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 To analyze the circuit-qi patterns during early embryonic period and at conception in congenital heart disease(CHD)patients based on the five-circuit and six-qi theory,and to explore the pathogenesis and etiology of CHD from a circuit-qi perspective.Methods With 16 400 non-CHD individuals as the healthy control group,a statistical analysis was performed for the circuit-qi patterns during early embryogenesis and at conception in 4 100 CHD patients(CHD group).Results The following factors were identified as significant predisposing factors for CHD:yearly circuit being excessive fire circuit during early embryogenesis,yearly qi being taiyang cold water of celestial qi combined with taiyin damp earth of terrestrial qi during early embryogenesis,yearly circuit being concurrent excessive fire circuit and earth circuit deficiency at conception,and yearly qi being taiyin damp earth of terrestrial qi paired with jueyin wind wood of celestial qi at conception(all P＜0.05 or P＜0.01).Conclusion There is a certain correlation between circuit-qi endowment during embryonic development and the prevalence of CHD.The core pathogenesis of CHD is rooted in heart-spleen insufficiency,with hyperactive heart-fire and cold kidney-water as its manifestations,and spleen deficiency failing in transportation serves as an important contributing factor in the development and progression of CHD.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective To investigate the relationship between peripheral blood thyroxine levels and cardiac function in elderly patients with chronic heart failure.Methods Seventy patients with chronic heart failure admitted into our hospital from January 2016 to December 2017 were enrolled as the study group,and 70 healthy subjects were collected as the control group.Left ventricular ejection fraction(LVEF)and serum thyroxine levels were measured in both groups.Results LVEF,serum levels of total triiodothyronine(TT3)and total thyroxine(TT4)were lower in the study group than in the control group[(37.3±2.4)％ vs.(58.5 ± 5.3) ％,(87.4 ± 8.7) mmol/L vs.(120.8±10.4) mmol/L,(8.6±1.7)mmol/L vs.(10.1 ± 1.3)mmol/L,t =30.486,20.609 and 5.864,P =0.000].LVEF,TT3 and TT4 in patients with grade lⅡ 、grade Ⅲ and grade Ⅳ Cardiac insufficiency were [(42.3±2.2)％、(37.9± 1.0)％ and(31.8±1.5)％,(104.2± 15.4) mmol/L、(89.7±4.6) mmol/L and(72.0±7.2)mmol/L,(9.3± 1.8)mmol/L、(8.8± 1.3) mmol/L and (8.1 ± 0.9) mmol/L]respectively.Serum levels of TT3 and TT4 and LVEF steadily declined as cardiac dysfunction grew more severe in patients with chronic heart failure(P =0.000).Conclusions Patients with chronic cardiac insufficiency are often combined with euthyroid sick syndrome,and serum levels of TT3 and TT4 can indicate the degree of abnormal cardiac systolic function.Therefore,low serum levels of T3 and T4 can be used as indicators for poor prognosis in patients with chronic heart failure.

The key factor of chemotherapy for brain disorders is to penetrate brain blood barrier(BBB). Receptor mediated en-docytosis is one of the mechanisms for drug carriers to cross the BBB. Angiopep-2(ANG)can specifically bind to low density lipopro-tein receptor-related proteins 1(LRP-1)overexpressed on BBB and glioma cells,thus exhibits a higher LRP-mediated BBB penetra-tion capability. Its targeting efficiency is higher than that of other targeting molecules such as transferrin and(TF)lactoferrin(LF). This paper introduces the structure and function of ANG,and its application in brain targeting delivery systems,in order to provide references for research and development of brain targeting preparations and guidance for therapy of brain diseases.

Objective To evaluate the risk of the occurrence of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer in the oral HPV carriers through a population-based investigation in Shanghai.Methods A total of 1200 cases of outpatients who attended the annual cervical examination and 50 preoperational cases of inpatients with CIN Ⅲ or invasive cervical cancer were enrolled from three clinical centers in Shanghai.The oral HPV infection was determined by real-time PCR.In 1200-case cross-sectional study,the incidence rate of CIN was compared between the oral HPV positive and negative cohort.In 1250-case case-control study,the positive rate of oral HPV DNA test was compared among normal control group,CIN Ⅰ-Ⅲ,and invasive cancer case groups,and all odds ratio (OR) values were calculated,respectively.The HPV transmission-related demographic and behavioral characters of the oral HPV carriers were also analyzed.Results The oral HPV carriers accounted for 5.9％ (71/1200) of the investigated outpatients.The oral HPV DNA positive rates were gradually increased with the cervical disease grades,which were 5.8％ (68/1182,normal),2/13 (CIN Ⅰ),1/5 (CIN Ⅱ),31.4％ (11/35,CIN Ⅲ) and 5/15 (invasive cancer).In cross-sectional cohort studies,the relative risks (RR) of CIN Ⅰ,Ⅱ were 2.9 and 4.0 for oral HPV carriers,respectively.In case-control study,the OR values for CIN Ⅰ-Ⅲ and invasive cervical cancer were 3.1(95％CI:1.6-10.1),4.2(95％CI:1.7-28.4),7.1(95％CI:4.8-19.8) and 10.1 (95％ CI:3.2-32.1),respectively.The oral sex and multi-sexual partner were two major risk factors for the oral and cervical HPV co-infection,HPV-related cervical cancer and precancerous diseases according to behavioral analysis.Conclusions There are complicated transmission pathways between oral and cervicalHPV.Oral HPV carriers should be intensively followed up and their oral HPV infection and HPV-related cervical diseases should be treated together.

Objective To investigate the function of the hypothalamic-pituitary-adrenal (HPA) axis in postmenopausal women with type 2 diabetes and visceral obesity. Methods Subjects were divided into three groups:control group(group C),type 2 diabetes mellitus with non-obesity group (group DM) and type 2 diabetes mellitus with visceral obesity group (group DM + OB). General clinical characteristics, morning blood cortisol concentrations and 24 h urine free cortisol of three groups were compared. Serum cortisol levels were also compared after 0.25 mg dexamethasone suppression test and followed by oral intake of 25 mg cortisone acetate. Results (1) There were no significant differences in basal cortisol levels, but after inhibition with dexamethasone the group DM + OB showed significantly higher cortisol level than that in the control group (P < 0.01). (2) Conversion of oral cortisone to plasma cortisol differed significantly between the group C (lower) and group DM + OB (P < 0.05). (3) Plasma LH and FSH concerntrations were significantly lower in group DM + OB compared with group C (P < 0.01). Conclusion In the postmenopausal women with type 2 diabetes mellitus, the negative feedback mechanism and hepatic 11β-HSD-1 activity were impaired, especially in those with visceral obesity.