Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female

Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Purpose: Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and Methods: In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization’s (WHO’s) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, in vitro embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI. Results: Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and high-quality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045). Conclusions Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.

OBJECTIVE To study the effects of the active component 17-hydroxy-jolkinolide B （HJB） of Euphorbia fischeriana on the proliferation and apoptosis of human triple-negative breast cancers （TNBC） MDA-MB-231 and MDA-MB-468 cells. METHODS MTT assay was adopted to detect the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation after treated with 0 （blank control），5，10，20，40，80 μmol/L HJB for 24， 48 and 72 h. Laser confocal microscope and flow cytometry were adopted to detect the apoptosis， mitochondrial membrane potential（MMP） and reactive oxygen species （ROS） of above 2 kinds of cells after treated with 0 （blank control）， 10，20，40 μmol/L HJB for 24 h. Western blot assay was used to detect the expressions of B cell lymphoma-2（ Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome-C （Cyt-C）， caspase-3， cleaved caspase- 3， caspase-9 and cleaved caspase-9. RESULTS Compared with blank control group， 5，10，20，40，80 μmol/L HJB could significantly increase the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation （P＜0.05）， in dose- and time- dependent trend. After 24 h treatment of HJB （10，20，40 μmol/L）， the apoptosis of above 2 kinds of cells increased， and the total apoptotic rate increased significantly （P＜0.05）； the mitochondrial membrane potential decreased significantly （P＜0.05）； the level of ROS increased significantly （P＜0.05）； the protein expressions of Bcl-2， caspase-3 and caspase-9 were decreased significantly （P＜ 0.05）， while the protein expressions of Cyt-C， Bax， cleaved caspase-3 and cleaved caspase-9 were increased significantly （P＜0.05）. CONCLUSIONS HJB can inhibit the proliferation of MDA-MB-231 and MDA-MB-468 cells， and induce their apoptosis.

Objective:To explore the effects of different feeding patterns on weight gain and feeding intolerance in hospitalized premature infants.Methods:The retrospective cohort study design was adopted. From April 2019 to October 2020, 155 premature infants admitted to the Neonatal Intensive Care Unit of China-Japan Friendship Hospital were selected as the study subject by convenience sampling. Premature infants were divided into a mixed feeding group ( n=47) and a formula milk feeding group ( n=108) based on their feeding patterns. The observation indicators included weight gain, feeding intolerance, infectious diseases, nutrition and other related indicators. Results:The weight change value and the weight change rate during hospitalization in the mixed feeding group were higher than those in the formula milk feeding group, with statistically significant differences ( P<0.05) . In terms of the total milk volume on the day of discharge, the mixed feeding group were higher than the formula milk feeding group, and the differences were statistically significant ( P<0.05) . During hospitalization, the number of new infectious diseases in the mixed feeding group was less than that in the formula milk feeding group, with a statistically significant difference ( P<0.05) . There was no statistically significant difference in the incidence of feeding intolerance between the two groups of premature infants ( P>0.05) , The incidence of vomiting in the formula milk feeding group was lower than that in the mixed feeding group, with a statistically significant difference ( P<0.05) . Conclusions:Mixed feeding is more conducive to promoting the weight gain of premature infants during hospitalization and reducing the occurrence of infectious diseases than formula milk feeding. The impact of two feeding patterns on feeding intolerance in hospitalized premature infants needs further comparative analysis.

Objective:To summarize the characteristics of genetic variation and prenatal diagnosis in pedigrees with X-linked adrenoleukodystrophy (X-ALD) and elucidate the value of prenatal diagnosis in preventing the birth of children with X-ALD.Methods:Twenty pedigrees, clinically diagnosed with X-ALD in Peking University First Hospital from November 2012 and March 2019, were included in this retrospective study. Genomic DNA was extracted from peripheral blood and amniotic fluid or chorionic villi samples of probands and their families for detecting variants in ATP-binding cassette subfamily D member 1 ( ABCD1) gene using polymerase chain reaction (PCR)-Sanger sequencing. Linkage analysis was also performed on five microsatellite markers near ABCD1 gene to exclude maternal contamination. Characteristics of ABCD1 gene variants and prenatal diagnosis of X-ALD pedigrees were summarized by descriptive statistics. Results:Twenty ABCD1 gene variants were identified in the 20 pedigrees. The variants in three probands that were not detected by next-generation sequencing were identified by PCR-Sanger sequencing. Among the mothers of the 20 probands, 17 carried ABCD1 variants and three did not. We performed 24 prenatal diagnoses on 20 pregnancies (24 fetuses) and identified eight fetuses with variants who were finally terminated. The 16 cases without variants were born alive. The validation results obtained after termination or delivery were consistent with those performed prenatally. Conclusions:No hotspot variants in ABCD1 gene are detected in these X-ALD patients and most variants are maternally inherited. PCR-Sanger sequencing is an effective method for detecting ABCD1 variants. Prenatal diagnosis for mothers who had a body with X-ALD could prevent another one from birth.

