ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

OBJECTIVES: To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula. METHODS: A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated. RESULTS: The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas. CONCLUSIONS The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans ; Male ; Female ; Child, Preschool ; Child ; Coronary Artery Disease/diagnostic imaging* ; Infant ; Mucocutaneous Lymph Node Syndrome ; Regression Analysis ; Coronary Vessels/diagnostic imaging* ; Echocardiography ; Adolescent

Doxorubicin is a commonly used antitumor drug for the treatment of various cancers.How-ever,its clinical application is greatly restricted by its severe cardiotoxicity.At present,doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms,depending on the dosage and dura-tion of exposure,which may eventually lead to the occurrence of heart failure.The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress,mitochondrial damage,calcium overload,dysregulation of autophagy,and apoptosis.In forensic medical practice,cases of poisoning or even car-diac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations.The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years,analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin,and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.

Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

Objective To investigate the association between triglyceride-glucose(TyG)index and the prevalence of gallstones in women,and to assess whether it can be used as a convenient indicator for the epidemiological survey of gallstones in women.Methods A total of 22 979 adult women who underwent physical examination in Subei People's Hospital of Jiangsu from January 2021 to June 2023 were enrolled,and according to the results of abdominal color Doppler ultrasound,they were divided into gallstone group with 1 763 women and non-gallstone group with 21 216 women.The independent samples t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.The multivariate logistic regression analysis,the restricted cubic spline analysis,the subgroup analysis,and mediating effect were used to investigate the association between TyG index and the risk of gallstones in women.Results The overall prevalence rate of gallstones was 7.7％in women.Compared with the non-gallstone group,the gallstone group had significantly higher age,BMI,FPG,TG,TyG index,TC,Hb,BUN,UA,SCr,TC,and LDL-C(all P<0.05),and the women with diabetes,fatty liver,hypertension,and hyperuricemia were more likely to have gallstones(all P<0.05).The multivariate logistic regression analysis showed that based on the quartiles of TyG index,the risk of gallstones in the Q3(8.97-9.38)group was 1.38(95％confidence interval[CI]:1.15-1.62,P<0.001)times that in the Q1(<8.63)group,and the risk of gallstones in the Q4(≥9.38)group was 1.39(95％CI:1.16-1.68,P<0.001)times that in the Q1 group.After adjustment for all covariates,TyG index,as a continuous variable,showed an independent positive correlation with the risk of gallstones(odds ratio[OR]=1.24,95％CI:1.11-1.39,P=0.004).The restricted cubic spline curve revealed a significant nonlinear association between TyG index and the risk of gallstones(P for non linear=0.008),and the threshold analysis showed statistical significance in the effect of TyG index below the inflection point of 8.95(OR=1.34,95％CI:1.15-1.97,P=0.042).The subgroup analysis showed that TyG index was significantly positively correlated with gallstones in women with a BMI of<25 kg/m2,an age of<50 years,an age of≥50 years,the absence of diabetes or fatty liver,total cholesterol<5.72 mmol/L,total bilirubin<21 μmol/L,a hemoglobin level of 110-150 g/L,and blood urea nitrogen<7.5 μmol/L(all P<0.05).A mediating analysis was performed for the subgroups with a statistically significant P value for interaction,and the results showed that BMI accounted for 23.0％of the mediating effect in the influence of TyG index on gallstones,and fatty liver and diabetes accounted for 15.7％and 21.0％,respectively.Conclusion In women,a higher TyG index indicates a higher risk of gallstones.Lowering TyG index may reduce the risk of gallstones by improving insulin sensitivity.

Objective To investigate the expression of microRNA-508-3p(miR-508-3p)in epithelial ovarian cancer(EOC)tissue,its impact on the migration and invasion of ovarian cancer cells,and its regulatory relationship with zinc-finger E-box-binding homeobox 1(ZEB1).Methods The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected.SKOV3 cells were divided into the NC mimic group(transfected with NC mimic),miR-508-3p mimic group(transfected with miR-508-3p mimic),si-NC group(transfected with si-NC),si-ZEB1 group(transfected with si-ZEB1)and co-transfection group(co-transfected with si-ZEB1 and miR-508-3p mimic).The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues,adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction.The Transwell assay was used to detect the cell migration and invasion abilities.Results The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40,the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95,and the differences were statistically significant(all P＜0.01).The migration cell number of the NC mimic,miR-508-3p mimic,si-NC,si-ZEB1 and co-transfection groups was 633.00±32.49,319.20±19.89,650.40±25.85,375.00±17.25 and 129.40±17.10;the invasion cell number was 527.20±25.01,288.60±16.68,520.00±25.83,293.40±18.37 and 76.60±8.76;the relative expression levels of miR-508-3p were 1.05±0.37,3.94±1.21,1.01±0.21,1.26±0.34 and 3.40±0.41;the relative expression levels of ZEB1 mRNA were 1.00±0.04,0.58±0.05,1.00±0.08,0.54±0.07 and 0.29±0.03,respectively.The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group,between the si-NC group and the co-transfection group(P＜0.01,P＜0.05).Conclusion MiR-508-3p is lowly expressed in EOC cancer tissue,and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To investigate the effect of Gd-hydroxyapatite(Gd-HA)stents with adipose mesenchymal cells(ADSCs)on the repair of knee articular cartilage defects.Methods To isolate,culture,and identify rabbit ADSCs by establishing a rabbit knee joint full-thickness cartilage defect model,a total of 18 rabbits were randomly divided into blank control group,Gd-HA scaffold group,and ADSCs+Gd-HA scaffold group.At week 12 and 24 after surgery,International Curtilage Repair Society(ICRS)score,HE,toluidine blue,modified red O bright green and ColⅡ were detected by immunohistochemical staining,then ColⅡand GAG mRNA expression levels were detected by O'Driscoll and Real-time PCR.ColⅡ protein expression was detected by Western blotting,GAG content was detected by DMMB,biomechanical strength was detected by indentation test,and PKH26 labeled ADSCs was used to trace the tissue engineering scaffold with Gd-HA composite ADSCs to evaluate the repair effect of rabbit knee cartilage defects.Results The ADSCs isolated and cultured in vitro showed good growth,stable phenotype and good directional differentiation through macroscopic observation and histological staining,it could be seen that the repair degree and effect of the knee joint full-thickness cartilage defect model implanted with Gd-HA scaffold group were better than those of the blank control group,while the cartilage repair situation of the ADSCs+Gd-HA scaffold group was better than that of the Gd-HA scaffold group(P＜0.05);The ICRS and improved O'Driscoll scores were higher than the other two groups(P＜0.05).Compared with the Gd-HA group,the ADSCs+Gd-HA group could produce ColⅡ and GAG during the process of cartilage repair,with stronger mechanical strength of the repaired tissue(P＜0.05);PKH26 labeled ADSCs were found in the repaired tissues of the ADSCs+Gd-HA group,and they were involved in the composition of newly formed tissues.Conclusion Gd-HA scaffold material combined with ADSCs has a good repair effect on full-thickness cartilage defects in the knee joint as a new type of biological material for repairing joint cartilage defects.