Apatinib remodels the immunosuppressive tumor ecosystem of gastric cancer enhancing anti-PD-1 immunotherapy.

Apatinib has been shown to clinically enhance anti-PD-1 immunotherapy for advanced gastric cancer (GC). However, the complexity of GC immunosuppression remains a challenge for precision immunotherapy. Here, we profile the transcriptomes of 34,182 single cells from GC patient-derived xenografts of humanized mouse models treated with vehicle, nivolumab, or nivolumab plus apatinib. Notably, excessive expression of CXCL5 in the CellCycle malignant epithelium, induced by anti-PD-1 immunotherapy and blocked by combined apatinib treatment, is found to be a key driver of tumor-associated neutrophil (TAN) recruitment in the tumor microenvironment through the CXCL5/CXCR2 axis. We further show that the protumor TAN signature is associated with anti-PD-1 immunotherapy-related progressive disease and poor cancer prognosis. Molecular and functional analyses in cell-derived xenograft models confirm the positive in vivo therapeutic effect of targeting the CXCL5/CXCR2 axis during anti-PD-1 immunotherapy. Altogether, our study elucidates the GC immunosuppressive landscape in anti-PD-1 immunotherapy and highlights potential targets for overcoming checkpoint immunotherapy resistance.

Elevated baseline LH/FSH ratio is associated with poor ovulatory response but better clinical pregnancy and live birth in Chinese women with PCOS after ovulation induction.

Background: What is the association between elevated baseline LH/FSH ratio and reproductive outcomes, especially ovulatory response, among Chinese women with polycystic ovary syndrome (PCOS) after ovulation induction. Methods: This was a secondary analysis of a multicenter randomized trial in 1000 women with PCOS from 21 sites (27 hospitals) in Mainland China. LH and FSH levels before ovulation induction and the main outcomes including ovulation, biochemical pregnancy, clinical pregnancy, miscarriage, and live birth were measured. A linear regression model, logistic regression models and Cox proportional hazard regression model were used to estimate the association between LH/FSH ratios and reproductive outcomes in PCOS. Results: LH/FSH ratio was significantly associated with age, body mass index (BMI), total testosterone (TT), estradiol (E2), free testosterone (FT), and antimullerian hormone (AMH). Anovulatory women had significantly higher LH/FSH ratio than ovulatory women (P = 0.003), especially in women with young age (P = 0.023), high BMI (P = 0.002), low E2 (P = 0.002), FT (P = 0.010), TT (P < 0.001) and AMH(P = 0.032). Women with elevated LH/FSH ratio were associated with lower ovulation (LH/FSH≥1 OR = 0.42, 95% CI, 0.26-0.68; LH/FSH≥2 OR = 0.32, 95% CI, 0.20-0.54; LH/FSH≥3 OR = 0.40, 95% CI 0.21-0.74) when compared with LH/FSH<1. The association was held after adjustment for treatment with or without the confounding factors. Although no association between LH/FSH ratio and biochemical pregnancy, women with 1 ≤ LH/FSH<2 were associated with higher clinical pregnancy (OR = 1.71; 95% CI, 1.09-2.67) and live birth (OR = 1.73; 95% CI, 1.09-2.75) compared to women with LH/FSH<1. Women with 2 ≤ LH/FSH<3 were associated with lower miscarriage rate (OR = 0.38; 95% CI, 0.16-0.93). Conclusions: Elevated baseline LH/FSH ratio in women with PCOS was associated with poor ovulatory response, but women were more likely to achieve clinical pregnancy and live birth than women with normal LH/FSH. It suggests LH and FSH in women with PCOS may play a role in successful pregnancy despite of negative impact in ovulation.

Insulin resistance in women with recurrent miscarriage: a systematic review and meta-analysis.

