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.

Small cell lung cancer (SCLC) is a highly malignant disease that has garnered significant attention in terms of treatment modalities and course management. Gaining an understanding of the clinical characteristics of SCLC, acquiring proficiency in screening, diagnosis, and treatment methods for this condition, as well as promptly addressing any adverse reactions to treatment are essential foundations for developing a scientific and rational pathological management plan for SCLC. By utilizing an intelligent whole course follow-up management platform, dynamic follow-up, timely warnings, and early interventions can enable high-quality whole life cycle management. This article aims to review the current treatment landscape of SCLC while exploring the challenges associated with implementing a comprehensive process-oriented management approach. The goal is to provide valuable insights for better managing SCLC patients and ultimately improving their quality of life and prognosis.
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Humans ; Small Cell Lung Carcinoma/diagnosis* ; Lung Neoplasms/diagnosis* ; Quality of Life ; Follow-Up Studies

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*

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.

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 investigate LI Dongyuan's theory of"any deficiency of spleen and stomach is a disease of the blood"and provide reference for modern clinical practice.[Methods]Taking Discussion on Internal and External Injuries,Treatise on Spleen and Stomach,Orchid Chamber of Secrets and Invention of Medicine as references,it starts from the connotation of"any deficiency of spleen and stomach is a disease of the blood",and explores the etiology and pathogenesis of the diseases,the theoretical construction and the clinical application respectively.[Results]Taking Inner Canon of Yellow Emperor and Zhongjing's academic thought as the source,absorbing CHENGs' and ZHU Xi's ideas of science.Being inspired by his teacher ZHANG Yuansu,and driven by his own clinical practice,LI Dongyuan put forward the academic thought of"any deficiency of spleen and stomach is a disease of the blood".From the Treatise on Spleen and Stomach-Treatise on the Prosperity and Decline of Spleen and Stomach,"any deficiency of spleen and stomach is a disease of the blood",which is a pathological state caused by the deficiency of spleen and stomach Qi and the weakness of elevation due to the disorders of emotions and moods,overwork and overdose,and uncontrolled diets,there fore causes insufficient blood production and too much blood consumption,and then leads to the deficiency of blood and Yin,and the essence of which is the disordered ascending,descending,floating and sinking of the human body's Qi.In treatment,LI Dongyuan always based on regulating blood,to restore the body's Qi,and harmonize Qi and blood as the goal,with"blood replenishment must have Yang Qi,Qi and blood double tonic""rising Yang must be in response to the time of the day,and make good use of the wind herbs""relieving heat must protect the Yin and blood,moderation in attacking and destroying".[Conclusion]Exploring this theory can help to view the relationship between Qi and blood from a new perspective,better grasp LI Dongyuan's academic thinking,and provide reference for the treatment of spleen and stomach diseases and blood diseases.

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 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.