Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To discuss the effect of KIAA1522 on the proliferation,migration,and invasion of lung cancer cells,and to clarify its signaling mechanism.Methods:Bioinformatics analysis was used to detect the expression levels of KIAA1522 mRNA and protein in 75 cases of human non-small cell lung cancer(NSCLC)tissues and adjacent normal lung tissues;immunohistochemical staining was used to detect the expression of KIAA1522 protein in NSCLC tissue and adjacent normal lung tissues;Western blotting method was used to detect the expression level of KIAA1522 protein in various lung cancer cell lines.KIAA1522-small interfering(siRNA)and over-expression plasmids were transfected into the lung cancer H1299 and A549 cells,respectively.The KIAA1522-siRNA experiment was divided into blank group,negative control group(si-NC group),KIAA1522-siRNA#1 group,and KIAA1522-siRNA#2 group.The KIAA1522 over-expression experiment was divided into control group,empty vector control group(OE-NC group,transfected with KIAA1522 over-expression empty vector plasmid),KIAA1522 overexpression group(OE-KIAA1522 group,transfected with KIAA1522 over-expression plasmid),KIAA1522 over-expression+MK2206 group[OE-KIAA1522+MK2206 group,co-transfected with KIAA1522 over-expression plasmid and protein kinase B(AKT)signaling pathway inhibitor MK2206],and MK2206 group(transfected with MK2206).Western blotting method was used to verify the transfection efficiencies of the cells in various groups;MTT assay was used to detect the proliferation activities of the lung cancer cells in various groups;cell scratch assay was used to detect the migration rates of lung cancer cells in various groups;Transwell chamber assay was used to detect the numbers of invasion lung cancer cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated AKT(p-AKT),total AKT(t-AKT),cyclin D1(Cyclin D1),vascular endothelial growth factor(VEGF),and epithelial-mesenchymal transition(EMT)-related proteins[vimentin(Vimentin),N-cadherin(N-cadherin),and E-cadherin(E-cadherin)]proteins in the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal lung tissue,the expression levels of KIAA1522 mRNA and protein in NSCLC tissue were significantly increased(P<0.05 or P<0.01).The immunohistochemistry staining results showed that compared with adjacent normal lung tissue,the positive expression rate of KIAA1522 protein in NSCLC tissue was significantly increased(P<0.05)and was associated with TNM stage(P<0.01).The Western blotting results showed that compared with normal lung epithelial cells BEAS-2B,the expression levels of KIAA1522 protein in lung cancer cell lines PC9,H1299,H460,A549,H1975,and H226 were significantly increased(P<0.05 or P<0.01).Compared with si-NC group,the expression levels of KIAA1522 protein in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the expression level of KIAA1522 protein in the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01).The MTT results showed that at 24,48,and 72 h of cell culture,compared with si-NC group,the proliferation activities of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the proliferation activity of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.05);compared with OE-KIAA1522 group,the proliferation activity of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the proliferation activity of the A549 cells in MK2206 group was significantly decreased(P<0.05).The cell scratch assay results showed that compared with si-NC group,the migration rates of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the migration rate of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the migration rate of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.05);compared with OE-KIAA1522+MK2206 group,the migration rate of the A549 cells in MK2206 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with si-NC group,the numbers of invasion H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the number of invasion A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the number of invasion A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the number of invasion A549 cells in MK2206 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.01);compared with OE-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522 group were significantly increased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly decreased(P<0.05);compared with OE-KIAA1522 group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522+MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05);compared with OE-KIAA1522+MK2206 group,the expression levels of Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).Conclusion:The KIAA1522 protein upregulates the expression of Cyclin D1,EMT-related proteins,and VEGF protein in lung cancer cells,promoting the proliferation,migration,and invasion of lung cancer cells,and its mechanism is related to the activation of the AKT signaling pathway.

Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

A centrifugation-free,single-reaction colorimetric method for detection of glucose,utilizing a dual nanozyme cascade system based on gold nanoparticles(AuNPs)and iron-doped carbon dots(FeCDs),was developed in this work.The AuNPs exhibited glucose oxidase-like activity to catalyze glucose oxidation for generation of H2O2,while the FeCDs demonstrated peroxidase-like activity to subsequently catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine(TMB).To prevent interference from the blue signal generated by self-aggregation of AuNPs in subsequent quantitative detection,the reaction system was terminated with HCl,converting oxTMB into a stable yellow product.Based on changes in the absorbance at 450 nm of this yellow solution,a quantitative relationship was established between glucose concentration and absorbance at 450 nm(A450).Experimental results demonstrated that this sensor achieved a linear detection range of 44 μmol/L to 11.11 mmol/L(R2=0.993)with a detection limit of 30.68 μmol/L and spiked recoveries of 97.9%-104.7%.By integrating smartphone-based color recognition capabilities,a rapid visual detection platform was established for quantification of glucose through RGB analysis.The validation experimental results using commercial glucose injection samples further confirmed the practical application potential of this methodology.

