BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCsExo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood.This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCsExo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess b-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry.Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

Objective : To analyze the epidemiological characteristics and pathogen spectrum of hand，foot mouth disease (HFMD) in Anhui province from 2015 to 2022，and to provide scientific evidence for prevention and control measures of HFMD． Methods : The surveillance data of hand，foot and mouth disease in Anhui province from 2015 to 2022 were analyzed by descriptive epidemiology. Real-time PCR was used to detect and classify HFMD samples. Results : A total of 650 590 HFMD cases were reported in Anhui province from 2015 to 2022，including 1 406 se- vere cases and 17 deaths．The annual reported incidence was 131. 45 /100 000．The epidemic features of“low incidence in odd years and high incidence in even years”were presented from 2015 to 2019．The incidence showed a continuous decline from 2020 to 2022．The monthly distribution showed the characteristics of bimodal epidemic，and the main peak was not obvious in 2020．Hefei，Fuyang，Bozhou，Chuzhou and Suzhou ranked the top five cities in terms of cumulative incidence．The age of onset was mainly distributed in children aged 5 years and below，accounting for 89. 26% of the total cases．The male to female ratio was 1. 48 ∶ 1．A total of 28 657 laboratory-confirmed cases had been reported from 2015 to 2022．EV71 cases accounted for 10. 57% ，Cox A16 cases accounted for 24. 90% ，and other enterovirus cases accounted for 64. 53%．The dominant pathogens showed dynamic changes in different years．Since 2018，the proportion of EV71 decreased significantly，and the proportion of other enteroviruses gradually increased to become the dominant pathogens．Among other enteroviruses，Cox A6 strain was dominant (80. 48% ) ． Conclusion This study suggests that the prevention and control of HFMD in Anhui province should be paid more attention from April to July and from October to December．The focus areas are the cities in northern Anhui and Hefei where the floating population is large．The focus of prevention and control is on children aged 5 years and below．Other enteroviruses have become the dominant pathogens of hand-foot-mouth disease in Anhui province，Cox A6 strain is dominant.

Objective To evaluate the clinical implementation value of bedside ultrasound monitoring of gastric residual volume in the guidance of enteral nutrition (EN) in severe patients with mechanical ventilation. Methods One hundred and forty-three patients undergoing nasal feeding EN and mechanical ventilation &ge; 72 hours in the Department of Intensive Care Unit (ICU) of Jinhua People's Hospital from May 2017 to August 2018 were enrolled, and they were randomly divided into two groups: a traditional control group (71 cases) and an ultrasound monitoring group (72 cases). The traditional control group applied 50 mL syringe to withdraw gastric juice from gastric tube, once every 4 hours, and then the EN protocol based on the gastric residual volume was adjusted; the ultrasound monitoring group used bedside ultrasound to monitor the gastric residual volume once every 4 hours, and then the EN protocol was adjusted accordingly. The changes of EN tolerance indexes e.g. abdominal distension, reflux vomiting, diarrhea, bowel sound hyperactivity or disappearance, intra-abdominal pressure, etc, the changes of incidence of ventilator-associated pneumonia (VAP), mechanical ventilation time and ICU hospitalization time in these two groups were observed. Results The incidences of abdominal distension, reflux vomiting, diarrhea, intestinal hyperactivity or disappearance of bowel sounds were significantly lower in the ultrasound monitoring group than those in the traditional control group [abdominal distension: 23.6% (17/72) vs. 28.2% (20/71), reflux vomiting: 18.1% (13/72) vs. 22.5% (16/71), diarrhea: 13.9% (10/72) vs. 14.1% (10/71), bowel sounds hyperactivity or disappearance: 9.7% (7/72) vs. 11.3% (8/71), all P < 0.05], the intra-abdominal pressure was obviously lower in the ultrasound monitoring group than that in the traditional control group [mmHg (1 mmHg = 0.133 kPa): 8.9±5.6 vs. 9.6±6.1, P < 0.05], and the incidence of VAP was significantly lower in the ultrasound monitoring group than that in the traditional control group [19.7% (14/72) vs. 23.9% (17/71), P < 0.05], the mechanical ventilation time and ICU hospitalization time were also significantly shorter in the ultrasound monitoring group than those in the traditional control group [mechanical ventilation time (days): 10.1±3.1 vs. 12.2±3.4, ICU hospitalization time (days): 16.8±4.2 vs. 20.6±4.8, all P < 0.05]. Conclusion The bedside ultrasound monitoring gastric residual volume can improve EN tolerance, reduce VAP incidence, and shorten the mechanical ventilation time and ICU hospitalization time in patients with mechanical ventilation.

