This study investigated the mechanism of autophagy in the differentiation processes of MC3T3-E1 cells under osteogenic induction(physiological) and alcohol(AL) intervention(pathological), as well as the mechanism by which icariin(ICA) affected osteogenic differentiation of MC3T3-E1 cells under the pathological condition of AL intervention. Osteogenic mineralized nodule staining confirmed that the cells could differentiate into osteoblasts. After determining the appropriate concentrations of AL and ICA using the CCK-8 assay, seven groups were set up in this study: complete medium(CM) group, osteogenic induction medium(OIM) group, OIM+0.25 mol·L~(-1) AL group, OIM+0.25 mol·L~(-1) AL+1×10~(-8) mol·L~(-1) ICA group, OIM+0.25 mol·L~(-1) AL+1×10~(-7) mol·L~(-1) ICA group, OIM+0.25 mol·L~(-1) AL+1×10~(-6) mol·L~(-1) ICA group, and OIM+0.25 mol·L~(-1) AL+1×10~(-5) mol·L~(-1) ICA group, with a culture period of 7 days. Alkaline phosphatase(ALP) staining was used to detect the relative ALP area. Western blot and RT-qPCR were employed to analyze the expression of osteogenesis-and autophagy-related proteins and mRNAs. Reactive oxygen species(ROS) staining was used to detect ROS levels, and apoptosis was assessed through mitochondrial membrane potential assays. The results showed that ICA increased the relative ALP area that had been reduced by AL intervention. AL down-regulated the expression levels of Wnt family member 1(Wnt1), along with the osteogenesis-related mRNAs Wnt1, β-catenin, Runt-related transcription factor 2(Runx2), osteoprotegerin(OPG), and ALP, thereby inhibiting osteogenic differentiation. ICA up-regulated the expression levels of the osteogenesis-related proteins and mRNAs that had been inhibited by AL, promoting osteogenic differentiation. AL inhibited typical autophagy, while ICA regulated Rubicon to suppress LC3-associated phagocytosis(LAP) and promote typical autophagy. ICA also reduced the ROS levels that were elevated by AL and decreased the apoptosis of osteoblasts induced by AL intervention. In conclusion, ICA can regulate Rubicon to inhibit LAP, promote typical autophagy, eliminate ROS, reduce apoptosis, and ultimately enhance the osteogenic differentiation of MC3T3-E1 cells under the pathological condition of AL intervention by modulating the Wnt/β-catenin signaling pathway.
Autophagy/drug effects* ; Animals ; Osteogenesis/drug effects* ; Mice ; Cell Differentiation/drug effects* ; Osteoblasts/metabolism* ; Ethanol/pharmacology* ; Flavonoids/pharmacology* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Aim To study the effects of different peri-ods of hypoxia on gastrointestinal stress in mice by sim-ulating hypoxia environment at high altitude in a low-pressure oxygen chamber.Methods The normal con-trol group and the model group for 1,3 and 5 days were set up according to different periods of hypobaric hypoxia.The intestinal propulsion rate,visceral sensi-tivity and pathological damage of gastrointestinal tract were detected after hypobaric hypoxia treatment.The contents of IL-1 β,IL-6 and TNF-α in gastrointestinal tract and the contents of gastrointestinal hormone,di-amine oxidase and D-lactic acid were detected by en-zyme-linked immunosorbent assay(ELISA).The ex-pressions of tight-junction protein and tight junction in-jury pathway protein in intestinal tissues were detected by Western blot.Results Compared with the control group,the intestinal propulsion rate of the model group was accelerated,and the intestinal sensitivity in-creased.The expression of intestinal mucosal injury markers increased.Gastrointestinal motility inhibiting hormone decreased and gastrointestinal motility promo-ting hormone increased.The expression of tight junc-tion proteins ZO-1,claudin-1,occludin and VASP of tight junction injury-related pathway decreased,while the expression of NF-κB,HIF-1α and VEGF in tight junction injury-related pathway increased.The expres-sions of IL-1 β,IL-6 and TNF-α in gastrointestinal tis-sue increased.The content of pepsin in gastric tissue increased.The injury of gastrointestinal tissue was less in the 1-day group,and more serious in the 3-day and 5-day groups.Conclusions Stress injury occurs in the gastrointestinal tract of mice at different time points in hypoxia and hypoxia environment,and the gastroin-testinal function injury is more serious after three days of exposure,which may be related to the activation of NF-κB/HIF-1α/VEGF/VASP pathway.

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. Conclusion CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.
Infant ; Adolescent ; Animals ; Child ; Male ; Humans ; Infant, Newborn ; Female ; Child, Hospitalized ; Cross-Sectional Studies ; Carbon Monoxide Poisoning/epidemiology* ; Pesticides ; Foodborne Diseases ; Hospitals ; Drug-Related Side Effects and Adverse Reactions ; China/epidemiology*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.