Objective:To investigate the effect of polyethylene glycol combined with simethicone on boston bowel preparation scale(BBPS) score and tolerance in patients with colonoscopy.Methods:From January 2018 to January 2019, 220 patients who underwent colonoscopy in Beijing Shijitan Hospital Affiliated to Capital Medical University were selected as the research objects.According to different bowel preparation schemes, they were divided into control group and observation group, 110 cases in each group.In the control group, 4 bags of compound polyethylene glycol electrolyte powder were added with cold boiled water to prepare 4 L solution for intestinal preparation.Starting 6 hours before endoscopy, 1 L solution was taken every hour, and the interval from the last time to the beginning of colonoscopy was≤4 h. On the basis of the control group, the observation group was given 30 mL simethicone emulsion 4 hours before endoscopy on the basis of the control group.The BBPS score, intracavitary liquid volume score, total score, tolerance and adverse reactions were compared between the two groups.Results:The whole colon score (7.16±0.61), left colon score (2.89±0.62), transverse colon score (2.78±0.64) and right colon score (1.58±0.49), intestinal cavity fluid score (1.47±0.48) and total score (8.84±0.87) of the observation group were higher than those of the control group ((5.13±0.76), (2.23±0.86), (2.15±0.76), (1.14±0.16), (0.91±0.55), (7.11±1.04)), and the differences were statistically significant ( t=21.854, 6.532, 6.652, 8.957, 8.054, 13.380, all P<0.05). The tolerance of the observation group (90.00%(99/110)) was higher than that of the control group (81.81%(90/110)), but the difference was not statistically significant( χ 2=3.043, P=0.081). The incidence of abdominal distension in the observation group (1.82%(2/110)) was lower than that in the control group (8.18%(9/110)), the difference was statistically significant(χ 2=4.690, P<0.05), and there was no significant difference in the incidence of electrolyte disorder, nausea and vomiting, hypoglycemia or hunger, palpitation and chest tightness between the two groups (all P>0.05). Conclusion:The application of polyethylene glycol combined with Spanish silicone oil in intestinal preparation can improve the intestinal cleanliness of patients, but does not increase the tolerance of patients compared with polyethylene glycol alone, but significantly reduces the incidence of abdominal distension.

Objective:To examine the mid- and long-term outcomes of endovascular aneurysm repair (EVAR).Methods:This was a retrospective cohort study of 540 patients with abdominal aortic aneurysm who received EVAR at Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University from January 2009 to December 2018. There were 503 males and 37 females, aged of (69±8) years (range: 44 to 87 years). Clinical data including concomitant disease, aneurysm size and surgical data were collected and patients were followed up after operation. The cumulative survival rate was assessed using the Kaplan-Meier estimator and multivariate Cox regression was used to analyze the independent prognosis factors.Results:The technical success rate was 91.1% (492/540). The perioperative mortality rate was 1.3% (7/540) and the follow-up rate was 91.7% (489/533). The median follow-up time was 45(63) months (range: 1 to 133 months). The all-cause mortality rate was 21.3% (104/489) and the aneurysm-related mortality rate was 6.3% (31/489) during follow-up period. The overall cumulative survival rate of 1-, 3-, 5- and 10-year were 95.1%, 84.0%, 69.5% and 38.6%, respectively, while freedom from aneurysm-related death were 98.4%, 93.3%, 88.4% and 84.4%. During the follow-up period, the complications rate was 9.0% (44/489), and the re-intervention rate was 4.9% (24/489). Cox regression analysis showed that elder age ( HR=2.15, 95 %CI: 1.41 to 3.26, P<0.01), preoperative aneurysm rupture ( HR=2.72, 95 %CI: 1.78 to 4.15, P<0.01) and short neck aneurysm ( HR=1.97, 95 %CI: 1.07 to 3.61, P=0.029) were independent prognosis factors for long-term survival after EVAR. Connclusion:EVAR has low perioperative mortality, high technical success rate, and satisfactory mid-and long-term outcomes.