ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective To explore the effect and possible mechanism of aerobic exercise and empagliflozin(EMPA)on isoproterenol(ISO)-induced pathological cardiac remodeling.Methods Mice were divided randomly into control(Con),ISO,exercise(EX)+ISO,EMPA+ISO,and EX+EMPA+ISO groups.Mice in the EX groups were trained continuously for 6 weeks,mice in the EMPA groups were gavaged continuously for 4 weeks,and mice in the ISO groups were injected subcutaneously with ISO for 7 days before dissection.After euthanasia,the whole heart mass index,left heart mass index,heart mass to tibial length ratio,and left heart mass to tibial length ratio were calculated by weighing and measuring.Pathological changes,collagen fiber deposition,and myocardial cell cross-sectional area in the hearts were detected by hematoxylin and eosin,Sirius red,and wheat germ agglutinin staining.The expression levels of genes and proteins related to cardiac fibrosis and hypertrophy,macrophage infiltration,ferroptosis,and the phosphoinositide 3-kinase(PI3K)/AKT pathway were examined by quantitative reverse transcription-polymerase chain reaction,Western Blot,and immunofluorescence staining.Results(1)The whole heart mass index,left heart mass index,heart mass to tibial length ratio,and left heart mass to tibial length ratio showed downward trends in the EX+ISO group compared with the ISO group.The whole heart mass index and left heart mass index were significantly decreased in the EMPA+ISO group(P＜0.01,P＜0.05),and the heart mass to tibial length ratio and left heart mass to tibial length ratio were both down regulated.Mice in the EX+EMPA+ISO group had a significant decrease in whole heart mass index(P＜0.05),and the other three indicators were all down-regulated.(2)Myocardial cells were more orderly in the three intervention groups compared with the ISO group,with significant reductions in inflammatory cell infiltration(P＜0.01),the area of cardiac fibrosis,and the cross-sectional area of myocardial cells(P＜0.001).(3)The mRNA and protein expression levels of Col 1 and Anp were significantly reduced in the three intervention groups compared with the ISO group(P＜0.05,P＜0.01,P＜0.001).Col 3 mRNA expression significantly reduced in the EMPA+ISO and EX+EMPA+ISO groups(P＜0.05),and showed a downward trend in the EX+ISO group.(4)Macrophage infiltration and IL-6 mRNA levels were significantly reduced in the three intervention groups compared with the ISO group(P＜0.05,P＜0.01,P＜0.001).(5)Nrf2 and Gpx4 mRNA levels were upregulated in the three intervention groups compared with the ISO group,with a significant increase in GPX4 protein expression(P＜0.01,P＜0.001)and a significant decrease in HO-1 protein expression(P＜0.01,P＜0.001).(6)Pi3k mRNA levels were significantly increased in the EX+ISO group compared with the ISO group(P＜0.05),and Pi3k mRNA was upregulated in the EMPA+ISO and EX+EMPA+ISO groups.Akt mRNA levels showed an upward trend in the three intervention groups.PI3K and phospho-AKT protein levels were significantly increased in the EX+ISO group(P＜0.01,P＜0.05),and showed an increasing trend in the EMPA+ISO and EX+EMPA+ISO groups.Conclusions Moderate intensity aerobic exercise,the novel hypoglycemic drug EMPA,and their combination can alleviate ISO-induced pathological cardiac remodeling,possibly via a mechanism related to activation of the PI3K/AKT signaling pathway and inhibition of cardiac ferroptosis.

Objective To explore the effect of deep learning image reconstruction(DLIR)algorithm combined with"double low"[low voltage(kV)and low contrast agent dosage]technique on the image quality of coronary computed tomography angiography(CCTA)in overweight patients compared with adaptive statistical iterative reconstruction(ASIR-V)and filtered back projection(FBP).Methods Fifty-two patients with body mass index(BMI)between 25.1 kg/m2and 28 kg/m2 who underwent CCTA scanning were prospectively selected,all of whom scanned on a GE Revolution APEX-CT with a tube voltage of 80 kV,a smart mA(500-1 300 mA),a noise index of 30,and a contrast dosage of 0.5 mL/kg;four groups of images were reconstructed for each patient,FBP,50％ASIR-V,DLIR-M,and DLIR-H.The CT and SD values of the aorta(AO)root,the proximal segment of the right coronary artery(RCA),the left circumflex(LCX),the left anterior descending branch(LAD)and the pericardial fat were measured,and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two doctors experienced in the diagnosis of cardiovascular disease were selected to subjectively score the reconstructed images using a double-blind method.The SD value,SNR value,CNR value and subjective scores of images in the four groups were compared.Results In the objective image quality evaluation,there were statistically significant differences in SD value,SNR value and CNR value of reconstructed images in the four groups(P＜0.05).As the four groups of reconstruction algorithms FBP,50％ASIR-V,DLIR-M,and DLIR-H were changed sequentially,the image SD value gradually decreased,the SNR value and CNR value gradually increased,and the DLIR-H group had the lowest SD value and the highest SNR and CNR values.In the subjective image quality evaluation,the subjective scores of the two doctors had good consistency(Kappa value=0.900),and the difference between them was statistically significant(P＜0.001).The subjective scores of DLIR-M and DLIR-H groups were higher.Conclusion DLIR algorithm combined with"double-low"technique can significantly improve the CCTA image quality of overweight patients,which is better than 50％ASIR-V and FBP.