PURPOSE: This review aimed to investigate the association of insulin resistance (IR) in women with recurrent pregnancy loss compared to women with normal pregnancy history. METHODS: PubMed, EMBASE, the Web of Science and Google Scholar databases were accessed to collect published observational studies that compared IR of recurrent pregnancy loss women with healthy women until the 6th of October 2022. Outcomes assessed in this review and meta-analysis included fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, glucose to insulin ratio. Mean differences, odds ratios with 95% confidence interval were pooled using the fixed or random effect models. Sensitivity analyses were performed to validate the robustness of the results. Review Manager version 5.4.1 and Stata version 8.0 were used. RESULTS: A total of nineteen studies involving 4453 individuals were included. Recurrent pregnancy loss patients presented significantly higher fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, and lower glucose to insulin ratios. Additionally, recurrent pregnancy loss patients had higher rates of IR as defined by abnormal fasting plasma insulin, homeostasis model assessment for IR, and glucose to insulin ratio. Sensitivity analyses validated the robustness of the results. CONCLUSION: In the current review, we show that recurrent pregnancy loss is associated with a higher degree of IR and highlight the importance of screening and treatment of IR.

Metabolic differences in women with premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: This review aimed to investigate the metabolic profile of women with premature ovarian insufficiency (POI) compared relative to women with normal ovarian functioning. METHODS: A systematic search of PubMed, EMBASE, and the Web of Science for observational studies published up until the 6th of July 2021 that compared the metabolic profile of POI women with a healthy control group were assessed. Mean differences (MD) and 95% confidence interval (CI) were pooled using the fixed or random effect models. RESULTS: A total of 21 studies involving 1573 women with POI and 1762 control women were included. POI patients presented significantly higher waist circumference, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and fasting glucose. Additionally, POI patients had marginally higher insulin level. However, the differences in systolic, and diastolic blood pressure were non-significant relative to the control group. CONCLUSIONS: POI is associated with alterations in certain metabolic parameters compared to control women. This finding highlights the importance of early screening and the lifelong management of metabolic health for women with POI.

Association between preconception serum lipid concentrations and treatment outcomes in women with PCOS who underwent ovulation induction.

RESEARCH QUESTION: What is the association between preconception serum lipid concentrations and reproductive outcomes after ovulation induction in women with polycystic ovary syndrome (PCOS)? DESIGN: A secondary analysis of a randomized controlled trial with 1000 PCOS women undergoing ovulation induction with clomiphene with or without acupuncture. Preconception serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) were measured. Outcomes were ovulation, conception, pregnancy, live birth and miscarriage. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 780 women ovulated; 320 women achieved conception, 218 had a clinical pregnancy, 205 had a live birth and 115 had a miscarriage. Serum lipid concentrations per one unit increment were independently associated with reproductive outcomes after controlling for confounders. Increasing LDL-C (OR 0.79, 95% CI 0.63-0.99) was independently associated with a lower chance of ovulation. Increasing total cholesterol (OR 0.76, 95% CI 0.62-0.92), LDL-C (OR 0.73, 95% CI 0.57-0.93), triglycerides (OR 0.74, 95% CI 0.58-0.95) and ApoB (OR 0.34, 95% CI 0.16-0.74) were independently associated with a lower chance of clinical pregnancy. Increased total cholesterol (OR 0.78, 95% CI 0.64-0.96), LDL-C (OR 0.77, 95% CI 0.60-0.99), triglycerides (OR 0.76, 95% CI 0.59-0.96) and ApoB (OR 0.39, 95% CI 0.18-0.86) were independently associated with a lower chance of live birth. Furthermore, increased total cholesterol (OR 1.43, 95% CI 1.06-1.93), LDL-C (OR 1.51, 95% CI 1.04-2.19) and ApoB (OR 3.82, 95% CI 1.17-12.41) were independently associated with a higher chance of miscarriage. CONCLUSIONS: Increased serum lipids were negatively associated with the reproductive outcomes of PCOS women undergoing ovulation induction with clomiphene with or without acupuncture.

Multi-Transcriptomic Analysis Reveals the Heterogeneity and Tumor-Promoting Role of SPP1/CD44-Mediated Intratumoral Crosstalk in Gastric Cancer.

