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*

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Objective The radioactivity level survey was carried out in Weizhou Island area of Beihai, to comprehensively master the radiation environment status in the area, understand the natural radioactivity level and its distribution law, and provide basic data for scientific evaluation of radiation environment quality. Methods According to the relevant standards and technical specifications, the air absorbed dose rate of gamma radiation in Weizhou Island area was monitored from April 2020 to March 2021, the concentrations of radionuclides in water, soil and other environmental samples were sampled and analyzed, and the monitoring results were analyzed and discussed in combination with the regional characteristics. Results The results show that the air absorbed dose rate of gamma radiation in Weizhou Island area ranges from 0.2～122 nGy/h; the activity concentrations of ²³⁸U, ²²⁶Ra, ²³²Th, ⁴⁰K and ¹³⁷Cs in solid samples range 17.0～37.3 Bq/kg, < 0.501～29.5 Bq/kg, < 0.766～54.3 Bq/kg, 18.7～369 Bq/kg and < 0.212～1.48 Bq/kg, respectively, the concentrations of U and Th in well water and reservoir water range 0.065～0.25 μg/L, 0.046～0.079 μg/L, the activities of ²²⁶Ra, ⁴⁰K, total α and total β range 1.42～3.08 mBq/L, 0.069～0.231 Bq/L, 0.025～0.163 Bq/L, 0.082～0.572 Bq/L, respectively, the concentrations of U and Th in seawater samples range 1.81～2.25 μg/L, 0.634～0.648 μg/L, and the activities of ²²⁶Ra, ⁴⁰K, ⁹⁰Sr and ¹³⁷Cs range 9.38～19.7 mBq/L, 11.3～11.8 Bq/L、0.193～0.866 mBq/L、1.13～1.42 mBq/L. Conclusion The environmental ionizing radiation level in Weizhou island of Beihai is in the range of background fluctuation and at a relatively low level, indicating that the radiation environmental quality of Weizhou Island and its surrounding areas is good.

Objective To analyze the incidence,risk factors and pathogens of stroke associated pneumonia (SAP) in patients with acute stroke in the intensive care unit (ICU).Methods One hundred and forty-two patients with acute stroke admitted in ICU from January 2012 to December 2013 were retrospectively studied.The data of medical history of patients,treatment,prognosis,and pathogens of SAP were collected.Data were analyzed by t test,Mann-Whitney U test,Pearson x2 test and muhivariable logistic regression.Results Of 142 patients,94 (66.2％) were contracted SAP of which 54.3％ were early-onset pneumonia (EOP≤72 h) and 45.7％ were late-onset pneumonia (LOP ＞72 h).The most common pathogens isolated from EOP were Staphylococcus aureus and Klebsiella pneumonia,while the most common pathogens isolated from LOP were Acinetobacter baumanii,Staphylococcus aureus and Pseudomonas aeruginosa.Multivariate logistic regression analysis demonstrated that hemorrhagic apoplexy,history of stroke,higher APACHE score,dysphagia,prolonged use of mechanical ventilation,prolonged stay in ICU,and hyperglycemia were the independent risk factors of SAP,and the odds ratios (OR) with 95％ confidence intervals (CI) were 10.917 (1.834-60.959),15.223 (1.947-96.969),1.607 (1.253-2.062),5.321 (1.225-26.519),1.809 (1.208-2.709),1.391 (1.085-1.783),1.534 (1.l01-2.138),respectively.While plasma albumin level was negatively associated with SAP (OR =0.809,95％ CI:0.674-0.971).The common risk factors of EOP and LOP were higher APACHE score and prolonged use of of mechanical ventilation.The independent risk factors of EOP were dysphagia (OR =4.331,95％ CI:1.330-14.098),history of stroke (OR =13.690,95％ CI:2.198-85.277) and chronic bronchitis (OR =12.907,95％ CI:1.203-138.542),While those of LOP were prolonged stay in ICU (OR =1.687,95 ％ CI:1.131-2.517),hemorrhagic apoplexy (OR =21.657,95％ CI:1.559-106.752) and low plasma albumin level (OR =0.782,95％ CI:0.637-0.961).There was no significant difference in mortality between EOP (49％) and LOP (44.2％) (P ＞ 0.05),but the mortality of SAP was significantly higher than that of non-SAP group.Conclusions The incidence rate and mortality of SAP are quite high in ICU.The pathogens and risk factors are different between EOP and LOP.This observation results suggest it is important to identify high-risk stroke patients,and to develop a novel treatment strategy and prophylactic measures facilitating limiting the complications of stroke.

