OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

ObjectiveTo investigate the association between neutrophil-to-lymphocyte and platelet ratio （NLPR） and recompensation in patients with hepatitis B cirrhotic ascites， and to establish an individualized risk prediction model. MethodsThe patients with hepatitis B cirrhotic ascites who were hospitalized in Department of Gastroenterology， The General Hospital of Western Theater Command of Chinese PLA， from January 2015 to December 2022 were enrolled. General information and laboratory markers were collected， and NLPR was calculated. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the chi-square test with correction was used for comparison of categorical data between two groups. The subjects were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set， univariate and multivariate binary Logistic regression analyses were used to investigate the independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites， and a nomogram was established； the receiver operating characteristic （ROC） curve was used to assess the value of the new model in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the Delong test was used for comparison of the area under the ROC curve （AUC）. The calibration curve and the decision curve were plotted for the model， and the model was assessed in terms of degree of fitting and predictive benefits. ResultsA total of 360 patients were enrolled， among whom134 achieved recompensation. There were 252 patients in the training set and 108 patients in the validation set， and there were no significant differences in baseline characteristics between the two groups （all P>0.05）. The Logistic regression analysis showed that the onset of hepatic encephalopathy （odds ratio ［OR］=0.066， 95% confidence interval ［CI］： 0.008 — 0.545， P=0.012）， NLPR （OR=0.950， 95%CI： 0.912 — 0.989， P=0.012）， alpha-fetoprotein （OR=1.012， 95%CI： 1.005 — 1.020， P<0.001）， and albumin （OR=1.096， 95%CI： 1.031 — 1.166， P=0.003） were independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites. The above four factors were included in a nomogram predictive model， which had an AUC of 0.776， a sensitivity of 66.5%， and a specificity of 76.3% in the training set and an AUC of 0.746， a sensitivity of 63.4%， and a specificity of 75.7% in the validation set， while Model for End-Stage Liver Disease score， Child-Pugh score， and albumin-bilirubin score had an AUC of 0.574， 0.628， and 0.621， respectively. The nomogram model had a better performance than the other three scores in predicting recompensation in patients with hepatitis B cirrhotic ascites （Z=4.191， 3.369， and 3.527， P<0.001， P=0.001， and P<0.001）. The calibration curve and the decision curve showed that the model had a good degree of fitting， and the decision made using this model could bring net benefits. ConclusionNLPR has a good value in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the nomogram model established can help to predict recompensation in such patients in clinical practice.

ObjectiveTo investigate the effect of the multidisciplinary team （MDT） management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled， and according to whether the MDT treatment regimen was implemented， they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected， and the patients were observed in terms of gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death from admission to the end of follow-up （January 2025）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events （gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death）， and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein （t=1.216， P=0.017） and ascites （χ²=4.515， P=0.034） at baseline. The patients were followed up for 14.6±6.2 months， and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups （χ²=4.573， P=0.024）， while there were no significant differences in the incidence rates of other outcome events between the two groups （all P>0.05）. The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding （hazard ratio=0.262， 95% confidence interval： 0.110 — 0.630， P=0.003）. ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension， while its long-term benefits require further follow-up verification.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95％confidence interval[CI]:0.2—1.0),STE(OR=1.5,95％CI:1.0—2.1),and PIIIP(OR=1.1,95％CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34％and a sensitivity of 96.36％,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

italic>Polygonum capitatum is a characteristic Miao medicine in Guizhou, commonly used in clinical practice to treat gastrointestinal and urinary tract infections. Research has found that it has good antibacterial and anti-inflammatory effects, and its main active ingredient is flavonoids. Lavonoid O-methyltransferase (FOMT) is a key enzyme for oxymethylation modification of flavonoid compounds. In order to understand the function and properties of FOMT protein in Polygonum capitatum, the transcriptome was sequenced by Illumina HiSeq 4000 high throughput sequencing technology. Then, the obtained transcripts were annotated and analyzed, and the whole genome of the FOMT gene family in Polygon capitalis was mined and identified. A total of 99 298 Unigenes were obtained, of which 71 514 were successfully annotated by the public database. In the genome of Polygonum capitatum, a total of 50 FOMT genes were identified. The phylogenetic tree showed that FOMT genes were divided into two subfamilies: caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT). Gene sequence analysis showed that the number of FOMT encoded amino acids ranged from 99 to 1 053 aa, the molecular weight ranged from 11 224.91 to 86 687.42 Da, and the isoelectric point ranged from 4.79 to 9.45. The 50 FOMT family members were hydrophobic proteins. Subcellular localization results showed that 54% of FOMT subfamily CCoAOMT and COMT members were located in cytoplasm and 28% were located in chloroplasts. The FOMT gene was tissue specific and highly expressed in the flowers of Polygonum capitatum, followed by the stems, and the least expressed in the roots. In this study, the FOMT gene family of Polygonum capitatum was identified and analyzed to provide theoretical basis for further study of FOMT function and biosynthesis of methylated flavonoids.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.