GC is a fatal disease with high heterogeneity and invasiveness. Recently, SPP1 has been reported to be involved in the tumor progression of multiple human cancers; however, the role of SPP1 in GC heterogeneity and whether it is associated with the invasiveness and mortality of GC remain unclear. Here, we combined multiple RNA sequencing approaches to evaluate the impact of SPP1 on GC. Through bulk RNA sequencing (bulk RNA-seq) and immunohistochemistry (IHC), we found that SPP1 was highly expressed in GC, and high levels of SPP1 were associated with macrophage infiltration, an advanced tumor stage, and higher mortality for advanced GC patients. Furthermore, through simultaneous single-cell and spatial analysis, we demonstrated that SPP1+ macrophages are tumor-specific macrophages unique to cancer and enriched in the deep layer of GC tissue. Cell-cell communication analysis revealed that SPP1/CD44 interactions between SPP1+ macrophages and their localized tumor epithelial cells could activate downstream target genes in epithelial cells to promote dynamic changes in intratumor heterogeneity. Moreover, these activated genes were found to be closely associated with poor clinical GC outcomes and with cancer-related pathways that promote GC progression, as shown by survival analysis and enrichment analysis, respectively. Collectively, our study reveals that tumor-specific SPP1+ macrophages drive the architecture of intratumor heterogeneity to evolve with tumor progression and that SPP1 may serve as a prognostic marker for advanced GC patients, as well as a potential therapeutic target for GC.

MiR-let-7d-3p inhibits granulosa cell proliferation by targeting TLR4 in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a typical reproductive and endocrinological disorder of women at child-bearing age. In this study, we used miRNA sequencing technology and verified miR-let-7d-3p as a vital miRNA in PCOS. RT-qPCR confirmed miR-let-7d-3p was significantly increased in granulosa cells (GCs) of PCOS. Cell counting kit-8 (CCK-8) identified the suppression of miR-let-7d-3p mimic in KGN cell proliferation and PI3K/Akt signaling pathway. Dual luciferase reporter assay proved that Toll-like receptor 4 (TLR4) was a target of miR-let-7d-3p, and TLR4 was significantly down-regulated by miR-let-7d-3p. Furthermore, over-expression of TLR4 promoted KGN cell proliferation and rescued the inhibition of miR-let-7d-3p on KGN cells. In conclusion, miR-let-7d-3p was a crucial miRNA up-regulated in GCs of PCOS, and inhibited cell proliferation by targeting TLR4 gene.

Hydrogel, a novel therapeutic and delivery strategy, in the treatment of intrauterine adhesions.

Intrauterine adhesions (IUAs) are caused by damage to the underlying lining of the endometrium. They' re related to disorder of endometrial repair. In recent years, hydrogels with controllable biological activity have been widely used for treating IUAs. They encapsulate estrogen, cytokines, cells, or exosomes, forming a delivery system to release therapeutic components for the treatment of IUAs. In addition, the hydrogel acting as a barrier can be degraded in the body automatically, reducing the risk of infection caused by secondary surgeries. In this review, we summarize the recent progress of hydrogels and their application in IUAs as both a novel alternative therapeutic and an artificial delivery strategy.

Associations of Serum Magnesium With Insulin Resistance and Testosterone in Women With Polycystic Ovary Syndrome.

Objective: This article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS). Materials and Methods: Overall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone. Results: In comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend <0.05) after adjusting confounding covariates. Logistic regression showed serum magnesium in quartile 1 and 2 were independently associated with insulin resistance status (Quartile 1: OR: 2.15, 95%CI: 1.35-3.40, P = 0.001; Quartile 2: OR: 1.90, 95%CI: 1.20-3.02, P = 0.006), while quartile 1 was marginally associated with hyperandrogenemia status (Quartile 1: OR: 1.45, 95%CI: 0.99-2.11, P = 0.055) after adjusting confounding covariates. Conclusion: The current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.

Predictive value of circulating sex hormone-binding globulin for gestational diabetes: a meta-analysis.

Aim: To detect predictive value of preconception or early pregnancy sex hormone-binding globulin (SHBG) for subsequent gestational diabetes mellitus (GDM). Materials & methods: We searched Embase, Medline, PubMed, Web of Science and Cochrane library up to January 2020. Studies assessing diagnostic performance of SHBG for GDM diagnosed by well-defined diagnostic criteria using oral glucose tolerance test. Results: Totally seven studies with 1947 women were included and 247 were diagnosed as GDM. SHBG had a combined diagnostic odds ratio of 6.68 (95% CI: 4.58-9.74), sensitivity of 0.70 (95% CI: 0.51-0.84), specificity of 0.74 (95% CI: 0.52-0.88), positive likelihood ratio of 2.49 (95% CI: 1.73-3.57) and negative likelihood ratio of 0.37 (95% CI: 0.23-0.61). The area under the summary receiver operating characteristic curve was 0.78 (95% CI: 0.74-0.82). Conclusion: SHBG had a predictive value for GDM and might improve GDM screening. However, heterogeneity between studies warrants more research into this topic.

