Accessing 1,8-Naphthyridone-3-carboxylic Acid Derivatives and Application to the Synthesis of Amfonelic Acid.

1,8-Naphthyridone-3-carboxyl is the core structure of several on-market antibacterial drugs. It has prompted significant interest from the synthetic community. Here, we report a practical synthesis of diversely functionalized 1,8-naphthyridone-3-carboxylic acid derivatives starting from readily available and inexpensive nicotinic acid derivatives. All key steps have been optimized. Furthermore, the usefulness of this protocol has been exemplified by the first synthesis of amfonelic acid.

Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer.

BACKGROUND: This study aims to investigate the expression of UBQLN1 in lung cancer (LC) tissue and the diagnostic capability of autoantibody to UBQLN1 (anti-UBQLN1) in the detection of LC and the discrimination of pulmonary nodules (PNs). METHODS: Sera from 798 participants were used to discover and validate the level of autoantibodies via HuProt microarray and Enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was applied to establish model. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic potential. Immunohistochemistry was performed to detect UBQLN1 expression in 88 LC tissues and 88 para-tumor tissues. qRT-PCR and western blotting were performed to detect the expression of UBQLN1 at the mRNA and protein levels, respectively. Trans-well assay and cell counting kit-8 (CCK-8) was used to investigate the function of UBQLN1. RESULTS: Anti-UBQLN1 was identified with the highest fold change by protein microarray. The level of anti-UBQLN1 in LC patients was obviously higher than that in NC or patients with benign lung disease of validation cohort 1 (P<0.05). The area under the curve (AUC) of anti-UBQLN1 was 0.610 (95%CI: 0.508-0.713) while reached at 0.822 (95%CI: 0.784-0.897) when combining anti-UBQLN1 with CEA, CYFRA21-1, CA125 and three CT indicators (vascular notch sign, lobulation sign and mediastinal lymph node enlargement) in the discrimination of PNs. UBQLN1 protein was overexpressed in lung adenocarcinoma (LUAD) tissues compared to para-tumor tissues. UBQLN1 knockdown remarkably inhibited the migration, invasion and proliferation of LUAD cell lines. CONCLUSIONS: Anti-UBQLN1 might be a potential biomarker for the diagnosis of LC and the discrimination of PNs.

A comparison analysis of the somatic mutations in early-onset gastric cancer and traditional gastric cancer.

BACKGROUND: Early onset gastric cancer (EOGC) has been on the rise in recent years and differs slightly in pathology from traditional gastric cancer (TGC). Somatic mutations have an essential role in the development of gastric cancer. We aimed to investigate these two types of gastric cancers at the level of somatic mutations and to further understanding of gastric cancer development. METHODS: Somatic mutation, copy number variation (CNV), and clinical information were obtained from TCGA and UCSC Xena. Samples were divided into EOGC (< 50 years old, N = 28) and TGC (≥ 50 years old, N = 395) groups based on age. R packages "maftools" and "sigminer" were used to identify mutation signatures, while CNV information was processed using GISTIC2.0. RESULTS: CDH1(21 %, P = 0.030) and ARID1A (28 %, P = 0.014) were more common in EOGC and TGC, respectively. The mutation frequency of ARID1A increased with age, while the opposite was true for CDH1. Sex, Lauren classifications, tumor mutation burden levels, mutation status of TP53, MUC6, NIPBL, KRAS, and copy number variation of the WOOX can affect the activity of the mutant signature. CONCLUSIONS: Early-onset gastric cancer and traditional gastric cancer have distinct somatic mutation signatures, each with its own relatively specific high-frequency mutated genes, and the gene's mutation frequency correlates with age. Several clinical factors and genetic status affect the activity of some mutational features in gastric cancer in both groups.

Global burden of stomach cancer attributable to smoking from 1990 to 2019 and predictions to 2044.

