Ti3C2 nanosheet-induced autophagy derails ovarian functions.

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. RESULTS: We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. CONCLUSION: Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells.

Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and ZEB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo. In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy.

Association between systemic lupus erythematosus and inflammatory bowel disease in European and East Asian populations: a two-sample Mendelian randomization study.

Background: Previous studies have shown a coexistence phenomenon between systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), but the causal relationship between them is still unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary statistics data to evaluate whether there was a causal relationship between the two diseases. Methods: Summary statistics for SLE and IBD were downloaded from the Open Genome-Wide Association Study and the International Inflammatory Bowel Disease Genetics Consortium. European and East Asian populations were included in this MR work. We adopted a series of methods to select instrumental variables that are closely related to SLE and IBD. To make the conclusion more reliable, we applied a variety of different analysis methods, among which the inverse variance-weighted (IVW) method was the main method. In addition, heterogeneity, pleiotropy, and sensitivity were assessed to make the conclusions more convincing. Results: In the European population, a negative causal relationship was observed between SLE and overall IBD (OR = 0.94; 95% CI = 0.90, 0.98; P < 0.004) and ulcerative colitis (UC) (OR = 0.93; 95% CI = 0.88, 0.98; P = 0.006). After removing outliers with Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), the results remained consistent with IVW. However, there was no causal relationship between SLE and Crohn's disease. In the East Asian population, no causal relationship was found between SLE and IBD. Conclusion: Our results found that genetic susceptibility to SLE was associated with lower overall IBD risk and UC risk in European populations. In contrast, no association between SLE and IBD was found in East Asian populations. This work might enrich the previous research results, and it may provide some references for research in the future.

Perinatal Outcomes and Related Risk Factors of Single vs Twin Pregnancy Complicated by Gestational Diabetes Mellitus: Meta-Analysis.

Objective: Perinatal outcomes and related risk factors of single vs twin pregnancy complicated with gestational diabetes mellitus (GDM) were clarified, providing evidence for developing preventive measures. Methods: The Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), CQVIP, Wanfang, and PubMed databases were searched for published research on the perinatal outcomes and risk factors of single and twin pregnancy complicated by GDM from 2000 to 2021. The quality of the included literature was evaluated according to the Newcastle-Ottawa Scale (NOS). Meta-analysis of the included literature was conducted using RevMan5.3 software. Results: Relative to a single pregnancy group, infertility, gestational weight gain, and family history of diabetes presented statistical significance in the twin pregnancy group (P < 0.05); gestational age at delivery, cesarean section, preterm birth < 37 weeks, and preeclampsia presented statistical significance in the twin pregnancy group (P < 0.05); and neonatal birth weight, small for gestational age (SGA), neonatal asphyxia, neonatal hypoglycemia, neonatal respiratory distress syndrome (NRDS), neonatal hyperbilirubinemia, and neonatal death presented statistical significance in the twin pregnancy group (P < 0.05). Conclusion: Infertility, prenatal weight gain, and diabetes in the family are all risk factors for postpartum impaired glucose metabolism in pregnant women with GDM who are carrying twins. The gestational age at delivery, cesarean section, preterm birth < 37 weeks, and preeclampsia of twin pregnant women with diabetes will affect the perinatal status of twin pregnant women. Neonatal birth weight, SGA, neonatal asphyxia, neonatal hypoglycemia, NRDS, neonatal hyperbilirubinemia, neonatal death, etc. should be paid special attention in the perinatal process.

Pre-pregnancy BMI was associated with gestational depressive phenotypes in a population of 12,099 women in Chongqing, China.

