Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics.

Introduction: Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity. Methods: Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400µg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). Results: In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4). Conclusion: These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Laparoscopic anatomical left hemihepatectomy guided by middle hepatic vein in the treatment of left hepatolithiasis with a history of upper abdominal surgery.

BACKGROUND: This study aimed to investigate the safety and efficacy of laparoscopic anatomical left hemihepatectomy guided by the middle hepatic vein (MHV) for the treatment of patients with hepatolithiasis who had a history of upper abdominal surgery. METHODS: Retrospective data analysis was performed on patients who underwent laparoscopic left hepatectomy for hepatolithiasis and with previous upper abdominal surgery at the Second Affiliated Hospital of Nanchang University from January 2018 to April 2022. According to the different surgical approaches, patients were divided into laparoscopic anatomical left hepatectomy guided by the MHV group (MHV-AH group) and laparoscopic traditional anatomical left hepatectomy not guided by the MHV group (non-MHV-AH group). RESULTS: This study included 81 patients, with 37 and 44 patients in the MHV-AH and non-MHV-AH groups, respectively. There was no significant difference in the basic information between the two groups. Five cases were converted to laparotomy, and the remaining were successfully completed under laparoscopy. Compared to the non-MHV-AH group, the MHV-AH group had a slightly longer operation time (319.30 min vs 273.93 min, P = 0.032), lower bile leakage rate (5.4% vs 20.5%, P = 0.047), stone residual rate (2.7% vs 20.5%, P = 0.015), stone recurrence rate (5.4% vs 22.7%, P = 0.028), and cholangitis recurrence rate (2.7% vs 22.7%, P = 0.008).There were no significant differences in the results of other observation indices between the groups. CONCLUSIONS: Laparoscopic anatomical left hepatectomy guided by the MHV is safe and effective in the treatment of left hepatolithiasis with a history of upper abdominal surgery. It does not increase intraoperative bleeding and reduces the risk of postoperative bile leakage, residual stones, stone recurrence, and cholangitis recurrence.

The influence of embryo stage on obstetric complications and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

Objective: To investigate the effect of embryo stage at the time of transfer on obstetric and perinatal outcomes in programmed frozen-thawed embryo transfer (FET) versus natural FET cycles. Design: Systematic review and meta-analysis. Setting: Not applicable. Patients: Women with programmed frozen-thawed embryo transfer (FET) and natural FET. Interventions: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Central Register of Controlled Trials (CCRT) were searched from 1983 to October 2022. Twenty-three observational studies were included. Primary outcome measure: The primary outcomes were hypertensive disorders of pregnancy (HDPs), gestational hypertension and preeclampsia (PE). The secondary outcomes were gestational diabetes mellitus (GDM), placenta previa, postpartum haemorrhage (PPH), placental abruption, preterm premature rupture of membranes (PPROM), large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm delivery (PTD). Results: The risk of HDP (14 studies, odds ratio (OR) 2.17; 95% confidence interval (CI) 1.95-2.41; P<0.00001; I2 = 43%), gestational hypertension (11 studies, OR 1.38; 95% CI 1.15-1.66; P=0.0006; I2 = 19%), PE (12 studies, OR 2.09; 95% CI 1.88-2.32; P<0.00001; I2 = 0%), GDM (20 studies, OR 1.09; 95% CI 1.02-1.17; P=0.02; I2 = 8%), LGA (18 studies, OR 1.11; 95% CI 1.07-1.15; P<0.00001; I2 = 46%), macrosomia (12 studies, OR 1.15; 95% CI 1.07-1.24; P=0.0002; I2 = 31%), PTD (22 studies, OR 1.21; 95% CI 1.15-1.27; P<0.00001; I2 = 49%), placenta previa (17 studies, OR 1.2; 95% CI 1.02-1.41; P=0.03; I2 = 11%), PPROM (9 studies, OR 1.19; 95% CI 1.02-1.39; P=0.02; I2 = 40%), and PPH (12 studies, OR 2.27; 95% CI 2.02-2.55; P <0.00001; I2 = 55%) were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer. Blastocyst transfer had a higher risk of HDP (6 studies, OR 2.48; 95% CI 2.12-2.91; P<0.00001; I2 = 39%), gestational hypertension (5 studies, OR 1.87; 95% CI 1.27-2.75; P=0.002; I2 = 25%), PE (6 studies, OR 2.23; 95% CI 1.93-2.56; P<0.00001; I2 = 0%), GDM (10 studies, OR 1.13; 95% CI 1.04-1.23; P=0.005; I2 = 39%), LGA (6 studies, OR 1.14; 95% CI 1.07-1.21; P<0.0001; I2 = 9%), macrosomia (4 studies, OR 1.15; 95% CI 1.05-1.26; P<0.002; I2 = 68%), PTD (9 studies, OR 1.43; 95% CI 1.31-1.57; P<0.00001; I2 = 22%), PPH (6 studies, OR 1.92; 95% CI 1.46-2.51; P<0.00001; I2 = 55%), and PPROM (4 studies, OR 1.45; 95% CI 1.14-1.83; P=0.002; I2 = 46%) in programmed FET cycles than in natural FET cycles. Cleavage-stage embryo transfers revealed no difference in HDPs (1 study, OR 0.81; 95% CI 0.32-2.02; P=0.65; I2 not applicable), gestational hypertension (2 studies, OR 0.85; 95% CI 0.48-1.51; P=0.59; I2 = 0%), PE (1 study, OR 1.19; 95% CI 0.58-2.42; P=0.64; I2not applicable), GDM (3 study, OR 0.79; 95% CI 0.52-1.20; P=0.27; I2 = 21%), LGA (1 study, OR 1.15; 95% CI 0.62-2.11; P=0.66; I2not applicable), macrosomia (1 study, OR 1.22; 95% CI 0.54-2.77; P=0.64; I2 not applicable), PTD (2 studies, OR 1.05; 95% CI 0.74-1.49; P=0.79; I2 = 0%), PPH (1 study, OR 1.49; 95% CI 0.85-2.62; P=0.17; I2not applicable), or PPROM (2 studies, OR 0.74; 95% CI 0.46-1.21; P=0.23; I2 = 0%) between programmed FET cycles and natural FET cycles. Conclusions: The risks of HDPs, gestational hypertension, PE, GDM, LGA, macrosomia, SGA, PTD, placenta previa, PPROM, and PPH were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer and blastocyst transfer, but the risks were not clear for cleavage-stage embryo transfer.

Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Objective: To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome. Method: We searched Pubmed, Medline (via Ovid, 1974 to 2020), EMBASE (via Ovid, 1974 to 2020), Cochrane Central Register of Controlled Trials (via Ovid), Web of Science, CNKI, WangFang and the Vip database from inception until April 2021. Two researchers independently screened articles, collected data and evaluated the quality, with Review manager 5.3 for meta-analysis. Results: Totally 20 randomized controlled studies with 1961 subjects were included. Meta analysis showed that pregnancy rate [RR=1.44 (1.28, 1.62), p<0.00,001], ovulation rate [RR=1.42 (1.14, 1.78), p=0.002] and matured oocytes rate [RR=1.08 (1.03, 1.13), p=0.002] of vitamin D supplementation group were significantly higher than those of control group. Meanwhile, early miscarriage rate [RR=0.44 (0.30, 0.66), p<0.00,001], androgen level [MD=-2.31 (-3.51, -1.11), p=0.0002], luteinizing hormone [MD=-1.47 (-2.57, -0.36), p=0.009], follicle stimulating hormone [MD=-0.15 (-0.24, -0.05), p=0.002], and premature delivery rate [RR=0.38, 95% CI (0.21, 0.70), p=0.002] were declined significantly than the controls. However, only one article suggested that the progesterone [MD=6.52 (4.52, 8.52), p<0.05] in the vitamin D intervention group was increased. There was no notable difference in the biochemical pregnancy rate [RR=0.95 (0.55, 1.63), p=0.84], gestational hypertension rate [RR=0.40, 95% CI (0.15, 1.11), p=0.08], gestational diabetes mellitus rate [RR=0.27, 95% CI (0.05, 1.39), p=0.11], fertilization rate [RR=1.05 (1.00, 1.10), p=0.04], cleavage rate [RR=1.03 (0.99, 1.06), p=0.17], high-quality embryo rate [RR=1.08 (0.98, 1.20), p=0.10], endometrial thickness [MD=0.10], 77 (-0.23, 1.77), p=0.13], estrogen level [MD=-0.34 (-1.55, 0.87), p=0.59], LH/FSH [MD=-0.14, 95% CI (-0.48, 0.20), p=1.00] and anti-Mullerian hormone [MD=-0.22 (-0.65, 0.21), p=0.32]. Conclusion: Vitamin D supplementation contribute to the higher pregnancy and ovulation rates, and lower androgen, LH, FSH and early miscarriage rates in women with PCOS, regardless of the use of ovulation induction drugs or assisted reproductive technologies. However, no significant improvement was observed in fertilization rate or cleavage rate. Due to the limitation in quality of involved studies, more high-quality RCTs are needed for further validation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021250284.

