Objective To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder(BD)based on electronic medical records of patients,and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.Methods A total of 2 352 patients diagnosed with BD and admitted to West China Hospital,Sichuan University were enrolled using the electronic medical records system of the hospital.The participants were divided into two subgroups,the bipolar disorder depression(BDD)group and the bipolar disorder mania(BDM)group.The logistic regression algorithm was used to train and validate the prediction model,and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.Results The logistic regression model demonstrated robust predictive performance across the BD,BDD,and BDM cohorts,with areas under the curve(AUC)of the receiver operating characteristic curves always exceeding 81.6%.The core predictive features included platelet distribution width(PDW),fibrinogen(FIB),platelet large cell ratio(P-LCR),activated partial thromboplastin time(APTT),prothrombin time(PT),and triglyceride(TG).The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.Conclusion The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms.Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

Objective To explore the inhibitory effect of Xinhui tangerine peel polysaccharides on the mouse skin fibroblasts so as to understand the underlying molecular mechanism.Methods We separated and purified the components of tangerine peel polysaccharides from Xinhui tangerine peel.C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study.We set up a blank control group(normal culture)and low-,medium-and high-dose experimental groups(50,100 and 200 μg/mL tangerine peel polysaccharides).After 24 hours of treatment,cell survival rate was assessed by CCK-8 assay.The mRNA and protein expression levels of collagen type Ⅰ(Col1a1),collagen type Ⅲ(Col1a3),TGF-β1 and ACTA2 in fibroblasts were examined by RT-qPCR and Western blotting.Smad3 was examined by Western blotting.Results The cell survival rate in the blank control group,the medium-and high-dose experimental groups was 100％,(90.54±6.74)％,and(78.90±4.24)％,respectively.The relative expression level of Col1a1 protein was 1.13±0.15,0.57±0.16,and 0.48±0.05,respectively;the relative expression level of Col3a1 protein was 0.81±0.13,0.49±0.11 and 0.50±0.03;the relative expression level of TGF-β1 protein was 1.11±0.15,0.60±0.13,and 0.33±0.11;the relative expression level of p-Smad3/Smad3 proteins was 0.96±0.05,0.75±0.06 and 0.71±0.03.The mRNA expression level of Col1a1 was 1.01±0.17,0.58±0.11,and 0.52±0.12;the mRNA expression level of Col3a1 was 1.01±0.12,0.56±0.19,and 0.65±0.14;the expression level of ACTA2 mRNA was 1.01±0.13,0.24±0.04,and 0.22±0.07;the mRNA expression level of TGF-β1 was 1.00±0.09,0.50±0.10,and 0.49±0.15.The relative expression levels of p-Smad3/Smad3 proteins were 0.86±0.06,0.66±0.06,0.55±0.13,0.43±0.09,0.35±0.06,and 0.27±0.12,respectively,after time-related treatment with high-dose tangerine peel polysaccharides.The above indicators in medium-and high-dose tangerine peel polysaccharide groups showed statistically significant differences compared to those in the blank control group(P＜0.05).Conclusion Tangerine peel polysaccharides can inhibit the cell proliferation and the synthesis of keloid-related genes on fibroblasts by inhibiting TGF-β1/Smad3 signaling pathway.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Solid-phase extraction(SPE)combined with surface-enhanced Raman spectroscopy(SERS)has emerged as a promising analytical technique for detection and analysis of trace components in complex sample matrices.SPE enriches analytes through selective adsorption and solvent elution,effectively increasing the concentration and signal intensity.SERS enables ultra-sensitive and highly selective molecular analysis through the use of SERS-active substrates engineered to amplify Raman signals.The integration of these two techniques overcomes the limitations of conventional Raman spectroscopy in low-concentration detection field,while significantly improving sample preparation efficiency and analytical accuracy.This review provided a comprehensive overview of the characteristics of three SPE-SERS coupling modes,including two-step,one-step,and online integration.Special emphasis was placed on recent advancements in one-step SPE-SERS approaches based on novel functional adsorbent materials such as graphene,metal-organic frameworks,covalent organic frameworks,and molecularly imprinted polymers.Furthermore,future directions and development prospects of SPE-SERS technology were discussed.

