Objective: To investigate the association between metabolic dysfunction associated steatotic liver disease (MASLD) and bone mineral density among children and adolescents, so as to provide evidence for the early prevention and intervention of bone health in this population. Methods: In September 2022, a method combining convenience sampling with cluster sampling was used to select 5 089 children and adolescents aged 6-18 years in 9 schools from kindergarten to senior high school in Tongzhou District, Beijing, for physical measurements, ultrasound measurements, blood biochemical index testing, and questionnaire surveys. Participants were categorized into three groups: the normal control group ( n =1 515), the metabolic abnormality group (MA, n = 3 007 ), and the MASLD group ( n =567). Multivariable linear regression model was applied to examine the association between MASLD and bone speed of sound (SOS), while multivariable Logistic regression model was used to assess the association between MASLD and low bone mineral density. Subgroup analysis was conducted by sex and age groups. Results: Compared with the normal control group, the MASLD group showed significantly lower SOS values ( β =-6.31, 95% CI =-9.63 to -2.99), lower SOS Z scores ( β = -0.21, 95% CI =-0.32 to -0.10), and higher susceptibility to low bone mineral density( OR =1.56, 95% CI =1.25-1.96)（all P <0.05）. No significant differences in SOS or odds of low bone density were observed between the MA and normal control groups (all P > 0.05). In sex stratified analyses, males with MASLD exhibited significantly lower SOS Z scores ( β =-0.35, 95% CI =-0.49 to -0.20 , P <0.05), whereas no significant difference was observed in females with MASLD ( β =-0.03, 95% CI =-0.21-0.15; P >0.05). When hepatic steatosis grade (0, 1, 2, and 3) was treated as a continuous variable, each one grade increase was associated with a 31% higher odds of low bone mineral density ( OR =1.31, 95% CI =1.13 to 1.53, P <0.05). Conclusions MASLD is significantly associated with low bone mineral density among children and adolescents, with a stronger association in males. Moreover, children and adolescents with hepatic steatosis have a higher risk of impaired bone health compared with those with metabolic abnormalities alone.

Objective: To investigate the association of the joint effect of body fat levels and dyslipidemia with cardiovascular structural abnormalities in children, so as to provide a scientific reference for the early prevention of cardiovascular damage. Methods: Based on the data from the second follow up (October 2021 to January 2022) of the Huantai Children Cardiovascular Health Follow up Cohort, 1 308 children with complete data were included. The fat mass percentage (FMP), fat mass index (FMI), subcutaneous fat mass (SFM) and visceral fat mass (VFM), left ventricular mass index (LVMI), relative wall thickness (RWT), thickening of carotid intima-media thickening (cIMT) , left ventricular hypertrophy (LVH) and left ventricular geometric remodeling (LVG), triglyceride (TG), total cholesterol (TC) ,high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were obtained. Multivariable Logistic regression model was used to analyze the associations of FMP, FMI, SFM and VFM with thickening of cIMT, LVH and LVG. The joint effects of these body fat indicators and dyslipidemia on the aforementioned cardiovascular outcomes were further explored. Restricted cubic spline model was used to examine the dose response relationships between body fat levels and cardiovascular structural abnormalities. Results: Elevated body fat levels were significantly associated with an increased risk of cardiovascular structural abnormalities, exhibiting J shaped dose response relationships (all P <0.05). Compared with the group with normal body fat and normolipidemia, the risks of thickening of cIMT, LVH, and LVG in the group with elevated FMP combined with dyslipidemia were higher[ OR (95% CI )=11.70 (6.49-21.27), 5.53 (2.97-10.17), 2.33 (1.30-4.05)]; in the group with elevated FMI combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )= 11.68 (6.43-21.38), 6.98 (3.73-12.92), 2.65 (1.50-4.61)]; in the group with elevated SFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=10.55 (5.83-19.24), 5.11 (2.71-9.45), 1.99 (1.11- 3.46 )]; and in the group with elevated VFM combined with dyslipidemia, the corresponding risks were higher[ OR (95% CI )=12.44 (6.76-23.14), 6.17 ( 3.31 -11.38), 2.30 (1.30-3.99)] (all P <0.05). Sex stratified analyses showed that the risk of thickening of cIMT in the combined exposure group of all four body fat indicators and dyslipidemia was significantly higher in girls than in boys (all P <0.01). Conclusions Elevated body fat levels and dyslipidemia have a combined effect in children, collectively increasing the risk of cardiovascular structural abnormalities. Prevention of cardiovascular damage in children should focus on both adiposity management and blood lipid regulation.

