BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective To investigate the functional brain characteristics of the frontal and bilateral tempo-ral regions during a verbal fluency task(VFT)in patients with stable schizophrenia using functional near-infrared spectroscopy(fNIRS),and to evaluate its potential clinical application in assisting the diagnosis of schizophrenia.Methods A total of 45 stable schizophrenia patients and 30 healthy controls were enrolled in the study.fNIRS was employed to assess brain activation patterns in the frontal and bilateral temporal lobes during the VFT.The integral values,centroid values,and slopes of the frontal and bilateral temporal lobes were measured.Differences in demographic characteristics,word count,and fNIRS-derived parameters between the two groups were analyzed.A logistic regression model and receiver operating characteristic(ROC)curve analysis were conducted to evaluate the diagnostic performance of the fNIRS measures in distinguishing schizophrenia patients from healthy controls.Results During VFT,the patient group demonstrated reduced word count and decreased integral values and slopes in the frontal lobe,as well as lower integral values in the bilateral temporal lobes,compared to the healthy control group(all P＜0.05).However,no statistically significant differences were observed between the two groups in terms of frontal lobe centroid value,temporal lobe centroid value,or bilateral temporal lobe slope(all P＞0.05).The logistic regression model indicated that the temporal lobe integral value was significantly associated with the diagnosis of schizophrenia(OR=0.979,P=0.005).ROC curve analysis revealed that the frontal lobe integral value,frontal lobe slope,and temporal lobe integral value exhibited acceptable discriminatory power for disease classification,with area under the curve(AUC)values of 0.681,0.644,and 0.779,respectively(all P＜0.05).Conclusion In stable schizophrenia,the integral values of the frontal and temporal lobes,as well as the slope of the frontal lobe,decrease during the VFT,suggesting potential clinical utility in differentiating individuals with schizophrenia from healthy controls.

Objective To investigate the functional brain characteristics of the frontal and bilateral tempo-ral regions during a verbal fluency task(VFT)in patients with stable schizophrenia using functional near-infrared spectroscopy(fNIRS),and to evaluate its potential clinical application in assisting the diagnosis of schizophrenia.Methods A total of 45 stable schizophrenia patients and 30 healthy controls were enrolled in the study.fNIRS was employed to assess brain activation patterns in the frontal and bilateral temporal lobes during the VFT.The integral values,centroid values,and slopes of the frontal and bilateral temporal lobes were measured.Differences in demographic characteristics,word count,and fNIRS-derived parameters between the two groups were analyzed.A logistic regression model and receiver operating characteristic(ROC)curve analysis were conducted to evaluate the diagnostic performance of the fNIRS measures in distinguishing schizophrenia patients from healthy controls.Results During VFT,the patient group demonstrated reduced word count and decreased integral values and slopes in the frontal lobe,as well as lower integral values in the bilateral temporal lobes,compared to the healthy control group(all P＜0.05).However,no statistically significant differences were observed between the two groups in terms of frontal lobe centroid value,temporal lobe centroid value,or bilateral temporal lobe slope(all P＞0.05).The logistic regression model indicated that the temporal lobe integral value was significantly associated with the diagnosis of schizophrenia(OR=0.979,P=0.005).ROC curve analysis revealed that the frontal lobe integral value,frontal lobe slope,and temporal lobe integral value exhibited acceptable discriminatory power for disease classification,with area under the curve(AUC)values of 0.681,0.644,and 0.779,respectively(all P＜0.05).Conclusion In stable schizophrenia,the integral values of the frontal and temporal lobes,as well as the slope of the frontal lobe,decrease during the VFT,suggesting potential clinical utility in differentiating individuals with schizophrenia from healthy controls.

AIM To evaluate the grade of Bletillae Rhizoma decoction piece.METHODS The morphological parameters and militarine,polysaccharide contents for authentic product were determined,after which relevant values of quality constants were calculated,gradation was performed.Electronic eye was adopted in the determination of decoction piece color,after which Pearson correlation analysis was applied to exploring the correlation between color and grade.With ADP as an inducer,the effects of different grades of decoction pieces on rabbit platelet aggregation were compared by turbidimetric method.RESULTS Twenty-nine batches of authentic products were divided into three grades,3 of which were the first-grade products[relative quality constant (A') was≥68.99],9 of which were the second-grade products (43.12≤A'<68.99),17 of which were the third-grade products (A'<43.12).A significant correlation was observable between color and grade.Various grades of decoction pieces could promote platelet aggregation,and the effect was enhanced with the increase of grade.CONCLUSION This study establishes the grade standard for Bletilla Rhizoma decoction piece for the first time,along with the improvement of high quality and excellent effect,which can provide basis for its grade application and quality control.