Objective:To evaluate the effect of dexmedetomidine on perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.Methods:Sixty elderly patients of either sex, aged≥ 60 yr, weighing 40-100 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with the Frail Scale score 3-5 points, scheduled for elective hip surgery under spinal-epidural anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and dexmedetomidine group (group D). Dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg at 10 min before anesthesia followed by a continuous infusion of 0.2 μg·kg -1·h -1 until 10 min before the end of surgery in group D. The equal volume of 0.9% sodium chloride solution was given at the corresponding time point in group C. Blood samples from the median cubital vein were collected before surgery (T 1) and at 1 and 3 days after surgery (T 2, 3) for determination of concentrations of serum S100β and neuron-specific enolase by enzyme-related immunosorbent assay. Postoperative delirium was assessed within 3 days after surgery using the Confusion Assessment Method. Cognitive function was evaluated by Mini-Mental State Examination at T 1 and 30 days after surgery. Results:Compared with the baseline at T 1, the concentrations of serum S100β and NSE were significantly increased at T 2 and T 3 in two groups ( P<0.05). Compared with group C, the concentrations of serum S100β and neuron-specific enolase and incidence of postoperative delirium and postoperative cognitive dysfunction were significantly decreased at T 2 and T 3 in group D( P<0.05). Conclusions:Dexmedetomidine can effectively decrease the occurrence of perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.

Objective: To understand the relationship between family environment and depressive symptoms among adolescent, and to provide a reference for adolescent mental health promotion and intervention. Methods: From September to December in 2021, a questionnaire survey on family environment and depressive symptoms was conducted among 8 102 middle school students by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Chi square test was used to compare the depression status of students in different family environments. Multivariate Logistic regression analysis was used to explore the relationship between family environment and depressive symptoms. Results: The detection rates of possible depression, likely depression and severe depression in adolescents were 11.2%, 5.9% and 8.4%, respectively. There were significant differences in the detection rate of depression by gender, academic period, urban and rural areas, family forms and only child statu( χ 2=87.60, 27.19, 6.65, 45.59, 4.78, P <0.05). Logistic regression analysis showed that adolescents in single parent families ( OR =1.45) and reorganized families( OR =1.69) were positively correlated with the occurrence of depressive symptoms compared with those in nuclear families( P <0.01). Conclusion Compared with nuclear families, the risks of adolescent depressive symptoms in single parent families and reorganized families are higher. Attention should be paid to the mental health education of teenagers from single parents and reorganized families to ensure the development of their physical and mental health.

Objective: To explore the correlation between physical activity and nutritional status of Chinese children and adolescents, and to provide references for the healthy development of Chinese adolescents. Methods: According to the six administrative regions of China (East China, Northwest China, North China, Central China, Southwest China and South China), 4 269 children and adolescents aged 7 to 18 were selected by stratified random sampling method. "Physical Activity Level Evaluation Questionnaire" was used to conduct a physical activity survey. Chi square test and non parametric test were used to analyze the physical activity status. Results: The overall detection rate of MVPA insufficiency in children and adolescents with normal BMI were 53.7%, 50.2%, 56.3%, and 52.5% in the wasting group, overweight and obese group, respectively. There was no significant difference in the detection rate of MVPA insufficiency between different nutritional status( χ 2=2.55, P >0.05); but in the 7-9 years old age group, the difference in the detection rate of MVPA insufficiency between different nutritional status were statistically significant( χ 2= 10.35, 8.86, 15.88, P <0.05). There were no significant differences in physical activity intensity and item types under different nutritional status ( P >0.05). Conclusion There are age differences in the correlation between physical activity and nutritional status of children and adolescents in my country.Therefore, the differences between different groups should be fully considered while formulating intervention policies.