Objective: To investigate the association between pre-pregnancy body mass index (BMI) and gestational depressive phenotypes. Methods: The pregnant women receiving the first prenatal examination (4th -13th week of gestation) in Chongqing Health Center for Women and Children were recruited between February 2020 and September 2021. Depressive phenotypes was assessed by the Patient Health Questionnaire (PHQ-9) and the Symptom Checklist 90 (SCL-90) scale at recruitment. Pre-pregnancy weight and height were self-reported by the participants. Demographic and obstetric characteristics were obtained from the hospital information system. The association between pre-pregnancy BMI and the scores of PHQ-9 or SCL-90 scale was investigated by uni-variate analysis with Kruskal-Wallis test and by multi-variate analysis with linear regression model with adjustment of age, parity, smoking, alcohol consumption, and assisted reproduction. The association between pre-pregnancy BMI and PHQ-9 or SCL-90 diagnosed depressive phenotypes was analyzed by Chi-square test and logistic regression respectively. Results: A total of 12,099 pregnant women were included, where 100% of them filled out the PHQ-9 scale and 99.6% filled out the SCL-90 scale, and 47.26% and 4.62% of the pregnant women had depressive phenotypes, respectively. Women with higher pre-pregnancy BMI had lower depressive phenotypes scores during pregnancy. Multivariable analysis of the PHQ-9 scale showed that overweight/obese subjects had a higher incidence of depressive phenotypes compared with subjects with normal BMI (OR=0.803, 95% CI [0.723, 0.892]). In a stratified analysis assessed by the PHQ-9, women who were overweight/obese prior to pregnancy were less likely to develop depressive phenotypes during pregnancy than women who were normal weight prior to pregnancy, regardless of whether they were nulliparous (OR=0.795, 95%CI[0.696,0.908]) or multiparous (OR=0.809, 95%CI[0.0.681,0.962]), while in the three age groups of 25-29 years, 30-34 years and ≥35 years, pre-pregnancy overweight/obesity were associated with lower risk of gestational depressive phenotypes. However, analysis of the SCL-90 scale showed no statistical association between depressive symptom and BMI. No substantial interaction was observed between BMI and parity or age. Conclusions: Increased pre-pregnancy BMI may be associated with reduced risk of gestational depressive phenotypes in Chinese women. Independent studies are warranted to validate the findings of the present study.

[Diagnostic Value of HBA2 in Different Types of Thalassemia].

OBJECTIVE: To explore the diagnostic value of HBA2 in different types of thalassemia by analyzing the sensitivity and missed diagnosis rate of HBA2 in different types of thalassemia. METHODS: 1 178 couples in the department of women's health of Chongqing maternal and child health hospital were selected for pregnancy examination. Peripheral venous blood was extracted and analyzed for parallel blood routine test, hemoglobin capillary electrophoresis and thalassemia gene detection. RESULTS: A total of 265 cases of thalassemia gene carriers were screened out in 1 178 couples； 91.3% ß0 heterozygous thalassemia and 94.74% ß+ heterozygous thalassemia could be screened out using HBA2 > 3.5% as cut-off value; 30.19% stationary α-thalassemia and 66.07% standard α-thalassemia could be screened out using HBA2 < 2.5% as cut-off value. The rate of missed diagnosis of α-thalassemia and ß-thalassemia was 47% and 1.01% respectively when the blood routine screening is positive. CONCLUSION: HBA2 shows different diagnostic value for different types of α-thalassemia and ß-thalassemia. The sensitivity of HBA2 > 3.5% is higher than that of HBA2 < 2.5%. More attention should be paid to the further screening of patients with normal electrophoresis results when the blood routine screening is positive.

[Prevalence and Genotypes Analysis of Thalassemia Among People of Reproductive Age in Yuzhong District of Chongqing Based on Next-Generation Sequencing].

