Objective To establish a risk prediction model of continuous renal replacement therapy(CRRT)withdrawal failure in patients with infectious shock complicating acute kidney injury(AKI)based on the decision tree algorithm,and to explore the influencing factors of CRRT withdrawal failure in patients with infectious shock complicating AKI.Methods 220 patients with infectious shock complicating AKI admitted to our hospital from May 2020 to May 2023 were retrospectively analyzed,and divided into success group and failure group according to the success or failure of the withdrawal,univariate and multivariate Logistic regression analysis were used to screen risk factors of CRRT withdrawal failure in patients with septic shock complicated with AKI,C-reactive protein/albumin(CRP/ALB)at admission and sepsis-related organ failure assessment(SOFA)score at withdrawal,acute physiology and chronic health evaluation(APACHE Ⅱ)score,N-terminal B-type natriuretic peptide(NT-proBNP)level at the beginning of CRRT,mean arterial pressure(MAP)grading,urine volume after withdrawal,and serum creatinine(Scr)level after withdrawal were taken into constructing a decision tree model and validating the model efficacy.Results In this study,there were 41.82％of patients failed to withdrawal.Combination of univariate and multivariate Logistic regression analysis showed that SOFA score at withdrawal,APACHE Ⅱ scores,urine volume after withdrawal,Scr level after withdrawal,NT-proBNP at the beginning of CRRT,and MAP grading,CRP/ALB at the time of admission were an independent risk factor for CRRT withdrawal failure in patients with septic shock complicated with AKI(P＜0.05).The results showed that the higher CRP/ALB was the most important influencing factor on the failure of CRRT evacuation in patients with infectious shock complicating AKI,and the area under the receiver operating characteristic curve was 0.965.Conclusion The decision tree model constructed by CRP/ALB at admission,SOFA score at withdrawal,urine volume after withdrawal,Scr level after withdrawal,APACHE Ⅱ score,and MAP grading has a better predictive efficacy of CRRT withdrawal failure in patients with infectious shock complicating AKI,which is a guideline for patients'prognostic assessment.

Objective To establish a risk prediction model of continuous renal replacement therapy(CRRT)withdrawal failure in patients with infectious shock complicating acute kidney injury(AKI)based on the decision tree algorithm,and to explore the influencing factors of CRRT withdrawal failure in patients with infectious shock complicating AKI.Methods 220 patients with infectious shock complicating AKI admitted to our hospital from May 2020 to May 2023 were retrospectively analyzed,and divided into success group and failure group according to the success or failure of the withdrawal,univariate and multivariate Logistic regression analysis were used to screen risk factors of CRRT withdrawal failure in patients with septic shock complicated with AKI,C-reactive protein/albumin(CRP/ALB)at admission and sepsis-related organ failure assessment(SOFA)score at withdrawal,acute physiology and chronic health evaluation(APACHE Ⅱ)score,N-terminal B-type natriuretic peptide(NT-proBNP)level at the beginning of CRRT,mean arterial pressure(MAP)grading,urine volume after withdrawal,and serum creatinine(Scr)level after withdrawal were taken into constructing a decision tree model and validating the model efficacy.Results In this study,there were 41.82％of patients failed to withdrawal.Combination of univariate and multivariate Logistic regression analysis showed that SOFA score at withdrawal,APACHE Ⅱ scores,urine volume after withdrawal,Scr level after withdrawal,NT-proBNP at the beginning of CRRT,and MAP grading,CRP/ALB at the time of admission were an independent risk factor for CRRT withdrawal failure in patients with septic shock complicated with AKI(P＜0.05).The results showed that the higher CRP/ALB was the most important influencing factor on the failure of CRRT evacuation in patients with infectious shock complicating AKI,and the area under the receiver operating characteristic curve was 0.965.Conclusion The decision tree model constructed by CRP/ALB at admission,SOFA score at withdrawal,urine volume after withdrawal,Scr level after withdrawal,APACHE Ⅱ score,and MAP grading has a better predictive efficacy of CRRT withdrawal failure in patients with infectious shock complicating AKI,which is a guideline for patients'prognostic assessment.