Correlation between spherical equivalent and biometry parameters in adult Cynomolgus macaque.

PURPOSE: To characterize the distribution of refractive and ocular biometry parameters and analyze the effect factors of the refractive status in cynomolgus monkey colonies. METHODS: A Population-based cross-sectional study was conducted in adult cynomolgus macaque colonies. Animals were anesthetized with Zoletil 50. Intraocular pressure was measured using the Icare tonometer. Cycloplegic refraction (three drops of 1% tropicamide) and corneal radius of curvature (CRC) were measured using an autorefractor. The spherical equivalent (SE) was calculated. Biometric measurements, including the anterior chamber depth (ACD), lens thickness (LT), and axial length (AL), were obtained by A-scan ultrasonography. The AL-to-CR ratio (AL/CRC) was calculated. Central corneal thickness (CCT) and choroidal thickness (ChT) were measured using the Heidelberg Spectralis HRA OCT. Multiple regression analysis was performed to explore the association between refraction and ocular biometry. RESULTS: Among 263 cynomolgus monkeys (aged 5-26 years), which consisted of 520 eyes, 29.42% had hyperopia, 27.12% had emmetropia, 33.27% had mild-to-moderate myopia and 10.19% had high myopia. The mean SE was -1.27 ± 3.44 Diopters (D). The mean CRC, CCT, AL, and ChT was 5.70 ± 0.22 mm, 454.30 ± 32.40 µm, 18.76 ± 0.89 mm and 188.96 ± 38.19 µm, respectively. The LT was the thickest in the hyperopic eyes. CRC was the lowest, and CCT was the thickest in high myopic eyes. AL increased, while ChT decreased as SE decreased. For the SE variance, AL alone explained 40.5%; age, AL, and CRC together explained 57.5%. CONCLUSIONS: The refractive characteristics and biometry parameters of cynomolgus monkeys are highly comparable to those of humans. AL, CRC, and ChT showed the similar variation tendency in cynomolguses when compared to humans. Cynomolgus monkeys with naturally-occurring refractive errors may be a good animal model for refractive studies.

Effect of different lymph node dissection methods on the number of lymph nodes detected and prognosis in gallbladder cancer.

At present, the extent of lymph node dissection (LND) for radical gallbladder cancer (GBC) is still controversial, and there is no evidence that LND improves prognosis, however, the latest guidelines for GBC recommend that removal of more than 6 lymph nodes facilitates staging of regional lymph nodes. The aim of this study is to investigate the effect of different LND methods on the number of lymph nodes detected and assess the prognostic factors during radical resection of GBC. This study retrospectively analyzed 133 patients (46 men and 87 women; average age: 64.01, range: 40-83 years) who underwent radical resection of GBC in a single center between July 2017 and July 2022, of which 41 underwent fusion lymph node dissection (FLND) and 92 underwent standard lymph node dissection (SLND). Baseline data, surgical results, number of LNDs, and follow-up data were analyzed. Each patient was followed up every 3 months. The total number of lymph nodes detected after the operation was 12.00 ± 6.95 versus 6.10 ± 4.71 (P < .05). The number of positive lymph nodes detected was (mean) 1.85 versus 0.78 and (percentage) 15.45% versus 12.83% (P < .05). Postoperative complications (8 vs 23, P > .05). The progression-free survival was 13 versus 8 months, the median survival time was 17 versus 9 months (P < .05). This study concluded that FLND can increase the detection rate of total lymph nodes and positive lymph nodes after surgery, which can prolong the survival time of patients.

Comprehensive Analysis of NABP2 as a Prognostic Biomarker and Its Correlation with Immune Infiltration in Hepatocellular Carcinoma.

