A functional spectrum of PROKR2 mutations identified in isolated hypogonadotropic hypogonadism.

Isolated hypogonadotropic hypogonadism (IHH) is a rare disease with hypogonadism and infertility caused by the defects in embryonic migration of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, hypothalamic GnRH secretion or GnRH signal transduction. PROKR2 gene, encoding a G-protein coupled receptor PROKR2, is one of the most frequently mutated genes identified in IHH patients. However, the functional consequences of several PROKR2 mutants remain elusive. In this study, we systematically analyzed the Gαq, Gαs and ERK1/2 signaling of 23 IHH-associated PROKR2 mutations which are yet to be functionally characterized. We demonstrate that blockage of Gαq, instead of MAPK/ERK pathway, inhibited PROK2-induced migration of PROKR2-expressing cells, implying that PROKR2-related IHH results primarily due to Gαq signaling pathway disruption. Combined with previous reports, we categorized a total of 63 IHH-associated PROKR2 mutations into four distinct groups according Gαq pathway functionality: (i) neutral (N, >80% activity); (ii) low pathogenicity (L, 50-80% activity); (iii) medium pathogenicity (M, 20-50% activity) and (iv) high pathogenicity (H, <20% activity). We further compared the cell-based functional results with in silico mutational prediction programs. Our results indicated that while Sorting Intolerant from Tolerant predictions were accurate for transmembrane region mutations, mutations localized in the intracellular and extracellular domains were accurately predicted by the Combined Annotation Dependent Depletion prediction tool. Our results thus provide a functional database that can be used to guide diagnosis and appropriate genetic counseling in IHH patients with PROKR2 mutations.

SIGMAR1 targets AMPK/ULK1 pathway to inhibit SH-SY5Y cell apoptosis by regulating endoplasmic reticulum stress and autophagy.

Distal hereditary motor neuropathy (dHMN) is a progressive neurological disease characterized by distal limb muscle weakness and amyotrophy. Sigma 1 receptor (σ1R), a gene product of SIGMAR1, mutations have been reported to induce dHMN, but its mechanism remains unknown. This study aims to explore the effect of C238T and 31_50del mutations in σ1R on neuronal SH-SY5Y cell functions. The SH-SY5Y cells that overexpressed σ1R, C238T mutant σ1R (σ1RC238T) or 31_50del mutant σ1R (σ1R31_50del) were constructed by pEGFPN1 vectors. We used Western blot (WB) and immunofluorescence (IF) staining to detect the expression of σ1R and green fluorescent proteins (GFP). Then, we evaluated the impact of σ1R mutation on apoptosis, autophagy, endoplasmic reticulum stress, and the involvement of the unfolded protein response (UPR) pathway in SH-SY5Y cells. We found that σ1RC238T and σ1R31_50del downregulated σ1R and promoted the apoptosis of SH-SY5Y cells. σ1RC238T and σ1R31_50del increased p-PERK, p-eIF2α, p-JNK, BIP, ATF4, CHOP, ATF6, XBP1, Caspase3, Caspase12 expressions and Ca2+ concentration, whereas decreased ATP content in SH-SY5Y cells. Besides, the expressions of LC3B, Lamp1, ATG7, Beclin-1 and phosphorylation of AMPK and ULK1 were increased, while the p62 level decreased after C238T or 31_50del mutation of σ1R. Additionally, AMPK knockdown abolished the apoptosis mediated by σ1RC238T or σ1R31_50del in SH-SY5Y cells. Our results indicated that C238T or 31_50del mutation in σ1R promoted motor neuron apoptosis through the AMPK/ULK1 pathway in dHMN. This study shed light on a better understanding of the neurons pathological mechanisms mediated by σ1R C238T and σ1R 31-50del in dHMN.

Hypomorphic and hypermorphic mouse models of Fsip2 indicate its dosage-dependent roles in sperm tail and acrosome formation.

