OBJECTIVE: To develop and validate a nomogram model for predicting 30-day mortality among elderly patients with sepsis-associated liver dysfunction (SALD), to identify high-risk patients and improve prognosis. METHODS: A retrospective cohort study was conducted using data extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for elderly patients with SALD who were first admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center between 2008 and 2019, including basic characteristics, severity scores, underlying diseases, infection foci, 24-hour vital signs, initial laboratory indicators, 24-hour complications, and prognosis related indicators. Patients were randomly assigned to training group and validation group in a ratio of 7 : 3. The training group used the LASSO regression analysis, as well as multivariate Logistic regression analysis to screen for independent risk factors for 30-day mortality. A nomogram prediction model was constructed, and receiver operator characteristic curve (ROC curve), calibration curves, and decision curve analysis (DCA) were used to evaluate the model, and validate the model using the validation cohort. RESULTS: A total of 630 elderly patients with SLAD were included in the study, including 441 in the training group and 189 in the validation group. Oxford acute severity of illness score (OASIS) for training group [odds ratio (OR) = 1.060, 95% confidence interval (95%CI) was 1.034-1.086], 24-hour pulse oxygen saturation (SpO₂; OR = 0.876, 95%CI was 0.797-0.962), initial mean corpuscular volume (MCV; OR = 1.043, 95%CI was 1.009-1.077), initial red blood cell distribution width (RDW; OR = 1.237, 95%CI was 1.123-1.362), initial blood glucose (OR = 1.008, 95%CI was 1.004-1.013), and initial aspartate aminotransferase (AST; OR = 1.000, 95%CI was 1.000-1.001) were independent risk factors for 30-day mortality in patients (all P < 0.05). Based on the above variables, a nomogram model was constructed, and the ROC curve showed that the area under the curve (AUC) of the model in the training group was 0.757 (95%CI was 0.712-0.803), with a sensitivity of 65.05% and a specificity of 74.90%; the AUC of the model in the validation group was 0.712 (95%CI was 0.631-0.792), with a sensitivity of 58.67% and a specificity of 81.58%. The calibration curves of the training and validation groups show that both the fitted curves were close to the standard curves. The Hosmer-Lemeshow test: the training group (χ ² = 6.729, P = 0.566), the validation group (χ ² = 13.889, P = 0.085), indicating that the model can fit the observed data well. The DCA curve shows that when the threshold probability of the training group was 16% to 94% and the threshold probability of the validation group was 27% to 99%, the net benefit of the model was good. CONCLUSIONS OASIS, 24-hour SpO₂, initial MCV, initial RDW, initial blood glucose and initial AST are independent risk factors for 30-day mortality in elderly patients with SALD. The nomogram based on these six variables demonstrates good predictive performance.
Humans ; Sepsis/complications* ; Retrospective Studies ; Nomograms ; Aged ; Prognosis ; Risk Factors ; Liver Diseases/mortality* ; Intensive Care Units ; ROC Curve ; Male ; Female ; Logistic Models

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

Over 2 million thoracoscopic pulmonary resections are performed globally each year,however,postoperative persistent air leak(PAL)remains a common and challenging complication.It not only prolongs hospital stays and increases treatment costs but may also lead to severe complica-tions,particularly inducing a higher risk in patients undergoing mechanical ventilation.In recent years,with the improvement of preoperative preventive measures,the advancement of surgical tech-niques,and the application of repair materials,the incidence of PAL has decreased.This review sys-tematically summarized the definition,clinical impact,risk factors and preventive strategies of PAL,and explored commonly used treatment modalities,such as thoracic drain management,pleurodesis and the application of novel repair materials.It also analyzed the effectiveness,safety and challenges of existing techniques.Furthermore,this review proposed the establishment of an enhanced recovery after surgery(ERAS)integrated pathway combining bovine pericardium(BP)patch with electro-me-chanical stapler and conducted corresponding treatment benefit-cost assessment.

OBJECTIVE To investigate the impact of inflammatory cytokines related to different endotypes of chronic rhinosinusitis on the transcriptome of nasal epithelial cells.METHODS Human primary nasal epithelial cells were cultured in vitro,and treated with type 1,type 2,and type 3 inflammatory cytokines IFN-γ(10 ng/ml),IL-4(50 ng/ml),and IL-17A(50 ng/ml),respectively.After 48 hours,cells were collected for RNA extraction and transcriptome analysis.Differentially expressed genes were identified,followed by functional annotation and pathway enrichment analysis.Additionally,common regulated genes among different cytokines were analyzed.RESULTS Treatment of primary nasal epithelial cells with IFN-γ,IL-4,and IL-17A induced significant transcriptomic alterations,with 650,540,and 192 differentially expressed genes,respectively,compared to the control group.Functional annotation and pathway enrichment analysis showed that IFN-γ was mainly associated with defense response to virus,antigen processing and presentation,leukocyte and lymphocyte mediated immunity,and NOD-like receptor signaling pathway;IL-4 was mainly related to the regulation of leukocyte chemotaxis,cell-cell adhesion,ECM-receptor interaction,and MAPK signaling pathway;IL-17A was involved in the regulation of neutrophil chemotaxis,response to molecule of bacterial origin,chemokine signaling pathway,and NF-κB signaling pathway.Genes commonly regulated by IFN-γ,IL-4,and IL-17A were identified,with DUOX2 being upregulated by all the three cytokines.CONCLUSION IFN-γ,IL-4,and IL-17A reshapes the transcriptomic profile of nasal epithelial cells,which mainly regulates signaling pathways related to defense response to virus,leukocyte chemotaxis,and response to bacteria,respectively.

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections