ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

OBJECTIVE: To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province. METHODS: Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression. RESULTS: The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66). CONCLUSION The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.
Female ; Humans ; Aged ; Menarche ; Menopause ; Regression Analysis ; Fertility ; China/epidemiology* ; Age Factors

Objective     To investigate the risk factors for postoperative complications Clavien-Dindo classification≥grade Ⅱ after lung cancer surgery. Methods     The patients who underwent lung cancer surgery in a multicenter observational study from November 2017 to January 2020 were included. The Clavien-Dindo classification of postoperative complications was analyzed. Logistic regression was used to identify the risk factors for complications≥ gradeⅡ. Results     A total of 388 patients were enrolled, including 203 males and 185 females with a mean age of 56.14±10.36 years. The incidence of postoperative complications was 25.52% (99/388) after lung cancer surgery and the incidence of complications≥gradeⅡ was 20.10% (78/388). The five most common postoperative complications were pneumonia (6.96%), prolonged pulmonary air leak (>7 days, 5.67%), incision dehiscence (4.64%), arrhythmia (3.87%), and postoperative pleural effusion (3.35%). Multivariate analysis showed that open surgery [reference: uniportal thoracoscopic surgery, OR=2.18, 95%CI (1.01, 4.70), P=0.047], extended resection [reference: sublobar resection, OR=2.86, 95%CI (1.11, 7.19), P=0.030; reference: lobectomy, OR=2.20, 95%CI (1.10, 4.40), P=0.026] and operative time≥3 h [OR=2.07, 95%CI (1.12, 3.85), P=0.021] were independent risk factors for postoperative complications≥gradeⅡ after lung cancer surgery. Conclusion     Surgical approach, extent of resection and operative time are independent influencing factors for postoperative complications≥gradeⅡ after lung cancer surgery.

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.
Absorbable Implants ; Cardiovascular Agents ; Coronary Artery Disease/surgery* ; Drug-Eluting Stents ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Prospective Studies ; Sirolimus ; Treatment Outcome

Objective To analyze the distribution of pathogens in the genital tract of infertile female,and comparing traditional methods with simultaneous amplification and testing (SAT) in the detection of UU,CT,NG and MG.Methods 467 female infertility patients were selected from the reproductive center of Suzhou Hospital Affiliated to Nanjing Medical University between June and September 2016 to analyze the distribution of UU,CT,MG and NG.The age was between 20 to 48 years old (mean 31.52±6.83 years old).352 cases of female patients with assisted reproductive technology were selected,aged from 21 to 46 years old (mean 30.67±6.67 years old).The swabs were tested by traditional methods or SAT.The sensitivity and specificity of the methods in detecting the pathogens were evaluated according to the experimental results.Results Among the 467 infertile women,the number of UU positive cases was the highest,the positive rate was 62.53％ (292/467),the positive rate of CT was 1.93％ (9/467) and the positive rate of NG was 0.21％ (1/467),and the positive rate of MG was 1.71％ (8/467).UU infection rate was higher in infertile women than normal control group 23.81％ (25/105) (x2 =52.01,P＜0.01).352 cases of female patients with assisted reproductive technology were selected for further analysis.For UU detection,the positive rate of swab samples detected by liquid culture was 48.9％,while the positive rate detected by SAT was 63.9％.Obviously the positive rate of SAT was higher than that of liquid culture.Swab culture and SAT results were analyzed by paired x2 test (x2 =41.93,P＜0.01).The positive rate of CT SAT was 1.71％,and the positive rate of CT-latex method was 0.28 ％.There was significant difference between CT latex method and SAT (Fisher exact probabilistic method statistical analysis,P＜0.005),which indicated that SAT method had a higher sensitivity.The positive rate (1.7 ％) and sensitivity (100％) of SAT were also higher than that of traditional method.Conclusion UU was the most common pathogen in female reproductive tract pathogens,followed by CT and MG.The SAT method has higher sensitivity than the conventional method in detecting of UU and CT.

Objective To summarize the surgery skills and evaluate the clinical outcome of submental island flap for repairing oral defect after radical resection of oral cancer. Methods A total of 25 consecutive patients underwent submental island flap reconstruction after ablative surgery for oral cancer from January 2015 to May 2017 were enrolled in this study. The patterns of venous return, the technique notes and postoperative complications were summarized. The oncological safety of submental island flap in oral reconstruction was analyzed. Results The submental island flaps were harvested with the sizes ranging from(5 cm×3 cm)to(12 cm×5 cm).The mean operation time was(350.5±50.5)min.The vein of the flap was found to drain into the facial vein,and then returned to the internal jugular vein in 17 patients(68.0%), into the external jugular vein in 4 patients(16%),and into the anterior jugular vein in 4 patients(16%).Twenty-four flaps survived completely,and 1 flap failed due to the damage of the submental artery.Wound infection occurred in only 1 patient, and primary wound healing was observed in the other 24 patients. Eight patients (32.0%) with cervical lymph node metastases were verified by the postoperative pathological examination, 4 patients were submandibular lymph node metastases.The prevalence of occult lymph node metastasis involving level Ⅰwas 16.0%.The mean follow-up period was (14.3 ± 5.2) months. Local recurrence was found in 1 patient and cervical recurrence in 2 patients without postoperative radiotherapy during the follow-up. Conclusion There are three various drainage patterns for the venous return of submental island flap.Our data suggest that vein drainage of the flap into the external jugular vein and the anterior jugular vein,which are previously overlooked,should receive greater attention during the harvest of submental flap to avoid venous congestion and flap loss.Close follow-up or postoperative radiotherapy are recommended for patients without cervical lymph node metastases.

The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54CD38and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA. After co-incubation of microvascular endothelial cells with TNF-α or IL-6, the expressions of endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity of activated protein C (APC) were examined. As the results showed, the IgG type plasma cells infiltration and the quantity of IgG type immune complex were increased in DSS group in comparison with control group. After incubation with IgG type immune complex, the levels of TNF-α and IL-6 in the supernatant of macrophages were increased (P < 0.01) in a concentration-dependent manner. Meanwhile, after incubation with TNF-α or IL-6, the expressions of EPCR and TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01), while the activity of APC was reduced (P < 0.05 or P < 0.01). These results suggested that the quantity of IgG type plasma cells increases in UC and forms immune complexes, which affect the secretion of cytokines from macrophage, thereby affecting the function of endothelial cells and finally inhibiting PCS in UC. Therefore, plasma cell may be a novel target for the treatment of UC.