matching tests,and thus can be used for blood transfusion compatibility testing in field conditions.[Chinese Medical Equipment Journal,2025,46(2):39-42]

Pressure ulcer is a common complication of long-term bed rest in intensive care unit(ICU)patients,which can increase the risk of infection and prolong ICU hospitalization.They are an important indicator of patient safety and nursing quality in medical institutions.Early prevention of pressure ulcer is an important means of controlling their development.At present,the prevention of pressure ulcer mainly involves timed flipping and the use of pressure reducing devices.However,during the flipping process,it often requires two or more nursing staff to complete,which increases the workload and also exacerbates the occurrence of occupational lower back pain among nursing staff.In addition,existing pressure reducing devices still have certain limitations in use,and their functions are single,often requiring the combination of multiple tools to increase material and financial resources.Based on this,the research team from the department of critical care medicine of Hospital of Chengdu University of Traditional Chinese Medicine,has designed a nursing device for preventing pressure ulcer in critically ill patients,and has obtained a National Utility Model Patent of China(Patent Number:ZL 202320609787.6).It has several inflation components and connecting structures.The inflation components are equipped with a connected air inlet,a connected air outlet,and a discharge port on the side;the inflatable components are fitted together and can be detachably connected through a connecting structure.The connected air inlet of one inflatable component corresponds to the connected air outlet of adjacent inflatable components.This device is connected by multiple inflation components,which lower or raise the height of the airbag through inflation and deflation,adjust the pressure on various parts of the patient's body,and solve the problem of labor-intensive and heavy workload in nursing work;In addition,multiple inflatable components can be detachably connected to form an inflatable mattress.When in use,the number of inflatable component connections can be selected according to the specific needs of different patients or nursing areas.The device is easy to operate,flexible in combination,and suitable for timed flipping pressure reduction regulation in pressure ulcer high-risk areas under various postures.It has good clinical application value.

Objective:To understand the status quo of general practice postgraduate researches through visualized analysis of masters′ theses.Methods:The master′s theses in general medicine from January 2007 to December 2022 were retrieved from China Knowledge and Wanfang databases. The number and regional distribution of theses, the degree-granting institutions were analyzed; the performed keywords were visualizde with CiteSpace and VOSviewer softwares.Results:A total of 1 688 master′s theses in general practice were included in the analysis. The highest number of theses ( n=345) were published in 2022. The theses from institutions in the eastern, central and western regions of China accounted for 45.67% (771/1 688), 22.16% (374/1 688) and 32.17% (543/1 688), respectively, and those in Shaanxi Province accounted for the highest proportion at 13.68% (231/1 688). A total of 3 755 keywords were included in the theses, and the top three were diabetes mellitus (115/3 755), risk factors (77/3 755) and clinical efficacy (71/3 755). The results of keyword clustering and timeline mapping showed that the research topics were mainly clustered around five themes: clinical treatment and drug efficacy/safety for diabetes mellitus, training of general practitioners and evaluation of general practice services, risk factors related to common chronic diseases in the community, risk factors and cognitive changes in cerebrovascular diseases, and pathogenic mechanisms of cardiovascular diseases. The results of the emergent words showed that recent research hotspots mainly included obesity, older adults, and cognitive function. Conclusions:The number of general practice master′s theses published in China is increasing rapidly with an uneven regional distribution; and the research topics are diverse, mainly focusing on the diagnosis and treatment of chronic diseases and analysis of related risk factors.

Objective:To understand the characteristics of faculty in high-level public health schools in China, and analyze the differences in age, area and school level.Methods:Based on the internet information, the faculty information of 18 high-level public health schools was collected for a descriptive analysis on faculty characteristics.Results:There were 1 642 faculty members in the schools of public health in China, in whom 51.8% were women, 92.8% had doctorate, 32.4% had postdoctoral experience and 56.8% were former students staying to teach. The average age of the faculty members was (45.6±9.8) years. Meanwhile the top three study subjects were epidemiology and health statistics (31.0%), occupational health and environmental sanitation (16.5%), and health toxicology (16.3%). In the faculty members aged >40 years, 90.2% had doctorate, 62.6% were former students staying to teach, and 24.7% had no educational background of public health. The proportions of faculty members aged ≤40 years in the three groups mentioned above were 98.2%, 45.8% and 39.1% respectively. In terms of study subject, big data study were mainly conducted in the schools with top subject ranking and the schools in developed areas.Conclusions:The public health faculty was characterized by cross education background and high capability. The study subjects and sub-disciplines varied with schools and areas.

Objective To investigate the pathogenic bacteria and risk factors of urinary tract infection (UTI) in elderly patients with type 2 diabetic mellitus (T2DM), and construct a prediction model. Methods Elderly patients with T2DM who were admitted to General Hospital of Western Theater Command from January 2020 to March 2023 were selected. They were divided into the observation group (100 cases) and the control group (82 cases) according to the presence or absence of UTI. Pathogenic bacteria was detected, and influencing factors were analyzed. A prediction model was constructed, and its predictive value was evaluated. Results Escherichia coli was the main pathogenic bacteria of UTI in elderly patients with T2DM. There were significant differences between the two groups in terms of age, 24 h urinary albumin (UALB), serum creatinine (Scr) , blood urea nitrogen (BUN), fasting blood glucose (FBG), gender, complications, course of T2DM , length of hospital stay and serum albumin (ALB) (P<0.05). Logistic regression analysis found that advanced age, long course of T2DM, FBG ≥11.1mmol/L and high 24 hUA1b/Scr level were risk factors for UTI in elderly patients with T2DM, and high ALB level was a protective factor. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the constructed model to predict UTI in patients with T2DM was 0.978. The sensitivity and specificity were 91.00% and 97.56%. Conclusion Escherichia coli are main pathogenic bacteria of UTI in elderly patients with T2DM. UTI is related to factors such as patient age, course of T2DM and FBG. The prediction model constructed based on these factors is of high value in predicting UTI in elderly patients with T2DM. It is worthy of promotion in diagnosis and treatment.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Melicope pteleifolia is a plant belonging to the Melicope genus of the Rutaceae family. Known for a bitter taste and cold nature, its stems and tender branches with leaves possess properties of clearing heat, detoxifying, dispelling wind, and removing dampness and can be used to treat sore throat, malaria, jaundice hepatitis, rheumatic bone pain, eczema, dermatitis, and sores and ulcers. In this study, 19 compounds were isolated from the chloroform and n-butanol extracts of M. pteleifolia leaves by using liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR)-guided separation techniques. The compounds were identified as isoleptonol(1), leptaones B-E(2-5), friedelin(6), evodionol(7), ethyl p-hydroxybenzoate(8), litseachromolaevane A(9), quercetin-7,3',4'-trimethyl ether(10), kokusaginin(11), 8-(1-hydroxyethyl)-5,6,7-trimethoxy-2,2-dimethyl-2H-1-benzopyran(12), ethyl p-hydroxycinnamate(13), 3-hydroxy-9-methyl-6H-benzo\[c\]chromen-6-one(14), agrimonolide(15), 7-hydroxycoumarin(16), scopoletin(17), isoscutellarein(18), and agrimonolide 6-O-glucoside(19). Among these, the new compounds included one chromene and four meroterpenoid(1-5). The anti-inflammatory activities of the newly identified compounds 1-5 were screened in vitro, showing that the five compounds(1-5) exhibited inhibitory effects on nitric oxide(NO) production in BV2 cells induced by lipopolysaccharide(LPS)/interferon(IFN)-γ, with IC_(50) values ranging from 12.25 to 36.48 μmol·L~(-1).
Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Rutaceae/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; Nitric Oxide/immunology*