Objective: To investigate the association between sleep duration and depressive symptoms in children and adolescents, so as to provide scientific evidence for promoting mental health and preventing depression among relevant populations. Methods: A total of 2 192 children and adolescents aged 10-17 years with complete data from the 2018 China Family Panel Studies Database were included. Eight item Center for Epidemiologic Studies Depressive Scale(CES-D8) was used to assess participants depressive levels, and sleep duration was assessed via questionnaire. Multivariate Logistic regression model was used to analyze the association between different sleep duration categories and depressive symptom occurrence among children and adolescents. A restricted cubic spline(RCS) model analyzed the dose response relationship between sleep duration and the risk of depressive symptoms occurrence and segmented Logistic regression models to identify dose response effects. Results: Among the surveyed children and adolescents, 524(23.91%) exhibited depressive symptoms. Compared to those with sufficient sleep, children aged 10-12 years had a higher risk of depressive symptoms on average per day( OR =1.66, 95% CI =1.19-2.33) and during weekdays( OR =1.76, 95% CI =1.26-2.46), as well as in adolescents aged 13-17 years on a daily basis( OR =1.40，95% CI =1.06-1.85) and during weekdays( OR = 1.48，95% CI =1.12-1.95), and excessive sleep in adolescents on rest days was also significantly associated with higher risk of depressive symptoms( OR =1.65，95% CI =1.11-2.43)(all P <0.05). RCS analysis results indicate that children s sleep duration exhibits a linear negative correlation with the risk of depressive symptoms(all P nonlinear >0.05), while adolescents sleep duration showed a U shaped association with depressive symptoms(all P nonlinear <0.05) on a daily basis, during weekdays and weekends, with potential threshold effects at 10.00, 9.88, and 9.60 hours, respectively. Conclusions Sleep duration among children and adolescents is associated with depressive symptoms, with notable age related differeneces. It is recommended to develop targeted age specific interventions to reduce the risk of depressive symptoms in children and adolescents.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective:To investigate the role of endoplasmic reticulum stress(ERS)-related long non-coding RNA(lnc RNA)Gm9795 in the progression of hepatocellular carcinoma(HCC).Methods:This retrospective cohort study included 80 HCC patients who underwent routine surgical procedures at Nanjing Jiangning Hospital from 2014 to 2020.Colecting clinical datas from all patients and using real-time fluorescence quantitative PCR to detect the expression level of Gm9795 in 80 patients'cancer and adjacent tissues,as well as in HCC cells(HepG2,Hep3B,HCCLM3,and Huh7).The correlation between Gm9795 expression and overall survival time and recurrence free survival time of HCC patients was analysised.Constructing HCCLM3 cells overexpressing Gm9795 through lentiviral infection,and constructing Huh7 cells silencing Gm9795 expression through liposome transfection.The proliferation ability of cells was evaluated using CCK-8 assay and colony formation assay,while the migration and invasion ability of cells were detected using Transwell assay.Identification of Gm9795 specific binding protein by mass spectrometry(MS).The effect of overexpressing or silencing Gm9795 expression on the expression of C/EBP homologous protein(CHOP)gene was detected by Western blotting.The CHOP gene was simultaneously transferred into HCCLM3 cells overexpressing Gm9795,and the effects of up-regulating CHOP expression level on the proliferation,migration,and invasion of HCCLM3 cells were evaluated using CCK-8 assay,colony formation assay,and Transwell assay.Results:Compared with adjacent tissues,the expression level of Gm9795 was significantly up-regulated in HCC tissues(P<0.001).The expression levels of Gm9795 in all HCC cells were significantly higher than in normal hepatocytes LO2(all P<0.05).Higher expression levels of Gm9795 were associated with aggressive clinical