Background: The DNA binding protein NABP2 (nucleic acid binding protein 2) is a member of the SSB (single-stranded DNA-binding) protein family, which is involved in DNA damage repair. Its prognostic significance and relationship with immune infiltration in hepatocellular carcinoma (HCC), however, remain unknown. Methods: The purpose of this study was to estimate the prognostic value of NABP2 and to investigate its possible immune function in HCC. By applying multiple bioinformatics methods, we gathered and analysed data from The Cancer Genome Atlas (TCGA), Cancer Cell Lineage Encyclopedia (CCLE), and Gene Expression Omnibus (GEO) to investigate the potential oncogenic and cancer-promoting role of NABP2, including the differential expression, prognostic value, immune cell infiltration association, and drug sensitivity of NABP2 in HCC. Immunohistochemistry and Western blotting were used to validate the expression of NABP2 in HCC. The knockdown of NABP2 expression by siRNA was further used to validate its role in hepatocellular carcinoma. Results: Our findings indicated that NABP2 was overexpressed in HCC samples and was related to poor survival, clinical stage, and tumour grade in HCC patients. Analysis of functional enrichment indicated that NABP2 was potentially involved in the cell cycle, DNA replication, G2M checkpoint, E2F targets, apoptosis, P53 signalling, TGFA signalling via NF-κB, and so on. NABP2 was shown to be significantly linked to immune cell infiltration and immunological checkpoints in HCC. Analyses of drug sensitivity predict a number of drugs that could potentially be used to target NABP2. Moreover, in vitro experiments verified the promoting effect of NABP2 on the migration and proliferation of hepatocellular carcinoma cells. Conclusion: Based on these findings, NABP2 appears to be a candidate biomarker for HCC prognosis and immunotherapy.

Is time-restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta-analysis of randomized controlled trials.

Time-restricted eating (TRE) is a new therapeutic strategy for the management of weight loss and dysmetabolic diseases. At present, TRE (8/16, 8 h eating:16 h fasting) is the most common form of TRE. Therefore, this meta-analysis included randomized controlled trials (RCTs) on TRE (8/16) in overweight and obese adults to determine its impact on body weight and metabolism. Articles reviewed from PubMed, Ovid MEDLINE, Embase, and Cochrane Central Register for the relevant RCTs that compared TRE (8/16) to non-TRE in overweight and obese adults. Eight RCTs were included in this meta-analysis. Participants following TRE (8/16) showed significant body weight reduction (mean difference [MD]: -1.48 kg, 95% confidence interval [CI]: -2.53 to -0.44) and fat mass reduction (MD: -1.09 kg, 95% CI: -1.55 to -0.63). There was no significant difference in lean mass change with TRE intervention (MD: -0.48 kg, 95% CI: -1.02 to 0.05, p = .08, I 2 = 41%). The energy restriction and early TRE (eTRE) subgroups resulted in greater weight loss. TRE (8/16) showed beneficial effects on the homeostatic model assessment of insulin resistance (HOMA-IR, MD: -0.32, 95% CI: -0.59 to -0.06), but had no significant effect on other parameters of glucose metabolism and lipid profiles. In conclusion, TRE (8/16), especially eTRE, or in combination with caloric intake restriction, is a potential therapeutic strategy for weight control in overweight and obese adults. TRE (8/16) also reduced HOMA-IR; therefore, it may have a positive effect on glucose metabolism.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

Laparoscopic Transcystic Common Bile Duct Exploration: 8-Year Experience at a Single Institution.

BACKGROUND: Laparoscopic transcystic common bile duct exploration (LTCBDE) is used to treat cholecystolithiasis and choledocholithiasis. This study aimed to investigate the safety, effectiveness and generalisability of LTCBDE in patients with cholecystolithiasis and choledocholithiasis based on our LTCBDE experience within 8 years. METHODS: Four hundred patients with cholecystolithiasis and choledocholithiasis (including 62 of cholecystolithiasis and choledocholithiasis with common bile duct no-dilatation) treated with LTCBDE at a single centre from January 2014 to February 2022 were retrospectively evaluated. They were divided into the first 200 and last 200 LTCBDE cases. The disease characteristics, cystic duct incision methods, surgical outcomes and follow-up data were analysed retrospectively. Each patient was followed up for > 3 months. RESULTS: Four hundred patients underwent LTCBDE, including 188 males and 212 females aged from 15 to 91 years (average age: 56 years). LTCBDE was successful in 377 (94.3%) patients, while treatment was converted to laparoscopic choledocholithotomy with T-tube drainage in 23 (5.8%), owing to intraoperative choledochoscope insertion failure. The CBD diameter (10.89 ± 1.76 vs 9.97 ± 2.39, P < 0.05), cystic duct diameter (4.62 ± 1.03 vs 5.03 ± 1.29, P < 0.05), and operation time (164.60 ± 24.30 vs 135.34 ± 30.00, P < 0.05). Residual stones were found in six (1.5%) patients and removed during the second operation; post-operative bile leakage was found in one (0.3%) patient, who was discharged safely after the second operation. CONCLUSIONS: Phase I LTCBDE is safe and effective in treating cholecystolithiasis and choledocholithiasis. With continuous technological advances, LTCBDE has been effectively promoted and applied.

