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Background. Inflammation plays a key role in the pathophysiology and progression of acute kidney injury (AKI). Red cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory index, and its prognostic effect on critically ill patients with AKI is rarely investigated. This work is aimed at investigating the association between RPR and in-hospital mortality in these patients. Methods. Data were extracted from the Medical Information Mart for Intensive Care III database. All-cause death during hospitalization was selected as the primary outcome. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, and the area under the curve (AUC) was applied to compare predictive ability among different indices. Cox proportional hazard models were utilized to assess the association between RPR and in-hospital mortality. Restricted cubic spline analysis for multivariate Cox model was performed to explore the shape of the relationship between RPR and mortality. Results. A total of 24,166 critically ill patients with AKI were included. The relationship of RPR and in-hospital mortality was nonlinear with a trend to rise rapidly and then gradually. For mortality prediction, RPR had the optimal cut-off value of 0.093, of which the AUC was 0.791 (95% confidence interval (CI): 0.773–0.810), which was higher than those of RDW, platelet, sequential organ failure assessment score, simplified acute physiology score II, neutrophil to lymphocyte ratio, and platelet to lymphocytes ratio. After adjustments for various confounders, high RPR showed a significant association with increased mortality with hazard ratios of 1.46 (95% CI: 1.40–1.55) for categorical variable and 1.88 (95% CI: 1.80–1.97) for continuous variables in the fully adjusted model. Conclusions. Elevated RPR on admission is substantially associated with high risk of in-hospital mortality in critically ill patients with AKI and thus may serve as a novel predictor of prognosis for these patients.

Introduction The purpose was to quantify the health effects of tobacco using data from the 2019 Global Burden of Disease study. Aims and Methods We collected detailed information on tobacco consumption overall as well as its individual aspects (smoking, secondhand smoke, and chewing tobacco) for the deaths and disability-adjusted life years (DALYs) for all-cause disease, cardiovascular disease, neoplasms, and chronic respiratory diseases, and their age-standardized rates (ASRs). Results Tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The ASRs of all tobacco-related deaths and DALYs declined from 1990 to 2019, to 108.55 deaths per 100 000 population and 2791.04 DALYs per 100 000 population in 2019. During any year the ASRs of all tobacco-related deaths and DALYs were higher in males than in females. The ASRs of all tobacco-related deaths and DALYs were highest in countries with a low-middle sociodemographic index (SDI) and lowest in high-SDI countries in 2019. Cardiovascular disease, neoplasms, and chronic respiratory diseases were the three leading causes of tobacco-related mortality. Conclusions Although the ASRs of deaths and DALYs related to tobacco have declined, the absolute number remain high. Tobacco control policies need to be strengthened further in order to reduce the heavy health burden of tobacco. Implications This study provides a detailed description on the health effects of tobacco, including maps of the current global burden of tobacco-related disease. Although the ASRs of tobacco-related deaths and DALYs have declined, the absolute numbers remain high—tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The findings may have implications for tobacco control. Countries where progress has been slower in reducing tobacco-related disease burden should study and consider implementing policies and strategies that have been applied in countries like Singapore which show the greatest declines for recent decades.

PurposeThis study aimed to provide a comprehensive assessment of burden estimates and the secular trend of blindness and vision loss, as measured by years lived with disability (YLDs), at the global, regional, and national levels.MethodsThe age-standardized YLD rates (ASYRs) due to blindness and vision loss and its subtypes, including moderate vision loss, severe vision loss, blindness, and presbyopia, from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in the ASYRs due to blindness and vision loss.ResultsIn 2019, the global ASYRs per 100,000 population was 327.98 for blindness and vision loss, specifically, 85.81 for moderate vision loss, 74.86 for severe vision loss, 95.03 for blindness, and 62.27 for presbyopia. From 1990 to 2019, the ASYRs due to blindness and vision loss slightly decreased. Females showed higher ASYRs than males in 2019. The global highest ASYRs were observed in South Asia and sub-Saharan Africa. Negative associations were found between the burden estimates of blindness and vision loss and the sociodemographic index levels. The EAPCs of ASYRs in blindness and vision loss were significantly negatively correlated with the ASYRs in 1990 and positively correlated with human development indices in 2019.ConclusionsGlobally, blindness and vision loss continue to cause great losses of healthy life. Reasonable resource allocation and health-service planning are needed for the prevention and early intervention of disabilities caused by vision loss.

ObjectiveMultiple myeloma (MM) imposes a heavy burden in China. Understanding the secular trend of MM burden and projecting its future trend could facilitate appropriate public health planning and improve the management of MM.MethodsSex-specific incidence and mortality rates of MM in China from 1990 to 2019 were collected from the Global Burden of Disease 2019 study. The secular trend of MM burden was analyzed by joinpoint regression. Age–period–cohort model was used to analyze the effects of age, period, and birth cohort on MM burden and project future trends up to 2044.ResultsFrom 1990 to 2019, the age-standardized incidence and mortality rates of MM continued to increase in males. For females, the age-standardized rates were stable in MM incidence and decreased in MM mortality. Males had a higher disease burden of MM than females. Age effects were the most significant risk factor for MM incidence and mortality. Moreover, the risk of MM incidence and mortality increased with increasing time period but decreased with birth cohort in males and females. The age-standardized incidence and mortality rates of MM in China is predicted to be continuously increasing over the next 25 years.ConclusionThe burden of MM in China is expected to continue to increase in the future, with significant sex difference. A comprehensive understanding of the risk characteristics and disease pattern of MM could help develop timely intervention measures to effectively reduce its burden.

We previously reported that sputum induction was more sensitive than throat swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two convalescent coronavirus disease 2019 (COVID-19) patients; however, the value and safety of induced sputum testing require further study. We conducted a prospective multi-center cross-sectional study to compare induced sputum to throat swabs for SARS-CoV-2 detection. Confirmed COVID-19 patients from six hospitals in six cities across China who received one or more negative RT-PCR result for SARS-CoV-2 were enrolled, and paired specimens (induced sputum and throat swabs; 56 cases) were assayed. In three paired samples, both the induced sputum and throat swabs were positive for SARS-CoV-2. The positive rate for induced sputum was significantly higher than for throat swabs both overall (28.6% vs 5.4%, respectively; p

BackgroundEating disorders (ED) have increasingly become a global topic of concern for public health. A better understanding of ED incidence is a basic requirement for improving its management. However, the temporal trend of ED incidence in China is still unknown.MethodsThe incidence rates of ED from 1990 to 2017 were collected from the Global Burden of Disease Study 2017 database according to the following: subtype, i.e. anorexia nervosa (AN) and bulimia nervosa (BN); sex; and age group. The average annual percent changes and relative risks were calculated using joinpoint regression and the age–period–cohort model, respectively.ResultsFrom 1990 to 2017, age-standardized incidence rates of ED continued to increase in males and females, and this variation trend was observed in AN and BN. Joinpoint regression analysis showed that the incidence rates increased in all age groups. Adolescents had the highest risk of developing ED, followed by young adults. Age effects were the most influential risk factor for ED incidence. Period effects showed that the risk of developing ED continuously increased with increasing time periods in BN, but not in ED and AN. Concerning the cohort effects, people born after the 1990s presented a higher risk of ED, though they presented a lower risk of BN as compared to the whole cohort.ConclusionsED incidence rates continue to increase in China, particularly among adolescents and young adults. Further etiological studies are needed to explain these increases and to facilitate the early identification of high-risk individuals.

Background. Acute kidney injury (AKI) is an important complication in critically ill patients, especially in sepsis and septic shock patients. Early prediction of AKI in septic shock can provide clinicians with sufficient information for timely intervention so that improve the patients’ survival rate and quality of life. The aim of this study was to establish a nomogram that predicts the risk of AKI in patients with septic shock in the intensive care unit (ICU). Methods. The data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database between 2001 and 2012. The primary outcome was AKI in the 48 h following ICU admission. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AKI. The performance of the nomogram was evaluated according to the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis, and clinical impact curve. Results. A total of 2415 patients with septic shock were included in this study. In the training and validation cohort, 1091 (64.48%) of 1690 patients and 475 (65.52%) of 725 patients developed AKI, respectively. The predictive factors for nomogram construction were gender, ethnicity, congestive heart failure, diabetes, obesity, Simplified Acute Physiology Score II (SAPS II), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), bilirubin, creatinine, blood urea nitrogen (BUN), and mechanical ventilation. The model had a good discrimination with the area under the ROC curve of 0.756 and 0.760 in the training and validation cohorts, respectively. The calibration curve for probability of AKI in septic shock showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusion. The proposed nomogram can quickly and effectively predict the risk of AKI at an early stage in patients with septic shock in ICU, which can provide information for timely and efficient intervention in patients with septic shock in the ICU setting.

