Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women that is a leading cause of infertility. Follicular development disorder, as the main cause of oligoovulation, is the key factor affecting the fertility of PCOS patients. Among them, the disorder of the ovarian microenvironment is an important inducement for follicular development disorder. Emerging research highlights that the ovarian microenvironment plays a sophisticated role in follicular development and maturation through various mechanisms, including the cellular constituents within the ovary, the extracellular matrix's structural support, adequate vascular supply, and the regulation of hormonal and growth factor signaling. These factors collectively ensure the normal growth and ovulation of follicles, thereby safeguarding female reproductive health. In women with PCOS, however, the ovarian microenvironment is compromised, leading to excessive extracellular matrix deposition and fibrosis, abnormalities in vascular architecture and function, immune-inflammatory reactions, and metabolic disturbances. These anomalies collectively hinder follicular growth and development, resulting in ovulation disorders. This comprehensive review will delve into the intricacies of these disruptions and their implications for fertility in PCOS patients.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

OBJECTIVE To build a Tibetan-language medication service platform based on"internet+"and evaluate its effect on improving medication compliance and safety of Tibetan patients with chronic disease.METHODS Medication guidance contents of commonly used drugs in the outpatient department were summarized,translated and recorded in Tibetan-language or video to form a"text-audio-video"multi-dimensional"internet+"Tibetan-language medication service platform.A total of 387 Tibetan outpatients with chronic disease in our hospital after the implementation of"internet+"Tibetan-language medication service platform(from January 2024 to June 2024)in our hospital were selected as the intervention group,and 387 Tibetan outpatients before the implementation(from January 2023 to June 2023)were selected as the control group.Patients in the control group received conventional window-based Chinese-language medication services,while patients in the intervention group received both conventional window-based Chinese-language medication service and"internet+"Tibetan-language medication service.The medication compliance of patients was evaluated using the 12-item Medication Compliance Scale.A six-level causality assessment was conducted as the principles for analyzing adverse drug reactions(ADR)set by the National Center for ADR Monitoring.Additionally,statistics were compiled on the occurrence of ADR that were assessed as"definite""probable"or"possible"in the causality assessment.RESULTS The proportion(31.0%)of patients with good medication compliance and compliance scores[39.0(37.0,42.0)]of patients in the intervention group were significantly better than control group[7.0%,21.0(19.0,23.0)](P＜0.05).There were no statistically significant differences in the incidence of various types of ADR or the overall incidence between the two groups(P＞0.05).CONCLUSIONS The"internet+"Tibetan-language medication service platform is constructed successfully;the service can effectively improve the medication compliance of Tibetan-language patients,but its effect on improving the medication safety of patients is limited.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women that is a leading cause of infertility. Follicular development disorder, as the main cause of oligoovulation, is the key factor affecting the fertility of PCOS patients. Among them, the disorder of the ovarian microenvironment is an important inducement for follicular development disorder. Emerging research highlights that the ovarian microenvironment plays a sophisticated role in follicular development and maturation through various mechanisms, including the cellular constituents within the ovary, the extracellular matrix's structural support, adequate vascular supply, and the regulation of hormonal and growth factor signaling. These factors collectively ensure the normal growth and ovulation of follicles, thereby safeguarding female reproductive health. In women with PCOS, however, the ovarian microenvironment is compromised, leading to excessive extracellular matrix deposition and fibrosis, abnormalities in vascular architecture and function, immune-inflammatory reactions, and metabolic disturbances. These anomalies collectively hinder follicular growth and development, resulting in ovulation disorders. This comprehensive review will delve into the intricacies of these disruptions and their implications for fertility in PCOS patients.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