Loss-of-function mutations in multiple morphological abnormalities of the sperm flagella (MMAF)-associated genes lead to decreased sperm motility and impaired male fertility. As an MMAF gene, the function of fibrous sheath-interacting protein 2 (FSIP2) remains largely unknown. In this work, we identified a homozygous truncating mutation of FSIP2 in an infertile patient. Accordingly, we constructed a knock-in (KI) mouse model with this mutation. In parallel, we established an Fsip2 overexpression (OE) mouse model. Remarkably, KI mice presented with the typical MMAF phenotype, whereas OE mice showed no gross anomaly except for sperm tails with increased length. Single-cell RNA sequencing of the testes uncovered altered expression of genes related to sperm flagellum, acrosomal vesicle and spermatid development. We confirmed the expression of Fsip2 at the acrosome and the physical interaction of this gene with Acrv1, an acrosomal marker. Proteomic analysis of the testes revealed changes in proteins sited at the fibrous sheath, mitochondrial sheath and acrosomal vesicle. We also pinpointed the crucial motifs of Fsip2 that are evolutionarily conserved in species with internal fertilization. Thus, this work reveals the dosage-dependent roles of Fsip2 in sperm tail and acrosome formation.

Correlation of serum homocysteine and cystatin C levels with prognosis in heart failure with preserved ejection fraction patients.

OBJECTIVE: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. RESULTS: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. CONCLUSION: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.

Should non-invasive prenatal testing be recommended for patients who achieve pregnancy with PGT?

OBJECTIVE: To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients. METHODS: This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022. RESULTS: In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication. CONCLUSION: Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

Transforaminal endoscopic lumbar discectomy using a 45° puncture angle and foraminotomy versus traditional THESYS for L5/S1 lumbar disc herniation: a prospective randomized controlled trial.

PURPOSE: Prospective comparison of the efficacy and safety of transforaminal endoscopic lumbar discectomy (TELD) with a 45° puncture angle versus traditional Thomas Hoogland endoscopy spine systems (THESYS) for the surgical treatment of L5/S1 lumbar disc herniation (LDH). METHODS: Consecutive patients with L5/S1 LDH who underwent TELD were randomized (1:1) assigned to the 45° TELD group and the THESYS group. Clinical outcomes were assessed at pre-operation, 1-day and 3/6-months post-operation till final follow-up. Surgical-related parameters, visual analogue scale (VAS) score, oswestry disability index (ODI), and modified MacNab criteria, and surgical complications were recorded and analysed. RESULTS: All patients were followed up for at least 24 months. Compared to the THESYS group, the 45° TELD group had a shorter operative time (P < 0.001) and intraoperative radiation time (P < 0.001) and a smaller VAS score for back pain (P < 0.001) and leg pain intraoperatively (P < 0.001). The VAS and ODI in the 45° TELD group were significantly better than those in the THESYS group within 3 months postoperatively. However, from 3 months on, both groups showed comparable VAS and ODI. There was no significant difference between the two groups of modified MacNab criteria. There were two cases of residual disc and two cases of recurrence that required reoperation in the THESYS group. CONCLUSION: For L5/S1 LDH, the 45° TELD technique was superior to traditional THESYS in terms of surgery-related parameters and faster improvement of VAS and ODI, with a lower complication rate.

The Efficacy of Sacubitril Valsartan Sodium in Combination with Levosimendan in the Treatment of Cardiorenal Syndrome and the Effect on Cardiac and Renal Function.

