The effect of replacing sedentary behavior with different intensities of physical activity on depression and anxiety in Chinese university students: an isotemporal substitution model.

BACKGROUND: Previous research has suggested that engaging in regular physical activity (PA) can help to reduce symptoms of depression and anxiety in university students. However, there is a lack of evidence regarding the impact of reducing sedentary behavior (SB) and increasing light-intensity PA (LPA) on these symptoms. This study aims to address this gap by using isotemporal substitution (IS) models to explore how substituting SB with LPA or moderate-to-vigorous PA (MVPA) affects depression and anxiety symptoms among university students. METHODS: The study recruited 318 university students with a mean age of 21.13 years. Accelerometers were used to objectively measure the time spent on SB, LPA, and MVPA, while depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Self-rating Anxiety Scale (SAS). IS models using multivariable linear regression were employed to estimate the associations between different behaviors and depression and anxiety symptoms when 30 min of one behavior was substituted with another. RESULTS: In the single-activity model, less SB (ß = 0.321, 95% CI: 0.089, 1.297) and more MVPA (ß = -0.142, 95% CI: -1.496, - 0.071) were found to be significantly and negatively associated with depression scores, while less SB (ß = 0.343, 95% CI: 0.057, 1.014), LPA (ß = 0.132, 95% CI: 0.049, 1.023), and more MVPA (ß = -0.077, 95% CI: -1.446, - 0.052) were significantly and negatively correlated with anxiety scores. The IS analysis revealed that substituting 30 min of SB with LPA (ß = -0.202, 95% CI: -1.371, - 0.146) or MVPA (ß = -0.308, 95% CI: -0.970, - 0.073) was associated with improvements in depressive symptoms. Substituting 30 min of SB with MVPA (ß = -0.147, 95% CI: -1.863, - 0.034) was associated with reduced anxiety symptoms. CONCLUSION: Replacing 30 min of SB with MVPA may alleviate depression and anxiety symptoms in university students. Further research is needed to explore the long-term effects of PA interventions on the mental health disorders of this population.

Research progress on the role of autophagy in the development of varicocele.

Varicocele (VC) is a common cause of infertility in men. Pathophysiological changes caused by VC, such as testicular hypoxia, high temperatures, oxidative stress, abnormal reproductive hormones, and Cd accumulation, can induce autophagy, thus affecting the reproductive function in patients with this condition. Autophagy regulators can be classified as activators or inhibitors. Autophagy activators upregulate autophagy, reduce the damage to the testis and epididymis, inhibit spermatogenic cell apoptosis, and protect fertility. In contrast, autophagy inhibitors block autophagy and aggravate the damage to the reproductive functions. Therefore, elucidating the role of autophagy in the occurrence, development, and regulation of VC may provide additional therapeutic options for men with infertility and VC. In this review, we briefly describe the progress made in autophagy research in the context of VC.

The role of fundamental movement skills on children's physical activity during different segments of the school day.

BACKGROUND: Although prior studies have demonstrated that children with high levels of fundamental movement skill (FMS) are more active throughout the day, little is known about children's FMS and their physical activity (PA) during different segments of the school day (e.g., recess, lunch break, and physical education). The present study focused on FMS and moderate-to-vigorous PA (MVPA) during school day and identifies the association between children's FMS and MVPA during different segments of the school day in China. METHODS: A total of 322 children (boys n = 163, girls n = 159; Mage = 8.12, SD = 1.22 years) from four elementary schools involved in this study. Children's FMS and MVPA were measured using the Test of Gross Motor Development-2nd edition (TGMD-2) and hip-mounted accelerometers. Data such as height, weight, and socio-economic status (SES) were also obtained. Multilevel mixed regression models were used to examine the cross-sectional associations between FMS and MVPA. Models were adjusted for gender, age, standardized body mass index, and SES. RESULTS: Children engaged in 32.19 min of MVPA during the whole school day. Boys were more active than girls and had higher object-control skills competency. Locomotor skills were positively associated with children's long recess (B = 1.063) and short recess time (B = 1.502) MVPA. Object-control skills were positively correlated with children's MVPA time during long recess (B = 1.244) and physical education (PE) lessons (B = 1.171). CONCLUSION: The findings highlight the importance of developing both locomotor and object-control skills in elementary schools to lead more MVPA engagement during different segments of the school day.