Predictive value of the number of frozen blastocysts in live birth rates of the transferred fresh embryos.

BACKGROUND: Blastocyst development by extended culture in vitro allows the embryos to 'select' themselves, thus successful growth to the blastocyst stage is a reflection of the developmental competence of cleavage stage embryos in a cohort. The study aims to determine whether the number of frozen blastocysts is associated with live birth rates of the transferred fresh embryos. METHOD: The retrospective study included 8676 cycles of first fresh embryo transfer from January 2016 to June 2019 at a fertility center of a university hospital. The patients with ≥ 10 oocytes retrieved were divided into three groups according to the number of frozen blastocysts: 0 (group 1), 1-2 (group 2), and ≥ 3 (group 3). The primary outcome measure was the live birth. The secondary outcome measures included clinical pregnancy rates and implantation rates. Logistic regression analysis was also performed. RESULTS: Live birth rates in patients with ≥ 3 and 1-2 frozen blastocysts were 47.6% and 46.1%, respectively, which were significantly higher than that in patients without blastocyst (36.0%). The clinical pregnancy rate in group 3 was 65.1%, which was also significantly higher than the other two groups (47.0% and 59.2%). The implantation rates were 35.5%, 47.6%, and 56.0% in the three groups, respectively (P < 0.001). Compared with groups of frozen blastocysts, 0 frozen blastocyst yielded a lower rate of live birth (the adjusted odds ratio: 0.526, 95% CI: 0.469, 0.612). CONCLUSION: In patients with optimal ovarian response that retrieved ≥ 10 oocytes, fresh embryos transfer followed by having blastocysts frozen is a strong indicator of pregnancy achievement, but the number of frozen blastocysts (if not = 0) has limited value in predicting live birth rates.

Quantitative study of preoperative staging of gastric cancer using intravoxel incoherent motion diffusion-weighted imaging as a potential clinical index.

PURPOSE: To determine the utility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging in quantitative analysis of preoperative tumor (T) and node (N) stages of gastric cancer, and to quantify the diagnostic threshold of IVIM parameters for serosal invasion and lymphatic metastasis. MATERIALS AND METHODS: From October 2016 to February 2020, 98 patients with gastric cancer who were receiving treatment in Zhongshan Hospital, China, were subject to an IVIM sequence imaging analysis. The IVIM sequence data were imported into software for post-processing of tumor regions of interest, and the IVIM parameters (the microvascular volume fraction (f), the molecular diffusion coefficient (D) and perfusion-related incoherent microcirculation (D*) were calculated. The variation of these IVIM parameters with different tumor-node metastasis (TNM) stages were analyzed by one-way analysis of variance. The IVIM parameters of serosal invasion and lymphatic metastasis were examined by receiver operating characteristic curve analysis and t-tests. RESULTS: A total of 98 gastric cancer patients (65 males and 33 females) with an average age of 61.9 years were enrolled in this study. There were 14 patients in stage T1, 14 in stage T2, 10 in stage T3 and 60 in stage T4a+b. There were 37 patients in stage N0, 19 in stage N1, 18 in stage N2 and 24 in stage N3. Statistically significant associations were found between the D values and T stages of gastric cancer. The D values of stage T4 cancers were significantly different from those of stage T2, T3 and T4 cancers. The D value decreased with increasing T stage. The mean D values of stages were 1.432 × 10-3 mm2/s (T1), 1.225 × 10-3 mm2/s (T2), 1.154 × 10-3 mm2/s (T3) and 0.9468 × 10-3 mm2/s (T4). The extent of the invasion of serosa was found to be significantly correlated with D value, with the diagnostic threshold for D being 1.107 × 10-3 mm2/s. In addition, different pathological N stages of gastric cancer lesions showed statistically significantly variations in f values, but no correlation was found with different N stages. Finally, the extent of lymphatic metastasis was found to be correlated with D values, with the diagnostic threshold being 1.1739 × 10-3 mm2/s. There was no statistically significant correlation between the IVIM MRI parameters and tumor size. The grade of tumor was found to be significantly correlated with D* value, with the diagnostic threshold for D* being 1.516 × 10-2 mm2/s. There was no statistically significant correlation between the ADC value and tumor size. There was a significant difference in the ADC values among different T and N stage cancers. ADC value had statistically significant to distinguish gastric cancer with or without serosal invasion, its detection efficiency was not as high as that of D value, with an AUC of 0.628 and 0.830, respectively. The ADC value was not statistically significant in distinguishing gastric cancer with or without lymphatic metastasis (P ≥ 0.05). The ADC value had not statistically significant in distinguishing gastric cancer between low and medium-high grade (P ≥ 0.05). CONCLUSION: We found that significant differences existed between whole-volume IVIM parameters of different T or N stages in gastric cancers, and were able to quantify different T or N stages of gastric cancer by the values of these parameters. The results of this quantitative study provide new tools for evaluating the prognosis of gastric cancer and will be valuable for the development of an new imaging method for determining the morphological stages of gastric cancer.