OBJECTIVES: This study aimed to assess the global temporal trends of stomach cancer attributable to smoking from 1990 to 2019 and to predict the global burden by 2044. STUDY DESIGN: This was a comprehensive analysis based on data provided by the Global Burden of Disease Study 2019. METHODS: Based on the Global Burden of Disease Study 2019, mortality, disability-adjusted life years (DALYs), and corresponding age-standardised rates of stomach cancer attributable to smoking by sociodemographic index (SDI), region, country, sex, and age were used to assess temporal trends from 1990 to 2019 by calculating the average annual percentage change (AAPC). In addition, the global burden of stomach cancer attributable to smoking up to 2044 was predicted using age-period-cohort models. RESULTS: Globally, in 2019, 17.96% of stomach cancer deaths (1.72 million) and 17.15% of stomach cancer DALYs (38.13 million) were attributable to smoking, representing an increase compared to 1990; however, smoking-attributable age-standardised rates of mortality (ASMRs) and DALYs (ASDRs) significantly declined to 2.12/100,000 and 45.82/100,000 in 2019, respectively. While stomach cancer ASMR and ASDR attributable to smoking decreased in all regions and in most countries, they increased by >10% in some countries. A positive correlation was found between SDI and age-standardised rates (rASMR = 0.28, P < 0.01; rASDR = 0.29, P < 0.01). By 2044, although global age-standardised rates for smoking-attributable stomach cancer are predicted to decline, deaths and DALYs are estimated to increase to 2.22 million and 42.14 million, respectively. CONCLUSIONS: Stomach cancer deaths and DALYs attributable to smoking have increased over the past 30 years and will continue to increase. Consequently, targeted prevention efforts and tobacco-control strategies need to be further developed and improved.

Prognostic value of lncRNA AFAP1-AS1 in breast cancer: a meta-analysis and validated study in Chinese population.

BACKGROUND: Long non encoding RNA (lncRNA) plays a crucial role in breast cancer. However, the prognostic role of AFAP1-AS1 in breast cancer remains unclear. AIMS: To investigate the relationship between the expression of long non-coding RNA actin filament-associated protein1 antisense RNA1 (AFAP1-AS1) and prognosis of breast cancer. METHODS AND RESULTS: Meta-analysis was performed to explore the correlation between AFAP1-AS1 and breast cancer. The AFAP1-AS1expression in patients with breast cancer tissue and adjacent normal tissue from 153 patients was determined by qRT-PCR. Bioinformatics and Cox proportional-hazards risk model were used to explore the relationship between expression of AFAP1-AS1 and prognosis. The combined analysis revealed a significant correlation between AFAP1-AS1 expression and both overall survival (hazard ratios, HR = 2.33, 95%Cl: 1.94-2.81, p < 0.001) as well as disease-free survival/progression-free survival (HR = 2.94, 95%CI: 2.35-3.67, p < 0.001). The relation between expression of AFAP1-AS1 and breast cancer was determined in 153 breast cancer and adjacent normal tissues. The findings revealed a significantly higher AFAP1-AS1expression levels in breast cancer tissues compared to adjacent normal tissues (p < 0.001). Additionally, patients exhibiting heightened levels of AFAP1-AS1 expression were correlated with an unfavorable prognosis (HR = 2.35, 95%CI: 1.47-3.74, p < 0.001), which aligns consistently with the findings of the pooled analysis. The subgroup analysis of clinical characteristics revealed a significant association between high expression of AFAP1-AS1 and TNM stage (HR = 1.72, 95%CI: 1.11-2.65, p = 0.015). CONCLUSION: This study demonstrated that AFAP1-AS1 acts as an oncogene and may serve as a novel prognostic marker for breast cancer, particularly in the Chinese population.

Trends in gastric cancer incidence and mortality in Asia and association analysis with human development index, 1990-2019.