Patients with Hemophagocytic Lymphohistiocytosis Who Need Intensive Care Can Be Successfully Rescued by Timely Using Etoposide-Based HLH Regimens.

Background: Hemophagocytic lymphohistiocytosis (HLH) patients who need intensive care usually have multiple organ failure and poor prognosis. However, the clinical characteristics, therapeutic efficacy and outcome in these critically ill HLH patients have remained unclear. Methods: We performed a retrospective study of 50 critically ill HLH patients from September 2013 to October 2022. Patients' information was collected, and the overall survival rate was estimated. Results: Fifty HLH patients need intensive care, and the median sequential organ failure assessment (SOFA) score was 8. 66.00% patients had septic shock, 60.00% had disseminated intravascular coagulation (DIC) and 56.00% had acute respiratory distress syndrome (ARDS). 64.00% patients needed vasoactive drugs, 60.00% needed invasive or non-invasive positive pressure mechanical ventilation, and 12.00% needed continuous renal replacement therapy (CRRT). Among 18 patients received the etoposide-based regimens, the median time for 17 patients to remove ECG monitoring was 13 days (4-30 days); the median time to remove respiratory support in 10 patients was 8.5 days (4-21 days); the median time for 5 patient to convert from dominant DIC to non-dominant DIC was 4 days (1-14 days) and the median time for 6 patients to stop using vasoactive drugs was 10 days (2-14 days). After 4 weeks of treatment, 7 patients were evaluated as NR, 6 achieved PR, and 5 could not be evaluated. The ORR was 55.56%. Up to the last follow-up, the OS rate of patients receiving etoposide-based regimens was 66.67%. In contrast, all 32 HLH patients in other groups died. Univariate analysis showed that PCT > 0.5 ug/L, PT prolonged > 6 s, TBil > 25umol/L, respiratory failure, renal failure, liver failure and did not receive etoposide- based regimens were the negative factors affecting survival (P = 0.001, 0.017, 0.043, 0.001, 0.000, 0.029, 0.000). Conclusion: HLH patients who need intensive care timely used etoposide-based HLH regimens might rescue critically ill patients successfully.

Association of 24hour movement behaviors with emotional and behavioral problems among left-behind children / 中国学校卫生

Objective@#To examine the association of 24 hour movement behaviors with emotional and behavioral problems among left behind children, so as to provide a theoretical reference for the practice of 24 hour activity interventions to promote emotional and behavioral problems in this population.@*Methods@#From February to May 2023, 1 117 left behind children in grades 4-6 from 10 primary schools in five cities in Zhejiang Province were selected using a convenient cluster sampling method to conduct a questionnaire survey examining 24 hour movement behaviors, as well as emotional and behavioral problems. The general linear model was adopted to analyze the association between satisfying the 24 hour movement behavior guidelines, and emotional and behavioral problems among left behind children.@*Results@#The sleep duration compliance rate was the highest (52.19%), while the moderate-to-vigorous PA (MVPA) compliance rate was the lowest (17.73%). The compliance rate of the three activities accounted for 7.43 %. There was a dose response between the number of guidelines satisfied, and the emotional and behavior of left behind children; that was, satisfaction of a higher number of guidelines was associated with a lower risk of emotional and behavioral problems among left behind children (difficulty factor: β=-0.56, 95%CI =-1.23--0.19; strength factor: β=0.50, 95%CI =-0.48-1.22, P < 0.01). Compared to satisfying none of the guidelines, satisfying the guidelines for screen time ( β=-0.23, 95%CI =-2.18- -0.14 ) and sleep duration ( β=-0.13, 95%CI =-1.66--0.11) was negatively correlated with the difficulty factor, while satisfying the guideline for MVPA ( β=0.13, 95%CI =0.09-1.08) and sleep duration ( β=0.18, 95%CI =0.09-1.40) was positively associated with the strength factor. In addition, satisfying two or all three of the guidelines was more strongly associated with these outcomes than satisfying one of the recommendations ( P <0.01).@*Conclusions@#Meeting the 24 hour movement behavior guidelines can improve emotional and behavioral problems among left behind children. It is necessary to raise their awareness of the effect of satisfying the 24 hour movement behavior guidelines and formulate comprehensive intervention measures.

