[Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent host: a case report].

Nocardiosis can be caused by various Nocardia spp., including Nocardia asteroides, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia otitidiscaviarum. As compared with the other Nocardia spp., Nocardia otitidiscaviarum appears to be rare which can spread through the bloodstream and affect multiple organs. The disease is usually seen in immunocompromised patients' but may also occur in immunocompetent patients. The clinical symptoms and laboratory and imaging examinations of the disease are nonspecific.Here, we reported a case of disseminated nocardiosis caused by infection with Nocardiosis otitidiscaviarum in an immunocompetent host to improve the knowledge and diagnosis of nocardiosis.

Prevalence and potential risk factors of chronic pruritus among community middle-aged and older population in Beijing, China.

BACKGROUND: Chronic pruritus is a common problem among older adults, with a significant impact on their quality of life. However, it is under-studied epidemiologically, especially among Chinese older adults. OBJECTIVE: The aim of this study was to identify the prevalence and explore the risk factors of chronic pruritus among the middle-aged and older adults in Beijing, China. METHODS: A total of 929 participants aged ≥35 years from six communities in Beijing, China, were interviewed. The survey collected the demographic characteristics, the experience of chronic pruritus (>6 weeks), chronic disease history, the level of physical activities and sleep quality. A population-based case-control study was conducted, including 178 chronic pruritus cases and 697 controls. A multivariate logistic regression model was performed to explore the risk factors of chronic pruritus. Additionally, a random forest algorithm was used to rank the importance of potential risk factors and analyse the overall interpretation of risk factors. RESULTS: The prevalence of chronic pruritus was 19.48% (181/929) among the Beijing middle-aged and elderly population. The findings indicated that older adults aged 65 years old or above, male, with college or higher degree, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease and osteoarthritis/rheumatism, and middle or low sleep quality were associated with the increased risk of chronic pruritus respectively. Physical activity level (≥3000 Met) was associated with a decreased risk of chronic pruritus. The rank according to the most contribution of chronic pruritus risk was sleep quality, education, physical activity level, osteoarthritis/rheumatism, age and gender. CONCLUSION: Prevalence of chronic pruritus was high among the Chinese middle-aged and elderly population. Age, gender, high education, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease, osteoarthritis /rheumatism and poor sleep quality may serve as risk factors of chronic pruritus. Moderate and high physical activity levels may serve as protective factors of chronic pruritus risk.

Long-term particulate matter 2.5 exposure and dementia: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to analyse the existing evidence on the association between particulate matter 2.5 (PM2.5) and dementia, including two of its subtypes, namely, Alzheimer's disease (AD) and vascular dementia (VaD). STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Cochrane and Web of Science databases were comprehensively searched for articles published between January 1900 and June 2022. All cohort studies that reported the influence of long-term exposure to PM2.5 on dementia, together with its subtypes, in adults aged ≥40 years, without any regional restriction were included. A random effects model was used to pool the hazard ratios (HRs) of PM2.5 for dementia, AD and VaD. Funnel plots, sensitivity analyses and subgroup analyses were performed to test publication bias and result stability. In addition, an explanation for the heterogeneity of the results was suggested. RESULTS: In total, 20 articles were selected for review; 18 included results on the long-term effects of PM2.5 on dementia, 13 on AD, and eight on VaD. Three group meta-analyses were performed to obtain the HRs and 95% confidence intervals (CIs). The pooled HRs were 1.40 (95% CI 1.23, 1.60) for dementia, 1.47 (95% CI 1.22, 1.78) for AD and 2.00 (95% CI 1.30, 3.08) for VaD per 10.0 µg/m3 PM2.5 increase. CONCLUSIONS: Long-term exposure to PM2.5 may increase the risk of dementia, including AD and VaD. These results highlight the need for further study on the detrimental impact of PM2.5 and the importance of strategies to mitigate increasing air pollution.

[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

[Research progress on health hazards and occupational protection of prolymethylmethacrylate bone cement in the operating room].