Identification of a MicroRNA Signature Associated With Lymph Node Metastasis in Endometrial Endometrioid Cancer.

BACKGROUND: Lymph node metastasis (LNM) is an important prognostic factor in endometrial cancer. Anomalous microRNAs (miRNAs) are associated with cell functions and are becoming a powerful tool to characterize malignant transformation and metastasis. The aim of this study was to construct a miRNA signature to predict LNM in endometrial endometrioid carcinoma (EEC). METHOD: Candidate target miRNAs related to LNM in EEC were screened by three methods including differentially expressed miRNAs (DEmiRs), weighted gene co-expression network analysis (WGCNA), and decision tree algorithms. Samples were randomly divided into the training and validation cohorts. A miRNA signature was built using a logistic regression model and was evaluated by the area under the curve (AUC) of receiver operating characteristic curve (ROC) and decision curve analysis (DCA). We also conducted pathway enrichment analysis and miRNA-gene regulatory network to look for potential genes and pathways engaged in LNM progression. Survival analysis was performed, and the miRNAs were tested whether they expressed differently in another independent GEO database. RESULT: Thirty-one candidate miRNAs were screened and a final 15-miRNA signature was constructed by logistic regression. The model showed good calibration in the training and validation cohorts, with AUC of 0.824 (95% CI, 0.739-0.912) and 0.821 (95% CI, 0.691-0.925), respectively. The DCA demonstrated the miRNA signature was clinically useful. Hub miRNAs in signature seemed to contribute to EEC progression via mitotic cell cycle, cellular protein modification process, and molecular function. MiR-34c was statistically significant in survival that a higher expression of miR-34c indicated a higher survival time. MiR-34c-3p, miR-34c-5p, and miR-34b-5p were expressed differentially in GSE75968. CONCLUSION: The miRNA signature could work as a noninvasive method to detect LNM in EEC with a high prediction accuracy. In addition, miR-34c cluster may be a key biomarker referring LNM in endometrial cancer.

Inhibition of circRNA circVPS33B Reduces Warburg Effect and Tumor Growth Through Regulating the miR-873-5p/HNRNPK Axis in Infiltrative Gastric Cancer.

BACKGROUND: Circular RNA VPS33B (circVPS33B) has been revealed to be upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct. METHODS: Expression of circVPS33B was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound-healing, or transwell assays. Protein levels were detected by Western blotting. Measurements of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were executed using an XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The regulatory mechanism of circVPS33B had been explored by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. In vivo tumorigenesis assay was executed to verify the oncogenicity of circVPS33B. RESULTS: CircVPS33B was upregulated in infiltrative GC tissues and cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, migration, invasion, EMT, and Warburg effect of infiltrative GC cells in vitro. Mechanically, circVPS33B regulated heterogeneous nuclear ribonucleoprotein K (HNRNPK) expression via sponging miR-873-5p. Furthermore, miR-873-5p inhibitor offset circVPS33B knockdown-mediated effects on malignant behaviors and Warburg effect of infiltrative GC cells. HNRNPK overexpression reversed the inhibitory impact of miR-873-5p mimic on malignant behaviors and Warburg effect of infiltrative GC cells. CONCLUSION: CircVPS33B accelerated Warburg effect and tumor growth through regulating the miR-873-5p/HNRNPK axis in infiltrative GC, manifesting that circVPS33B might be a potential target for infiltrative GC treatment.