[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Chidamide, Decitabine, Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study from a Single-Center.

OBJECTIVE: Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. METHODS: Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). RESULTS: A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). CONCLUSIONS: The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.

[Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma].

OBJECTIVE: To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed. RESULTS: APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively. CONCLUSION: The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.

Low-Voltage Solution-Processed Zinc-Doped CuI Thin Film Transistors with NOR Logic and Artificial Synaptic Function.

Low-voltage Zn-doped CuI thin film transistors (TFTs) gated by chitosan dielectric were fabricated at a low temperature. The Zn-doped CuI TFT exhibited a more superior on/off current ratio than CuI TFT due to the substitution or supplementation of copper vacancies by Zn ions. The Zn-doped CuI films were characterized by scanning electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy. The Zn-doped CuI TFTs exhibited an on/off current ratio of 1.58 × 104, a subthreshold swing of 70 mV/decade, and a field effect mobility of 0.40 cm2V-1s-1, demonstrating good operational stability. Due to the electric-double-layer (EDL) effect and high specific capacitance (17.3 µF/cm2) of chitosan gate dielectric, Zn-doped CuI TFT operates at a voltage below -2 V. The threshold voltage is -0.2 V. In particular, we have prepared Zn-doped CuI TFTs with two in-plane gates and NOR logic operation is implemented on such TFTs. In addition, using the ion relaxation effect and EDL effect of chitosan film, a simple pain neuron simulation is realized on such a p-type TFTs for the first time through the bottom gate to regulate the carrier transport of the channel. This p-type device has promising applications in low-cost electronic devices, complementary electronic circuit, and biosensors.

A novel prognosis-prediction model based on coagulation indicators in secondary hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In the present retrospective study, we aimed to investigate coagulation disorders and their outcome implications in patients with secondary HLH. We evaluated clinical characteristics and the relationship between coagulation indices and prognosis in HLH patients (n = 141). The information, including clinical symptoms, laboratory indicators, and coagulation indices, was evaluated. Coagulation disorders and bleeding events occurred in 95 (67.4%) and 60 (42.6%) patients, respectively. A coagulation index analysis primarily showed elevated levels of D-Dimer, the international standardized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), while the prothrombin activity, fibrinogen levels, and platelet levels were significantly decreased. Dominant disseminated intravascular coagulation (DIC) occurred in 76 patients (53.9%). Patients with lymphoma-associated hemophagocytic syndrome (LAHS) frequently exhibited apparent coagulation disorders. Multivariate analysis revealed that age ≥ 29.5 years, bleeding events, APTT ≥ 47.3 s, fibrinogen ≤ 1.68 g/L, and absolute neutrophil counts (ANC) of ≤ 1.21 × 109/L were independent prognostic factors. We thereby devised a prognostic scoring system and stratified patients into low-risk (0-2 points), intermediate-risk (3-4 points), and high-risk (5-7 points) groups, and the 1-year overall survival rates in the above-mentioned groups were 66.40%, 40.00%, and 2.30%, respectively (P < 0.0001). In conclusion, coagulation dysfunctions and bleeding tendencies were common characteristics in HLH patients. We constructed a novel prognostic score model based on APTT, fibrinogen level, ANC, age, and bleeding events, which had superior prognostic value compared with these markers alone.

Effects of different exercise modalities and intensities on body composition in overweight and obese children and adolescents: a systematic review and network meta-analysis.