Objective To investigate the therapeutic efficacy of Huangqi Guizhi Wuwu Decoction combined with monosialotetrahexosyl ganglioside(GM1)in the treatment of spinal cord injury(SCI)and to observe its effect on neuritin and neurofilament light chain protein(NFL).Methods A retrospective study was carried out in 100 cases of SCI patients.The patients admitted to Baoji Hospital of Traditional Chinese Medicine and Baoji People's Hospital from February 2022 to May 2024 were divided into a control group and a study group according to the treatment method,with 50 patients in each group.The control group was given GM1 combined with methylprednisolone,and the study group was given Huangqi Guizhi Wuwu Decoction combined with GM1.The course of treatment covered three weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,American Spinal Injury Association(ASIA)scores for evaluating the degree of spinal cord injury,Modified Ashworth Spasticity Scale(MASS)and Manual Muscle Testing(MMT)scores for assessing muscle tone and muscle strength,scores of Functional Ambulation Category Scale(FAC)and Lower-Extremity Motor Subscale(LEMS)of ASIA for assessing lower extremity motor function,and serum levels of neuron-specific enolase(NSE),glial fibrillary acidic protein(GFAP),nerve growth factor(NGF),S100B protein(S100B),Neuritin,and NFL.After treatment,the clinical efficacy and the incidence of complications in the two groups were compared.Results(1)After three weeks of treatment,the total effective rate of the study group was 90.00%(45/50)and that of the control group was 74.00%(37/50),and the intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the study group was significantly superior to that of the control group(P<0.05).(2)After treatment,the two groups presented a decrease in the scores of TCM symptoms of limb numbness,limb paralysis,dysuria,irregular defecation,pale complexion,swelling and pain at injured spot,palpitation and spontaneous sweating,and shortness of breath and fatigue when compared with those before treatment(P<0.05),and the decrease of the scores in the study group was significantly superior to that in the control group(P<0.01).(3)After treatment,the evaluation of ASIA scores for the degree of spinal cord injury showed that the motor function,tactile and pain scores in the two group were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(4)After treatment,MASS and MMT scores for assessing muscle tone and muscle strength in the two groups were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(5)After treatment,the FAC score and LEMS scores for assessing lower extremity motor function in the two groups were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(6)After treatment,the serum levels of NSE,GFAP,NGF,S100B,Neuritin,and NFL in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the study group was significantly superior to that in the control group(P<0.01).(7)The incidence of complications in the study group was 6.00%(3/50),and that in the control group was 16.00(8/50),the comparison between the two groups showed that the difference was not statistically significant(P>0.05).Conclusion Huangqi Guizhi Wuwu Decoction combined with GM1 exerts remarkable efficacy in treating patients with SCI,and is effective on relieving clinical symptoms,reducing the degree of spinal cord injury,enhancing the motor function of the lower extremitiess,and improving the muscle strength and tone.Its therapeutic mechanism may be related to the improvement of the expression level of serum factors such as Neuritin and NFL.

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

The choice of biopsy method is critical in diagnosing prostate cancer (PCa). This retrospective cohort study compared systematic biopsy (SB) or cognitive fusion-targeted biopsy combined with SB (CB) in detecting PCa and clinically significant prostate cancer (csPCa). Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center (Shanghai, China) between January 2019 and December 2023 were analyzed. Propensity score matching (PSM) was used to balance baseline characteristics, and detection rates were compared before and after PSM. Subgroup analyses based on prostate-specific antigen (PSA) levels and Prostate Imaging-Reporting and Data System (PI-RADS) scores were performed. Primary and secondary outcomes were the detection rates of PCa and csPCa, respectively. Of 2572 men, 1778 were included in the PSM analysis. Before PSM, CB had higher detection rates for both PCa (62.9% vs 52.4%, odds ratio [OR]: 1.54, P < 0.001) and csPCa (54.9% vs 43.3%, OR: 1.60, P < 0.001) compared to SB. After PSM, CB remained superior in detecting PCa (63.1% vs 47.9%, OR: 1.86, P < 0.001) and csPCa (55.0% vs 38.2%, OR: 1.98, P < 0.001). In patients with PSA 4-12 ng ml -1 (>4 ng ml -1 and ≤12 ng ml -1 , which is also applicable to the following text), CB detected more PCa (59.8% vs 40.7%, OR: 2.17, P < 0.001) and csPCa (48.1% vs 27.7%, OR: 2.42, P < 0.001). CB also showed superior csPCa detection in those with PI-RADS 3 lesions (32.1% vs 18.0%, OR: 2.15, P = 0.038). Overall, CB significantly improves PCa and csPCa detection, especially in patients with PSA 4-12 ng ml -1 or PI-RADS 3 lesions.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Propensity Score ; Retrospective Studies ; Middle Aged ; Aged ; Image-Guided Biopsy/methods* ; Prostate-Specific Antigen/blood* ; Prostate/diagnostic imaging*

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.