OBJECTIVE: To investigate the prevalence and gene distribution of thalassemia among people at reproductive age in yuzhong district, Chongqing. METHODS: 1000 pre -pregnancy examination couples in yuzhong district were investigated. Peripheral venous blood was extracted and next-generation sequencing was used to screen the thalassemia genes. RESULTS: Among the 1000 pregnant couples, the thalassemia gene carrying rate was 7.45%, the carrying rate of α and ß thalassemia genes were 4.60% and 2.10%, respectively. The most common α thalassemia genotypes in αα/-α3.7 (53.26%), αα/--SEA (23.91%), αα/-α4.2 (11.96%); and the most common genotypes in ß thalassemia genotypes were mainly Codons17 (A＞T) (26.19%)、Condon41/42 (-TTCT) (26.19%)、IVS-II-654 (C＞T) (14.29%) At the same time, 3 cases of α and ß complex thalassemia and 3 pairs of homotypic thalassemia genes were detected, more over, 12 cases of 5 new genes were found. CONCLUSION: Yuzhong district of Chongqing is a high incidence area of thalassemia, and the diversity of gene mutation types is relatively rich. Screening for thalassemia before pregnancy is of great significance to improve the quality of population.

[Comparision of the Efficacy of Different Thalassemia Screening Strategies Used for the Couple of Pre-Pregnancy in Yuzhong District of Chongqing City].

OBJECTIVE: To compare the efficacy of different thalassemia screening strategies used for the couple of pre-pregnancy. METHODS: A total of 1 159 couples were recruited in Chongqing health center for women and children from January 2019 to June 2019. Routine blood test, hemoglobin test and thalassemia gene test were performed for all the coulpes. The efficacy of thalassemia screening strategies were compared. Strategy 1: Hemoglobin was tested if the woman's MCV <80 fl and/or MCH <27 pg, and test for thalassemia genes was required further according to the result of hemoglobin test. If the woman was a thalassemia carrier, it is recommended that the man would receive the corresponding thalassemia gene test, and if the man carried the same type of thalassemia gene, so it meant positive. Strategy 2: the woman's blood cut-off value was MCV<82 fl and/or MCH<27 pg, and the follow-up procedure was the same as strategy 1. Strategy 3: If both of cople showed MCV (<80 fl) and/or MCH (<27 pg), the couple would be tested for hemoglobin electrophoresis, and if both of the couple showed abnomal result of hemoglobin electrophoresis, the couple would be tested for thalassemia gene. If the couple carried the same thalassemia gene, it meant positive. Strategy 4: If one of the couple or both of them showed MCV (<80 fl) and/or MCH (<27 pg), the couple would be tested for hemoglobin electrophoresis, if the couple showed MCV (<80 fl) and/or MCH (<27 pg) and/or the abnormal result of hemoglobin test, genetic test for thalassemia test were performed. RESULTS: A total of 15 couples were thalassemia positive. According to the ROC curve, the area under the curve of strategy 2 was the largest but the cost was the highest. The area under the curve of strategy 4 was slightly less than that of strategy 2, but the cost was lower. CONCLUSION: Strategy 4 is recommended in the case of high degree of male cooperation and strategy 2 is recommended in the case of low degree of male cooperation.

Practice and service models of adolescent outpatient clinic / 中国学校卫生

Objective@#Practice of setting up campus clinics in school,to explore adolescent outpatient service mode to better meet the diversified demands of teenagers,and to promote more effective implementation of adolescent health care.@*Methods@#Campus-based adolescent outpatient clinics were established in 2 universities in Chongqing,a questionnaire survey was conducted among 136 students who participated in the consultation, campus-based outpatient services and adolescents’ satisfaction towards the services were analyzed. Hospital adolescent outpatient services were compared before and after the establishment of campus adolescent clinic.@*Results@#Most of adolescent outpatient clinic in hospitals offered disease-based treatment instead of consultation. The overall satisfaction rate was 94.85%, and the satisfaction towards service ability, communication skills, outpatient time arrangement, and privacy protection was 96.32%, 96.32%, 88.97% and 94.12%, respectively. After the establishment of campus adolescent outpatient clinics, adolescent outpatient services in hospital increased dramatically including consultation.@*Conclusion@#It is necessary to offer adolescent outpatient services in schools, which are more helpful for the diversified demands of teenagers.