Objective We tried to develop a reliable,stable and effective customized ECLS system through a well designed in vitro and in vivo study.Methods An in vitro test model of the ECLS system,mainly consisting of a pseudo-patient (a blood reservoir),bladder,oxygenator,pump tube (outer diameter:1/4 inch),roller pump and the heater,was built.Performances of the pump,monitors,and the heater were observed every day.The precision of the pump flow (pressure monitor or the heater) was compared with a transonic flow-meter (Medtronic ECMO system or thermometer).The monitors were tested to see if they could meet the requirements.Four healthy and two mild ARDS piglets were supported with the customized ECLS system for 24 hours.Hemodynamics,lung mechanics,gas change and hematological parameters of the piglets and performances of the machine were recorded.Agreement between the customized ECLS system and other devices including the transonic flow-meter,Medtronic ECMO system and thermometer was evaluated by the Bland-Altman method.Results The pump,the monitors,and the heater functioned well without accidently stopping working.The 95％ limits of agreement of pump flow,pre-pump pressure,post-pump pressure,post-membrane pressure,and temperature were (-0.04 L/min,0.03 L/min),(-3 mmHg,3 mmHg),(-5 mmHg,6 mmHg),(-6 mmHg,6 mmHg),(0.1 ℃,0.3 ℃).The pressure monitors and the bladder could alarm and stop the pump fast during a 100 times trail.The bubble detector could respond well (alarm and stop the pump) to 60 of the 100 bubbles injected into the circuit.The alarming temperature of the heater was (42.3±0.2) ℃.The customized ECLS worked well without complications throughout the in vivo test.A temporary decrease of Cdyn and increase of A-aDO2 and OI were observed in healthy piglets while an escalating trend of Cdyn and a downtrend of A-aDO2 and OI in ARDS piglets.Mean arterial blood pressure of the piglets supported with the customized ECLS system maintained stable while the Hb and PLT decreased.Conclusion In vitro and in vivo test showed the pump,pressure monitors and the heater of the customized ECLS system functioned well,and the feasibility,safety and stability of the system were preliminarily verified from the cytosol of the cell to the lumen of the sarcoplasmic reticulum.