ObjectivesTo provide a comprehensive assessment of the estimated burden and trend of urolithiasis at the global, regional, and national levels.MethodsThe age-standardized rates (ASRs) of the incidence and disability-adjusted life years (DALYs) of urolithiasis from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 database. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in urolithiasis burden.ResultsIn 2019, the ASRs of the incidence and DALYs were 1,394.03/100,000 and 7.35/100,000, respectively. The ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019 with EAPCs of −0.83 and −1.77, respectively. Males had a higher burden of urolithiasis than females. In 2019, the highest burden of urolithiasis was observed in regions with high–middle sociodemographic index (SDI), particularly in Eastern Europe, Central Asia, and Southeast Asia. The burden of urolithiasis increased in most countries or territories. The burden of urolithiasis and SDI had a non-linear relationship, and the estimated value of urolithiasis burden was the highest when the SDI value was ~0.7.ConclusionGlobally, the ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019, but an increasing trend was observed among many countries. More effective and appropriate medical and health policies are needed to prevent and early intervene in urolithiasis.

BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas. METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance, Epidemiology, and End Results database, and randomly divided into the training (n = 853) and the validation (n = 366) cohorts. Based on the Cox regression model, nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient. The performance of the nomograms was measured according to discrimination, calibration, and clinical utility. Moreover, we compared the predictive accuracy of the nomograms with that of the traditional staging system. RESULTS In the training cohort, age, marital status, histological type, T stage, N stage, M stage, and chemotherapy were selected to construct nomograms. Compared with the American Joint Committee on Cancer 7th staging system, the nomograms were generally more discriminative. The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction. Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system. With respect to decision curve analyses, the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities. CONCLUSION The nomograms show improved predictive accuracy, discrimination capability, and clinical utility, which can be used as reliable tools for risk classification and treatment recommendations.

Polydatin (PD), an active component of Chinese herbs, is reported to have many biological functions, such as cardioprotective actions, anti-inflammatory activities, and antitumor effects. In this study, we investigated the effects of PD on body weight control, glucose and lipid metabolic regulation, and anti-inflammation in a high-fat-diet- (HFD-) induced obese mice model. After treatment of PD (100 mg/kg/d for 4 weeks), HFD mice reduced body weight, retroperitoneal fat mass, and adipose cell sizes; significantly lowered serum total cholesterol triglyceride (TG) and low-density lipoprotein (LDL) levels; and increased high-density lipoprotein (HDL) levels compared with the HFD control mice. Further studies showed that PD downregulated the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involving in the regulation of adipocyte differentiation, in the retroperitoneal fat of HFD mice. Additionally, PD significantly upregulated the mRNA and protein expressions of leptin, an adipocyte-derived anorexic hormone that regulates food intake and energy expenditure, in the adipose tissues of HFD mice. Moreover, PD reduced the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in the retroperitoneal and epididymal tissues of HFD mice, suggesting that PD prevented adipose tissue inflammation. In conclusion, PD may serve as a pharmaceutic candidate for obesity-related lipid metabolism, anti-inflammation, and body weight loss.

Early identification of severe acute pancreatitis (SAP) is critical for clinical decision-making. The apolipoprotein B-to-apolipoprotein A1 ratio (ApoB/A1 ratio) reflects the balance between pro-inflammation and anti-inflammation in vivo. This study investigated the association between serum ApoB/A1 ratio at admission and acute pancreatitis (AP) severity. A total of 375 patients with first attack of AP were retrospectively recruited from January 2014 to December 2017. The severity of AP was assessed at admission based on the 2012 revised Atlanta Classification. Serum lipids levels were tested on the first 24 h of hospitalization, of which the correlations with clinical features or scoring systems were also measured. The ApoB/A1 ratio markedly increased across disease severity of AP. The ApoB/A1 ratio, expressed as both quartile and continuous variables, was significantly associated with a high risk of SAP, even after adjustment for other conventional SAP risk factors. The ApoB/A1 ratio positively correlated with the revised 2012 Atlanta Classification, Ranson score, Bedside Index for Severity in AP score, Modified Computed Tomography Severity Index score, and Acute Physiology and Chronic Health Evaluation II score for AP severity. The optimal cut-off value of ApoB/A1 ratio for detecting SAP was 0.88, with a sensitivity of 83.08% and a specificity of 69.03%. Serum ApoB/A1 ratio at admission is closely correlated with disease severity in patients with AP and can serve as a reliable indicator for SAP in clinical setting.

