BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Objective This study aims to systematically evaluate the protective role of quercetin(QCT),a naturally occurring flavonoid,against oxidative damage in human endometrial stromal cells(HESCs)induced by hydrogen peroxide(H2O2).Oxidative stress,such as that induced by H2O2,is known to contribute significantly to cellular damage and has been implicated in various reproductive health issues.The study is focused on investigating how QCT interacts with specific molecular pathways to mitigate this damage.Special attention was given to the p38 MAPK/NOX4 signaling pathway,which is crucial to the regulation of oxidative stress responses in cellular systems.By elucidating these mechanisms,the study seeks to confirm the potential of QCT not only as a protective agent against oxidative stress but also as a therapeutic agent that could be integrated in treatments of conditions characterized by heightened oxidative stress in endometrial cells.Methods In vitro cultures of HESCs were treated with QCT at different concentrations(0,10,20,and 40 μmol/L)for 24 h to verify the non-toxic effects of QCT on normal endometrial cells.Subsequently,250 μmol/L H2O2 was used to incubate the cells for 12 h to establish an H2O2-induced HESCs injury model.HESCs were pretreated with QCT for 24 h,which was followed by stimulation with H2O2.Then,CCK-8 assay was performed to examine the cell viability and to screen for the effective intervention concentration.HESCs were divided into 3 groups,the control group,the H2O2 model group,and the H2O2+QCT group.Intracellular levels of reactive oxygen species(ROS)were precisely quantified using the DCFH-DA fluorescence assay,a method known for its accuracy in detecting and quantifying oxidative changes within the cell.The mitochondrial membrane potential was determined by JC-1 staining.Annexin Ⅴ/PI double staining and flow cytometry were performed to determine the effect of QCT on H2O2-induced apoptosis of HESCs.Furthermore,to delve deeper into the cellular mechanisms underlying the observed effects,Western blot analysis was conducted to measure the expression levels of the critical proteins involved in oxidative stress response,including NADPH oxidase 4(NOX4),p38 mitogen-activated protein kinase(p38 MAPK),and phosphorylated p38 MAPK(p-p38 MAPK).This analysis helps increase understanding of the specific intracellular signaling pathways affected by QCT treatment,giving special attention to its potential for modulation of the p38 MAPK/NOX4 pathway,which plays a significant role in cellular defense mechanisms against oxidative stress.Results In this study,we started off by assessing the toxicity of QCT on normal endometrial cells.Our findings revealed that QCT at various concentrations(0,10,20,and 40 μmol/L)did not exhibit any cytotoxic effects,which laid the foundation for further investigation into its protective roles.In the H2O2-induced HESCs injury model,a significant reduction in cell viability was observed,which was linked to the generation of ROS and the resultant oxidative damage.However,pretreatment with QCT(10 μmol/L and 20 μmol/L)significantly enhanced cell viability after 24 h(P<0.05),with the 20 μmol/L concentration showing the most substantial effect.This suggests that QCT can effectively reverse the cellular damage caused by H2O2.Furthermore,the apoptosis assays demonstrated a significant increase in the apoptosis rates in the H2O2 model group compared to those in the control group(P<0.01).However,co-treatment with QCT significantly reversed this trend(P<0.05),indicating QCT's potential protective role in mitigating cell apoptosis.ROS assays showed that,compared to that in the control group,the average fluorescence intensity of ROS in the H2O2 model group significantly increased(P<0.01).QCT treatment significantly reduced the ROS fluorescence intensity in the H2O2+QCT group compared to the that in the H2O2 model group,suggesting an effective alleviation of oxidative damage(P<0.05).JC-1 staining for mitochondrial membrane potential changes revealed that compared to that in the control,the proportion of cells with decreased mitochondrial membrane potential significantly increased in the H2O2 model group(P<0.01).However,this proportion was significantly reduced in the QCT-treated group compared to that of the H2O2 model group(P<0.05).Finally,Western blot analysis indicated that the expression levels of NOX4 and p-p38 MAPK proteins were elevated in the H2O2 model group compared to those of the control group(P<0.05).Following QCT treatment,these protein levels significantly decreased compared to those of the H2O2 model group(P<0.05).These results suggest that QCT may exert its protective effects against oxidative stress by modulating the p38 MAPK/NOX4 signaling pathway.Conclusion QCT has demonstrated significant protective effects against H2O2-induced oxidative damage in HESCs.This protection is primarily achieved through the effective reduction of ROS accumulation and the inhibition of critical signaling pathways involved in the oxidative stress response,notably the p38 MAPK/NOX4 pathway.The results of this study reveal that QCT's ability to modulate these pathways plays a key role in alleviating cellular damage associated with oxidative stress conditions.This indicates not only its potential as a protective agent against cellular oxidative stress,but also highlights its potential for therapeutic applications in treating conditions characterized by increased oxidative stress in the endometrium,thereby offering the prospect of enhancing reproductive health.Future studies should explore the long-term effects of QCT and its clinical efficacy in vivo,thereby providing a clear path toward its integration into therapeutic protocols.