There are many occupational risk factors in operating room work. Polymethyl methacrylate (PMMA) , as a kind of common bone filling and repairing material, is widely used in the fixation of artificial joints, oral braces and orthopedic prosthesis. However, PMMA will release methyl methacrylate (MMA) monomer when it is implanted into human tissues and polymerized to harden, which is toxic to the body. This paper analyzes harmful factors in using PMMA bone cement, and then explores corresponding occupational protection knowledge, in order to reduce the occurrence of occupational hazards related to PMMA bone cement and enhance the self-protection ability of the operation room medical staff.

Using a Dedicated Interventional Pulmonology Practice Decreases Wait Time Before Treatment Initiation for New Lung Cancer Diagnoses.

PURPOSE: While there is significant mortality and morbidity with lung cancer, early stage diagnoses carry a better prognosis. As lung cancer screening programs increase with more pulmonary nodules detected, expediting definitive treatment initiation for newly diagnosed patients is imperative. The objective of our analysis was to determine if the use of a dedicated interventional pulmonology practice decreases time delay from new diagnosis of lung cancer or metastatic disease to the chest to treatment initiation. METHODS: Retrospective chart analysis was done of 87 consecutive patients with a new diagnosis of primary lung cancer or metastatic cancer to the chest from our interventional pulmonology procedures. Demographic information and time intervals from abnormal imaging to procedure and to treatment initiation were recorded. RESULTS: Patients were older (mean age 69) and former or current smokers (72%). A median of 27 days (1-127 days) passed from our diagnostic biopsy to treatment initiation. A median of 53 total days (2-449 days) passed from abnormal imaging to definitive treatment. Endobronchial ultrasound-guided transbronchial needle aspiration was the most commonly used diagnostic procedure (59%), with non-small cell lung cancer the majority diagnosis (64%). For surgical patients, all biopsy-negative lymph nodes from our procedures were cancer-free at surgical excision. CONCLUSIONS: Compared to prior reports from international and United States cohorts, obtaining a tissue biopsy diagnosis through a gatekeeper interventional pulmonology practice decreases median delay from abnormal imaging to treatment initiation. This finding has the potential to positively impact patient outcomes and requires further evaluation.

3D-QSAR pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation toward identifying lead compounds for NS2B-NS3 protease inhibitors.

NS2B-NS3 protease has been identified to serve as lead drug design target due to its significant role in West Nile viral (WNV) and dengue virus (DENV) reproduction and replication. There are currently no approved chemotherapeutic drugs and effective vaccines to inhibit DENV and WNV infections. In this work, 3D-QSAR pharmacophore model has been developed to discover potential inhibitory candidates. Validation through Fischer's model and decoy test indicate that the developed 3D pharmacophore model is highly predictive for DENV inhibitors, which was then employed to screen ZINC chemical library to obtain reasonable hits. Following ADMET filtering, 15 hits were subjected to further filter through molecular docking and CoMFA modeling. Finally, top three hits were identified as lead compounds or potential inhibitory candidates with IC50 values of ∼0.4637 µM and fitness of ∼57.73. It is implied from CoMFA modeling that substituents at the side site of benzotriazole such as a p-nitro group (e.g. biphenyl head) and a carbonyl (e.g. carboxylate function) at the side site of furan or amino group may improve bioactivity of ZINC85645245, respectively. Molecular dynamics simulations (MDS) were performed to discover new interactions and reinforce the binding modes from docking for the hits also. The QSAR and MDS results obtained from this work should be useful in determining structural requirements for inhibitor development as well as in designing more potential inhibitors for NS2B-NS3 protease.