OBJECTIVES: To describe the epidemiological time trends and gender, age and regional differences of gastric cancer in Asia during 1990-2019, and to analyze the association between the human development index (HDI) and the statistical indicators of the burden of disease. METHODS: Describing trends in age-standardized incidence rates (ASIR) and age-standardized mortality rate (ASMR) in Asia from 1990 to 2019 based on GBD-reported population-based surveillance of gastric cancer in Asia. Obtained ASIR, ASMR, and mortality to incidence ratios (MIR) for gastric cancer in different countries in 2019, with association analysis by Kruskal-Wallis nonparametric test. RESULTS: The annual percentage change in ASIR and ASMR in Asia from 1990 to 2019 was - 1.20% and - 1.91%. Male gastric cancer patients have higher ASIR and ASMR than female gastric cancer patients. Decreasing trends in ASIR and ASMR for the total population in five Asian regions. From 1990 to 2019, the average annual change in ASMR was - 2.45%, - 1.43%, - 0.53%, - 0.62%, and - 0.27% for Central Asia, East Asia, high-income Asia-Pacific, South Asia, and Southeast Asia, respectively (p < 0.05). Both incidence and mortality were concentrated in the age groups of 85-89 and 89-94 years. Classifying Asian countries into different levels of HDI, only MIR was associated with HDI levels. CONCLUSION: ASIR and ASMR of gastric cancer in the total population, different regions, and countries in Asia from 1990 to 2019 showed an overall decreasing trend. The MIR index is suggestive of survival rates and the role of cancer care in individual countries. Asian countries should develop different strategies for gastric cancer screening and prevention according to high-risk age, high-risk gender and HDI.

Associations of physical activity types and intensity with cardiovascular diseases by age and gender among 18,730 Chinese adults.

The associations of physical activity (PA) intensity and types with CVD (cardiovascular diseases) in different population are inconsistent and remains not very clear. A total of 7854 males and 10,876 females over 15 years were selected by multistage random sampling methods. In males, moderate-intensity physical activity (MPA) had no effect, while vigorous-intensity physical activity (VPA) played a significant protective role (OR = 1.319 and 0.615). However, in females, both MPA and VPA had significant protective effects (OR = 0.593 and 0.537). VPA presented as a significant protective factor in stroke patients and combined CVDs for males in all age groups; however, in females, the results suggested that, for those aged over 60-74 years, MPA was a protective factor. Furthermore, for the middle-aged or younger participants, the area under the curves (AUCs) of work, housework, and leisure activity were generally higher than that of other types, while for patients aged over 60 years, the AUCs of sedentary time and sleep activity seemed much higher. VPA had a better protective effect for preventing cardiovascular events, while the young and female population could benefit from MPA as well. Regardless of the types of PA, leisure activities were strongly recommended, and young people were much more likely to benefit from exercise than older people.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study.

OBJECTIVE: This study aimed to screen and identify common variants and long noncoding RNA (lncRNA) single nucleotide polymorphisms (SNPs) associated with gastric cancer risk, and construct prediction models based on polygenic risk score (PRS). METHODS: The risk factors associated with gastric cancer were screened following meta-analysis and bioinformatics, verified by population-based case-control study. We constructed PRS and weighted genetic risk scores (wGRS) derived from the validation data set. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate model. RESULTS: The PRS was divided into 10 quantiles, with the 40-60% quantile as a reference. A risk gradient was revealed across quantile of the PRS, the risk of gastric cancer in the highest 10 quantile of PRS was 3.24-fold higher than that in control population (OR = 3.24, 95%CI: 2.07, 5.06). For NRI and IDI, PRS combinations were significantly improved compared to wGRS model combinations (P < 0.001). The model of PRS combined with lncRNA SNPs, smoking, drinking and Helicobacter pylori infection was the best-fitting model (AIC = 117.23, BIC = 122.31). CONCLUSION: The model based on PRS combined with lncRNA SNPs, H. pylori infection, smoking, and drinking had the optimal predictive ability for gastric cancer risk, which was helpful to distinguish high-risk groups.

Autoantibody signatures discovered by HuProt protein microarray to enhance the diagnosis of lung cancer.