Objective To investigate the prevalence of feeding intolerance (FI),and to explore the FI within 7 days of ICU admission in association with clinical outcome in critically ill patients.Methods The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24h were recruited from March 2014 to August 2014,and all clinical,laboratory,and survival data were prospectively collected.The AGI (acute gastrointestinal injury) grade was daily assessed based on gastrointestinal (GI) symptoms,feeding details and organ dysfunction within the first week of ICU stay.The intra-abdominal pressures (IAP) was measured using AbViser device.Results Of 550 patients enrolled,418 were assessed in GI symptoms and feeding details within 7 days of ICU stay.The mean age and SOFA score were (65.1 ± 18.3) years and (8.96 ±4.10),respectively.Of them,355 patients (84.9％) were under mechanical ventilation support,and 37 (8.85％) received renal replacement therapy.The mean length of time for enteral feeding was (30.8 ±26.2) h,and the prevalence of FI on the 3rd and 7th day of ICU stay accounted for 39.2％ and 25.4％,respectively.Compared to those with FI within 7 days of ICU stay,the patients without FI had higher rate of successively weaning from mechanical ventilation (21.3％ vs.5.7％,P =0.003) and higher rate of withdrawal of vasoactive medication (45.5％ vs.20.0％,P =0.037),as well as lower mortality rate of 28-day (24.4％ vs.38.7％,P =0.004) and 60-day (29.6％ vs.44.3％,P =0.005).In multivariate Cox regression model with adjustment for age,sex,participant center,serum creatinine and lactate,AGI grade on the first day of ICU stay,and comorbidities,the FI within 7 days of ICU stay (x2 ≥ 7.24,P ＜ 0.01) remained to be independent predictors for 60-day mortality.After further adjusted for SOFA score,the FI within 7 days of ICU stay (HR =1.71,95％ CI:1.18-2.49;P =0.006) and AGI grade on the first day of ICU stay (HR =1.33,95 ％ CI:1.07-1.65;P =0.009) could provide independent prognostic values of 60-day mortality.Conclusions There is high rate of FI occurred within 7 days of ICU stay,and is significantly associated with worse outcome.In addition,this study also provides evidence to further support that measurement of gastrointestinal dysfunction could increase value of SOFA score in outcome prediction for the risk of 60-day mortality.

Objective To understand the correlations between HIV-1 subtypes and changes in CD4+T cell count over time in patients with different subtypes of HIV-1 infection.Methods A total of 94 patients who were diagnosed with HIV-1 infection in Nanjing and received at least twice CD4+T cell counting test before antiretroviral therapy (ART) were recruited in this study.Descriptive analysis was used to present the rates of CD4+T cell decline for different HIV-1 subtypes.Logistic regression analysis and nonparametric test were conducted to investigate the factors responsible for CD4+T cell decline and to analyze the correlations between the rates of CD4+T cell decline and HIV-1 subtypes.Results The median monthly rate of CD4+T cell decline was-2.20 [interquartile range (IQR):-11.36-2.13] cell/μl.Of all patients,25.5% (24/94) had a significant decline (≥30%) in CD4+T cell count.Compared with the patients infected with CRF01_AE,those infected with CRF07_BC (OR=0.28,95%CI: 1.7-6.5) or other subtypes (OR=0.16,95%CI: 1.0-2.9) had a lower risk of significant decline in CD4+T cell count.In addition,results of the nonparametric test showed that the patients infected with CRF01_AE (M=-21.54,IQR:-30.97——11.92 cell/μl) had a faster CD4+T cell loss than those infected with CRF07_BC (M=-11.26,IQR:-14.06——5.63 cell/μl) (P=0.033).Conclusion HIV-1 subtype is associated with the rate of CD4+T cell decline.It is important to monitor the changes in CD4+T cell count in patients infected with CRF01_AE and to carry out timely ART.

Objective: To study the feasibility of ¹⁸F-fluoro-L-dihydroxyphenylalanine positron emission tomography/Computed tomography (¹⁸F-DOPA PET/CT) scanning in the localization and differential diagnosing of focal versus diffuse form of pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH). Method: Twenty-four patients were diagnosed with HH between January, 2016 and February, 2017 in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University using an integrated clinical and biochemical diagnostic protocol, domestic ¹⁸F-DOPA PET/CT imaging technique were applied after MRI and ultrasound failed to detect pancreas lesions. Pancreas ¹⁸F-DOPA standardized uptake values (SUV) were measured, and pancreas′ lesions were dually analyzed via visual method and pancreas percentage SUV method. Among these patients, 9 patients received surgical pancreatic lesion resections, the correlations among surgical outcomes, histopathological findings and ¹⁸F-DOPA PET/CT scan results were analyzed. Result: Seven patients were detected with focal form of pancreas lesions, the mean peak of SUV was 4.7±1.7(2.6-7.1), and 17 patients were found to have diffuse form lesions after ¹⁸F-DOPA-PET/CT scanning. Among the 24 cases, 9 patients (7 showed focal and 2 showed diffuse ¹⁸F-DOPA PET/CT pancreatic uptake)were euglycemic without any medical support after surgery; the resected pancreatic tissue histopathological results were consistent with that of PET/CT imaging. Only one patient, who responded to medical treatment before surgery, had temporary hyperglycemia after operation. Conclusion Domestic ¹⁸F-DOPA PET/CT could successfully locate and differentiate the pancreatic lesions and thus improve the success of surgery.