Objective: To learn the status and influencing factors of development among infants at ages of 0 to 36 months in Xiaoshan District, Hangzhou City, so as to provide the reference for promoting healthy development of infants. Methods: Infants at ages of 0-36 months who underwent physical examination in Child Health Clinic of Xiaoshan District Community Health Service Center were selected in 2022. General data of infants and their mothers were collected through questionnaires, and the development status of infants was screened by Age and Stages Questionnaire (third edition). Factors affecting the development status were identified using a multivariable logistic regression model. Results: A total of 2 519 infants were investigated, including 1 339 males (53.16%) and 1 180 females (46.84%). There were 608 infants with abnormal development of at least one functional area of communication (CM), gross motor (GM), fine motor (FM), problems solving (CG) and personal-social (PS). The abnormal rate was 24.14%, and the abnormal rates of the above functional areas were 9.77%, 6.59%, 7.98%, 6.39% and 9.33%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.563, 95%CI: 1.191-2.052), mother's childbearing age (≥35 years, OR=1.411, 95%CI: 1.001-1.988), mother's educational level (lower than junior college, OR=1.460, 95%CI: 1.116-1.912) were factors affecting abnormal development of CM; preterm birth (OR=2.323, 95%CI: 1.315-4.103) was factors affecting abnormal development of GM; gender (male, OR=1.654, 95%CI: 1.225-2.232) was factors affecting abnormal development of FM; gender (male, OR=1.511, 95%CI: 1.086-2.102) and mode of delivery (cesarean section, OR=1.460, 95%CI: 1.060-2.010) were factors affecting abnormal development of CG; gender (male, OR=1.340, 95%CI: 1.019-1.763) and birth weight (low birth weight, OR=1.985, 95%CI: 1.149-3.432) were factors affecting abnormal development of PS. Conclusions The rate of abnormal development among infants at ages of 0 to 36 months in Xiaoshan District is 24.14%. Gender, preterm birth, mode of delivery, birth weight, mother's childbearing age and mother's educational level could affect the development status of infants.

【Objective】 To explore the effects of breastfeeding on the immune response of CD4⁺T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. 【Methods】 A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children′s Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4⁺ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. 【Results】 Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). 【Conclusions】 Breastfeeding has a regulatory effect on the immune response of infant CD4⁺ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective: To explore the effects of grandparent involvement in parenting on health related behaviors among urban preschool children, so as to provide a basis for the development of interventions for unhealthy behaviors among preschool children with different parenting pattern. Methods: A total of 5 431 preschool children aged 3-6 years old in Xinbei District, Changzhou City, were selected by census method during January to October, 2022. General household characteristics and health related behaviors of children were investigated by questionnaires, and the differences in health related behaviors with different parenting pattern involving grandparents were explored by the χ 2 test. A multifactorial Logistic regression model was used to analyze the effects of grandparenting on preschool children s health behaviors. Results: About 51.2% of preschoolers were raised by both parents, 46.1 % were co parented by grandparents, and 2.7% were raised by grandparents. After multifactorial Logistic regression analysis controlling for age, gender, annual household income, and family structure, children co parented by grandparents had a reduced risk of screen exposure time>1 h/d ( OR =0.79, P <0.05), with increased risks of outdoor activity time<2 h/d ( OR =1.30, P < 0.05 ), sleep duration <10 h/d ( OR =1.31, P <0.05), sleep difficulties ( OR =1.39, P <0.05) and adverse eating behaviors ( OR =1.20， P < 0.05), compared with children parented by both parents. Children raised by grandparents were at increased risk for outdoor activity time<2 h/d ( OR =2.19) and unhealthy eating behaviors ( OR =1.39) ( P <0.05). Conclusions Compared with children raised by both parents, the incidence of unhealthy behaviors is increased in children raised by parents and grandparents and in children raised by full grandparents. Active intervention should be focused on unhealthy behaviors of preschool children with pareting involving grandparents to promote the physical and mental health of preschool children.

Objective:To investigate the effects of disialyllacto-N-tetraose (DSLNT) on low molecular weight metabolic profile of intestinal contents in neonatal rats with necrotizing enterocolitis (NEC), in an attempt to explore the protective mechanism of DLSNT on intestinal tract of neonates.Methods:Immediately after birth, SD rats were randomly divided into the control group, the NEC group and the NEC+ DSLNT group according to random number tale method.All rats were hand-fed by special formula milk.Rats in the NEC group and NEC+ DSLNT group were exposed to hypoxia (950 mL/L nitrogen, 10 min, thrice per day) and cold stress (4 ℃, 10 min, thrice per day) for continuous 3 days to establish rodent NEC model.Rats in the NEC+ DSLNT group were hand-fed with special formula containing 300 μmol/L DSLNT.All rats were sacrificed after 72 h, and intestinal contents were collected from ileum and colon, followed by untargeted metabolomic determination with the ultrahigh-performance liquid chromatography Q extractive mass spectrometry (UHPLC-QE-MS) method.The terminal ileum was examined by hematoxylin-eosin staining.The metabolome data were analyzed with multivariable analysis using SIMCA 14.1.The metabolites that met both variable importance in the projection (VIP) >1 in the orthogonal partial least squares analysis (OPLS-DA) model and P<0.05 in the t-test were screened as differential metabolites between groups. Results:DSLNT reduced the incidence of NEC and pathological scores of ileum tissue from neonatal rats with NEC [3.0(2.0, 3.0) scores vs.1.0(1.0, 2.0) scores, P<0.01], and also significantly suppressed inflammatory infiltration.OPLS-DA model based on the metabolome data determined by UHPLC-QE-MS could perform effective discrimination between the NEC group and the control group, as well as the NEC+ DSLNT group and the NEC group.There were 64 differential metabolites between the NEC group and the control group (VIP value>1 and P<0.05 for the OPLS-DA model). These metabolites included docosahexaenoic acid (+ 288.0%, P=0.028), xanthine (+ 372.1%, P=0.007), L-arginine (+ 233.1%, P=0.027), L-leucine (+ 232.7%, P=0.015), N-acetylneuraminic acid (-41.6%, P=0.014), and so forth.These metabolites were associated with 34 metabolic pathways.Among them, such 6 pathways as arginine biosynthesis, arginine and proline metabolism were the most disturbed pathways affected by NEC.There were 15 diffe-rential metabolites in between NEC+ DSLNT group and NEC group, which included D-mannose (-73.5%, P=0.032), xanthine (-63.4%, P=0.008), linoleic acid (+ 137.9%, P=0.047), nicotinamide adenine dinucleotide (+ 278.2%, P=0.005), and so forth.These metabolites were mapped to 7 metabolic pathways, among them, linoleic acid metabolism pathway was the most relevant differential pathway affected by DSLNT.There were 8 overlapped meta-bolites in both comparison strategies, and the variation trend of these overlapped metabolites in the NEC group was significantly reversed by DSLNT supplementation. Conclusions:DSLNT could significantly attenuate the NEC pathological damage caused by hypoxia/cold stress in neonatal rats.This protective effect is associated with the improvement of the metabolic profile of intestinal contents caused by NEC and the modulation of the linoleic acid metabolic pathway.The early preventive supplementation of DSLNT is of great significance in maintaining neonatal intestinal homeostasis and preventing the process of NEC.