Serum Lipid Levels and Treatment Outcomes in Women Undergoing Assisted Reproduction: A Retrospective Cohort Study.

Objective: To evaluate associations between serum lipid levels and treatment outcomes in women undergoing assisted reproduction. Materials and Methods: The study included 2011 women who underwent in vitro fertilization/intracytoplasmic sperm injection with fresh embryo transfer. Serum lipid evaluation included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Ovarian stimulation outcomes included endometrial thickness and the number of oocytes retrieved, and reproductive outcomes included live birth, clinical pregnancy, and miscarriage. Results: Higher HDL-C quartiles were associated with more oocytes retrieved. Lower TC (quartile 1 odds ratio [OR] 1.59 [1.21-2.08], quartile 3 OR 1.36 [1.04-1.77]), LDL-C (quartile 1 OR 1.41 [1.07-1.86]), and TG (quartile 2 OR 1.39 [1.06-1.84]) were independently associated with clinical pregnancy after adjusting for potential confounders. Lower LDL-C (quartile 1 OR 2.22 [1.58-3.13], quartile 2 OR 1.78 [1.27-2.50], quartile 3 OR 1.51 [1.07-2.13]), TC (quartile 1 OR 1.39 [1.00-1.93]), TG (quartile 1 OR 1.44 [1.03-2.03], quartile 2 OR 1.46 [1.04-2.04], quartile 3 OR 1.44 [1.04-1.99]), and higher HDL-C (quartile 2 OR 0.71 [0.51-0.99]) were independently associated with live birth. Higher LDL-C (quartile 1 OR 0.44 [0.30-0.66], quartile 2 OR 0.49 [0.33-0.73], quartile 3 OR 0.63 [0.43-0.94]) and lower HDL-C (quartile 1 OR 1.60 [1.07-2.39]) were independently associated with miscarriage. Conclusions: Serum lipid levels were associated with treatment outcomes in women undergoing assisted reproduction.

Clinical characteristics, cause analysis and infectivity of COVID-19 nucleic acid repositive patients: A literature review.

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and lives. The virus is still spreading throughout the world, and the cumulative number of confirmed cases is increasing. After patients with COVID-19 are treated and discharged, some have repeated clinical symptoms and become positive for nucleic acid tests a second time. Through analysis and review of the existing literature, the proportion of repositive patients in the discharged patient population and their clinical characteristics were systematically described for the first time. Furthermore, an in-depth analysis of the causes of repositive nucleic acid tests and the potential transmission of the disease provides the basis for the management and protection of discharged patients with COVID-19.

Effect of Hyperinsulinemia and Insulin Resistance on Endocrine, Metabolic, and Reproductive Outcomes in Non-PCOS Women Undergoing Assisted Reproduction: A Retrospective Cohort Study.

Objective: To evaluate the effect of hyperinsulinemia (HI) and insulin resistance (IR) on endocrine, metabolic, and reproductive outcomes in women without polycystic ovary syndrome (PCOS) undergoing assisted reproduction. Materials and Methods: The study included 1,104 non-PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection-fresh embryo transfer. HI was evaluated by serum fasting insulin (FIN), and IR was evaluated by homeostatic model assessment of insulin resistance index (HOMA-IR). In addition, biometric, sex hormone, and metabolic parameters were measured. Independent t-test, linear, and logistic regression examined associations between HI, IR, and endocrine, metabolic, ovarian stimulation characteristics, and reproductive outcomes. Results: Women with HI and IR had lower levels of progesterone, luteinizing hormone, follicle-stimulating hormone, estradiol, high-density lipoproteins, and increased levels of triglycerides low-density lipoproteins. For ovarian stimulation characteristics, those with HI and IR had a longer duration of stimulation, a higher total gonadotropin dose, and a lower peak estradiol level. Linear regression confirmed these associations. For reproductive outcomes, HI and IR were not associated with clinical pregnancy, live birth, and miscarriage. Conclusions: HI and IR did not impair reproductive outcomes in non-PCOS women undergoing assisted reproduction.