Objective To approach the correlation between angiopoietin-2 (Ang-2) levels and degree of lung injury and prognosis and its clinical significance in patients with acute respiratory distress syndrome (ARDS). Methods A prospective observation was conducted. Fifty-three ARDS patients admitted to Department of Critical Care Medicine of Third Affiliated Hospital of Anhui Medical University from January 2012 to March 2014 were enrolled. According to the criteria of the Berlin Definition of ARDS,the patients were divided into mild group (n=15),moderate group(n=22)and severe group(n=16). Meanwhile,ARDS patients were further divided into survival group(n=29)and non-survival group(n=24)according to 28-day outcomes. Twenty cases of non-ARDS patients were served as control. The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,oxygenation index(PaO2/FiO2),lung injury score(LIS)were recorded within 24 hours after admission. And the plasma levels of Ang-2,interleukin-6(IL-6)and C-reaction protein (CRP)were measured. The independent risk factors of ARDS were analyzed by univariate and multivariable logistic regression. Receiver operating characteristic curve(ROC)was plotted to evaluate the value of Ang-2 in predicting ARDS. Results Compared with non-ARDS group,APACHEⅡ score,SOFA score,LIS score,mortality were significantly increased,PaO2/FiO2 was significantly decreased,and plasma Ang-2,IL-6,CRP were significantly elevated〔APACHEⅡscore:20.7±5.0 vs. 14.1±5.3,SOFA score:7.7±3.5 vs. 3.5±2.1,LIS score:1.69±0.71 vs. 0.28±0.27,PaO2/FiO2(mmHg,1 mmHg=0.133 kPa):159.5±61.3 vs. 394.0±63.2,mortality:45.3%(24/53) vs. 20.0%(4/20),Ang-2(μg/L):4.73(2.59,6.99)vs. 1.22(0.61,1.52),IL-6(ng/L):56.50(27.15,139.90)vs. 13.05(4.38,15.55),CRP(mg/L):95.75(41.74,189.72)vs. 10.56(3.92,21.36),P<0.05 or P<0.01〕. Each index increased or decreased more significantly with the aggravation of the disease. It was shown by correlation analysis that the plasma levels of Ang-2 was significantly positive correlated with IL-6(r=0.468,P=0.000),CRP(r=0.492,P=0.000),APACHEⅡscore(r=0.560,P=0.000),SOFA score(r=0.508,P=0.000)and LIS score (r=0.588,P=0.000),significantly negatively correlated with PaO2/FiO2(r=-0.685,P=0.000). Factors, APACHEⅡ score,LIS score,PaO2/FiO2,Ang-2 and IL-6 founded statistical significance in univariate analysis were analyzed using multivariable logistic regression. High APACHEⅡscore at admission〔odds ratio(OR)=1.316, 95% confidence interval(95%CI)=1.040-1.633,P=0.022〕and increased plasma Ang-2 levels(OR=1.287, 95%CI=1.041-1.760,P=0.038)were the independent prognostic factors for the 28-day mortality in ARDS. The area under the ROC curve of Ang-2 was 0.964,the optimal critical value of Ang-2 was 1.79μg/L,the specificity was 90.0%,and sensitivity was 92.5%. Plasma levels of Ang-2 was better in predicting ARDS than APACHEⅡscore, SOFA score and IL-6. Conclusions The plasma level of Ang-2 was significantly increased in patients with ARDS. The plasma level of Ang-2 was correlated with the severity of acute lung injury and had important prognosis evaluation.

Objective To determine whether stroke volume variation (SVV) in relation to volume loading in mechanically ventilated patients with septic shock.Methods Data of thirty-two mechanically ventilated patients with septic shock admitted from Dec 2009 to May 2012 were prospectively analyzed.Cardiac index (CI),stroke volume (SV),systemic vascular resistance index (SVRI) and stroke volume variation (SVV) were measured by FloTrac/Vigileo before and after fluid resuscitation (250 mL saline in 10 min).Patients with an increase in SV (△SV) ≥ 10％ and ＜ 10％ after fluid volume loading were classified as responders and non-responders,respectively.The comparisons between these two sorts of patients were assessed by using two sample Student' s t-test,and comparisons between changes before and after fluid challenge were assessed by using a paired Student' s t-test.A Pearson' s correlation analysis was employed for evaluate the correlation between △SV and other haemodynamic variables.The roles of SVV,central venous pressure (CVP),mean artery pressure (MAP) and the changes of CVP (△CVP),MAP (△MAP) after fluid administration in predicting volume responsiveness were evaluated by receiver operating characteristic (ROC) curve.Results Thirty-two patients with septic shock were included in this study.There were 54 instances of fluid challenge performed,among which 35 instances were defined as response group.Significantly increased SV induced by fluid challenge was assigned into response group (83.6 ± 15.6) mL vs.(68.5 ± 14.2) mL,P ＜0.01,while in non-response group,there were no significant change in SV (P ＞0.05).SVV was significantly correlated with SV before fluid loading (r =0.522,P ＜ 0.01).The area under the ROC curve (AUC) for stroke volume variation (SVV) was 0.898 (95％ CI:0.796-1.000).Using SVV ≥ 11.5％ as the threshold to predict fluid responsiveness,the sensitivity was 94％ and specificity was 84％.Conclusions SVV can be used to predict fluid responsiveness in patients with septic shock.

Objective:To investigate the curative effect of early enteral nutrition support in patients with COPD complicated with respiratory failure.Methods: When mechanical ventilation began,63 patients in the acute phase of COPD complicated with respiratory failure were divided into two groups: the early enteral nutrition group(EEN group,n=32) or the delayed enteral nutrition group(DEN group,n=31).After two weeks,the nutritional indexes,the times of mechanical ventilation,the incidence of complication and the mortality were observed.Results: Two weeks later,there was significant difference between EEN group and DEN group in total protein,albumin,prealbumin and hemoglobin(P