Objective: To investigate the effects of sacubitril valsartan sodium combined with levosimendan on improving cardiac and renal functions in patients with CRS. Methods: 90 patients with the cardiorenal syndrome who were hospitalized in our hospital from February 2020 to February 2022 were selected and divided into two groups, the control group, and the joint group, according to both single and double number methods, with 45 cases in each group. Patients who met the diagnostic criteria for CRS, were older than 18 years of age, had NYHA class II to IV, and had stage 1 or 2 chronic kidney disease were included in the study. Patients with severe hypersensitivity to the drugs used in this test, haemodynamic instability, combined hyperthyroidism, malignancy, severe pulmonary hypertension, cardiogenic shock, malignant arrhythmias and pregnant women were excluded. Among them, the control group was treated with sacubitril valsartan sodium alone, and the joint group was treated with levosimendan supplemented with the treatment method of the control group. The treatment effect, the improvement of cardiac and renal function, and the incidence of adverse reactions were compared between the two groups of CRS patients, and the prognostic effect was followed up 6 months after treatment. Results: The total effective rate of treatment in the joint group was 95.56%, which was significantly higher than that in the control group of 80.00%, and the difference was statistically significant by using χ2 test (P < .05). After treatment, LVEF, LVEDD, and NT-proBNP levels in both groups were significantly improved compared with those before treatment (P < .05), and the improvement effect of each index in the joint group was more significant than that in the control group (P < .05). After treatment, the levels of SCr, BUN, and UA in both groups were significantly lower than those before treatment (P < .05), and the levels of each index in the joint group were significantly lower than those in the control group, statistical analyses showed significant differences (P < .05) using t test. The incidence of adverse effects such as tachycardia, premature ventricular contractions, heart failure, and myocardial ischaemia was 22.22% in the combined group, which was significantly lower than 42.22% in the control group, and the difference in the total incidence between the two groups was statistically significant by χ2 test (P < .05). One case of malignant arrhythmia and five cases of recurrence of heart failure occurred 6 months after surgery in the combined group, which were significantly lower than the eight and twelve cases in the control group. Conclusion: Sacubitril valsartan sodium combined with levosimendan can significantly improve the therapeutic effect of CRS, with significant improvement in cardiac and renal function of CRS patients, and its incidence of adverse effects and long-term prognostic effects are lower than those of sacubitril valsartan sodium alone. This combination therapy offers a promising new direction for CRS management, warranting further investigation in larger, multicenter trials.

Circ_0000419 acts as a tumor suppressor in gastric cancer development via regulating miR-300/RGMB axis.

OBJECTIVE: Dysregulated circular RNAs (circRNAs) have been verified to function in the development of gastric cancer (GC). The current study was designed to investigate the role of circ_0000419 in GC progression, and the potential mechanistic pathway. METHODS: Relative expression of circ_0000419, microRNA-300 (miR-300) and Repulsive Guidance Molecule B (RGMB) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Cell metastasis, including migration and invasion, was assessed by wound healing and Transwell assays. Glucose consumption and lactate production were examined using kits. The association between miR-300 and circ_0000419 or RGMB was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Role of circ_0000419 in vivo was determined by xenograft experiment. RESULTS: Circ_0000419 and RGMB were downregulated, while miR-300 was upregulated in GC tissues and cells. Gain of circ_0000419 inhibited migration, invasion and glycolysis in GC cells, which was attenuated by introduction of miR-300 or silencing of RGMB. Circ_0000419 sponged miR-300, and RGMB was direct target of miR-300. Circ_0000419 overexpression could block GC tumor growth in vivo. CONCLUSION: Circ_0000419 inhibited GC cell migration, invasion and glycolysis through regulation of miR-300/RGMB axis, at least in part, affording a molecular target for GC treatment.

Association of Long-term Ambient Fine Particulate Matter (PM2.5) and Incident CKD: A Prospective Cohort Study in China.

RATIONALE & OBJECTIVE: Increasing evidence has linked ambient fine particulate matter (ie, particulate matter no larger than 2.5 µm [PM2.5]) to chronic kidney disease (CKD), but their association has not been fully elucidated, especially in regions with high levels of PM2.5 pollution. This study aimed to investigate the long-term association of high PM2.5 exposure with incident CKD in mainland China. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 72,425 participants (age ≥18 years) without CKD were recruited from 121 counties in Hunan Province, China. EXPOSURE: Annual mean PM2.5 concentration at the residence of each participant derived from a long-term, full-coverage, high-resolution (1 × 1 km2), high-quality dataset of ground-level air pollutants in China. OUTCOMES: Incident CKD during the interval between the baseline examination of each participant (2005-2017) and the end of follow-up through 2018. ANALYTICAL APPROACH: Cox proportional hazards models were used to estimate the independent association of PM2.5 with incident CKD and the joint association of PM2.5 with temperature or humidity on the development of PM2.5-related CKD. Restricted cubic splines were used to model exposure-response relationships. RESULTS: Over a median follow-up of 3.79 (IQR, 2.03-5.48) years, a total of 2,188 participants with incident CKD were identified. PM2.5 exposure was associated with incident CKD with an adjusted hazard ratio of 1.71 (95% CI, 1.58-1.85) per 10-µg/m3 greater long-term exposure. Multiplicative interactions between PM2.5 and humidity or temperature on incident CKD were detected (all P < 0.001 for interaction), whereas an additive interaction was detected only for humidity (relative risk due to interaction, 3.59 [95% CI, 0.97-6.21]). LIMITATIONS: Lack of information on participants' activity patterns such as time spent outdoors. CONCLUSIONS: Greater long-term ambient PM2.5 pollution is associated with incident CKD in environments with high PM2.5 exposure. Ambient humidity has a potentially synergetic effect on the association of PM2.5 with the development of CKD. PLAIN-LANGUAGE SUMMARY: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 µm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term exposure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

Using affected embryos to establish linkage phase in preimplantation genetic testing for thalassemia.