Introduction: Childhood and adolescent overweight and obesity are global public health issues. Previous studies on exercise and overweight and obese children have produced inconsistent findings and lacked comparisons between different exercise modalities and intensities. Therefore, a network meta-analysis is necessary to provide evidence-based intervention programs. This study aims to identify the effects of different exercise modalities and intensities on changes in body composition in overweight and obese children and adolescents. Methods: A search for randomized controlled trials was conducted on Web of Science, PubMed, Scopus, and Embase involving exercise interventions aimed at improving body composition (body fat percentage, BMI, fat mass, fat-free mass, body weight) in overweight and obese children and adolescents. A random effects network meta-analysis was performed using STATA 14.0 software within a frequentist framework. The literature quality was assessed using the Cochrane Risk of Bias Tool 2.0. Results: Thirty-two papers involving 1,452 participants were included. There were six types of intervention involved in the study, including moderate intensity aerobic exercise, high-intensity aerobic exercise, moderate intensity resistance exercise, high-intensity resistance exercise, moderate intensity combined exercise, and high-intensity combined exercise. The network meta-analysis results revealed that high-intensity combined exercise was the best exercise mode for improving BMI [mean difference in kg/m2 = -1.65, 95% CI (-3.27, -0.02)] and reducing fat mass [mean difference in kg = -2.87, 95% CI (-4.84, -0.91)]. Moderate intensity combined exercise was the best mode for weight loss [mean difference in kg = -4.58, 95% CI (-5.94, -3.22)] and improvement in body fat percentage [mean difference in% = -2.52, 95% CI (-3.83, -1.20)]. High-intensity resistance exercise had the optimal effect in increasing fat-free mass [mean difference in kg = 1.10, 95% CI (0.22, 1.99)]. Conclusion: In conclusion, the study found that combined exercise, whether moderate or high intensity, was more effective than any other exercise modality in improving body fat percentage and BMI, reducing fat mass and weight. Resistance exercise was the most effective in increasing fat-free mass.

[Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores].

OBJECTIVE: To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers. METHODS: One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis. RESULTS: The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis. CONCLUSION: The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Effects of fundamental movement skills on health-related quality of life in Chinese school-age children: the mediating role of physical fitness level.

Background: The primary purpose of this study is to analyze the relationship between school-age children's fundamental movement skills (FMS), physical fitness levels, and the health-related quality of life (HRQoL); To explore the mediating role of physical fitness levels between school-age children's FMS and HRQoL. Methods: In the cross-sectional survey in 2021, 334 school-age children aged 6-10 (8.20 ± 1.16) were recruited from primary schools in Jinhua City, Zhejiang Province, China. Test of Gross Motor Development 2 (TGMD-2), National Standards for Students' Physical Health, and Pediatric Quality of Life Inventory TM Version 4.0 (PedsQL™ 4.0) were used to investigate the FMS, physical fitness level, and HRQoL of school-age children. Hierarchical regression was used to analyze the relationship among FMS, physical fitness levels, and HRQoL. Bootstrap is used to evaluate the mediating role of physical fitness levels in the relationship between FMS and HRQoL. Results: The higher the FMS and physical fitness, the higher the school-age children's HRQoL, physical functioning, social functioning, and school functioning (r = 0.244-0.301, p < 0.01). In addition, developing children's FMS promotes physical fitness levels (r = 0.358, p < 0.01). The regression analysis results of controlling gender, age, and body mass index z (BMI-z) scores showed that FMS significantly positively predicted the physical functioning (ß = 0.319, p < 0.01), social functioning (ß = 0.425, p < 0.01), and school functioning (ß = 0.333, p < 0.01) of school-age children. When the physical fitness level enters the regression equation, the absolute value of the regression coefficient of FMS decreases. However, it can still significantly predict the physical functioning (ß = 0.211, p < 0.01) and school functioning (ß = 0.142, p < 0.05) of school-age children. Simple intermediary analysis shows that physical fitness level plays an intermediary role between FMS, physical functioning (indirect effect = 0.089 [95% Confidence interval (CI) = 0.015,0.195]), and school functioning (indirect effect = 0.065 [95% CI = 0.007,0.150]). Conclusion: This study shows that physical fitness levels mediate the relationship between FMS and HRQoL. Encouraging the development of FMS and promoting physical fitness levels of school-age children can effectively improve the HRQoL of school-age children.