Hyperandrogen-induced polyol pathway flux increase affects ovarian function in polycystic ovary syndrome via excessive oxidative stress.

AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in the women of childbearing age. It is characterized by hyperandrogenism and abnormal follicular growth and ovulation. The polyol pathway is a glucose metabolism bypass pathway initiated by aldose reductase (ADR). Androgen induces the expression of ADR in the male reproductive tract, which has a general physiological significance for male reproductive function. Here we investigate whether hyperandrogenemia in PCOS leads to increased flux of the polyol pathway in ovarian tissue, which in turn affects follicular maturation and ovulation through oxidative stress. MAIN METHODS: We used clinical epidemiological methods to collect serum and granulosa cells from clinical subjects for a clinical case-control study. At the same time, cell biology and molecular biology techniques were used to conduct animal and cell experiments to further explore the mechanism of hyperandrogen-induced ovarian polyol pathway hyperactivity and damage to ovarian function. KEY FINDINGS: Here, we find that hyperandrogenism of PCOS can induce the expression of ovarian aldose reductase, which leads to the increase of the polyol pathway flux, and affects ovarian function through excessive oxidative stress. SIGNIFICANCE: Our research has enriched the pathological mechanism of PCOS and may provide a new clue for the clinical treatment of PCOS.

Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex.

Single cell approaches have increased our knowledge about the cell type composition of the non-human primate (NHP), but a detailed characterization of area-specific regulatory features remains outstanding. We generated single-cell transcriptomic and chromatin accessibility (single-cell ATAC) data of 358,237 cells from prefrontal cortex (PFC), primary motor cortex (M1) and primary visual cortex (V1) of adult female cynomolgus monkey brain, and integrated this dataset with Stereo-seq (spatial enhanced resolution omics-sequencing) of the corresponding cortical areas to assign topographic information to molecular states. We identified area-specific chromatin accessible sites and their targeted genes, including the cell type-specific transcriptional regulatory network associated with excitatory neurons heterogeneity. We reveal calcium ion transport and axon guidance genes related to specialized functions of PFC and M1, identified the similarities and differences between adult macaque and human oligodendrocyte trajectories, and mapped the genetic variants and gene perturbations of human diseases to NHP cortical cells. This resource establishes a transcriptomic and chromatin accessibility combinatory regulatory landscape at a single-cell and spatially resolved resolution in NHP cortex.

The influence of perinatal maternal exposure to dibutyl phthalate on glucolipid metabolism in adult female offspring.

BACKGROUND: Maternal exposure to dibutyl phthalate (DBP) may result in obesity in female offspring. However, the underlying mechanisms remain elusive. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with different doses of DBP and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring. RESULTS: Although the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P < 0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P < 0.001). Decreased serum level of triglyceride (P = 0.001) in F1 female offspring was found in DBP group as compared to control, especially in medium and high DBP. However, none difference was found for fasting glucose, prolactin, HOMA-IR, fasting insulin, total cholesterol, adiponectin. Different protein levels of GPR30 were observed in muscle of female offspring among four groups (P = 0.016). The protein level of AKT seemed higher in DBP group but without statistical significance (P = 0.05). None difference was observed for the protein levels of PI3K, p-AKT, pAKT/AKT, PTEN, GLUT4, InsR, IRS. CONCLUSION: Maternal perinatal exposure to DBP might induce obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring.

Systematic Review and Meta-analysis: Changes of Gut Microbiota before and after Menopause.

