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BACKGROUND: Churches can be important settings for promoting physical activity (PA) among Latinos. Little is known about what factors across the church context – social, organizational, physical (outdoor spaces) – are associated with Latinos’ PA to inform faith-based PA interventions. This study investigated associations of church contextual factors with Latinos’ PA. METHODS: We used cross-sectional data from a Latino adult sample recruited from six churches that each had an adjacent park in Los Angeles, CA (n=373). Linear or logistic regression models examined associations of church PA social support, PA social norms, perceived quality and concerns about the park near one’s church, and church PA programming with four outcomes: accelerometer-based moderate-to-vigorous PA (MVPA) and self-reported adherence to PA recommendations, use of the park near one’s church, and park-based PA. RESULTS: Park quality and concerns were positively associated with using the park near one’s church. Church PA programming was positively associated with park-based PA. None of the factors were related to accelerometer-based MVPA or meeting PA recommendations. CONCLUSIONS: Findings suggest targeting church PA programming and nearby parks may be key for improving Latinos’ park use. Church and local parks department partnerships may help enhance park conditions to support churchgoing Latinos’ PA and health.

Cancer and surgery put a physiologic and psychological burden on patients with lung cancer. The active cycle of breathing technique (ACBT) has been considered as an effective airway clearance method for patients with lung diseases. Its effectiveness on perioperative outcomes in patients with lung cancer warrants study.This prospective study explored the effects of the ACBT on patients with lung cancer undergoing surgical resection.Patients were randomly allocated to the intervention (N = 34) or control group (N = 34). The intervention group received the ACBT, and the control group received usual pre-/postoperative breathing exercises. Outcomes included dyspnea, exercise capacity, anxiety, depression, and postoperative pulmonary complications. Intention-to-treat analysis was also performed.Dyspnea, anxiety, depression, and postoperative pulmonary complications were significantly improved at discharge for patients in the intervention group.

Objective To evaluate the effects of early ambulation on elderly patients’ postoperative physical functional outcomes, complications, 90‐day readmission rate, and the length of postoperative hospital stay. Methods This is a prospective cohort study conducted between June 2019 and December 2019. The study enrolled 86 elderly patients (39 males) with newly diagnosed lumbar degenerative disease undergoing single‐segment decompression and fusion surgerywere enrolled. Of all 86 patients, 39 voluntarily joined the early ambulation group, and 47 joined the regular ambulation group. The early ambulation group included patients ambulated within 4 h postoperatively, whereas the regular ambulation group included patients who were ambulatory at a minimum of 24 h after surgery. Participants’ baseline characteristics, surgical information, ambulation ability, degree of pain, functional scores, postoperative complications, 90‐day readmission rate, and length of postoperative hospital stay were recorded. Results Participants’ baseline demographic characteristics were balanced between the early ambulation group and the regular ambulation group. The operative time and blood loss were similar between groups. The time before the first‐time ambulation was 4 ± 0.5 h in the early ambulation group and 28 ± 4.5 h in the regular ambulation group. Ambulating distance was significantly longer in the early ambulation group compared with the regular ambulation group on the 1st (63 ± 45 vs 23 ± 60 m), the 2nd (224 ± 100 vs 101 ± 130 m), and the 3rd (280 ± 102.5 vs 190 ± 170 m) ambulation days based on generalized estimating equation analyses. Generalized estimating equation analyses also demonstrated that the ambulating time was longer in the early ambulation group compared with the regular ambulation group on the 1st (10 ± 5 vs 10 ± 5 min), the 2nd (19 ± 7 vs 15 ± 5 min), and the 3rd (22 ± 16.5 vs 27 ± 12 min) ambulation days. Patients in the regular ambulation group experienced a higher degree of pain than the early ambulation group patients, with an odds ratio of 1.627 (P = 0.002). Short‐term functional independence was superior in the early ambulation group, with a lower Roland–Morris disability questionnaire score (P = 0.008) and Oswestry disability index (P, This was a prospective cohort study focused on the ambulation of elderly patients undergoing lumbar decompression and fusion surgery. Early ambulation in elderly patients after surgery significantly improved postoperative functional status and shortened postoperative hospital stay. It decreased the incidence of complications and did not increase the 90‐day readmission rate.

This meta-analysis was conducted to systematically evaluate the efficacy and safety of auricular acupressure on sleep quality in patients with lung cancer. Nine articles with a total of 802 patients were retrieved after searching on 11 electronic databases. Results of the meta-analysis showed that auricular acupressure improved sleep score (standard mean difference: -0.80, 95% confidence intervals: -1.30 to -0.30, P = .002) and reduced sleep disturbance rate (risk ratio: 0.65, 95% confidence intervals: 0.51-0.84, P = .001) and sleep medicine usage (risk ratio: 0.26, 95% confidence intervals: 0.11-0.65, P = .004) significantly. Our review suggests that auricular acupressure is effective and relatively safe in improving sleep quality among patients with lung cancer.

Introduction: Metabolic memory is one of the causes of diabetic retinopathy, and astragalus polysaccharide (APS) has great advantages in the treatment of diabetes. However, the effect of APS on metabolic memory remains to be investigated. Methods: Retinal pigment epithelial cell line ARPE-19 and primary retinal pigment epithelial cells were used to verify the effect of APS on mitochondria damage and apoptosis induced by high glucose-induced metabolic memory. The relationship between miR-182 and Bcl-2 was confirmed by a luciferase activity assay. Western blotting and quantitative reverse-transcriptase polymerase chain reaction were conducted to investigate the changes in mitochondrial damage- and apoptosis-associated markers. The cell mitochondrial membrane potential was assessed by JC-1 fluorescence. Terminal deoxynucleotidyl transferase dUTP nick end labelling staining and flow cytometry assays were performed to determine the occurrence of apoptosis. Results: Treatment with high glucose followed by normal glucose significantly upregulated the expression of miR-182 and downregulated the expression of its target Bcl-2, and APS treatment reversed the above effects. Additionally, APS treatment restored mitochondrial function and inhibited apoptosis in cells in a state of metabolic memory. The effects of APS against mitochondrial damage and apoptosis were partially inhibited after miR-182 overexpression. Conclusion: APS alleviated mitochondrial damage and apoptosis induced by metabolic memory by regulating the miR-182/Bcl-2 axis, which might serve as a new strategy for the treatment of diabetic retinopathy.