Enzyme-Catalyzed Hydrogen-Deuterium Exchange between Environmental Pollutants and Enzyme-Regulated Endogenous Metabolites.

Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D38-bis(2-ethylhexyl) phthalate (D38-DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A2 (PLA2)], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D38-DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D38-DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA2, and this process mediated H-D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.

[Research Progress of Allogeneic Hematopoietic Stem Sell Trans-plantation in the Treatment of Adult Hemophagocytic Lympho-histiocytosis --Review].

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.

Associations between 24-h movement behaviours and BMI in Chinese primary- and middle- school students.

Purposes: This cross-sectional study aimed to examine the associations between the 24-h movement behaviours and body mass index (BMI) of students from China by using compositional data analysis. Methods: A total of 389 students aged 6-16 years participated in this study. Accelerometers were used to measure moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SED), and sleep. Weight and height were objectively measured. The association between 24-h movement and BMI was analyzed by using compositional data analysis. Results: Time reallocation using minutes and proportions created major differences to the results. Reallocating 10 min from other movement behaviours to MVPA was associated with decreased BMI z-score of 1.372 to 0.158 among primary-school students. Reallocating 10 min from sleep and SED to MVPA, and from sleep and SED to LPA were associated with decreased BMI z-score of 0.505 to 0.017 among middle-school students. Reallocating 10% of time from all other components to SED and sleep were associated with a higher BMI z-score by 0.148 (95%CI: 0.020; 0.276) and 0.125 (95%CI: 0.046; 0.204), while reallocating time to MVPA was associated with a decrease in BMI z-scores of 0.132 (95%CI: -0.193; -0.070) among primary-school students. Reallocating 10% of time from all other components to SED was associated with a higher BMI z-score of 0.254 (95%CI: 0.165; 0.345), whereas reallocating time to MVPA and LPA was associated with a decrease in BMI z-scores of 0.039 (95%CI: -0.073; -0.005) and 0.093 (95%CI: -0.153; -0.033) among middle-school students. Conclusion: Research results of 10-min one-to-one reallocation may be treated cautiously due to uneven distribution of time in 24-h movement behaviours. Based on the results of 10% one-to-remaining reallocation, replacing SED with MVPA may be an appropriate target for adiposity intervention in primary-school students, while increasing MVPA or LPA at the expense of SED may be effective in controlling adiposity of middle-school students in China.

Molecular docking and in vitro evaluations reveal the role of human cytochrome P450 3A4 in the cross-coupling metabolism of phenolic xenobiotics.

Metabolism generally transforms xenobiotics into more polar and hydrophilic products, facilitating their elimination from the body. Recently, a new metabolic pathway that transforms phenolic xenobiotics into more lipophilic and bioactive dimer products was discovered. To elucidate the role of cytochrome P450 (CYP) enzymes in mediating this cross-coupling metabolism, we used high-throughput screening to identify the metabolites generated from the coupling of 20 xenobiotics with four endogenous metabolites in liver microsomes. Endogenous vitamin E (VE) was the most reactive metabolite, as VE reacted with seven phenolic xenobiotics containing various structures (e.g., an imidazoline ring or a diphenol group) to generate novel lipophilic ethers such as bakuchiol-O-VE, phentolamine-O-VE, phenylethyl resorcinol-O-VE, 2-propanol-O-VE, and resveratrol-O-VE. Seven recombinant CYP enzymes were successfully expressed and purified in Escherichia coli. Integration of the results of recombinant human CYP incubation and molecular docking identified the central role of CYP3A4 in the cross-coupling metabolic pathway. Structural analysis revealed the π-π interactions, hydrogen bonds, and hydrophobic interactions between reactive xenobiotics and VE in the malleable active sites of CYP3A4. The consistency between the molecular docking results and the in vitro human cytochrome P450 evaluation shows that docking calculations can be used to screen molecules participating in cross-coupling metabolism. The results of this study provide supporting evidence for the overlooked toxicological effects induced by direct reactions between xenobiotics and endogenous metabolites during metabolic processes.