Prevalence, Pattern and Predictors for Dyslipidemia of Chinese Women With Polycystic Ovary Syndrome.

Objective: To investigate the prevalence, pattern and risk predictors for dyslipidemia among Chinese women with polycystic ovary syndrome (PCOS). Study Design and Methods: A total of 1,000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in 27 hospitals across China in a randomized controlled trial. Anthropometric, metabolic parameters, sex hormone, and lipid levels were measured at the baseline visit. Dyslipidemia was defined according to total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) level. Independent t-test and logistic regression were used to identify predictors for dyslipidemia. Area under the receiver operating characteristic curve (AUC) was calculated. Results: A total of 41.3% of the women had dyslipidemia, and the prevalence of abnormal TC, LDL-C, HDL-C, and TG were 8.6, 9.1, 26.9, and 17.5%, respectively. Logistic regression found that age, waist circumference, insulin, follicle-stimulating hormone, and sex hormone-binding globulin were independent predictors for dyslipidemia. When combining these predictors, the AUC was 0.744. The cut-off points were age >28.5 years, waist circumference >86.5 cm, insulin >96.0 pmol/L, follicle-stimulating hormone <5.6 mIU/mL, and sex hormone-binding hormone <31.0 nmol/L, respectively. Conclusion: Dyslipidemia was common in Chinese women with PCOS, and low HDL-C level was the predominant lipid abnormality. Age, waist circumference, follicle-stimulating hormone, insulin and sex hormone-binding globulin were predictive for dyslipidemia among Chinese women with PCOS.

Decreased Sex Hormone-Binding Globulin Indicated Worse Biometric, Lipid, Liver, and Renal Function Parameters in Women with Polycystic Ovary Syndrome.

OBJECTIVE: To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. RESULTS: In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95-0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695-0.770. SHBG <26.75 mmol/L is the cutoff point with the best Youden index, which has a sensitivity of 0.656 and specificity of 0.698. CONCLUSIONS: Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081.

Comparison of GnRH-a Prolonged Protocol and Short GnRH-a Long Protocol in Patients with Thin Endometrium for Assisted Reproduction: A Retrospective Cohort Study.

PURPOSE: Gonadotrophin releasing hormone agonist (GnRH-a) is widely used for pituitary down-regulation and recruiting more follicles in assisted reproduction. However, no information is available on its value for patients with thin endometrial thickness. PATIENTS AND METHODS: This was a retrospective cohort study of 302 patients with endometrium <8 mm undergoing fresh embryo transfer at a fertility center of a university hospital from January 2016 and December 2018. In 148 cycles of the GnRH-a prolonged protocol, one depot of 3.75 mg GnRH-a was injected on day 2 of the menstrual cycle, while in 154 cycles of the short GnRH-a long protocol, 0.1 mg of GnRH-a was injected daily from the mid-luteal phase. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and characteristics of stimulation procedures. RESULTS: Live birth rates and clinical pregnancy rates were significantly higher in the GnRH-a prolonged protocol group than in the other group (36.5% vs 20.8%, P=0.002; 43.9% vs 28.2%, P=0.006, respectively). The live birth rate was significantly increased in the prolonged protocol group (crude OR: 2.190, 95% CI: 1.311, 3.660; adjusted OR: 2.458, 95% CI: 1.430, 4.224) compared with that in the reference group. The implantation rate of the former group was also significantly higher than that of the latter group (35.4% vs 15.9%, P=0.000). There was no significant difference in miscarriage rates between the two protocols. In terms of stimulation procedures, the GnRH-a prolonged protocol group required significantly higher Gn time (10.9 vs 9.5 days, P=0.000) and Gn consumption (2625.0 vs 2047.5 IU, P=0.000) than the short GnRH-a long protocol group. CONCLUSION: The GnRH-a prolonged protocol in fresh embryo transfer cycles yielded better clinical outcomes of patients with thin endometrium than the short GnRH-a long protocol.