Abstract In recent decades, there is a decreasing trend in physical activity, which might be associated with decline in physical and mental health among children and adolescents in China. The outbreak and spread of the COVID-19 further aggravated this trend. Under the background of normalized epidemic prevention and control, in order to deeply understand the relationship between physical activity and physical and mental health of children and adolescents, this study sorted out relevant domestic and foreign literatures, and analyzed the effects of physical activity on children and adolescents health and fitness. The positive effects of physical activity, cognition, and mental health were found to be significantly different in the type, intensity, and time of physical activity in the related health effects.

Objective:To screen out the differentially regulated metabolites by the analysis of serum metabolic fingerprints, and to provide potential biomarkers for diagnosis of lung cancer.Methods:A total of 228 subjects were enrolled in Changhai Hospital from January 27, 2021 to June 4, 2021, including 97 newly diagnosed lung cancer patients and 131 healthy individuals. Serum samples were collected from the enrolled cohort according to a standard procedure, and the enrolled cohort was divided into a training set and a completely independent validation set by stratified random sampling. The metabolic fingerprints of serum samples were collected by previously developed nano-assisted laser desorption/ionization mass spectrometry (nano-LDI MS). After age and gender matching of the training set, a diagnostic model based on serum metabolic fingerprints was established by machine learning algorithm, and the classification performance of the model was evaluated by receiver operating characteristic (ROC) curve.Results:Serum metabolic fingerprint for each sample was obtained in 1 minute using a novel nano-LDI MS, with consumption of only 1 μl original serum sample. For the training set, the area under ROC curve (AUC) of the constructed classifier for diagnosis of lung cancer was 0.92 (95% CI 0.87-0.97), with a sensitivity of 89% and specificity of 89%. For the independent validation set, the AUC reached 0.96 (95% CI 0.90-1.00) with a sensitivity of 91% and specificity of 94%, which showed no significant decrease compared to training set. We also identified a biomarker panel of 5 metabolites, demonstrating a unique metabolic fingerprint of lung cancer patients. Conclusion:Serum metabolic fingerprints and machine learning were combined to establish a diagnostic model, which can be used to distinguish between lung cancer patients and healthy controls. This work sheds lights on the rapid metabolic analysis for clinical application towards in vitro diagnosis.

Objective:To explore the effects of long non-coding RNA (lncRNA) FAM224A on the proliferation and migration of ovarian cancer cells by regulating the expression of miRNA-590-3p (miR-590-3p).Methods:Human ovarian cancer cell lines OC3, SKOV-3, HO-8910, A2780 and human normal ovarian epithelial cell line IOSE80 were selected, and the relative expression of FAM224A in each cell line was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The cell line with the lowest relative expression level of FAM224A was screened for follow-up experiment. The cells were divided into FAM224A group (transfected with FAM224A mimic gene) and control group (transfected with control mimic gene). CCK-8 method and cell scratch test were used to detect the cell proliferation and migration ability of the two groups. The bioinformatics website LncBase v.2 predicted that the target gene that FAM224A might complementarily bind to was miR-590-3p. qRT-PCR was used to detect the relative expression levels of miR-590-3p and forkhead box protein A2 (FOXA2) mRNA, and the expressions of related proteins were detected by Western blot.Results:The relative expression levels of FAM224A in ovarian cancer cell lines OC3, SKOV-3, HO-8910, A2780 and normal ovarian epithelial cell line IOSE80 were 0.23±0.04, 0.65±0.05, 0.45±0.03, 0.63±0.08 and 1.02±0.11, respectively, and the difference was statistically significant ( F = 14.78, P < 0.01), and the cell line with the lowest relative expression level of FAM224A was OC3. The results of CCK-8 method showed that the proliferation ability of OC3 cells in the FAM224A group was lower than that in the control group on the 2nd, 3rd, 4th and 5th day of culture (all P < 0.05). The scratch healing rates of OC3 cells in the FAM224A group and the control group were (18.6±2.3)% and (71.7±7.2)%, respectively, and the difference was statistically significant ( t = 6.99, P < 0.01). The relative expression levels of FAM224A in OC3 cells in the FAM224A group and the control group was 12.36±1.45 and 1.14±0.24, respectively ( t = 13.08, P < 0.01); the relative expression levels of miR-590-3p were 0.19±0.06 and 1.04±0.20, respectively ( t = 4.01, P < 0.01); the relative expression levels of FOXA2 mRNA were 6.37±1.37 and 1.05±0.08, respectively ( t = 3.86, P < 0.01). Compared with the control group, the expression of FOXA2 protein in OC3 cells in the FAM224A group was increased, the expressions of cell proliferation protein cyclin-dependent kinase 2 (CDK2) and cyclin D3 were decreased, and the expression of cell migration protein Snail was decreased. Conclusions:FAM224A is low expressed in ovarian cancer cell lines. FAM224A reduces the proliferation and migration ability of ovarian cancer OC3 cells by inhibiting the expression of miR-590-3p.