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective To explore the inhibitory effect of Xinhui tangerine peel polysaccharides on the mouse skin fibroblasts so as to understand the underlying molecular mechanism.Methods We separated and purified the components of tangerine peel polysaccharides from Xinhui tangerine peel.C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study.We set up a blank control group(normal culture)and low-,medium-and high-dose experimental groups(50,100 and 200 μg/mL tangerine peel polysaccharides).After 24 hours of treatment,cell survival rate was assessed by CCK-8 assay.The mRNA and protein expression levels of collagen type Ⅰ(Col1a1),collagen type Ⅲ(Col1a3),TGF-β1 and ACTA2 in fibroblasts were examined by RT-qPCR and Western blotting.Smad3 was examined by Western blotting.Results The cell survival rate in the blank control group,the medium-and high-dose experimental groups was 100％,(90.54±6.74)％,and(78.90±4.24)％,respectively.The relative expression level of Col1a1 protein was 1.13±0.15,0.57±0.16,and 0.48±0.05,respectively;the relative expression level of Col3a1 protein was 0.81±0.13,0.49±0.11 and 0.50±0.03;the relative expression level of TGF-β1 protein was 1.11±0.15,0.60±0.13,and 0.33±0.11;the relative expression level of p-Smad3/Smad3 proteins was 0.96±0.05,0.75±0.06 and 0.71±0.03.The mRNA expression level of Col1a1 was 1.01±0.17,0.58±0.11,and 0.52±0.12;the mRNA expression level of Col3a1 was 1.01±0.12,0.56±0.19,and 0.65±0.14;the expression level of ACTA2 mRNA was 1.01±0.13,0.24±0.04,and 0.22±0.07;the mRNA expression level of TGF-β1 was 1.00±0.09,0.50±0.10,and 0.49±0.15.The relative expression levels of p-Smad3/Smad3 proteins were 0.86±0.06,0.66±0.06,0.55±0.13,0.43±0.09,0.35±0.06,and 0.27±0.12,respectively,after time-related treatment with high-dose tangerine peel polysaccharides.The above indicators in medium-and high-dose tangerine peel polysaccharide groups showed statistically significant differences compared to those in the blank control group(P＜0.05).Conclusion Tangerine peel polysaccharides can inhibit the cell proliferation and the synthesis of keloid-related genes on fibroblasts by inhibiting TGF-β1/Smad3 signaling pathway.

Objective:To explore the rehabilitation effect of multi-factor intervention based on the Finnish model of prevention of cognitive impairment in the elderly on patients with cognitive impairment after first-episode stroke, and to provide reference for rehabilitation nursing of cognitive impairment after stroke.Methods:The quasi-experiment research scheme was adopted and convenience sampling method was used to select participants with first-episode stroke cognitive impairment hospitalized in the General Hospital of Tianjin Medical University Airport Site. The 50 patients admitted from January to June 2022 were selected as the control group, and 50 patients admitted from July to December 2022 were selected as the intervention group. The control group received routine rehabilitation nursing and health education, and the intervention group received the Finnish model of prevention of cognitive impairment in the elderly on patients before discharge on the basis of the control group. The Mini-Mental State Examination (MMSE) and Health Education Compliance Assessment Scale for Stroke Patients were used to evaluate the changes of overall cognitive function and rehabilitation compliance before intervention, 3 and 6 months after intervention.Results:The final control group included 49 cases, including 35 males and 14 females, aged (64.67 ± 7.47) years old; the intervention group included 50 cases, 32 males and 18 females, aged (66.68 ± 8.75) years old. Before intervention, there were no significant differences in overall cognitive function and compliance of rehabilitation score ( P>0.05). At 3 and 6 months after intervention, the overall cognitive function score, the total score on compliance of rehabilitation, dimension scores of diet compliance, exercise rehabilitation compliance and health behavior compliance of the intervention group were (26.36±2.36) , (125.96 ± 13.80) , (23.30 ± 5.26) , (27.72 ± 4.46) , (43.66 ± 6.80) and (27.26 ± 3.71) , (152.44 ± 9.06) , (30.12 ± 6.42) , (33.32 ± 3.02) , (52.36 ± 4.70) , respectively. They were higher than the control group (24.04 ± 4.50) , (116.67 ± 10.26) , (19.31 ± 3.95) , (25.29 ± 3.45) , (40.59 ± 4.33) and (24.27 ± 4.33) , (138.92 ± 16.71) , (24.20 ± 4.48) , (30.00 ± 5.53) , (47.65 ± 8.03) , and the differences had statistical significance ( t values were -5.31- -2.67, all P<0.05). According to the variance analysis of repeated measurement, intergroup and time factor, the interaction between groups and time had significant impact on general cognitive function score, the total score of rehabilitation compliance, the dimension scores of diet, exercise rehabilitation and health behavior compliance ( Fgroup values were 8.33-18.08, Ftime values were 135.71-944.69, Finteraction values were 5.46-27.30, all P<0.05) . Time factor had significant impact on patient medication adherence score ( Ftime=206.23, P<0.05) . Conclusions:Multi-factor intervention based on the Finnish model of prevention of cognitive impairment in the elderly can improve the overall cognitive function and rehabilitation compliance of patients with cognitive impairment after first-episode stroke.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Objective To explore the therapeutic mechanism of Liuwei Buqi(LWBQ)Formula for chronic obstructive pulmonary disease(COPD)in rat models.Methods SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide(LPS)instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks,starting at the 5th week of modeling.After the treatments,the rats were examined for lung pathologies,lung function,total cell count and white blood cell count in bronchoalveolar lavage fluid(BALF),and serum levels of IL-6,TNF-α,IL-18 and NO.The mRNA expressions of NLRP3,ASC,caspase-1,GSDMD-N,IL-1β,and IL-18 in the lung tissue were detected with qRT-PCR.Results Compared with the normal control rats,the COPD rat models had severe lung pathologies and showed significantly decreased lung function,increased total cell and leukocyte subset counts in BALF,and increased serum levels of IL-6,TNF-α,IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue.Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function,reduced total cell and leukocyte counts in BALF,and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue.The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference,but BALF cell counts,serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment.Conclusion LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.