BACKGROUND: This study aimed to evaluate the ability of next-generation sequencing (NGS) to conduct preimplantation genetic testing (PGT) for thalassemia using affected embryos. METHODS: This study included data from 36 couples who underwent PGT for thalassemia without probands and relative pedigrees. NGS results were compared with prenatal diagnosis results. RESULTS: Thirty-six couples (29 α-thalassemia and 7 ß-thalassemia) underwent 41 PGT cycles (31 α-thalassemia and 10 ß-thalassemia). Analysis using NGS produced conclusive results for all biopsied blastocysts (100%, 217/217). One hundred and sixty (73.7%, 160/217) were unaffected by thalassemia. Preimplantation genetic testing for aneuploidy revealed that 112 (70.0%, 112/160) were euploid. Single blastocysts were transferred into the uteri of 34 women (53 frozen embryo transfer [FET] cycles). Thirty-two cycles resulted in clinical pregnancies, with a clinical pregnancy rate of 60.1% (32/53) per FET cycle. Twenty-two cycles (22 couples) resulted in 23 live births, with a live birth rate of 43.4% (23/53; 3 cycles were ongoing pregnancies). All 25 embryos' prenatal diagnosis results and/or thalassemia gene analyses after delivery were concordant with the NGS-PGT results. Seven embryos (21.9%, 7/32) were miscarried before 12 weeks' gestation, and the abortion villus in four showed a normal karyotype and thalassemia results consistent with the NGS-PGT results. Aborted fetus samples from 3 cycles were not available because the pregnancy lasted less than 5 weeks. CONCLUSION: NGS can be used to conduct PGT for thalassemia using affected embryos as a reference. TRIAL REGISTRATION: Retrospectively registered.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

Heterogeneity and Molecular Markers for CNS Glial Cells Revealed by Single-Cell Transcriptomics.

Glial cells, including astrocytes, oligodendrocytes, and microglia, are the major components in the central nervous system (CNS). Studies have revealed the heterogeneity of each glial cell type and that they each may play distinct roles in physiological processes and/or neurological diseases. Single-cell sequencing (scRNA-seq) technology developed in recent years has extended our understanding of glial cell heterogeneity from the perspective of transcriptome profiling. This review summarizes the marker genes of major glial cells in the CNS and reveals their heterogeneity in different species, CNS regions, developmental stages, and pathological states (Alzheimer's disease and spinal cord injury), expanding our knowledge of glial cell heterogeneity on both molecular and functional levels.

Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.

In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury.

Does current ovarian endometrioma increase the time for DOR patients to reach live birth in IVF?

BACKGROUND: The contents of ovarian endometrioma (OMA) such as inflammatory mediators, reactive oxygen species, and iron may disrupt normal folliculogenesis and result in subsequent oocyte apoptosis. Therefore, women with OMA have a potential risk of diminished ovarian reserve (DOR). The purpose of this study is to compare the in vitro fertilization (IVF) outcomes and efficiency between DOR patients with and without current OMA. METHODS: This retrospective case-control study included a total of 493 women with DOR (serum anti-Müllerian hormone level < 1.1 ng/mL). Ninety patients with OMA (Group A) underwent 191 IVF cycles and 403 patients without ovarian OMA (Group B) underwent 888 IVF cycles in our center between January 2014 and December 2018. Basal characteristics and IVF outcomes were compared between Group A and Group B. Time to achieve live birth were compared between patients with live birth in two groups (Group A1, 31 patients; Group B1, 132 patients). RESULTS: Clinical and demographic characteristics of patients were similar respectively between groups (A vs. B, A1 vs. B1). There were no statistically significant differences in implantation rate, live birth rate per OPU and per ET cycle and the cumulative live birth rate per patient and per patient with good-quality embryos between Group A and Group B (P > 0.05). Total time to achieve live birth has no statistically significant difference between Group A1 and Group B1 (P > 0.05). CONCLUSION: For DOR women, presence of endometrioma did not affect the IVF outcomes. Even the time to get live birth was not prolonged by current OMA.