Objective: To analyze the influence of growing experience on non-heterosexual orientation among male college students. Methods: From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation. Results: Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ²=9.06,P=0.029). Compared with the individuals of very good relationship with parents, those with bad relationship (OR=3.3, 95%CI: 1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9). Conclusions This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.

Objective To study the expression of Nuclear factor E2 related factor 2 (Nrf2) ,Superoxide Dis‐mutas 1 (SOD1) ,and Heme Oxygenase- 1( HO -1) factors related to Nrf2 signaling pathway in noise-induced cochlear injury of rats .Methods A total of 30 SD rats were randomly and equally assigned into the following 2 groups :noise group and normal control group .The rats in noise group were exposed to an 115 dB SPL continuous steady white noise for 12 hours ,then 1 day ,3 days ,and 7 days later ,the rats receveid the ABR and DPOAE testing after noise exposure .Both RT -PCR and Peggy Sue trace protein detection techniques were used to detect gene ex‐pression in Nrf2 /Keapl-ARE signaling pathway and the protein levels by cochlear tissue sampling after noise ex‐posure 7 days later .Results The ABR thresholds in the noise group was higher than those of in normal control group after noise exposure 1 ,3 ,and 7 days later (P<0 .05) .The DPOAE values of noise group were significantly lower than those of normal control group (P<0 .05) .The up -regulation of expression of Nrf2 ,SOD1 ,HO -1 mRNA(1 .11 ± 0 .05 ,1 .45 ± 0 .12 ,1 .15 ± 0 .03) in noise group were higher than those of in the normal control group after noise exposure 7 days later (1 .00 ± 0 .02 ,1 .10 ± 0 .12 ,0 .92 ± 0 .08) ,and the differences were statistically sig‐nificant (P<0 .05) .And in Peggy Sue trace detection system ,we also found SOD1 ,HO -1 protein levels in noise group were higher than those of in normal control group .Conclusion After the noise -induced cochlear injury in rat ,Nrf2 expression in the cochlea increased and up-regulatd expression of downstream gene and protein content such as antioxidant enzymes SOD1 and HO-1gene by regulating Nrf2 /Keapl-ARE signaling pathway ,which may be involved in protection against oxidative stress injury in noise-induced cochlear injury of rat .

Objective:To investigate the effect and elucidate the mechanism of the selective cyclooxygenase-2(COX-2)inhibitor NS-398 on apoptosis and survivin, XIAP and c-IAP1 expressions of hepatocarcinoma cell lines. Methods:The proliferation of hepatocarcinoma BEL-7402 cells treated with NS-298 at different concentrations were evaluated by MTT assay. The apoptosis was detected by flow cytometry (FCM) and TUNEL assay. Expressions of COX-2, survivin, XIAP and c-IAP1 were analyzed by immunocytochemical staining. Results: NS-398 significantly inhibited cell proliferation of BEL-7402 cells and induced apoptosis. Immunocytochemisty indicated that the expressions of COX-2, survivin, XIAP and c-IAP1 were significantly down-regulated in BEL-7402 cells by NS-398 treatment compared with untreatment group (P<0.01). Conclusion:NS-398 inhibits the proliferation and induced apoptosis of BEL-7402 cells. The mechanism may be related with down-regulation of the survivin, XIAP and c-IAP1 expression.