Aim To study the effect of astragaloside (AS-Ⅳ) in CLP-induced septic mice.Methods C57BL/6 mice were randomly divided into the sham group, CLP group and CLP+ AS-Ⅳ group.Two days before operation, AS-Ⅳ (10 mg·kg-1) solution was intragastrically administered into CLP +AS-Ⅳ group, and the other groups were treated with normal saline.A sepsis model was established by cecal ligation and puncture (CLP).Blood, peritoneal fluid and tissue organs were collected at 6 h and 24 h.Neutrophils of blood were purified by Percoll density gradient.Transwell was used to detect the chemotaxis function of neutrophils.The killing activity of neutrophils was detected by coculture with E.coli.Results The survival rate of AS-Ⅳ-pretreated septic mice significantly increased.The number of neutrophils in peritoneal fluid was enhanced markedly.The number of bacteria in the peritoneal fluid, blood and tissue organs such as liver, lung and kidney significantly decreased after AS-Ⅳ pretreatment.The chemotaxis and killing activity of neutrophils increased significantly in AS-Ⅳ-treated mice (P<0.05).Conclusion Astragaloside displays an immunoprotective effect in CLP-induced septic mice, which is related to the upregulation of CXCR2 expression on neutrophils and the increase of neutrophil antibacterial activity.

The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P＜0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P＜0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P＜0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P＜0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P＜0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.

Objective:To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS).Methods:A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children′s Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results:The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses ( t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions:Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0％-2.5％per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.