Objective To explore the effects of standardized environmental enrichment(EE)on cognitive function and serum brain-derived neurotrophic factor(BDNF)levels in patients with post-stroke dementia.Methods A prospective study was conducted,including 80 patients with post-stroke dementia admitted to Department of Traditional Chinese Medicine Rehabilitation,910th Hospital of the Joint Logistics Support Force of Chinese PLA from January 2021 to May 2023.Patients were randomly divided into control group,cognitive training(COG)group,aerobic exercise training(AE)group and environmental enrichment(EE)group,with 20 cases in each group.All patients received routine treatment,with COG group receiving additional cognitive function training(30 minutes each time),AE group receiving additional aerobic exercise training(30 minutes each time),and EE group receiving both aerobic exercise and cognitive function training(15 minutes of aerobic exercise training and 15 minutes of cognitive training each time).The training was conducted once a day,5 days a week,for a total of 8 weeks.The patients'mini-mental state scale(MMSE),modified Barthel index(MBI),Hamilton depression scale(HAMD),stroke-specific quality of life(SS-QOL)score and serum levels of BDNF were assessed before treatment,at 4 weeks and 8 weeks of treatment,respectively.Results Before treatment,there were no significant differences in general information,MMSE,MBI,HAMD,SS-QOL scores,and serum levels of BDNF among the four groups(P＞0.05).After 4 and 8 weeks of treatment,the above indicators of the four groups were improved compared with those before treatment,with all differences being statistically significant(P＜0.05).Inter-group comparison showed that after 4 and 8 weeks of treatment,MMSE,MBI,SS-QOL scores,and serum BDNF levels in COG,AE and EE groups were significantly higher than those in control group,and HAMD scores were significantly lower than those in control group(P＜0.05).In addition,MMSE,MBI,SS-QOL scores and BDNF levels of group EE were better than those of other 3 groups,while HAMD scores were lower than those of other 3 groups,with all differences being statistically significant(P＜0.05).There was no significant difference in above outcome indicators between COG group and AE group after 4 and 8 weeks of treatment(P＞0.05).Conclusion Standardized enrichment environment can significantly enhance cognitive function,daily living abilities of post-stroke dementia patients,alleviate depression symptoms,and improve the quality of life,which may be related to the increase in serum BDNF levels.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To investigate the effect of dapagliflozin-mediated miR-98-5p on high glucose-induced damage in human renal tubular epithelial cells.Methods Blood samples from patients with diabetic nephropathy(DN)and healthy individuals were collected.The expression of serum miR-98-5p was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),and kidney injury-related indicators were measured using a biochemical immunoassay analyzer.HK-2 cells were cultured in vitro and randomly divided into control group(5 mmol·L-1 glucose),HG group(30 mmol·L-1 glucose),experimental-L group(30 mmol·L-1 glucose+20 μmol·L-1 dapagliflozin),experimental-H group(30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),anti-miR-NC group(transfected with anti-miR-NC+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),and anti-miR-98-5p group(transfected with anti-miR-98-5p+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin).Cell viability was evaluated using the cell counting kit 8(CCK-8)assay 24 hours after drug treatment;miR-98-5p expression in cells was detected by RT-qPCR;cell apoptosis rate was measured by flow cytometry,apoptosis-related protein expression was detected by Western blot;and inflammatory cytokine expression was measured by enzyme-linked immunosorbent assay.Results The expression levels of miR-98-5p in the serum of DN patients and healthy individuals were 1.00±0.25 and 0.39±0.05,respectively,showing a significant difference between the two groups(P＜0.05).The expression levels of miR-98-5p in the control group,HG group,experimental-H group,anti-miR-NC group,and anti-miR-98-5p group were 1.00±0.09,0.31±0.04,0.72±0.06,0.75±0.07 and 0.22±0.03;the cell survival rates were(100.00±3.36)％,(51.63±5.89)％,(79.46±9.90)％,(82.88±5.71)％and(59.69±7.43)％;apoptosis rates were(3.52±0.20)％,(35.80±3.67)％,(16.43±1.57)％,(15.71±1.42)％and(29.37±2.18)％;tumor necrosis factor-α(TNF-α)levels were(22.46±1.67),(68.37±6.05),(34.45±2.47),(35.11±2.84)and(60.46±3.56)pg·mL-1,respectively.The differences among these indicators were all statistically significant when comparing the HG group to the control group,the experimental-H group to the HG group,and the anti-miR-98-5p group to the anti-miR-NC group(all P＜0.05).Conclusion Dapagliflozin can alleviate high glucose-induced HK-2 cell damage by upregulating the expression of miR-98-5p,inhibiting inflammation,and reducing cell apoptosis.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.