Evaluation of factors associated the expression of anti-HBs in children in Hunan Province, China.

BACKGROUND AND OBJECTIVES: Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically. METHODS: The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P < 0.10) in chi-square test or T test were further assessed with collinearity and chosen for univariate and multivariate logistic regression analysis by the stepwise backward maximum likelihood method (αin = 0.05, αout = 0.10). RESULTS: A total of 5838 samples (3362 males, 57.6%) were enrolled. In total, the incidence of negative anti-HBs increased with age[OR = 1.037(1.022-1.051)]. Multivariate logistic regression analysis illustrated that anemia[OR = 0.392(0.185-0.835)], age[OR = 2.542(1.961-3.295)] and Vit D[OR = 0.977(0.969-0.984)] in 0.5-2.99 years subgroup, Zinc deficiency[OR = 0.713(0.551-0.923] and age[OR = 1.151(1.028-1.289)] in 3-5.99 years subgroup, Vit D[OR = 0.983(0.971-0.995)] in 12-18 years subgroup had significant association with anti-HBs. CONCLUSIONS: This retrospective study illustrated that age, anemia status, zinc deficiency and vitamin D were associated with anti-HBs expression in specific age groups of children, which could serve as a reference for the prevention of HBV.

Re-analysis of whole blastocysts after trophectoderm biopsy indicated chromosome aneuploidy.

BACKGROUND: To compare the concordance between trophectoderm (TE) analysis and whole blastocyst analysis of embryos from chromosomal structural rearrangement (SR) carriers. METHOD: Sixty-three abnormal blastocysts identified by preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) were included. The whole blastocysts were processed through multiple displacement amplification cycle and sequenced for 24-chromosome aneuploidy screening by next-generation sequencing (NGS). The sequencing results were compared with those of TE biopsy from the same blastocysts and the primary chromosomal rearrangement of the couples. RESULTS: Analysis of the 63 blastocysts showed 68% (43/63) complete concordance between TE sequencing analysis and whole blastocyst results. Approximately one third (20/63, 32%) of the sequencing results showed some level of discordance between the two samples. Of these, 14% (9/63) of the embryos were identified as euploid after whole blastocyst sequencing. Among them, seven blastocysts were classified as chromosome mosaicism (five whole chromosomes, two segmental) after TE analysis, while two displayed non-SR related segmental changes in the TE biopsy. Of the original analyses, 70% (44/63) of findings were associated with the primary parental chromosomal rearrangement, while 30% (19/63) had no association. CONCLUSIONS: TE biopsy with NGS for PGT-SR is an efficient strategy to identify embryos suitable for transfer. While there was a high concordance between TE and whole blastocyst chromosome results, some embryos classified as mosaic in the original analysis and therefore unsuitable for transfer were reclassified as chromosomally balanced. To maximize the number of embryos available for PGT-SR patients, we suggest that embryos with mosaic non-SR chromosomal rearrangement should be stored and considered for transfer after appropriate counseling.

Is psychological flexibility a mediator between perceived stress and general anxiety or depression among suspected patients of the 2019 coronavirus disease (COVID-19)?

This study is aimed to investigate the status of general anxiety and depression among suspected patients of COVID-19 and explore whether psychological flexibility can serve as a mediator between perceived stress and general anxiety or depression. Total of 180 participants completed the online questionnaire which comprised demographic information, the Perceived Stress Scale (PSS), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 9-item Patients Health Questionnaire (PHQ-9), the Acceptance and Action Questionnaire-II (AAQ-II) and the Cognitive Fusion Questionnaire (CFQ). Statistical methods including correlation analysis, multiple linear regression analysis and structural equation model were used in this study. The scores of 23.9% (43/180) and 34.4% (62/180) of participants were higher than the cut points of GAD-7 and PHQ-9 respectively. Psychological flexibility was significantly correlated with perceived stress, general anxiety and depression. Multiple regression analyses showed the possible mediation effect of psychological flexibility between perceived stress and general anxiety or depression. The structural equation model confirmed that psychological flexibility partially mediated between perceived stress and general anxiety or depression. Our findings suggested the potential benefit of Acceptance and Commitment Therapy (ACT) as a psychological support approach in suspected patients of COVID-19 because ACT targets psychological flexibility.