Long Non-coding RNA-mRNA Correlation Analysis Reveals the Potential Role of HOTAIR in Pathogenesis of Sporadic Thoracic Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Long non-coding RNA (lncRNA) play important roles in many diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA network and dissect lncRNAs that might contribute to the pathogenesis of STAA. METHODS: Differentially expressed lncRNAs and mRNAs between four ascending aortic specimens derived from STAA and four controls from patients who had undergone coronary artery bypass graft (CABG) were identified by microarray analysis. Gene Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented with differentially expressed genes. An lncRNA in the correlation network HOX transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR expression was examined by quantitative real time polymerase chain reaction in STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n = 2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role in apoptosis, cell proliferation, and expression of collagen types I and III. RESULTS: Five percent of lncRNAs were significantly differentially expressed in STAA patient samples compared with controls. GO enrichment analysis suggested differentially expressed genes were significantly enriched in the process of extracellular matrix organisation and leukocyte migration. lncRNA-mRNA interaction network revealed HOTAIR was associated with genes involved in extracellular matrix organisation. Moreover, HOTAIR expression was significantly decreased in STAA specimens and it negatively correlated with aortic diameter. HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation. Furthermore, both mRNA and protein levels of collagen types I and III expression were suppressed after HOTAIR knockdown. CONCLUSION: Transcriptomic and lncRNA-mRNA correlation analysis revealed HOTAIR was downregulated in STAA and associated with genes involved in extracellular matrix remodelling. In vitro experiments confirmed that knockdown of HOTAIR could induce apoptosis and suppress collagen types I and III expression in human aortic smooth muscle cells.

[Safety and feasibility of sheathless transfemoral aortic valve implantation].

Objective: To investigate the safety and feasibility of sheathless transfemoral aortic valve replacement (TAVR). Methods: In this prospective study, we enrolled 23 patients with severe aortic stenosis (AS) who were inoperable or at high-risk for surgical aortic valve replacement operation in Fuwai hospital From September 2012 to June 2015. Multislice spiral CT and angiography of femoral artery showed that all patients had minimal femoral artery diameters (<6.5 mm) and severe calcification which was not suitable for transfemoral TAVR through sheath. We attempted to apply the sheathless transfemoral TAVR using Venus-A prosthesis without sheath insertion, and procedure related complication during the procedure and hospital stay were observed. Results: The 6 mm×30 mm balloon was used for femoral artery predilation in 1 patient with iliofemoral artery stenosis before delivery system was transported. In the other 22 patients, the delivery system was transported directly. A total of 21 patients finished TAVR with transfemoral sheathless technique. In 2 patients, prosthesis was unable to fully expand after release due to severe valve calcification, and patients received urgent surgical aortic valve replacement. One patient had valve dislocation into the ascending aorta that was not related to the sheathless replacement technique, and delivery system and Venus-A valve were removed after femoral artery was opened surgically, and repeated sheathless TAVR implantation was performed and was successful. Moderate aortic regurgitation occurred in 2 patients immediately after procedure, and trace or mild aortic regurgitation was detected in rest of the patients. One patient had puncture site rupture and bleeding after procedure, and was successfully treated by balloon compression without blood transfusion. Complete atrioventricular block occurred in 3 patients within 24 hours after procedure and lasted after 48-72 hours, permanent pacemakers were implanted in these patients. Conclusion: The sheathless transfemoral technique in TAVR is safe and feasible in severe aortic stenosis patients with small access vessel diameter.

Continuous plasma filtration adsorption in treatment of severe infection-induced multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome (MODS), a high-risk disease, has a fatality rate of 70%. To improve treatment of this disease, in recent years many scholars have explored the pathological and physiological changes of MODS. To observe the curative effect of continuous plasma filtration adsorption (CPFA) in the treatment of MODS, we selected 96 patients who were diagnosed with severe infection-induced MODS and were treated in the First Affiliated Hospital of Zhengzhou University between February 2012 and October 2014 and divided them into an observation group and a control group. Besides conventional treatment, the observation group was also given CFPA in combination with high volume hemofiltration (HVHF), while the control group only received HVHF. Changes of blood routine index, balance of electrolyte and acid-base as well as vital signs were observed before and after treatment. Also, blood, kidney and blood gas were examined. For all patients, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were recorded at the start of treatment (0 h), and 5 h and 10 h after treatment. It was found that both therapies could lower blood urea nitrogen (BUN) and creatinine levels and maintain balance of electrolyte and acid-base, but had no obvious influence on leukocyte, blood platelet and hematocrit. In the observation group, PaO(2)/FiO(2) and mean arterial pressure (MAP) were significantly improved after surgery (P less than 0.05), while Acute Physiology and Chronic Health Evaluation (APACHE) II score had an obvious decrease (P less than 0.05). In contrast, the control group was observed with insignificantly changed PaO(2)/FiO(2), MAP and APACHE II score (P>0.05). TNF-α, IL-6 and CRP levels of the two groups had no statistically significant difference at the start of treatment (P>0.05), but TNF-α, IL-6 and CRP levels of the observation group became remarkably lower than those of the control group 5 h and 10 h after treatment (P less than 0.05). Therefore, CPFA is proved to be safe and effective in treating patients with severe infection-induced MODS as it can lower the level of proinflammatory cytokines and improve the level of anti-inflammatory cytokines; thus, it is worthy of clinical promotion.