To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.以父母为供者的单倍体造血干细胞移植治疗地中海贫血患者的临床疗效.探讨以父母为供者的单倍体造血干细胞移植治疗重型地中海贫血患者的临床疗效.回顾性分析2016年7月1日至2020年7月1日于厦门大学附属中山医院完成以父母为供者的单倍体造血干细胞移植治疗重型地中海贫血患者13例，对植入情况、GVHD发生率、感染等并发症及长期生存情况进行分析.13例患者中，12例成功植入，移植成功率92.3%，中位粒细胞植入时间为12.5（9-22）d，中位血小板植入时间为21（12-34）d，1例原发性植入失败。3例aGVHD（25%），经治疗完全缓解。3例cGVHD（25%），其中1例为广泛型，正在治疗中。1例合并重症细菌感染（7.7%），2例移植后发生CMV血症（15.4%），未发现CMV靶器官受累证据。3例发生 EB病毒血症（23.1%），其中1例移植后出现EB病毒相关性淋巴细胞增殖性疾病。未发现侵袭性真菌感染病例。至随访结束，13例患者全部存活，12例脱离输血，无移植相关死亡病例。预期3年总生存率100%，3年无地中海贫血生存率92.3.以父母为供者的单倍体移植模式治疗地中海贫血，供体来源可靠，植入成功率高，GVHD发生率低，可作为解决地中海贫血儿童供者来源问题的有效方法.

Objective The purpose of the study is to present a comprehensive systematic review of the effects of park-based interventions on health outcomes among youth, defined as children and adolescents. Data Source Web of Science, MEDLINE, and Scopus databases searched through November 2020. Study Inclusion and Exclusion Criteria Interventions conducted in publicly accessible parks that evaluated health outcomes (i.e., physical, mental, and emotional); focused on children and adolescents (up to 18 years old, or up to 22 years old for individuals with developmental needs); and was published in English, Spanish, and Chinese. Data Extraction Two independent reviewers extracted data and assessed the quality of the 15 included studies using the Guide to Community Preventive Services tool. Data Synthesis Descriptive summary of study characteristics and summarized methodological quality of the studies. Results Twelve studies were person-based interventions involving the evaluation of health outcome changes in cohorts, and the remaining studies were park-based, focused on changing the park environment and observing changes in youth participation in parks. All identified interventions were positively associated with individual-level and park-level outcomes ranging from body weight, moderate-to-vigorous-intensity physical activity, park utilization, and health behavior knowledge. Conclusions This systematic review demonstrated that parks as sites of interventions can provide an environment that promotes health and wellbeing for youth. Nevertheless, the number of relevant studies were limited, thus it is important to leverage and expand on existing knowledge of the utility of parks as sites of intervention to address health concerns at this critical juncture of the life course.

The intestinal mucosa is a highly compartmentalized structure that forms a direct barrier between the host intestine and the environment, and its dysfunction could result in a serious disease. As T cells, which are important components of the mucosal immune system, interact with gut microbiota and maintain intestinal homeostasis, they may be involved in the process of intestinal barrier dysfunction. P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effects of extracellular adenosine triphosphate and is expressed by most innate or adaptive immune cells, including T cells. Current evidence has demonstrated that P2X7R is involved in inflammation and mediates the survival and differentiation of T lymphocytes, indicating its potential role in the regulation of T cell function. In this review, we summarize the available research about the regulatory role and mechanism of P2X7R on the intestinal mucosa-derived T cells in the setting of intestinal barrier dysfunction.

Sarcopenia is a serious public health problem associated with the loss of muscle mass and function. The purpose of this study was to identify molecular markers and construct a ceRNA pathway as a significant predictor of sarcopenia. We designed a prediction model to select important differentially expressed mRNAs (DEMs), and constructed a sarcopenia associated ceRNA network. After correlation analysis of each element in the ceRNA network based on clinical samples and GTEX database, C2C12 mouse myoblasts were used as a model to verify the identified ceRNA pathways. A new model for predicting sarcopenia based on four molecular markers SEPP1, SV2A, GOT1, and GFOD1 was developed. The model was used to construct a ceRNA network and showed high accuracy. Correlation analysis showed that the expression levels of lncDLEU2, SEPP1, and miR-181a were closely associated with a high risk of sarcopenia. lncDLEU2 inhibits muscle differentiation and regeneration by acting as a miR-181a sponge regulating SEPP1 expression. In this study, a highly accurate prediction tool was developed to improve the prediction outcomes of sarcopenia. These findings suggest that the lncDLEU2-miR-181a-SEPP1 pathway inhibits muscle differentiation and regeneration. This pathway may be a new therapeutic target for the treatment of sarcopenia.

Background Tibet, a region where average elevation is above 3500 m and socio-economic development is relatively lower, was not included in National Oral Health Survey over decades. The cross-sectional study aimed to investigate the status of dental caries and associated factors in Tibetan adults. Methods Participants aged 35–44, 55–64 and 65–74 years were selected. Decayed, missing, and filled tooth (DMFT), decayed and filled root (DF-Root) and root canal index (RCI) were used to evaluate dental caries. Questionnaire survey on demographic information, socioeconomic status, dietary habits, and oral health knowledge and behavior was conducted. Mann-Whitney U test, logistic regression were used for the statistical analyses. Results A total of 446 participants were enrolled in the survey. Of these: 222 (49.8%) were females, 224 (50.2%) were males; 149 (33.4%), 151 (33.9%), 146 (32.7%) were aged 35–44, 55–64 and 65–74 years respectively. The mean DMFT (SD) was 7.62 (4.84), 12.46 (8.16), and 21.38 (8.93). The filling rate was very low in all age groups (1.77%, 0.98%, 0.45%). The mean DF-Root (SD) was 0.50 (1.04), 1.04 (2.02), 1.32 (2.14), respectively. Root caries index was 42.27, 44.78 and 57.60%. Older age (65–74 age group) was positively associated with crown caries (odds ratio = 31.20, 95% confidence interval: 10.70–90.96). College degree and above and brushing teeth at least once a day were negatively associated with crown caries (odds ratio = 0.28, 95% confidence interval: 0.09–0.89; odds ratio = 0.39, 95% confidence interval: 0.21–0.72, respectively). Rural area, high income level and brushing teeth at least once a day were negatively and tooth with attachment loss was positively associated with root caries. Conclusions The status of dental caries in the adults in Tibet is severe and the treatment rate is very low. The study suggests a correlation between crown caries and the variables age, level of education and frequency of tooth brushing; correlation between root caries and residence, income level, frequency of tooth brushing and exposed root surfaces. These findings could be as reference to develop community based interventions to reduce the prevalence of caries in Tibet.

BackgroundPostoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol.MethodsThis multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint.ResultsThe VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2and T3. Adverse events and vital signs were similar for the two groups at each timepoint.ConclusionsNalbuphine can provide effective and safe pain relief in patients after ambulatory surgery.Trial registrationThe registration number isChiCTR-IOR-16010032, the date of registration was 2016-11-28.

PurposeThe popularization of the internet has promoted the implementation of China's national fitness strategy and created conditions for Chinese residents to participate in sports. The internet is an essential medium for disseminating sports knowledge, and the use of the internet can change sport participation behaviors. Therefore, the internet can be used to popularize sports knowledge and promote the participation of all people in sports and thus improve the health of the entire population. This study attempts to empirically analyse how the use of the internet changes sport participation behavior.MethodUtilizing data from the 2017 China General Social Survey, a probit model, ivprobit model, and bias-corrected non-parametric percentile bootstrap test were used to analyse the impact of internet use on sport participation behavior.ResultsThe empirical results show that internet use significantly increased the probability of participation in sports by Chinese residents. Heterogeneity test results showed that internet use was more effective in promoting sport participation in middle-aged groups, groups of older persons, unmarried groups, and groups with a high school education or above. The mediating effect test results showed that internet use influenced residents' participation in sports by promoting social interaction, leisure and entertainment, and learning and recharging.ConclusionsThe internet has changed participation in sports; specifically, the use of the internet promotes sport participation. Additionally, internet use has a more obvious impact on improving the sport participation behavior of middle-aged, older, unmarried, and middle- and higher-educated individuals. Internet social interaction, internet entertainment and internet learning are effective channels to encourage Chinese residents to participate in sports and improve their health.

ObjectiveOur study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women.DesignThe serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher’s exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset.SettingThe study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College.PatientsA total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis.Main Outcome MeasureSerum circulating estradiol and leptin level.ResultsThe level of estradiol was significantly higher (PP = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P>0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038).ConclusionCirculating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.

Background Breast cancer (BC) is an age‐related disease. Long noncoding RNAs (lncRNAs) have been proven to be crucial contributors in tumorigenesis. This study aims to develop a novel lncRNA‐based signature to predict elderly BC patients’ prognosis. Methods The RNA expression profiles and corresponding clinical information of 182 elderly BC patients were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) between BC and adjacent normal samples were used to construct the signature in the training set through univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis. Kaplan–Meier analysis and time‐dependent receiver operating characteristic (ROC) analysis were used to evaluate the predictive performance. Besides, we developed the nomogram. Gene set enrichment analysis (GSEA) was performed to reveal the underlying molecular mechanisms. Results We constructed the five‐lncRNA signature (including LEF1‐AS1, MEF2C‐AS1, ST8SIA6‐AS1, LINC01224, and LINC02408) in the training set, which successfully divided the patients into low‐ and high‐risk groups with significantly different prognosis (p = 0.000049), and the AUC at 3 and 5 years of the signature was 0.779 and 0.788, respectively. The predictive performance of this signature was validated in the test and entire set. The 5‐lncRNA signature was an independent prognostic factor of OS (p = 0.007) and the nomogram constructed by independent prognostic factors was an accurate predictor of predicting overall survival probability. Besides, several pathways associated with tumorigenesis have been identified by GSEA. Conclusions The 5‐lncRNA signature and nomogram are reliable in predicting elderly BC patients’ prognosis and provide clues for clinical decision‐making., The five‐lncRNA signature (including LEF1‐AS1, MEF2C‐AS1, ST8SIA6‐AS1, LINC01224, and LINC02408) successfully divided elderly breast cancer patients into low‐ and high‐risk groups with significantly different prognosis, and the predictive accuracy of the signature was better than all the single genes and clinical characteristics. The five‐lncRNA signature was an independent prognostic factor of overall survival, and the nomogram constructed by independent prognostic factors was an accurate predictor of predicting overall survival probability.

Introduction: Air embolism has the potential to be serious and fatal. In this paper, we report 3 cases of air embolism associated with endoscopic medical procedures in which the patients were treated with hyperbaric oxygen immediately after diagnosis by transesophageal echocardiography. In addition, we systematically review the risk factors for air embolism, clinical presentation, treatment, and the importance of early hyperbaric oxygen therapy efficacy after recognition of air embolism. Patient Concerns: We present 3 patients with varying degrees of air embolism during endoscopic procedures, one of which was fatal, with large amounts of gas visible in the right and left heart chambers and pulmonary artery, 1 showing right heart enlargement with increased pulmonary artery pressure and tricuspid regurgitation, and 1 showing only a small amount of gas images in the heart chambers. Diagnoses: Based on ETCO2 and transesophageal echocardiography (TEE), diagnoses of air embolism were made. Interventions: The patients received symptomatic supportive therapy including CPR, 100% O2 ventilation, cerebral protection, hyperbaric oxygen therapy and rehabilitation. Outcomes: Air embolism can causes respiratory, circulatory and neurological dysfunction. After aggressive treatment, one of the 3 patients died, 1 had permanent visual impairment, and 1 recovered completely without comorbidities. Conclusions: While it is common for small amounts of air/air bubbles to enter the circulatory system during endoscopic procedures, life-threatening air embolism is rare. Air embolism can lead to serious consequences, including respiratory, circulatory, and neurological impairment. Therefore, early recognition of severe air embolism and prompt hyperbaric oxygen therapy are essential to avoid its serious complications.

DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a highly conserved kinase whose hyperactivation is critically involved in a variety of human tumors. The role of DEPTOR playing in pituitary adenoma (PA) is largely unknown. Here, we reported that DEPTOR was downregulated in PA tissues, especially dopamine-resistant prolactinomas. Consistently, overexpression of DEPTOR inhibited pituitary tumor GH3 and MMQ cells proliferation in vitro and in vivo, and sensitized GH3 and MMQ cells to cabergoline (CAB), a dopamine agonist (DA). Conversely, knockdown of DEPTOR promoted GH3 and MMQ cells proliferation, and conferred cells resistance to CAB. Mechanistically, DEPTOR inhibited both mTOR Complex 1 (mTORC1) and 2 (mTORC2) activities in PA cells. In addition, DEPTOR expression level was increased to suppress mTOR kinase activity via decreasing E3 ubiquitin ligase, βTrCP1, in response to CAB. Furthermore, DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB. Taken together, our results suggest that DEPTOR may be a potential target for the treatment of PAs.

Objectives This study was designed to test whether serum vitamin D levels affected Helicobacter pylori (H. pylori) infection and eradication rates. Methods A multicenter observational prospective cohort study was conducted. A total of 496 H. pylori − positive (H. pylori +) and 257 H. pylori‐negative (H. pylori −) patients were enrolled from four hospitals in China. Baseline serum vitamin D levels were measured and a 13C‐urea breath test (UBT) was performed for all the participants. The H. pylori + patients were divided into two subgroups based on their serum vitamin D levels (

BACKGROUND This study aimed to systematically evaluate the therapeutic effects of acupotomy combined with acupuncture and moxibustion on knee osteoarthritis (KOA), which was expected to provide a reference for clinical treatment of KOA using traditional Chinese medicine (TCM). METHODS The databases PubMed, Embase, Medline, Ovid, and Springer were searched to retrieve randomized controlled trials (RCTs) on KOA treatment by acupotomy combined with acupuncture and moxibustion. The search time was set as from the date the database was established to 31 December 2020. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment on the included literature, and Review Manager 5.3 software was used for meta-analysis. RESULTS A total of 10 RCTs were included in this study, including 1,073 participants. Meta-analysis results showed that compared with the control group, the clinical treatment efficiency of the experimental group was higher [mean difference (MD) =5.72; 95% confidence interval (CI): 3.39 to 9.64; Z=6.54; P

The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock.This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes.A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016).In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials.Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

Infection with SARS-CoV-2 can lead to Coronavirus disease-2019 (COVID-19) and result in severe acute respiratory distress syndrome (ARDS). Recent reports indicate an increased rate of fungal coinfections during COVID-19. With incomplete understanding of the pathogenesis and without any causative therapy available, secondary infections may be detrimental to the prognosis. We monitored 11 COVID-19 patients with ARDS for their immune phenotype, plasma cytokines, and clinical parameters on the day of ICU admission and on day 4 and day 7 of their ICU stay. Whole blood stimulation assays with lipopolysaccharide (LPS), heat-killed Listeria monocytogenes (HKLM), Aspergillus fumigatus, and Candida albicans were used to mimic secondary infections, and changes in immune phenotype and cytokine release were assessed. COVID-19 patients displayed an immune phenotype characterized by increased HLA-DR+CD38+ and PD-1+ CD4+ and CD8+ T cells, and elevated CD8+CD244+ lymphocytes, compared to healthy controls. Monocyte activation markers and cytokines IL-6, IL-8, TNF, IL-10, and sIL2Rα were elevated, corresponding to monocyte activation syndrome, while IL-1β levels were low. LPS, HKLM and Aspergillus fumigatus antigen stimulation provoked an immune response that did not differ between COVID-19 patients and healthy controls, while COVID-19 patients showed an attenuated monocyte CD80 upregulation and abrogated release of IL-6, TNF, IL-1α, and IL-1β toward Candida albicans. This study adds further detail to the characterization of the immune response in critically ill COVID-19 patients and hints at an increased susceptibility for Candida albicans infection.

Osteoporosis is the most susceptible disease for people over 60. The main cause of osteoporosis is the decreased osteogenic differentiation of mesenchymal stem cells (MSCs). Here we showed that upstream stimulatory factor 2 (USF2)/microRNA-34a (miR-34a)/bone morphogenetic protein 3 (BMP3) axis regulated osteogenic differentiation of BMSCs. USF2 and miR-34a expression were examined using qPCR. Protein levels of BMP3 and osteogenic markers expression were evaluated using both western blot and qPCR. Activity of ALP was determined by ALP assay kit. Mineralization capacity of hBMSCs was assessed using ARS. Besides, CHIP assay was employed to verify whether USF2 could bind to miR-34a promoter. Finally, RIP assay and dual-luciferase reporter assay were employed to verify whether miR-34a directly bound to BMP3. Our results suggested that miR-34a was upregulated during osteogenic differentiation of BMSCs, and miR-34a overexpression could enhance osteogenic differentiation of BMSCs. USF2 could positively regulate miR-34a expression by interacting with its promoter. USF2 overexpression enhanced osteogenic differentiation of BMSCs, while miR-34a inhibition reversed the effect. Besides, BMP3 was the target of miR-34a. MiR-34a overexpression enhanced osteogenic differentiation of BMSCs, which was abolished by BMP3 overexpression. Taken together, USF2 enhanced osteogenic differentiation of BMSCs via downregulating BMP3 by interacting with miR-34a promoter.