This study aims to discover novel autoantibodies against tumor-associated antigens (TAAs) and establish diagnostic models for assisting in the diagnosis of lung cancer and discrimination of pulmonary nodules (PNs). Ten autoantibodies to TAAbs (TAAbs) were discovered by means of protein microarray and their serum level was also higher in 212 LC patients than that in 212 NC of validation cohort 1 (P < 0.05). The model 1 comprising 4 TAAbs and CEA reached an AUC of 0.813 (95%CI: 0.762-0.864) for diagnosing LC from normal individuals. Five TAAbs existed a significant difference between 105 malignant pulmonary nodules (MPNs) and 105 benign pulmonary nodules (BPNs) patients in validation cohort 2 (P < 0.05). Model 2 could distinguish MPNs from BPNs with an AUC of 0.845. High-throughput protein microarray is an efficient approach in discovering novel TAAbs which could be used as biomarkers in lung cancer diagnosis.

Micro-TESE surgery combined with ICSI regimen in the treatment of non-obstructive azoospermia patients and its effect analysis.

This study aimed to analyze the clinical effects of microdissection testicular sperm extraction (micro-TESE) surgery combined with an intracytoplasmic sperm injection (ICSI) regimen in the treatment of non-obstructive azoospermia (NOA) patients with different etiologies. In total, 128 NOA patients participated in this study, in which they received infertility treatment by micro-TESE surgery combined with an ICSI regimen, and all patients were divided into three groups [the Klinefelter syndrome (KS), the idiopathic and the secondary NOA groups]. In addition, the sperm retrieval rate (SRR), fertilization rate, embryo development status and clinical treatment effects were analyzed. Among the 128 NOA patients, the SRR of KS NOA patients was 48.65%, those of idiopathic and the secondary patients were 33.82% and 73.91%, respectively. Regardless of etiologies, there was no correlation with age, hormone value or testicular volume. Further analysis showed that the SRR of the KS group was positively related with testosterone (T) values, and the SRR of the secondary group had a positive relationship with follicle-stimulating hormone or luteinizing hormone values. In the subsequent clinical treatment, the retrieved sperm was subjected to ICSI and achieved good treatment effects, especially in the secondary group, and the implantation rate (55.56%) and clinical pregnancy rate (68.42%) were both higher than those of the idiopathic group (28.75% and 40.00%) and KS group (22.05% and 30.77%). Micro-TESE surgery combined with ICSI insemination is the most effective treatment regimen for NOA patients. The SRR of NOA patients with different etiologies are related to certain specific factors, and micro-TESE surgery seems to be the ideal and only way to have biological children.

Increased lncRNA AFAP1-AS1 expression predicts poor prognosis in gastric cancer: Evidence from published studies and followed up verification.

AIM: The purpose of this study was to clarify the influence of long non-coding RNA actin fiber-associated protein-1 antisense RNA 1 (lncRNA AFAP1-AS1) on the prognosis of gastric cancer (GC). METHODS: Based on meta-analysis, the association between the expression of AFAP1-AS1 and the prognosis of GC was estimated. GC tissue and non-cancer tissues from 136 patients were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and verified by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier and Cox proportional hazards models were conducted to analyze the correlation between AFAP1-AS1 expression and GC prognosis. RESULTS: The pooled analysis from five studies revealed that the AFAP1-AS1 expression was significantly associated with GC overall survival (hazard ratio (HR) = 2.49 and 95% confidence interval (95% CI): 2.02-3.08, p < 0.001). Compared with non-cancer tissues, AFAP1-AS1 expression level of GC tissues were significantly upregulated (p < 0.001), which was confirmed by the results of GEPIA. The area under the receiver-operating characteristic (ROC) curve was 0.893, and the high expression of AFAP1-AS1 was correlated with poor prognosis in patients with GC (p = 0.005). Clinical grade (HR = 1.912, 95% CI: 1.246-2.934, p = 0.003), pathologic tumor node metastasis (pTNM) (HR = 2.393, 95% CI: 1.431-4.033, p = 0.001), log odds of positive lymph nodes (LODDS) (HR = 2.910, 95% CI: 1.787-4.793, p < 0.001) and AFAP1-AS1 expression (HR = 2.393, 95% CI: 1.869-3.064, p < 0.001) were independent prognostic factors for GC revealed by multivariate Cox-regression analysis. CONCLUSION: This study demonstrated that the AFAP1-AS1 may be a novel biomarker for the diagnosis and prognosis of GC.