pathological features,including tumor size,multiple tumors,Barcelona Clinic Liver Cancer(BCLC)staging,and portal vein tumor thrombus(all P<0.05).The results of multivariate analysis showed that high expression level of Gm9795 was an independent prognostic factor for overall survival and recurrence free survival in HCC patients(both P<0.05).The higher expression of Gm9795 was significantly correlated with shorter overall survival and recurrence free survival in the cohort(both P<0.01).Compared with the Vector group,the proliferation,migration,and invasion of HCCLM3 cells were significantly enhanced in the Gm9795 overexpression group(all P<0.01);Compared with the siNC group,the proliferation,migration,and invasion of Huh7 cells were significantly reduced in the siGm9795-1 and siGm9795-2 groups(all P<0.01).CHOP was identified as a Gm9795 specific binding protein by MS.Compared with the Gm9795+Vector group,the Gm9795+CHOP group showed significant reductions in proliferation,migration,and invasion of HCCLM3 cells(all P<0.01).Conclusions:Gm9795 is up-regulated in HCC tissues,and the high expression of Gm9795 is an independent prognostic factor for the overall survival of HCC patients.Gm9795 promotes the proliferation and invasion of HCC cells in vitro,and its mechanism may be related to the inhibition of ERS mediated by CHOP signaling pathway.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Helicobacter pylori(Hp)is a major pathogen that causes peptic ulcer,mucosa-associated tissue lymphoma and gastric cancer.Adhesion colonization is a prerequisite for the pathogenesis of Hp.After infec-tion,Hp first uses urease to neutralize gastric acid,and then it adapts to the environment through motility and chemotactic swimming of flagella.Finally,Hp adheres to gastric epithelial cells through outer membrane pro-teins.Some outer membrane proteins have the biological effect of transporting virulence factors,mediating in-flammation and assisting Hp to produce pathological changes on human body.This paper reviews the mecha-nism of main colonization factors of Hp.

Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

Objective: To explore the association between the joint association of screen time on weekdays and weekends with self rated sleep quality among adolescents, providing scientific basis for improving adolescent sleep health. Methods: Using data from "Huantai Children s Cardiovascular Health Follow up Cohort" survey conducted during November to December 2023, a total of 1 197 adolescents aged 12-17 years with complete demographic characteristics, physical measurements, and questionnaire data were included. The dose response relationship between screen time and sleep quality was evaluated by restrictive cubic splines (RCS). Based on screen time on weekdays and weekends (normal: < 2 h/d; excessive: ≥ 2 h/d), adolescents were categorized into 4 groups. Multivariate Logistic regression models were used to analyze the association between the combined effect of screen time on weekdays and weekends and sleep quality. Results: The RCS analysis results showed that there was a linear dose response relationship between average daily screen time and poor sleep quality in adolescents (non linear P >0.05). The results of multiple Logistic regression analysis showed that adjusting for potential covariates,compared with adolescents having normal screen time on both weekdays and weekends, those with excessive screen time on both weekdays and weekends had increased risk of poor sleep quality ( OR=2.51, 95%CI=1.33-4.62, P <0.01). Sex stratified analysis revealed that girls with excessive screen time on both weekdays and weekends had increased odds of poor sleep quality ( OR=3.03, 95%CI=1.23-7.14, P =0.01), compared to girls who had normal screen time on both weekdays and weekends. Conclusions A linear dose response relationship exists between daily screen time and poor sleep quality in adolescents. Excessive screen time on both weekdays and weekends is positively associated with poor sleep quality, particularly more pronounced among female adolescents.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.