Background Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. Methods A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. Results A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. Conclusions Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The impact of prenatal diagnosis on the survival outcome of infants with congenital heart disease (CHD) is still unclear. This study aimed to compare the 1-year survival rate between the prenatally and postnatally diagnosed infants with CHDs. A single-center population-based retrospective cohort study was performed on data from all infants diagnosed with CHD born between January 1998 and December 2017. Among infants with isolated CHDs, the 1-year Kaplan–Meier survival probabilities for prenatal and postnatal diagnosis were estimated. Cox proportional hazard ratios were adjusted for critical CHD (CCHD) status and gestational age. A total of 424 (40 prenatally and 384 postnatally) diagnosed infants with CHDs were analyzed. Compared with non-CCHDs, infants with CCHDs were more likely to be prenatally diagnosed (55.0% vs 18.0%; P

Kawasaki disease (KD) is a form of systemic vasculitis that occurs in children under the age of 5 years old. Due to prolonged fever and elevated inflammatory markers that are found in both KD and sepsis, the treatment approach differs for each. We enrolled a total of 420 children (227 KD and 193 sepsis) in this study. Logistic regression and a nomogram model were used to analyze the laboratory markers. We randomly selected 247 children as the training modeling group and 173 as the validation group. After completing a logistic regression analysis, white blood cell (WBC), anemia, procalcitonin (PCT), C-reactive protein (CRP), albumin, and alanine transaminase (ALT) demonstrated a significant difference in differentiating KD from sepsis. The patients were scored according to the nomogram, and patients with scores greater than 175 were placed in the high-risk KD group. The area under the curve of the receiver operating characteristic curve (ROC curve) of the modeling group was 0.873, sensitivity was 0.893, and specificity was 0.746, and the ROC curve in the validation group was 0.831, sensitivity was 0.709, and specificity was 0.795. A novel nomogram prediction model may help clinicians differentiate KD from sepsis with high accuracy.

Background The evidence for the safety of high-flow nasal cannula (HFNC) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients is conflicting. Objectives To evaluate the intubation and mortality risks of HFNC compared to non-invasive ventilation (NIV) and conventional oxygen therapy (COT) for AECOPD patients. Methods A search of electronic databases was performed. Studies that used HFNC to treat AECOPD patients were identified. Results Seven RCTs and one observational study were included. There were no differences in intubation risk (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.49 to 1.78, p = 0.84, very low certainty) and mortality risk (RR 0.91, 95% CI 0.46 to 1.79, p = 0.77, very low certainty) for HFNC compared with NIV. No data were available for intubation or mortality risk for HFNC compared with COT. Conclusion For AECOPD patients, low-quality evidence indicates that HFNC does not increase intubation and mortality risks compared to NIV.

BACKGROUND Lung cancer is one of the leading causes of mortality and morbidity. Viburnum grandiflorum is a medicinal herb known for its wide spectrum of pharmacological activities, but its anti-cancer properties against lung cancer cells have not been previously investigated. The present study elucidated the antitumor effect and associated mechanism of methanol extract of Viburnum grandiflorum extract (VGE) against lung cancer cells. MATERIAL AND METHODS The viability of H1650, HCC827, and H1299 cells was measured using MTT assay. Apoptosis and cell cycle progression were determined by flow cytometry using annexin-V/PI and JC-1 stains, respectively. The Lipofectamine Plus reagent (Invitrogen) was used for transfection of caspase-9 plasmid to H1650 and H1299 cells. RESULTS The results showed decreased H1650, HCC827, and H1299 cell viability by VGE, which occurred in a concentration- and time-dependent manner. The VGE treatment significantly increased the rate of apoptosis in H1650 (P

Autoimmune hemolytic anemia (AIHA) is a rare disease in which autoantibodies target red blood cells (RBCs), leading to anemia that ranges from no symptoms to severe life-threatening hemolysis. Little is known about the severity of anemia, blood transfusion efficiency and risk of transfusion-related reactions among hospitalized AIHA patients, especially in those with incompatible RBC transfusions. A retrospective study was conducted among hospitalized AIHA patients from January 2009 to December 2015 in a large tertiary care medical center in southwest China. A total of 450 AIHA hospitalized patients were recruited, of whom 97.3% had warm AIHA, 30.3% had primary AIHA, and 90.7% were treated with corticosteroids. On admission, approximately 3% of patients had an hemoglobin (Hb)

This study was funded by the National Natural Science Foundation of China (grant 31272131 and 31372040), Shanghai Science and Technology Committee Rising‐Star Program (19QB1404600), and The Key Project for New Agricultural Cultivar Breeding in Zhejiang Province, China (2016C02052‐5).

Aberrant expression of long noncoding RNA H19 has been associated with tumour progression, but the underlying molecular tumourigenesis mechanisms remain largely unknown. Here, we report that H19 expression is frequently downregulated in human primary pituitary adenomas and is negatively correlated with tumour progression. Consistently, upregulation of H19 expression inhibits pituitary tumour cell proliferation in vitro and tumour growth in vivo. Importantly, we uncover a function of H19, which controls cell/tumour growth through inhibiting function of mTORC1 but not mTORC2. Mechanistically, we show that H19 could block mTORC1-mediated 4E-BP1 phosphorylation without affecting S6K1 activation. At the molecular level, H19 interacted with 4E-BP1 at the TOS motif and competitively inhibited 4E-BP1 binding to Raptor. Finally, we demonstrate that H19 is more effective than cabergoline treatment in the suppression of pituitary tumours. Together, our study uncovered the role of H19-mTOR-4E-BP1 axis in pituitary tumour growth regulation that may be a potential therapeutic target for human pituitary tumours., LncRNA H19 has been shown to be aberrantly expressed in different cancers. Here, the authors show that H19 lncRNA is downregulated in pituitary adenomas and H19 is able to impede pituitary tumorigenesis via disruption of 4E-BPB1 and Raptor interaction to inhibit the phosphorylation of 4E-BP1.

The concentrations of nine trace metals (Cr, Mn, Co, Ni, Cu, Zn, Rb, Cd, and Pb) were measured in different tissues of two pelagic and five demersal fish species collected from the Miri coast, Sarawak. The sequence of accumulation of trace metals in different tissues were: liver > gill > gonad > muscle. Zn (301.00 μg g−1) and Cd (0.10 μg g−1) was the maximum and minimum accumulated elements. According to the Hazard Index calculation, none of the elements will pose any adverse health effects to humans for both ingestion rates (normal and habitual fish consumers) proposed by USEPA, except for Pb and Cd in certain fish species. On the basis of the results, the level of elements in the edible muscle tissues of all the analyzed fish species from the Miri coast are below the maximum permissible limits of Malaysian and International seafood guideline values and safe for consumers.