Objective: To systematically evaluate the differences in intestinal flora before and after menopause. To provide a possible mechanism for perimenopausal syndrome and provide a basis for probiotics as adjuvant therapy. Methods: MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, and VIP databases were searched. The included studies were case-control studies. Results: Three case-control studies were included, with a total of 156 people. At the phylum level, there were no differences between premenopausal and postmenopausal women. At the genus level, the relative abundances of A. odoratum and B. cholerae were higher in postmenopausal women than in premenopausal women, with no differences among other genera. The Shannon diversity index increased after menopause, but no differences were found. Only one study found a positive association of estradiol with Gammaproteobacteria and Myxococcales and a negative association with Prevotellaceae. Conclusions: On the basis of previous studies, it was found that there was no significant difference at the phylum level between postmenopausal women and premenopausal women, but Odoribacter and Bilophila increased at the genus level in postmenopausal women. The class of Gammaproteobacteria may be positively correlated with estradiol. Limited by the number of included studies, more high-quality clinical studies are needed for validation.

Falsely elevated serum estradiol in woman of reproductive age led to unnecessary intervention and delayed fertility opportunity: a case report and literature review.

BACKGROUND: The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. CASE: A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto's thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. CONCLUSIONS: Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

Effects of metformin on pregnancy outcome, metabolic profile, and sex hormone levels in women with polycystic ovary syndrome and their offspring: a systematic review and meta-analysis.

Background: Researches of the efficacy and safety of metformin on long-term pregnancy outcomes remains conflicted. We performed an updated systematic review and meta-analysis to systematically investigate the effect of metformin treatment on pregnancy outcome, metabolic profile, and sex hormone characteristics in women with polycystic ovary syndrome (PCOS) and their offspring. Methods: The PubMed, Embase, and Cochrane Library databases were searched from inception to July 10, 2021 with the keywords "metformin", "PCOS", and "pregnancy". Randomized controlled studies reported pregnant related outcomes after metformin intervention among PCOS women were included, while abstracts and reviews were excluded. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer's Handbook 5.0. Random effects models were used to evaluate the pooled risk ratios (RR) and 95% confidence intervals (95% CI) of pregnancy outcome, metabolic profile, and sex hormone levels. Results: Eighteen studies were included. The majority of trials were in medium methodological quality. In terms of pregnancy complications among women with PCOS, metformin treatment was associated with a significantly reduced risk of preterm delivery (RR =0.37, 95% CI: 0.23-0.61), pregnancy-induced hypertension (PIH) and preeclampsia (RR =0.45, 95% CI: 0.24-0.83) and macrosomia (RR =0.26, 95% CI: 0.11-0.64). In terms of offspring, metformin significantly associated with larger head circumference (MD =0.29, 95% CI: 0.13-0.45) and higher long-term body mass index (BMI) measures (MD =0.37, 95% CI: 0.17-0.56). In terms of metabolic profile and sex hormone characteristics, a significant decrease in homeostatic model assessment for insulin resistance (HOMA2-IR) scores was found in mothers (MD =-0.32, 95% CI: -0.63 to -0.02), whereas a significant increase of sex hormone binding globulin (SHBG) levels was detected in offspring (MD =0.33, 95% CI: 0.01-0.65). Discussion: Although the relative low quality of randomized controlled trials (RCTs) and limited results made it difficult to draw a definite conclusion, our study showed that metformin treatment during pregnancy can reduce the risk of pregnancy complications but may have impacts on increasing SHBG levels and long-term BMI in offspring.

Effects of leukocytospermia on the outcomes of assisted reproductive technology.

Leukocytospermia is one of the common causes of male infertility, and its effects on the clinical outcomes of assisted reproduction are controversial. There are no recommendations for the management of leukocytospermia in cases of assisted reproductive technology (ART). To investigate the impact of leukocytospermia on ART, we retrospectively compared the clinical outcomes in ART couples with or without leukocytospermia and further analysed the impact of the insemination method itself by split insemination treatment in ART couples with leukocytospermia. In this study, leukocytospermia was detected in 133 patients, namely 63 in the conventional in vitro fertilization (IVF) group, 38 in the intracytoplasmic sperm injection (ICSI) group and 32 in the split insemination group. Leukocytospermia has a negative influence on the parameters of semen samples; however, leukocytospermia did not affect the clinical outcomes of IVF or ICSI. Different insemination methods did not affect the fertilization, clinical pregnancy or live birth rates. In the split insemination study, no significant differences in clinical pregnancy and live birth rates between the IVF and ICSI groups were found; however, the numbers of two pronuclei (2PN), available embryos and good-quality embryos in the ICSI group were higher than those in the IVF group. Leukocytospermia may be a risk factor affecting semen parameters, and more attention should be given to IVF insemination. Leukocytospermia has no significant negative effect on the outcomes of ART. ICSI may obtain better embryos than IVF, but it cannot improve the clinical pregnancy and live birth rates.