AIM:To compare the recovery of psy-chomotor function after intravenous anesthesia with remazolam or propofol compound alfentanil in patients undergoing painless gastrointestinal en-doscopy.METHODS:78 patients undergoing pain-less gastrointestinal endoscopy were randomly di-vided into group RA and group PA.Remiazolam or propofol combined with alfentanil were given intra-venously in group RA or group PA.The blood pres-sure,heart rate,respiratory rate and saturation of puls oxygen were recorded before procdure(T1),during checking(T2),awaking from anaesthesia(T3)and at discharging from PACU(T4).Psychomo-tor function,as measured by the Trieger's dot test(TDT)and digit symbol substitution test(DSST),were evaluated before anesthesia(T1),at discharg-ing from PACU(T4),1 h(T5)and 2 h(T6)after checking.RESULTS:From assessment of the TDT,number of dots missed(NDM),maximum distance of dots missed(MDDM)and average distance of dots missed(ADDM)at T4,T5 were significantly lower than those at T1 in two groups.The comple-tion rates and accuracy rates of DSST at T4,T5 were significantly lower than those at T1.Results of TDT and DSST at T6 were not significantly differ-ent to those at T1.The results of NDT,MDDM and ADDM at T4,T5 in group RA were significantly low-er than those in group PA.The completion rates and accuracy rates of DSST at T4,T5 in group RA increased significantly compared with group PA.Compared to group PA,the incidence of hypoten-sion was significantly lower in group RA.There was no significant difference in the incidence of respira-tory depression between the two groups.CONCLU-SION:Psychomotor function was fully recovered 2 h after surgery when remazolam compound alfent-anil was used for painless gastrointestinal endosco-py.Compared with propofol,psychomotor function recovery in the remazolam group was faster and there were fewer adverse effects after surgery in group RA.

Objective:To investigate the short-term effects of acute fructose intake on serum antioxidant capacity and liver enzymes in healthy young adults.Methods:From January to June 2019, 64 healthy young subjects were recruited, and divided into 75 g glucose group, 25 g fructose group, 50 g fructose group and 75 g fructose group by random digits table method with 16 cases each. The subjects took corresponding amounts of glucose or fructose according to grouping. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione peroxidase (GPX), superoxide dismutase (SOD), C-Jun amino terminal kinase (JNK), malondialdehyde (MDA) and 8-OH deoxyguanine (8-OHdG) before taking sugar and 30, 60, 120, 180 min after taking sugar, and the changes of ALT, AST and LDH at 30, 60, 120 and 180 min after taking sugar compared with that before taking sugar.Results:One case in 50 g fructose group, 2 cases in 75 g fructose group and 1 case in 75 g glucose group dropped out due to adverse reaction; finally, 15 cases in 75 g glucose group, 16 cases in 25 g fructose group, 15 cases in 50 g fructose group and 14 cases in 75 g fructose group completed the study. The increase of ALT and AST after taking sugar in 25 g fructose group, 50 g fructose group and 75 g fructose group was significantly higher than that in 75 g glucose group, and there were statistical differences ( P<0.05); there was no statistical difference in the change of LDH after taking sugar among 4 groups ( P>0.05). One hundred and eighty min after taking sugar, the receiver operating characteristic (ROC) curve analysis result showed that there were no statistical differences in the areas under curve of ALT, AST and LDH among 4 groups ( P>0.05). There was no statistical difference in SOD before taking sugar among 4 groups ( P>0.05); the SOD 60 min after taking sugar in 50 g fructose group and 75 g fructose group, and SOD 180 min after taking sugar in 25 g fructose group, 50 g fructose group and 75 g fructose group were significantly lower than those in 75 g glucose group: (4.84 ± 1.88) and (4.38 ± 1.12) μg/L vs. (6.25 ± 1.65) μg/L, (4.46 ± 1.66), (5.22 ± 1.66) and (3.99 ± 0.96) μg/L vs. (6.55 ± 1.78) μg/L, and there were statistical differences ( P<0.05). There were no statistical differences in the changes of JNK, GPX, MDA and 8-OHdG before and after taking sugar among 4 groups ( P>0.05). The ROC curve 180 min after taking sugar analysis result showed that the area under curve of SOD in 75 g fructose group was significantly lower than that in 75 g glucose group (9.06 ± 1.88 vs. 12.74 ± 3.15), and there was statistical difference ( P<0.05); there were no statistical differences in the areas under curve of GPX, JNK, MDA and 8-OHdG among 4 groups ( P>0.05). Conclusions:Acute fructose intake can lead to the decrease of antioxidant capacity, and the increasing of oxidative damage and liver enzymes in healthy adults.