Conduct disorder is one of the least widely recognized and studied psychiatric disorders. This study aimed to comprehensively analyze the burden of conduct disorder at the global, regional, and national levels based on the Global Burden of Disease (GBD) 2019 estimates. Globally, the age-standardized prevalence rates (ASPRs) of conduct disorder slightly increased from 1990 to 2019 with an estimated annual percentage change (EAPC) at 0.147. Males had a higher burden than females, but females had a greater increment in ASPRs than males over time. In 2019, the highest ASPR of conduct disorder was observed in Western Europe, followed by Eastern Europe, with the lowest one found in East Asia, then South Asia. However, the most significant increment in ASPRs was observed in high-income North America, followed by East Asia, and South Asia. The EAPCs at the national level were negatively associated with the ASPRs in 1990. The burden of conduct disorder continues to increase globally, especially in high-income North America, East Asia, and South Asia, and should have more attention focused on it.

The aim of this study was to analyze the secular trends of conduct disorder (CD) incidence in China from 1990 to 2019 under the joinpoint analysis and the age-period-cohort framework.The sex-specific incidence rates of CD from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database according to the age group. The joinpoint regression and the age-period-cohort model were conducted using the average annual percent changes and relative risks as size effects, respectively.From 1990 to 2019, age-standardized rates (ASRs) of CD incidence showed an overall increasing trend in both sexes, and this variation trend was observed in almost all age groups. The annual sex-specific ASRs were lower in China than those worldwide but were rapidly growing. Age effects were the most significant risk factor for CD, with the highest risk in adolescents aged 10 to 14 years, followed by children aged 5 to 9 years, but a relatively lower risk in adolescents aged 15 to 19 years than in other age groups. However, period and cohort effects were not statistically significant.CD incidence rates in China have been increasing in both sexes from 1990 to 2019. Further studies are necessary to explain the etiology of these increases and promote the early identification of individuals at risk for developing CD.

Microglia-mediated neuroinflammation is tightly correlated with the etiology and progression of neurodegenerative disorders, including Parkinson's disease (PD). Nilotinib, a c-Abl inhibitor used for chronic myeloid leukemia, has been proven effective in relieving PD progression. However, whether nilotinib could affect neuroinflammation is largely unknown. In this current study, we investigated the role of nilotinib in microglia-mediated neuroinflammatory response in Parkinson's disease. Lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and mouse brains were used as models for Parkinson's disease. Our results demonstrated that nilotinib significantly suppressed LPS-induced neuroinflammation by reducing the production of pro-inflammatory factors including iNOS, COX-2, IL-1β, IL-6 and TNF-α in BV2 cells. Moreover, pretreatment of nilotinib attenuated the neurotoxicity of LPS-treated microglial conditioned medium to MES23.5 dopaminergic (DA) neurons. Mechanismly, nilotinib inhibited NF-κB signaling pathway and suppressed the nuclear translocation of p65 upon LPS stimulation. In LPS-injected mouse brains, nilotinib administration markedly suppressed the activation of microglia and down-regulated COX-2 as well as IL-1β expression. Most importantly, nilotinib effectively protected against microglial activation-mediated mouse DA neuronal loss. Taken together, our study suggests that nilotinib exerts anti-neuroinflammatory effect and protects DA neurons from activated microglia-induced inflammatory damage through suppressing NF-κB signaling pathway, indicating its potential application in further clinical trials.

Aim Eating disorders have increasingly become a public health concern globally. This study aimed to reveal the burden of eating disorders at the global, regional and national levels using the Global Burden of Disease (GBD) Study 2017 data. Methods We extracted the age-standardised rates (ASRs) of prevalence and disability-adjusted life years (DALYs) and their 95% uncertainty intervals (UIs) of eating disorders, including anorexia nervosa and bulimia nervosa, between 1990 and 2017 from the GBD 2017 data. The estimated annual percentage changes (EAPCs) were calculated to quantify the secular trends of the burden of eating disorders. Results The ASRs of prevalence and the DALYs of eating disorders continuously increased worldwide from 1990 to 2017 by an average of 0.65 (95% UI: 0.59–0.71) and 0.66 (95% UI: 0.60–0.72), respectively. The burden of eating disorders was higher in females than in males, but the increment in ASRs was greater in males than in females over time. In 2017, the highest burden of eating disorders was observed in the high sociodemographic index (SDI) regions, especially Australasia (ASR of prevalence = 807.13, 95% UI: 664.20–982.30; ASR of DALYs = 170.74, 95% UI: 113.43–244.14, per 100 000 population), Western Europe and high-income North America. However, the most significant increment of the burden of eating disorders was observed in East Asia (EAPC for prevalence = 2.23, 95% UI: 2.14–2.32; EAPC for DALYs = 2.22, 95% UI: 2.13–2.31), followed by South Asia. An increasing trend in the burden of eating disorders at the national level was observed among most countries or territories. The countries with the top three highest increasing trends were Equatorial Guinea, Bosnia and Herzegovina and China. Positive associations were found between the burden estimates and the SDI levels in almost all geographic regions during the observed 28-year period. We also found that the human development indexes in 2017 were positively correlated with the EAPCs of the ASRs of prevalence (ρ = 0.222, P = 0.002) and DALYs (ρ = 0.208, P = 0.003). Conclusion The highest burden of eating disorders remains in the high-income western countries, but an increasing trend was observed globally and in all SDI-quintiles, especially in Asian regions that were highly populous. These results could help governments worldwide formulate suitable medical and health policies for the prevention and early intervention of eating disorders.