[Tumor necrosis factor-α inhibitor protects against myocardial ischemia/reperfusion injury via Notch1 mediated inhibition of oxidative/nitrative stress in traumatic mice].

OBJECTIVE: To test the effects of TNF-α inhibitor Etanercept on myocardial ischemia/reperfusion (MI/R) injury in posttraumatic mice, and explore related mechanisms. METHODS: Traumatic mouse model was established with Noble-Collip drum. Five days after trauma, Notch1 was knocked down by intramyocardial injection of Notch1 small interfering RNAs (siRNA) or scrambled siRNA (20 µg). Seven days after trauma, mice were subjected to MI/R (30 minutes ischemia followed by reperfusion). Sham operation was similarly performed without coronary artery ligation. Ten minutes before reperfusion, mice received Etanercept (8 mg/kg, i. p.). ELISA was used to detect plasma levels of TNF-α and troponin I (cTnI) and myocardial nitrotyrosine content. Twenty-four hours after reperfusion, left ventricular ejection fraction (LVEF) was measured by echocardiography. Infarct size was determined by Evans blue/2, 3, 5-triphenyl tetrazolium chloride (TTC) double staining. Cardiac caspase-3 activity was detected using a caspase-3 kit. Myocardial TNF-α and Notch1 intracellular domains (Notch1 ICD) expressions were determined by Western blot. Chemiluminescence was used to assess myocardial superoxide anion content. RESULTS: (1) Compared to vehicle group, Etanercept treatment significantly reduced cTnI content, infarct size and caspase-3 activity (all P<0.01), while obviously increased LVEF (P<0.01). (2) Etanercept treatment also significantly reduced plasma and myocardial TNF-α contents (P<0.01), whereas markedly increased myocardial Notch1 ICD content (P<0.05). (3) Compared to scrambled siRNA group, Notch1 deficiency significantly increased cTnI content, infarct size and caspase-3 activity (P<0.05), whereas obviously reduced LVEF (P<0.05). (4) Etanercept significantly reduced myocardial superoxide anion and nitrotyrosine content (P<0.01), which was reversed by downregulation of Notch1 (P<0.05). CONCLUSIONS: TNF-α inhibitor Etanercept can alleviate MI/R injury after trauma by reducing myocardial oxidative/nitrative stress via activating Notch1 signaling pathway.

Overexpression of MicroRNA-145 Promotes Ascending Aortic Aneurysm Media Remodeling through TGF-ß1.

OBJECTIVE: In this study the role of microRNA-145 expression in ascending aortic aneurysm wall media remodeling was examined. METHODS: Aortic wall samples were obtained from 10 patients who had undergone surgery for ascending aortic aneurysm. Control aortic tissue samples were obtained from 10 patients who had undergone coronary artery bypass graft. The levels of microRNA-145 were analyzed using real time quantitative reverse transcriptase polymerase chain reaction, and western blots were used to determine the expressions of osteopontin (OPN) and collagen. In vitro cultures of vascular smooth muscle cells (VSMCs) were established from both patient groups. The VSMCs were transfected with either microRNA-145 mimics or microRNA-145 inhibitors to determine the effect of microRNA-145 on the expression of OPN and collagen. Furthermore, cells were co-transfected with microRNA-145 mimics and TGF-b1 siRNA to investigate whether TGF-b1 is involved in the process that microRNA-145 increases the expression of OPN and collagen. RESULTS: Aortic microRNA-145, OPN and collagen III was increased in ascending aortic aneurysm patients compared with controls (p < .05). VSMCs transfected with microRNA-145 mimics increased the expression of both OPN (average of 1.59-fold, p < .05) and collagen III (mean of 1.71-fold, p < .05). Cells transfected with microRNA-145 inhibitors decreased expression of both OPN and collagen III compared with negative controls. In addition, the inhibition of TGF-b1 decreased the positive effect of microRNA-145 on the expression of OPN and collagen III. CONCLUSION: The increased expression of microRNA-145 promotes media remodeling through TGF-b1 in the aortic aneurysm wall.