Objective The objective of this study is to investigate whether there is a correlation between a high TyG index(serum triglyceride glucose index)and higher mortality rates among patients undergoing peritoneal dialysis(PD).Methods This study utilized a single-center retrospective cohort as the basis for its methods..From January 1,2007 to December 31,2015,a total of 519 PD patients kept under observation until December 31,2018.There searchers employed the Kaplan-Meier method and Cox proportional hazards modelsto examine the cor-relation between TyG index levels and mortality.Results Over a period of 40.5 months,104(20.0%)individuals with Parkinson's disease passed away,with 55(52.9%)of these deaths attributed to cardiovascular disease(CVD).The serum median TyG index at baseline was 8.44(6.48,11.94).Through Cox regression analysis subject to the adjustments of such parameters as gender,age,body mass index(BMI),presence of cardiovascular disease,hypertension,diabetes mellitus,hemoglobin,serum albumin,serum Ferritin,total cholesterol,renal residual function(RRF),An increased risk of all-cause mortality(HR = 2.22,95%CI:1.43～3.44,P＜0.001)and CVD mortality(HR = 2.50,95%CI:1.34～4.65,P = 0.004)was observed with a higher baseline TyG index(8.44).A comparable impact was observed in the correlation between the average TyG index over time(TA-TyG index)and both all-cause mortality and CVD mortality.(HR = 1.90,95%CI:1.25～2.90,P = 0.003;HR = 2.05,95%CI:1.14～3.70,P = 0.017,respectively).Conclusion PD patients with a higher serum TyG index have a greater risk of all-cause mortality and mortality related to cardiovascular disease.

Objective To investigate the effects and molecular mechanisms of decorin(DCN),imatinib mesylate,and sunitinib malate on the malignant phenotype of gastrointestinal stromal tumor cells.Methods Western blotting was used to detect changes in the expres-sion of DCN and its downstream proteins after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in gastrointestinal stromal tumor cells(GIST-882).Cell counting kit-8,scratch,and Transwell assays were performed to validate the changes in cell proliferation,migration,and invasion abilities after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells.Results Compared with the control group,DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells increased the expression levels of DCN protein,decreased the expression levels of epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase 1/2(ERK1/2),and phosphorylated ERK1/2(p-ERK1/2)proteins,and significantly reduced cell proliferation,migration,and invasion abilities.Conclusion DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination affect the MAPK signaling pathway by downregulating the expression of EGFR,thereby regulating the proliferation,migra-tion,and invasion abilities of gastrointestinal stromal tumor cells.