Estimation of gastric cancer burden attributable to Helicobacter pylori infection in Asia.

BACKGROUND: Helicobacter pylori causes large burden of gastric cancer (GC) in Asia. We aimed to comprehensively quantify the burden of GC attributable to H. pylori infection in Asia. METHODS: We searched related articles from January 1998 to December 2020 to obtain the prevalence and relative risks (or odds ratio) of GC associated with H. pylori in Asia. The burden of GC attributable to H. pylori infection was quantified by Population Attributable Fraction (PAF) and Disability-adjusted life-years (DALYs). RESULTS: We quantified the burden of GC attributable to H. pylori infection with 415.6 thousand DALYs and 38.03% PAF through the five included Asian countries in 2019. The study found that the burden had obvious regional differences. The DALYs ranged from 298.9 thousand in China to 1.9 thousand in Malaysia, and the PAFs were between 58.00% in Japan and 30.89% in China. The average prevalence of H. pylori in the included general population was estimated to be 56.29%. CONCLUSIONS: Helicobacter pylori poses a huge disease burden of GC to the population, and its eradication should receive attention, especially in the countries with high incidence of and mortality due to GC.

Melatonin Protects Mitochondrial Function and Inhibits Oxidative Damage against the Decline of Human Oocytes Development Caused by Prolonged Cryopreservation.

Melatonin (MT) can improve the effect of cryopreservation on oocytes by suppressing oxidative stress and maintaining the permeability of the oolemma. In this study, MT was firstly applied to human oocytes' cryopreservation to explore the effect of prolonged cryopreservation on developmental competence and its role. Collected in vitro-matured human oocytes were cryopreserved in MT-containing or MT-free medium for 0 and 6 months; after warming, viable oocytes were assessed for developmental viability, intracellular protein expression, mitochondrial function, and oxidation-antioxidant system. Meanwhile, fresh oocytes were set as the control. The results showed that with the extension of cryopreservation time, the developmental competence of oocytes gradually declined, accompanied by the down-regulation of most mitochondrial function-related proteins, the reduction in ATP and GSH production, the increase in ROS accumulation, and the aggravation of the imbalance of ROS/GSH in oocytes. However, the participation of MT seemed to effectively mitigate these negative effects. Therefore, we speculate that melatonin may maintain normal ATP production and ROS/GSH balance in cryopreserved oocytes by protecting mitochondrial function and inhibiting oxidative damage, thereby effectively maintaining the developmental competence of human oocytes in prolonged cryopreservation.

Maternal and neonatal exposure to risk factors for neonates with moderate or severe hypoxic ischemic encephalopathy: a cross-sectional study.

BACKGROUND: To investigate the association between maternal and neonatal exposure to the relevant influencing factors and risk of moderate or severe hypoxic ischemic encephalopathy (HIE), and the possible interactions in the Chinese population. METHODS: A cross-sectional study comprising 228 neonates from Henan Children's Hospital during the five-year period 2015-2020 in China was conducted. All neonatal basic demographic information and clinical records were documented from the neonatal HIE database. Comparisons between mild HIE and moderate or severe HIE were conducted with the t-test or Wilcoxon rank-sum test for continuous variables and the Chi-square test for categorical variables. Unconditional multiple logistic regression models were used to generate the odds ratios(ORs) and 95% confidence intervals(CIs). In addition, we also used an additive model to test for possible biological interactions among the factors. RESULTS: Of the 228 neonates, the males had a statistically significantly higher frequency compared with the females between the two groups (P = 0.030). Trend analysis results found that with the decreased of the neonatal birth weight, the detection rates of moderate or severe HIE in males and females were gradually increased (Ptrend < 0.05). The detection of moderate or severe HIE in males and females increased with the decreased of neonatal gestational age at birth(Ptrend < 0.05). However, no interaction was detected between neonatal birth weight and gestational age at birth based on the additive model, the Relative Excess Risk of Interaction and 95% CI was 0.821(-0.046,1.687). The adjusted multiple logistic regression model showed that low birth weight(ORadj:1.965, 95%CI:1.086-4.127),premature infant(ORadj:1.557, 95%CI:1.589-4.862),1-min Apgar's score < 7(ORadj:5.618, 95%CI:3.724-7.353),intrauterine distress(ORadj:4.916, 95%CI:3.431-7.398),amniotic fluid contamination (ORadj:3.965, 95%CI:2.153-5.782) significantly increased the risk of neonatal moderate or severe HIE. CONCLUSION: Neonates with low birth weight, premature infant,1-min Apgar's score < 7, intrauterine distress, amniotic fluid contamination are risk factors for moderate or severe HIE. Notably, we found no biological interaction between risk factors based on the additive model, these findings may help to inform prevention strategies, as this may effectively reduce the incidence of neonatal moderate or severe HIE.