Metabolic syndrome and the risk of breast cancer among postmenopausal women in North-West China.

OBJECTIVE: To determine whether metabolic syndrome (MetS) and its components are risk factors for breast cancer among postmenopausal women in China. METHODS: Based on the baseline data of the Jinchang Cohort, a case-control study was carried out among postmenopausal women, including 43 cases and 86 controls. Both MetS and its components were evaluated. Odds ratios and 95% confidence intervals (CI) for the association were estimated by conditional logistic regression analysis. RESULTS: The odds ratio of postmenopausal breast cancer was 3.505 (95% CI 1.282-9.583) for MetS, 3.016 (95% CI 1.044-8.715) for body mass index (BMI) ≥ 25 kg/m(2), and 3.191 (95% CI 1.253-8.125) for dyslipidemia. There was no significant association between postmenopausal breast cancer and hypertension as well as diabetes. Women with four metabolic factors showed greater risk for postmenopausal breast cancer (p(trend) < 0.05). Dyslipidemia and BMI ≥ 25 kg/m(2) showed most significant interaction on breast cancer (odds ratio = 11.359; 95% CI 2.663-48.450). With BMI ≥ 25 kg/m(2), the interaction of dyslipidemia and other metabolic factors on breast cancer was higher than that without BMI ≥ 25 kg/m(2). CONCLUSION: This case-control study suggested that MetS was associated with an elevated risk of breast cancer among postmenopausal women in north-west China. Overweight and dyslipidemia had the strongest adverse effects on postmenopausal breast cancer.

Mitochondrial transfer RNA mutations and hypertension.

Mutations in mitochondrial DNA have been found to be associated with hypertension. Of these, mitochondrial transfer RNA (mt-tRNA) is a hot spot for these pathogenic mutations. It is generally believed that these mutations may result in the failure of mt-tRNA metabolism, thereby worsening mitochondrial dysfunction and resulting in hypertension. mt-tRNA is known for its high frequency of polymorphisms and mutations, and the number of reports regarding mt-tRNA mutations and hypertension is increasing significantly. To better understand the molecular basis of maternally inherited hypertension, we reassessed the link between four mt-tRNA mutations (G15927A in tRNA(Thr), C7492T in tRNA(Ser(UCN)), A4386G in tRNA(Gln), and C14686T in tRNA(Glu)) and hypertension. We first used the phylogenetic approach to investigate the deleterious roles of these mutations, then we used RNA Fold Web Server to predict the minimum free energy of these mt-tRNAs with and without mutations. Using the pathogenicity scoring system, we found that the G15927A and C7492T mutations are classified as pathogenic while all other studied mutations are neutral polymorphisms. Our study provides valuable information for the detection of pathogenic mt-tRNA mutations in hypertension.

Primary fallopian tube carcinoma--a retrospective analysis of 66 cases.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare malignant gynecologic oncology. There was no consensus on the outcome related clinicopathological characteristics. Present study aims to determine the prognosis associate factors in PFTC. MATERIALS AND METHODS: In this retrospective study, the authors identified 50 PFTC patients in Jiangsu Institute of Cancer Research and 16 cases in the Affiliated People's Hospital of Inner Mongolia Medical College between 1988 and 2013. Disease surveillance was conducted based on the follow-up protocol of MD Anderson Cancer Center. Cox proportional hazards model and log-rank test were used to assess the associations between potential clinicpathologic characteristics and the survival durations. RESULTS: The median progression free survival (PFS) and overall survival (OS) of PFTC were 36.9 and 62.7 months, respectively. FIGO Stage (p < 0.01, 0.01), grade (p = 0.02, 0.03), tumor residual after initial debulking surgery (p = 0.05, 0.01), nadir CA-125 (p = 0.01, 0.01) were independently related with PFS and OS. The PFS and OS of patients with Stage II PFTC were similar as those with Stage III-IV (30.7 vs 28.3 and 61.9 vs 49.2 months, respectively) but poorer than those of Stage I cases (N/A). The PFS of patients with paclitaxel-based chemotherapy was longer than those with other regime (51.3 vs 33.1 months), but not OS (62.7 vs 42.6 months). The outcome of patients underwent optimal initial cytoreduction surgery was better than those of suboptimal ones (PFS 56.4 vs 21.2 months and OS 65.3 vs 47.9 months, respectively). CONCLUSIOn: PFTC patients with FIGO Stage II disease should be regarded as advanced disease. Paclitaxel based chemotherapy was associated with longer PFS but not OS in PFTC.