Drinking behavior among government employees in Changsha and its influencing factors. / é•¿æ²™å¸‚å ¬èŒäººå‘˜é¥®é ’è¡Œä¸ºçŽ°çŠ¶åŠå ¶å½±å“å› ç´ .

OBJECTIVES: To analyze the prevalence and influencing factors for drinking behavior and heavy drinking among government employees in Changsha and provide a basis for carrying out interventions for drinking behaviors and formulating public health promotion plans for government employees. METHODS: Government employees were recruited consecutively from the Health Management Center of a general hospital in Changsha between December 2017 and December 2018. Information on sociodemograpic characteristics, drinking behaviors, life events, and psychosocial characteristics was collected using a standard set of questionnaire. Drinking behavior was defined as drinking once or more per week for the past 12 months. The differences in drinking rates and excessive drinking rates among groups with different characteristics were compared. Multivariate analysis was performed to analyze the associated factors of drinking behaviors and heavy drinking for government employees. RESULTS: A total of 6 190 people completed this investigation. The overall drinking rate of government employees in Changsha was 21.9%, and the rate of drinking was higher in males than that in females (44.7% vs 4.0%, P<0.01). Among the participants who drinked, the heavy drinking rates of males and females were 26.4% and 10.1%, respectively, while the harmful drinking rates of males and females were 6.0% and 2.2%, respectively. The results of multivariate logistic regression analysis showed that smoking, below high school education level, frequency of social intercourse ≥ 2 times per week, and having married or the divorced/widowed marital status were associated with alcohol drinking for male governmental employees. While aged 41 to 60 years old, frequency of social intercourse ≥ 2 times per week, life events stimulation ≥8 points were the risk factors for female; male, aged 41 to 60 years old, smoking, frequency of social intercourse≥ 2 times per week, and life events stimulation ≥1 point were the risk factors for heavy drinking. CONCLUSIONS: The drinking and heavy drinking rates of government employees are high in Changsha. Marital status, physical exercise, and frequency of social intercourse are the common influencing factors of male drinking behavior and female drinking behavior. The life events stimulation is the influencing factor of heavy drinking.

Ubiquitin-specific protease 19 blunts pathological cardiac hypertrophy via inhibition of the TAK1-dependent pathway.

Ubiquitin-specific protease 19 (USP19) belongs to USP family and is involved in promoting skeletal muscle atrophy. Although USP19 is expressed in the heart, the role of USP19 in the heart disease remains unknown. The present study provides in vivo and in vitro data to reveal the role of USP19 in preventing pathological cardiac hypertrophy. We generated USP19-knockout mice and isolated neonatal rat cardiomyocytes (NRCMs) that overexpressed or were deficient in USP19 to investigate the effect of USP19 on transverse aortic constriction (TAC) or phenylephrine (PE)-mediated cardiac hypertrophy. Echocardiography, pathological and molecular analysis were used to determine the extent of cardiac hypertrophy, fibrosis, dysfunction and inflammation. USP19 expression was markedly increased in rodent hypertrophic heart or cardiomyocytes underwent TAC or PE culturing, the increase was mediated by the reduction of Seven In Absentia Homolog-2. The extent of TAC-induced cardiac hypertrophy, fibrosis, dysfunction and inflammation in USP19-knockout mice was exacerbated. Consistently, gain-of-function and loss-of-function approaches that involved USP19 in cardiomyocytes suggested that the down-regulation of USP19 promoted the hypertrophic phenotype, while the up-regulation of USP19 improved the worsened phenotype. Mechanistically, the USP19-elicited cardiac hypertrophy improvement was attributed to the abrogation of the transforming growth factor beta-activated kinase 1 (TAK1)-p38/JNK1/2 transduction. Furthermore, the inhibition of TAK1 abolished the aggravated hypertrophy induced by the loss of USP19. In conclusion, the present study revealed that USP19 and the downstream of TAK1-p38/JNK1/2 signalling pathway might be a potential target to attenuate pathological cardiac hypertrophy.