Clinicopathological and prognostic value of lncRNAs expression in gastric cancer: A field synopsis of observational studies and databases validation.

BACKGROUND: The purpose of this study was to evaluate existing evidence in the field of long non-coding RNAs (lncRNAs) and prognosis of gastric cancer. METHODS: A comprehensive literature search was performed through the electronic database. The combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of overall survival (OS), disease-free survival (DFS), or progression free survival (PFS) were calculated to assess the strength of the association. Kaplan-Meier (KM) plotter was used to verify lncRNA HOX transcript antisense RNA (HOTAIR) expression and OS. RESULTS: Overall, a significant correlation between high lncRNAs expression and poor OS was explored in patients with gastric cancer (HR = 1.78, P < .001). Subgroup analysis based on statistical methods indicated the high expression of lncRNAs in log-rank (HR = 1.87, P < .001) and multivariate analysis (HR = 1.71, P < .001) were all significantly correlated with the poor OS. Clinicopathological parameters analysis showed the lncRNA expression were significantly associated prognosis, including TNM stage, tumor size, pathological differentiation, lymph nodes metastasis, distance metastasis, invasion depth and Lauren's classification. It was consistent with the verification results of bioinformatics database for lncRNA HOTAIR (P < .001). CONCLUSION: Our study confirmed the expression of lncRNAs and clinicopathological features may serve as effective indicators of prognosis in patients with gastric cancer.

Association between overweight, obesity and sleep duration and related lifestyle behaviors is gender and educational stages dependent among children and adolescents aged 6-17 years: a cross-sectional study in Henan.

BACKGROUND: To investigate the associations between overweight, obesity and sleep duration and related lifestyle behaviors in children and adolescents at different gender and educational stages. METHODS: A cross-sectional study comprising 18723 children and adolescents with a stratified cluster sampling method of Henan Province was conducted in 2019. A self-reported questionnaire was used to collect the information about demographic characteristics as well as sleep and lifestyle behaviors. Anthropometric measurements (height and weight) were taken and body mass index was computered as an indicator of overweight and obesity. The Chi-square test, one-way analysis of variance and multiple logistic regression were used to data analysis. RESULTS: Among the respondents, 12657(67.6%) were with normal weight, 3711(19.8%) were overweight and 2355(12.6%) were obesity. The average age of the participants was 12.6 years old. The proportion of overweight and obesity in the 10191 boys was 18.7% and 14.2% respectively. The proportion of overweight and obesity in the 8532 girls was 21.2% and 10.6% respectively. In trend analyses, sleep duration at different gender found with the decreased of the sleep duration, the proportions of overweight/obesity in boys and girls were gradually increased (Ptrend<0.05). In the adjusted logistic regression models, the results showed stratified by gender, compared with the recommended sleep duration group, students with very short sleep duration and short sleep duration showed an increased ORadj of 2.56 and 2.13 in boys, 2.34 and 2.09 in girls respectively. According to different educational stages, those in very short sleep duration and short sleep duration showed an increased ORadj of 2.15 and 1.69 in primary school, 2.26 and 1.58 in middle school, 2.23 and 1.51 in high school respectively. CONCLUSIONS: Children and adolescents with very short sleep duration and short sleep duration may increase the risk of overweight/obesity, the association differed based on the gender-specific and educational stages-specific. Gender and educational stages should be regarded as specific characteristics for the effects on overweight/obesity in Henan Province.