Prognostic and assessment value of hyperglycemia and glycosylated hemoglobin in critical patients.

Hyperglycemia is common in critical patients and high blood glucose levels have a negative effect on their prognosis. The aim of this study was to investigate the effect of hyperglycemia and glycosylated hemoglobin (GHb) in critical patients. A total of 648 critical patients were enrolled in the study and received a random blood glucose test when they entered the emergency department. If blood glucose was more than 11.1 mM, a GHb test was followed within 24 h. All patients were followed up for 28 days. According to diabetes mellitus (DM) history, GHb value, and outcome of follow-up, patients were divided into different groups, and mortality rates were calculated, respectively. Hyperglycemia was found in 67.44% (437/648) of patients, and 51.49% (225/437) and 48.51% (212/437) had normal and elevated GHb levels, respectively. At the end of the follow-up period, 14 of the normal GHb patients and 32 of the elevated GHb patients died (6.22 and 15.09%, respectively). In the normal GHb group, 53 had a DM history, 23 were newly diagnosed with DM, and 149 had hospital-related hyperglycemia (HRH); the mortality rates were 11.32% (6/53), 8.70% (2/23), and 4.03% (6/149), respectively. In the elevated GHb group, 114 had a DM history, 83 were newly diagnosed with DM, and 15 had HRH; the mortality rates were 13.16% (15/114), 19.27% (16/83), and 6.67% (1/15), respectively. Hyperglycemia and GHb might play important roles in the prognosis and assessment for critical patients, and the prognosis would vary according to the different causes of hyperglycemia.

Efficacy of tension-free vaginal tape obturator and single-incision tension-free vaginal tape-Secur, hammock approach, in the treatment of stress urinary incontinence.

AIM: Aim of the present study was to compare the efficacy of tension-free vaginal tape obturator and single-incision tension-free transvaginal tape Secur, hammock approach, in the treatment of stress urinary incontinence. METHODS: Clinical data of patients who received anti-incontinence surgery between June 2008 and July 2012 were retrospectively analyzed. Efficacy and early failure rate of the tension-free vaginal tape obturator and tension-free vaginal tape-Secur hammock approach were assessed by cough test and criteria of International Consultation on Incontinence Questionnaire-Short Form. Intraoperative and postoperative complications were also computed. RESULTS: There were 28 patients in the tension-free vaginal tape obturator group while 32 patients in the tension-free vaginal tape-Secur group. The mean operation time, intraoperative blood loss and inpatient days after surgery between the two groups showed no significant difference. The catheter retention time of the tension-free vaginal tape obturator group was longer than in the tension-free vaginal tape-Secur group. The cure rate of the tension-free vaginal tape obturator and tension-free vaginal tape-Secur groups were respectively 84% and 80%, and the recurrence rates were 14.3% and 16.7%, without significant difference. The scores of International Consultation on Incontinence Questionnaire-Short Form in two groups both decreased after surgery, but there was no difference between the two groups. There were no serious complications in the two groups. CONCLUSION: Our study demonstrated that both tension-free vaginal tape obturator and tension-free vaginal tape-Secur can achieve a cure rate over 80% while with little complications, showing both methods are reliable to treat stress urinary incontinence.

Pace of Aging in older adults matters for healthspan and lifespan.