Glioblastoma (GBM) is the most commonly diagnosed solid tumor outside the central nervous system. However, genetic factors underlying GBM remain largely unclear. Previous studies indicated that Glial fibrillary acidic protein (GFAP) might play an important role in the aggressiveness of GBM and also contributed to its poor overall survival. The present study aims to test (1) the associations between GFAP single nucleotide polymorphisms (SNPs) and GBM cells chemoresistance and metastasis, and (2) the molecular mechanism accounting for their effects. Four tagging SNPs of GFAP were initially genotyped in 667 subjects and the significant SNP was further analyzed via online bioinformatical tools. SNP rs11558961 was found to be significantly associated with GBM susceptibility. It was predicted to influence microRNA(miR)-139 binding to 3'UTR of GFAP gene. In functional experiments, we found that cells transfected with rs11558961 G-allele constructs had lower baseline luciferase activities and were more responsive to miR-139 changes, compared to C-allele constructs. Moreover, rs11558961 C>G variant reduced the chemoresistance of GBM cells and migration capability. In conclusion, rs11558961 might influence the chemoresistance and progression of GBM cells via promoting the binding of miR-139, ultimately decrease the susceptibility of GBM. This investigation will shed light on the optimizing for clinical trial design and individualizing of therapeutic plans.

Background Neuromyelitis optica spectrum disorder (NMOSD) occurs worldwide in all ethnicities. Recently, population-based studies have shown that NMOSD is more common among non-White populations. There is scarce data about NMOSD prevalence in South East Asian populations. Methods (1) A population-based study was undertaken to estimate NMOSD prevalence in the multi-ethnic Penang Island, Malaysia, comprising Chinese, Malays, and Indians. Medical records of NMOSD patients followed up at the Penang General Hospital (the neurology referral centre in Penang Island) were reviewed. The 2015 diagnostic criteria of the International Panel for NMO Diagnosis were used for case ascertainment. (2) A review of population-based prevalence studies of NMOSD worldwide was carried out. PubMed and conference proceedings were searched for such studies. Results Of the 28 NMOSD patients, 14 were residents of Penang Island on prevalence day [13 (93%) Chinese and one (7%) Malay]. All 14 patients were females and aquaporin 4 seropositive. The prevalence of NMOSD in Penang Island was 1.99/100,000 population; according to ethnicities, the prevalence in Chinese was significantly higher than in Malays (3.31/100,000 vs 0.43/100,000, respectively, p = 0.0195). Conclusion Based on our and other population-based studies, among Asians, East Asian origin populations (Chinese and Japanese) appear to have higher NMOSD prevalence than other Asian ethnic groups. Worldwide, Blacks seem to have the highest NMOSD prevalence. More studies in different geographical regions and ethnic groups will be useful to further inform about potential factors in NMOSD pathogenesis.

Cancer cells frequently exhibit aerobic glycolysis, known as the Warburg effect. An et al. identify a novel RNA regulatory activity of BAG3, a protein implicated in various cancers. BAG3 enhances posttranscriptionally the expression of Hexokinase 2, the first enzyme involved in glycolysis, and it reprograms glucose metabolism by pancreatic cancer cells., Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.

Aims Lipocalin‐2 is a pro‐inflammatory molecule characterized by a highly diversified pattern of expression and structure–functional relationships. In vivo, this molecule exists as multiple variants due to post‐translational modifications and/or protein–protein interactions. Lipocalin‐2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non‐polyaminated lipocalin‐2 (npLcn2) plays a causal role in the pathogenesis of obesity‐associated medical complications. The present study examined the presence of npLcn2 in samples from healthy volunteers or patients with cardiac abnormalities and evaluated npLcn2 as a biomarker for cardiometabolic risk assessment. Methods and results Immunoassays were developed to quantify npLcn2 in blood and urine samples collected from 100 volunteers (59 men and 41 women), or venous plasma and pericardial fluid samples obtained from 37 cardiothoracic surgery patients. In healthy volunteers, npLcn2 levels in serum are significantly higher in obese and overweight than in lean subjects. After adjustment for age, gender, smoking, and body mass index (BMI), serum npLcn2 levels are positively correlated with heart rate, circulating triglycerides, high‐sensitivity C‐reactive protein (hsCRP), and creatinine in plasma. The npLcn2 levels in urine are significantly increased in subjects with metabolic syndrome and positively correlated with BMI, heart rate, circulating triglycerides, and urinary aldosterone. In cardiothoracic surgery patients, the circulating concentrations of npLcn2 are higher (more than two‐fold) than those of healthy volunteers and positively correlated with the accumulation of this protein in the pericardial fluid. Heart failure patients exhibit excessive expression and distribution of npLcn2 in mesothelial cells and adipocytes of the parietal pericardium, which are significantly correlated with the elevated plasma levels of npLcn2, total cholesterol, and creatinine. Conclusions Quantitative and qualitative evaluation of npLcn2 in human biofluid samples and tissue samples can be applied for risk assessment of healthy individuals and disease management of patients with obesity‐related cardiometabolic and renal complications.

Fetal cardiovascular malformations is widely focused and screened, but the accuracy of screening is not satisfactory. In this study, we compared the types of congenital heart malformation, accompanying diseases and fetal outcomes in the first and second trimesters of pregnancy to clarify the advantage of early screening. From January 2013 to June 2018, 230 fetuses were diagnosed with congenital heart malformations using ultrasound method in Qilu Hospital of Shandong University, and divided into 2 groups:the first trimester fetuses (group A) and the second trimester fetuses (group B). In addition, we collected and organized medical data of 347 cases diagnosed with congenital heart disease during 1998 to 2005 (group C). We compared the spectrum of congenital heart disease, associated comorbidities and outcome of fetuses diagnosed with congenital heart disease. There were differences in the types and incidence of cardiac malformations between the first and second trimesters of pregnancy. The number of cases of non-cardiac malformation, congenital heart disease with single ventricular circulation, fetal intrauterine death and premature pregnancy termination was significantly lower in the late stage (group A and group B) than that in the early stage (group C). More patients were screened for trisomy 21, 18, 13 syndromes and Turner syndrome in group A than group B (P