Objective::Observational studies indicate that insomnia may increase the risk of developing and/or dying from cardiovascular diseases, especially coronary artery disease (CAD). Our purpose is to explore the underlying causal relationship between genetic variants susceptible to insomnia and the risk of CAD by Mendelian randomization analysis.Methods::The study was conducted using publicly available statistical data on genetic variants identified from a genome-wide association meta-analysis of insomnia ( n = 113,006 individuals) and a genome-wide association meta-analysis of CAD ( n = 184,305 individuals), which consisted of both cases and non-cases. The genetic association between variants and CAD was assessed by the variants’ association with insomnia, and estimations were integrated by an inverse-variance weighted meta-analysis. Results::Among the Mendelian randomized analytical sample, 8 variants were associated with insomnia complaints and CAD. And there was no pleiotropic association with the latent confounders. In addition, in the inverse-variance weighted meta-analysis (the estimations combined from the 8 variants), the odds ratio was 1.15 (95% CI: 1.05-1.25; P= 0.002) for CAD, and in the weighted method analysis, the odds ratio was 1.14 (95% CI: 1.03-1.27; P= 0.015) for CAD. Conclusions::All of the data indicated that some valuable variants might involve in the development of CAD by leading the insomnia. Therefore, insomnia might be a causal factor for CAD, and improving the quality of sleep might be a new way for populations with insomnia to prevent CAD.

Objective::Observational studies indicate that insomnia may increase the risk of developing and/or dying from cardiovascular diseases, especially coronary artery disease (CAD). Our purpose is to explore the underlying causal relationship between genetic variants susceptible to insomnia and the risk of CAD by Mendelian randomization analysis.Methods::The study was conducted using publicly available statistical data on genetic variants identified from a genome-wide association meta-analysis of insomnia ( n = 113,006 individuals) and a genome-wide association meta-analysis of CAD ( n = 184,305 individuals), which consisted of both cases and non-cases. The genetic association between variants and CAD was assessed by the variants’ association with insomnia, and estimations were integrated by an inverse-variance weighted meta-analysis. Results::Among the Mendelian randomized analytical sample, 8 variants were associated with insomnia complaints and CAD. And there was no pleiotropic association with the latent confounders. In addition, in the inverse-variance weighted meta-analysis (the estimations combined from the 8 variants), the odds ratio was 1.15 (95% CI: 1.05-1.25; P= 0.002) for CAD, and in the weighted method analysis, the odds ratio was 1.14 (95% CI: 1.03-1.27; P= 0.015) for CAD. Conclusions::All of the data indicated that some valuable variants might involve in the development of CAD by leading the insomnia. Therefore, insomnia might be a causal factor for CAD, and improving the quality of sleep might be a new way for populations with insomnia to prevent CAD.

Infancy is a critical period for the formation and development of intestinal flora, the intestinal flora mainly comes from the exchange between matrix and infants.Cesarean section, early exposure to antibiotics and formula feeding may disrupt the establishment of microbiota and adversely affect health.Human milk oligosaccharides (HMOs) is a group of unconjugated polysaccharides with diverse structures.It is rich in breast milk, and can regulate the composition of infant intestinal flora and have a beneficial impact on infant′s intestinal health.In order to understand the characteristics of the infant gut bacteria colonize, and the effect of HMOs on the intestinal flora, this review is as follows in this regard.