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal care and nutrition, from those caused by ongoing changes in people's bodies due to aging. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in data from N=13,626 older adults in the US Health and Retirement Study, integrates longitudinal data on blood biomarkers, physical measurements, and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability, and mortality. Pace of Aging can advance the population science of healthy longevity.

Association between Dried Fruit Intake and DNA Methylation: A Multivariable Mendelian Randomization Analysis.

OBJECTIVES: Observational studies have reported associations between dried fruit intake and DNA methylation(DNAm). However, inherent flaws in observational study designs make them susceptible to confounding and reverse causality bias. Consequently, it is unclear whether a causal association exists. In the present study, we aimed to investigate the causal associations between dried fruit intake and DNAm. METHODS: We performed two-sample Mendelian randomization (MR) using the IEU Open GWAS database aggregated data. Forty-three single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables (IVs) were selected as exposure. DNAm outcomes include Gran (estimated granulocyte proportions); AgeAccelGrim(GrimAge acceleration); Hannum (Hannum age acceleration); IEAA(Intrinsic epigenetic age acceleration), AgeAccelPheno( PhenoAge acceleration), and DNAmPAIadjAge (DNAm-estimated plasminogen activator inhibitor-1 levels). We used the MR pleiotropy residual sum and outlier test (MRPRESSO) and Radial-MR test to identify any level of multi-effect outliers and assessed the causal effect estimates(after removing outliers). The primary causal effects were estimated using inverse-variance weighted (IVW) method and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy.The direct effects of dried fruit intake on DNAm were estimated using multivariable mendelian randomization (MVMR). RESULTS: Leveraging two-sample MR analysis, we observed statistically significant associations between dried fruit intake with a lower AgeAccelGrim(ß=-1.365, 95% confidence intervals [CI] -2.266 to -0.464, PIVW=2.985×10-3) and AgeAccelPheno (ß= -1.933, 95% CI -3.068 to -0.798, PIVW=8.371×10-4). By contrast, the effects level on Gran (ß=0.008, PIVW=0.430), Hannum(ß=-0.430, PIVW=0.357), IEAA(ß=-0.184, PIVW=0.700), and DNAmPAIadjAge (ß=-1.861, PIVW=0.093) were not statistically significant. MVMR results adjusting for the potential effects of confounders showed that the causal relationship between dried fruit intake and AgeAccelGrim(ß= -1.315, 95% CI -2.373 to -0.258, PIVW=1.480×10-2) and AgeAccelPheno(ß= -1.595, 95% CI -2.987 to -0.202, PIVW=2.483×10-2) persisted. No significant horizontal polymorphism was found in the sensitivity analysis. CONCLUSION: Our MR study suggested that increased dried fruit intake is associated with slower AgeAccelGrim and AgeAccelPheno. It can providing a promising avenue for exploring the beneficial effects of dried fruit intake on lifespan extension.

Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis.

Breast cancer is the most common cancer in women worldwide. Studies have suggested that Ras-related protein 25 (Rab25), a member of Rab small GTPase family, is involved in the pathogenesis of breast cancer. In this study, we investigated whether the expression of Rab25 correlated with lymphatic metastasis in breast cancer and whether the expression of Rab25 was positively correlated with oestrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer. Breast cancer tissues from 42 invasive ductal breast cancer patients with or without lymphatic metastasis were collected and the levels of Rab25 mRNA and protein measured by quantitative real-time PCR and immunohistochemistry, respectively. The mRNA level of Rab25 was significantly increased in invasive ductal breast cancer with lymphatic metastasis compared to that in invasive ductal breast cancer without lymphatic metastasis. Immunohistochemical analysis demonstrated that Rab25 and vascular endothelial growth factor (VEGF) were highly expressed in invasive ductal breast cancer with lymphatic metastasis regardless of whether the cancer is ER and PR positive or negative. Higher expression of Rab25 positively correlated with VEGF expression. However, the expressions of Rab25 in ER and PR-positive cancers were much higher than ER and PR-negative cancers regardless of whether lymphatic metastasis occurred. These data suggest that higher level of Rab25 was associated with lymphatic metastasis, specifically in ER and PR-positive breast cancer. The better understanding of the mechanism of Rab25 may provide a basis for the development of a novel therapeutic target in breast cancer.