Background Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson's disease (PD) that has no standard cure at present. Theacrine, a purine alkaloid from Chinese tea Kucha, has been speculated to benefit the neurodegeneration in PD, through similar actions to its chemical analogue caffeine, albeit excluding side effects. Theacrine has nowadays gained a lot of interest for its multiple benefits, while the investigations are weak and insufficient. Hypothesis/Purpose It is well-known that tea has a wide range of functions, especially in the prevention and treatment of neurodegenerative diseases. Theacrine is an active monomer compound in Camellia assamica var. kucha Hung T. Chang & H.S.Wang (Kucha), which appears to be effective and safe in PD therapy. The aim of this study is to examine its actions in diverse PD models and explore the mechanisms. Study Design For determination of theacrine's effects, we employed diverse oxidative damage-associated PD models, including 6-OHDA-treated rats, MPTP-treated mice/zebrafish and MPP+-treated SH-SY5Y cells, and using caffeine, selegiline and depranyl as positve control. For investigation and verification of the mechanisms, we utilized approaches testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression. Methods We employed behavioral tests including spontaneous activity, pole, swimming, rotarod and gait, immunohistochemistry, HPLC, flow cytometry, immunohistochemistry, Western blot, gene knockdown by siRNA and overexpression by plasmid in this study. Results Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD (6-OHDA-treated rats and in MPTP-treated mice and zebrafish). The followed data of MPP+-treated SH-SY5Y cells indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction. Further investigations illustrate that theacrine activates SIRT3 directly. It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function. This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene, demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons. Conclusion Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions.

BACKGROUND: Chronic kidney disease (CKD) is a serious global public health challenge, but there is limited information on the connection between air pollution and risk of CKD. OBJECTIVE: The aim of this study was to investigate the association between long-term exposure to particulate matter (PM) with an aerodynamic diameter of less than [Formula: see text] ([Formula: see text]) and the development of CKD in a large cohort. METHODS: A total of 100,629 nonCKD Taiwanese residents age 20 y or above were included in this study between 2001 and 2014. Ambient [Formula: see text] concentration was estimated at each participant's address using a satellite-based spatiotemporal model. Incident CKD cases were identified by an estimated glomerular filtration rate (eGFR) of less than [Formula: see text]. We collected information on a wide range of potential confounders/modifiers during the medical examinations. Cox proportional hazard regression was applied to calculate hazard ratios (HRs). RESULTS: During the follow-up, 4,046 incident CKD cases were identified, and the incidence rate was 6.24 per 1,000 person-years. In contrast with participants with the first quintile exposure of [Formula: see text], participants with the fourth and fifth quintiles exposure of [Formula: see text] had increased risk of CKD development, adjusting for age, sex, educational level, smoking, drinking, body mass index, systolic blood pressure, fasting glucose, total cholesterol, and self-reported heart disease or stroke, with an HR [95% confidence interval (CI)] of 1.11 (1.02, 1.22) and 1.15 (1.05, 1.26), respectively. A significant concentration-response trend was observed ([Formula: see text]). Every [Formula: see text] increment in the [Formula: see text] concentration was associated with a 6% higher risk of developing CKD (HR: 1.06, 95% CI: 1.02, 1.10). Sensitivity and stratified analyses yielded similar results. CONCLUSIONS: Long-term exposure to ambient [Formula: see text] was associated with an increased risk of CKD development. Our findings reinforce the urgency to develop global strategies of air pollution reduction to prevent CKD. https://doi.org/10.1289/EHP3304.

To evaluate the effect of health education on schistosomiasis in Kunshan City, so as to provide the evidence for making the consolidating strategy in the late stage of interruption of schistosomiasis transmission.The residents, middle school students and elementary school students were randomly sampled from one community, one middle school and one elementary school of each of two towns and they were investigated with interviews and questionnaires for the implementation of health education on schistosomiasis prevention and control.A total of 452 middle school students (232 cases) and primary school students (220 cases) were surveyed. The awareness rate of total schistosomiasis knowledge was 98.21% among the students (the awareness rate of basic schistosomiasis knowledge was 98.42% and the awareness rate of preventive schistosomiasis knowledge was 98.01%). Among the 220 elementary school students, the awareness rate of total schistosomiasis knowledge was 97.21% (the awareness rate of basic schistosomiasis knowledge was 97.60% and the awareness rate of preventive schistosomiasis knowledge was 96.82%). Among the 232 middle school students, the awareness rate of total schistosomiasis knowledge was 99.17% (The effect of health education on schistosomiasis prevention and control is very well, and the total awareness rate of schistosomiasis prevention and control knowledge among the population has reached the goal (more than 95%) of the medium- and long-term planning of schistosomiasis prevention and control in Kunshan City.

AimsTo evaluate the effects of habitual leisure-time physical activity (LTPA) on incident type 2 diabetes in a prospective cohort of Chinese adults with impaired fasting glucose (IFG).Methods44 828 Chinese adults aged 20–80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was identified by fasting plasma glucose ≥7 mmol/L. The participants were classified into four categories based on their self-reported weekly LTPA: inactive, low, moderate, or high. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated with adjustment for established diabetic risk factor.ResultsAfter 214 148 person-years of follow-up, we observed an inverse dose–response relationship between LTPA and diabetes risk. Compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR 0.80, 95% CI 0.71 to 0.90; PConclusionsOur results show higher levels of LTPA are associated with a lower risk of diabetes in IFG subjects. These data emphasise the urgent need for promoting physical activity as a preventive strategy against diabetes to offset the impact of population ageing and the growing obesity epidemic.

Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated. A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting. Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia. Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

Background: As a novel molecular markerof non-small cell lung cancer (NSCLC), PRDI-BF1 and RIZ homology domain containing protein 14 (PRDM14) is over-expressed in NSCLC tumor tissues. Extracellular matrix degradation mediated by the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) is one of the most important mechanism in lung cancer metastasis. This study aimed to determine if PRDM14 promoted the migration of NSCLC cells through extracellular matrix degradation mediated by change of MMP/TIMP expression. Methods: The expression of PRDM14 was down-regulated in human cell line A 549 after transfection with lentiviral vector-mediated short-hairpin ribonucleic acids (shRNAs) which targeted the PRDM14 promoter. Cellular migration of shRNA-infected cells was detected by a scratch wound healing assay and transwell cell migration assay. Expression levels of MMP1, MMP2, TIMP1, and TIMP2 were measured by quantitative real-time polymerase chain reaction (RT-PCR). Results: Migration of PRDM14-shRNA-infected cells was significantly inhibited relative to control cells as measured by the scratch wound healing (P < 0.05) and transwell cell migration assays (P < 0.01). The expression of MMP1 in A549 cells infected by PRDM14-shRNA was down-regulated significantly (P < 0.01), whereas the expression of TIMP1 and TIMP2 was up-regulated significantly (P < 0.01). Conclusions: PRDM14 accelerates A549 cells migration in vitro through extracellular matrix degradation. PRDM14 is considered as a potential therapeutic target in metastatic NSCLC.

A critical issue in the analysis of clinical trials is patients’ noncompliance to assigned treatments. In the context of a binary treatment with all or nothing compliance, the intent-to-treat analysis is a straightforward approach to estimating the effectiveness of the trial. In contrast, there exist three commonly used estimators with varying statistical properties for the efficacy of the trial, formally known as the complier average causal effect. The instrumental variable estimator may be unbiased, but can be extremely variable in many settings. The as treated and per protocol estimators are usually more efficient than the instrumental variable estimator, but they may suffer from selection bias. We propose a synthetic approach, which incorporates all three estimators in a data driven manner. The synthetic estimator is a linear convex combination of the instrumental variable, per protocol, and as treated estimators, resembling the popular model-averaging approach in the statistical literature. However, our synthetic approach is nonparametric; thus, it is applicable to a variety of outcome types without specific distributional assumptions. We also discuss the construction of the synthetic estimator using an analytic form derived from a simple normal mixture distribution. We apply the synthetic approach to a clinical trial for post-traumatic stress disorder.

The metabolic impact of inadequate sleep has not been determined in healthy individuals outside laboratories. This study aims to investigate the impact of sleep duration on five metabolic syndrome components in a healthy adult cohort.A total of 162121 adults aged 20-80 years (men 47.4%) of the MJ Health Database, who were not obese and free from major diseases, were recruited and followed up from 1996 to 2014. Sleep duration and insomnia symptoms were assessed by a self-administered questionnaire. Incident cases of five metabolic syndrome components were identified by follow-up medical examinations. Cox proportional hazard ratios (HRs) were calculated for three sleep duration categories "6 hours/day (short)," "6-8 hours/day (regular)," and "8 hours/day (long)" with adjustment for potential confounding factors. Analyses were stratified by insomnia symptoms to assess whether insomnia symptoms modified the association between sleep duration and metabolic syndrome.Compared to regular sleep duration, short sleep significantly (p.001) increased the risk for central obesity by 12% (adjusted HR 1.12 [1.07-1.17]), for elevated fasting glucose by 6% (adjusted HR 1.06 [1.03-1.09]), for high blood pressure by 8% (adjusted HR 1.08 [1.04-1.13]), for low high-density lipoprotein-cholesterol by 7% (adjusted HR 1.07 [1.03-1.11]), for hypertriglyceridemia by 9% (adjusted HR 1.09 [1.05-1.13]), and for metabolic syndrome by 9% (adjusted HR 1.09 [1.05-1.13]). Long sleep decreased the risk of hypertriglyceridemia (adjusted HR 0.89 [0.84-0.94]) and metabolic syndrome (adjusted HR 0.93 [0.88-0.99]). Insomnia symptoms did not modify the effects of sleep duration.Sleep duration may be a significant determinant of metabolic health.

This study was to evaluate the bactericidal effect of Er:YAG laser-activated sodium hypochlorite irrigation (Er:YAG + NaOCl) on biofilms of Enterococcus faecalis clinical isolate.It was reported that Er:YAG + NaOCl had effective bactericidal effect on laboratory-adapted E. faecalis strain, while no study has reported its effect on the clinical isolate.Eighteen E. faecalis strains were isolated from 39 root-filled teeth with periapical lesions, and their biofilm formation abilities were evaluated using the crystal violet staining method. Extracted human root canals were prepared to a 40#/.04 K3 instrument and contaminated with the E. faecalis isolate that presented the strongest biofilm formation ability for 4 weeks. The infected canals then received treatments of syringe irrigation with normal saline (NS) or NaOCl, ultrasonic activated irrigations US + NS and US + NaOCl, and Er:YAG laser-activated irrigations Er:YAG + NS and Er:YAG + NaOCl. The root canals were examined using scanning electron microscopy (SEM). The bacterial reductions were evaluated using the cell count method.SEM results showed that biofilm-like structures formed on the root canal walls after 4-week bacterial incubation. Er:YAG + NaOCl completely removed the E. faecalis biofilm from the root canal wall and made it the cleanest and most smooth surface among the treatment groups. Bacterial reductions in the treatment groups were presented in a descending order of Er:YAG + NaOCl (98.8%), US + NaOCl (98.6%)NaOCl (94.0%)Er:YAG + NS (91.9%)US + NS (78.1%)NS (51.1%) (p 0.05).The Er:YAG + NaOCl showed an effective bactericidal effect on biofilms of E. faecalis isolate, which may be considered an effective protocol for root canal treatment.

Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. In addition, DRD5 protein was highly expressed in the majority of human pituitary adenomas, and treatment of different human pituitary tumor cell cultures with the DRD5 agonist SKF83959 resulted in growth suppression, and the efficacy was correlated with the expression levels of DRD5 in the tumors. Furthermore, we found that DRD5 was expressed in other human cancer cells such as glioblastomas, colon cancer, and gastric cancer. DRD5 activation in these cell lines suppressed their growth, inhibited MTOR activity, and induced autophagy. Finally, in vivo SKF83959 also inhibited human gastric cancer cell growth in nude mice. Our studies revealed novel mechanisms for the tumor suppressive effects of DRD5 agonists, and suggested a potential use of DRD5 agonists as a novel therapeutic approach in the treatment of different human tumors and cancers.