Objective:To summarize the prenatal diagnosis features, classification and pregnancy outcome of anomalous origin of one pulmonary artery branch from the aorta (AOPA).Methods:This study involved 14 cases who were prenatally diagnosed with AOPA in Guangzhou Women and Children's Medical Center between June 2016 and August 2022. Prenatal and postnatal echocardiographic features, postpartum diagnosis, surgical treatment and pregnancy outcome in these cases were summarized and analyzed by descriptive analysis.Results:Out of the 14 fetuses, there were seven fetuses with proximal-type AOPA (including three isolated AOPA, three Berry syndrome and one with interruption of the aortic arch, aorticopulmonary septal defect and ventricular septal defect) and another seven with isolated distal-type of AOPA. Among the seven cases of proximal-type AOPA, two were terminated and five were born alive. The postpartum diagnosis was consistent with the prenatal diagnosis in the five babies who later underwent surgical treatment with good outcomes. Among the seven cases of distal-type AOPA, one was terminated; two were initially diagnosed as AOPA in the neonatal period but then as unilateral absence of pulmonary artery (UAPA) due to tapering or closure of the ductus arteriosus during follow-up; the other four were confirmed with UAPA after delivery. All of the six neonates underwent surgical treatment with good outcomes.Conclusions:Prenatal diagnosis and classification of AOPA should be as accurate as possible. It is recommended that the distal-type of AOPA could be diagnosed as UAPA after delivery and treated according to UAPA. Both kinds of patients should be treated with surgery timely after delivery to ensure a good prognosis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of childbearing age. Its etiology is complex and its clinical manifestations are highly heterogeneous. Poor endometrial receptivity is an important reason for pregnancy failure after PCOS ovulation induction in spite of high ovulation rate. This paper reviewed the relationship between endometrial receptivity and abnormal mechanisms such as oxidative stress, chronic low-grade inflammation, metabolic abnormalities, endocrine disorders and endometrial hormone receptors in order to provide theoretical reference for clinicians to diagnose and treat PCOS women involving the endometrial receptivity.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of childbearing age. Its etiology is complex and its clinical manifestations are highly heterogeneous. Poor endometrial receptivity is an important reason for pregnancy failure after PCOS ovulation induction in spite of high ovulation rate. This paper reviewed the relationship between endometrial receptivity and abnormal mechanisms such as oxidative stress, chronic low-grade inflammation, metabolic abnormalities, endocrine disorders and endometrial hormone receptors in order to provide theoretical reference for clinicians to diagnose and treat PCOS women involving the endometrial receptivity.

Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
Micelles ; Drug Carriers/chemistry* ; Polymers/chemistry* ; Fluorescence Resonance Energy Transfer ; Polyethylene Glycols/chemistry*

Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the
Biocompatible Materials ; Hydrogels ; Micelles ; Nanocomposites ; Polymers

BACKGROUND:With the development and improvement of liver transplantation technology, patients waiting for or undergoing liver transplantation have continued to increase in number. Due to their fears and concerns about post-transplantation rehabilitation, patients are under physical and mental stress, most of whom are shown to have a variety of mental disorders that affect rehabilitation. At present, mental problems of liver transplant patients are more concentrated in post-transplantation research, while patients waiting for liver transplantation do not get enough mental assessment and intervention.
OBJECTIVE:To investigate the suitable mode of cognitive-behavioral therapy for liver transplant recipients waiting for donor liver and to evaluate the effect to improve patient’s physical and mental state.
METHODS:Twelve liver transplant patients who underwent pre-transplantation assessment were randomly divided into experimental group and control group, each group with six cases. The control group received conventional treatment. The experimental group received cognitive-behavioral therapy in addition to conventional treatment. Self-rating anxiety scale (SAS) and vital signs were measured in the two groups on admission, 1 week and 3 weeks after admission.
RESULTS AND CONCLUSION:The SAS score of the experimental group was lower than that of the control group at 1 and 3 weeks after admission, and SAS score decreased as the intervention extended. The systolic blood pressure of the experimental group was lower than that of the control group at 3 weeks after admission, but there was no significant difference in diastolic blood pressure between two groups. The heart rate of the experimental group was lower than that of the control group at 1 and 3 weeks after admission. The respiratory rate of the experimental group was lower than that of the control group at 3 weeks after admission. Cognitive-behavioral therapy can reduce the level of anxiety and keep vital signs stable with good feasibility and effectiveness in patients waiting for liver transplantation.