The Effectiveness of Video Decision Aid on Advance Care Planning With Adult Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The purpose of this review was to examine the effect of video decision aids on adult patients' advance care planning-related outcomes. Seven English electronic databases (PubMed, Cochrane, MEDLINE, EMBASE, PsycINFO, CINAHL, OpenGray) and 3 Chinese databases (CNKI, WanFang, and VIP) were searched to identify relevant studies. Fourteen randomized controlled trials were included. The results of the meta-analysis showed that video decision aids reduced patients' preferences for life-prolonging care (risk ratio [RR], 0.43; 95% confidence interval [CI], 0.31-0.61; P < .01), cardiopulmonary resuscitation (RR, 0.54; 95% CI, 0.46-0.64; P < .01), and intubation tube placement (RR, 1.65; 95% CI, 1.09-2.48; P = .02) and increased patients' willingness to have a goals-of-care conversation (RR, 1.87; 95% CI, 1.32-2.65; P = .0004) and knowledge of advance care planning (RR, 0.80; 95% CI, 0.50-1.09; P < .01). However, because of the variability among the studies, the results have limitations. Future research needs to increase the sample size and improve the experimental design to confirm the impact of video decision aids on advance care planning.

Component analysis of relationship between 24 hour movement behavior and physical fitness in college students / 中国学校卫生

Objective@#To explore the relationship between 24 hour movement behavior and physical fitness in college students, so as to provide a reference for physical fitness interventions for college students.@*Methods@#A survey was conducted from September 23 to November 12, 2022, involving 342 college students selected from one comprehensive college among Shanghai City, Hubei Province and Zhejiang Province. Accelerometers were used to measure 24 hour movement behavior, and programs specified in the National Physical Fitness Standards for Students (2014 revision) were used to evaluate physical fitness. Compositional linear regression was used to analyze the association between 24 hour movement behavior and physical fitness. The effects of compositional isotemporal substitution of 24 hour movement behavior on physical fitness were also examined.@*Results@#The geometric means for sleep, sedentary behavior, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 515.89, 678.88 , 196.30, 48.92 min/d, respectively, and the comprehensive physical fitness score was (73.09±8.55). The proportion of participants who passed the fitness test was 72.51%. Overall, 20.76% had excellent or good scores, whereas 6.73% failed. Compositional linear regression indicated that physical fitness was significantly positively associated with MVPA ( β =2.55) and LPA ( β = 5.88 )( P <0.05), but no significantly associated with sleep ( β =-5.18) and sedentary behavior ( β =-3.24)( P >0.05). Isotemporal substitution indicated that reallocation of 15 minutes from sleep and sedentary behavior to MVPA resulted in a 0.71 and 0.64 point increase in physical fitness, respectively. Similarly, reallocating the same duration to LPA led to a 0.50 and 0.43 point increase in physical fitness, respectively. Dose response analysis revealed that the mutual substitution of LPA with sedentary behavior and sleep had symmetry, whereas the mutual substitution of MVPA with sedentary behavior and sleep had asymmetry. The effectiveness of replacing sleep or sedentary behavior with MVPA in improving physical fitness decreased with increasing allocation time, whereas the adverse effects of replacing MVPA with sleep or sedentary behavior increased with increasing allocation time.@*Conclusion@#In the context of 24 hour movement behavior, increasing the time spent on LPA and MVPA is beneficial for physical fitness among college students. It should be recommend that college students actively transition from sedentary behavior to engaging in physical activity, with a particular emphasis on incorporating MVPA.