Embryological Characteristics of Human Oocytes With Agar-Like Zona Pellucida and Its Clinical Treatment Strategy.

Zona pellucida (ZP) abnormalities are the cause of low fertility or infertility, agar-like ZP is more common in abnormal ZP. The purpose of this exploration is to systematically analyze the fertilization competence of agar-like ZP oocytes, the development characteristics of subsequent embryos as well as the results of embryo transfer, aiming to explore effective clinical treatment strategies. A total of 58 patients with agar-like ZP were set as the case group and the control group involved 3866 patients, in which the patients' oocytes presented normal ZP. BMI, basal hormone levels, and hormone levels were similar in both groups. The case patients suffered significantly longer infertility years than control (p<0.05), and most patients were diagnosed with pelvic inflammatory diseases. A distinct difference was observed in the structure of oocyte corona cumulus complexes between the two groups. The embryo development parameters, which include the rates of cleavage, high-quality embryo, blastocyst, and high-quality blastocyst in the case group were greatly lower than that in the control group (p<0.05). The rates of cumulative clinical pregnancy and live birth were comparable between the two groups. In the subsequent follow-up, thirty-four of the 58 patients receiving intracytoplasmic single sperm injection (ICSI) or early rescue ICSI (R-ICSI) treatment successfully gave birth to babies, and all of the newborns were with no neonatal defects. In addition, the fertilization rate of the R-ICSI group was significantly lower than that of the ICSI group (p<0.05). The occurrence of agar-like ZP impairs the development competence of human oocytes, however, the human oocytes with agar-like ZP can develop into healthy offspring, and an ICSI regimen is the optimal treatment strategy for them.

Application of Two Blastocyst Biopsy Strategies in Preimplantation Genetic Testing Treatment and Assessment of Their Effects.

Background: Blastocyst biopsy has become the most mainstream biopsy method. Currently, there are two blastocyst biopsy strategies. Many studies have compared the advantages and disadvantages between blastomere and blastocyst biopsy, but fewer articles have compared the two blastocyst biopsy strategies. For the moment, no published studies have explored the entire set of information on embryo development, next-generation sequencing results, and clinical outcomes, including the baby's health status with the two blastocyst biopsy strategies. Methods: A total of 323 preimplantation genetic testing cycles from April 2018 to May 2020, including 178 cycles with Strategy A and 145 cycles with Strategy B. Strategy A was to create a laser-assisted zona pellucid opening for cleavage embryo on the third day after insemination, but Strategy B was not. Strategy A performed a biopsy for artificially assisted hatching blastocysts, while Strategy B performed a biopsy for expanded blastocysts on day 5 or 6. In this study, embryo development, next-generation sequencing results, pregnancy outcomes, and offspring health of the two strategies were compared and analyzed. Results: There were no statistical differences between the two groups in the rate of fertilization, blastocyst and abortion. The rate of cleavage from Strategy A was slightly higher than Strategy B, and the rate of high-quality cleavage embryo was lower than Strategy B, while the rate of high-quality blastocyst was higher than Strategy B. The rate of no-results blastocyst was significantly lower than Strategy B. In particular, the rate of biochemical pregnancy, clinical pregnancy, and live birth of Strategy A were significantly lower than those of Strategy B. The average Apgar scores of newborns were ≥8 in both groups, and there was no significant difference in average height and weight. In Strategy A, a baby was born with thumb syndactyly, and Strategy B had no congenital disabilities. Conclusions: Blastocyst biopsy strategy without laser-assisted zona pellucid drilling on day 3 achieves better clinical treatment effects. Therefore, Strategy B is an optimal treatment regime for PGT.

Effect of melatonin on the clinical outcome of patients with repeated cycles after failed cycles of in vitro fertilization and intracytoplasmic sperm injection.

To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10-11, 10-9, 10-7 and 10-5 M MT medium respectively, and 10-9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10-9 M MT, these 140 MT culture cycles were designated as the experimental group (10-9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10-9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10-9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10-9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.Trial registration: ChiCTR2100045552.