Objective:To investigate the correlation between serum uric acid levels and thyroid hormones in hospitalized elderly gout patients.Methods:A total of 646 hospitalized gout patients, including 616 males and 30 females, aged(68.8±5.1)years, who were hospitalized at the Department of Gout, Chu Hsien-I Memorial Hospital from April 2014 to December 2019, were retrospectively analyzed.Clinical information was collected and relevant biochemical tests were conducted.Serum uric acid (SUA)levels were divided into quartiles and their associations with thyroid hormone levels were analyzed.Results:With the increase of SUA, body mass index, the prevalence of obesity, the prevalence of dyslipidemia, and the prevalence of fatty liver, the number of involved joints, cholesterol, low-density lipoprotein cholesterol, triacylglycerol, and homeostasis model assessment trended upward significantly( P<0.05); FUA showed a downward trend( F=9.42, P>0.05). The prevalence of subclinical hypothyroidism in older patients was 11.3%(73 cases). With the increase of SUA, the prevalence of subclinical hypothyroidism and free triiodothyronine levels showed an upward trend, whereas free thyroxine levels showed a downward trend( P<0.01). Conclusions:In elderly gout patients, the prevalence of subclinical hypothyroidism increases with SUA levels.Hyperuricemia and multiple metabolic disorders are independent risk factors for subclinical hypothyroidism in these patients.

Objective:To investigate the acute effect of fructose intake on serum uric acid, plasma glucose, and insulin levels in healthy young adults.Methods:Sixty-four healthy young subjects were recruited, and randomized to 25 g, 50 g, 75 g fructose group, and 75 g glucose group( n=16) by random number table. The anthropometric parameters, blood pressure, heart rate were measured. Several biochemistry parameters were measured, which were serum uric acid, plasma glucose, plasma insulin, serum total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C) at 0, 60, 120, and 180 min before and after ingestion of fructose or glucose. Results:(1) The serum uric acid level after fructose administration increased significantly than after glucose over 3 h, and peaked at 60 min. The increment of uric acid at 60 min and area under curve of uric acid at 3 h after fructose administration were significantly higher than those of glucose. The increment of uric acid at 60 min increased significantly as fructose dose was increased, especially in the 75 g fructose (increment rate of uric acid at 60 min in 25g, 50g, 75g fructose groups were 9.33%, 13.11%, 17.69% vs 0.75% respectively; Areas under curve of uric acid were 1 674.1±410.38, 1 598.3±417.03, 1 504.6±292.46 vs 1 434.8±328.94, P<0.01). (2) The glucose and insulin levels increased after fructose/glucose intake in four groups with top augment in glucose followed by 75 g fructose. The increase peaked at 30 min, began to decline at 120 min, and returned to fasting level at 180 min. The area under curve of insulin at glucose group was significantly higher than those among fructose groups. With the increase of fructose dose, the increment rate of glucose and insulin at 60 min also increased obviously, especially in the 75 g fructose (the increment rates of glucose at 60 min in 25 g, 50 g, 75 g fructose, 75 g glucose were 7.40%, 8.29%, 13.74%, 28.22% respectively; The increment rates of insulin at 60 min were 54.29%, 115.25%, 185.58%, 730.31% respectively, P<0.01). (3) There were no difference of cholesterol, triglyceride, and LDL-C after fructose/glucose ingestion. Conclusion:Acute fructose intake can lead to the increase of uric acid and insulin; Moreover, the increments of uric acid and insulin after fructose consumption were dependent on fructose dose.