Objective As a result of the pandemic of COVID‐19, the public have been experiencing psychological distress. However, the prevalence of psychological distress during the COVID‐19 pandemic remains unknown. Our objective was to evaluate the prevalence of psychological distress during COVID‐19 outbreak and their risk factors, especially their internal paths and causality. Methods A nationwide cross‐sectional survey of the prevalence of mental disorders was conducted. We used Hospital Anxiety and Depression Scale (HADS) to estimate the prevalence of anxiety and depression. The internal paths and the causality of the psychological health were analyzed using a structural equation modeling (SEM) approach. Results A total of 24,789 respondents completed the survey. We found that the overall prevalence of anxiety, depression, combination of anxiety, and depression were 51.6% (95% CI: 51.0–52.2), 47.5% (95% CI: 46.9–48.1), and 24.5% (95% CI: 24.0–25.0), respectively. The risk of psychological disorders in men was higher than that in women. The status of psychological health was different across different age groups, education levels, occupations, and income levels. The SEM analysis revealed that inadequate material supplies, low income, low education, lack of knowledge or confidence of the epidemic, and lack of exercise are major risk factors for psychological distress. Conclusions The evidence from this survey poses serious challenges related to the high prevalence of psychological distress, but also offers strategies to deal with the mental health problems caused by the COVID‐19 pandemic., In national cross‐sectional survey with largest participants in china, we pose serious challenges related to the high prevalence of psychological distress, find out major risk factors for them, and then offer evidence‐based strategies to deal with the mental health problems caused by the COVID‐19 pandemic. Our research also provides evidences for other countries suffering from the COVID‐19 to take public health interventions to relieve the public psychological pressure.

The incidence of rectal cancer has meaningfully increased in young patients. However, quantitative evaluation for the competing data of early-onset rectal cancer is lacking. So, we performed a competing risk analysis to calculate the cumulative incidence of death for patients with early-onset rectal cancer and developed a nomogram to predict the probability of cancer-specific mortality for these patients. We abstracted data of patients with early-onset rectal cancer between 2004 and 2016 by using the Surveillance, Epidemiology, and End Results program database. The cumulative incidence function was used to calculate the crude cancer-specific mortality of early-onset rectal cancer. Fine and Gray’s proportional sub-distribution hazard model was adopted to explore the risk factors of cancer-specific death. Then, we establish a nomogram to predict their 3-, 5-, and 10-year probabilities. We identified 9917 patients with early-onset rectal cancer, and they were randomly divided into training (n = 6941) and validation (n = 2976) cohorts. In the training cohort, the 3-, 5-, and 10-year cumulative incidences of cancer-specific death after diagnosis for early-onset rectal cancer were 11.4%, 19.9%, and 28.8%, respectively. Fine and Gray’s model showed that sex, race, marital status, histology, T stage, N stage, M stage, examined lymph nodes, and pretreatment carcinoembryonic antigen were independently associated with cancer-specific mortality. Such factors were selected to develop a prognostic nomogram. The competing risk nomogram has an ideal performance for predictive cancer-specific mortality in early-onset rectal cancer.

MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11b+Gr-1+ MDSCs in peripheral circulation and decreased Gr-1+ cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD.

This study aimed to analyze the effect and mechanism of immunization of oral

Kisspeptin, encoded by the Kiss1 gene, and its receptor GPR54 have a central regulatory role in the male reproduction. However, their functions in peripheral tissues, such as testes, remain unclear. This study investigated the local expressions and function of Kiss1/GPR54 in goats' testes. The mRNA expression of Kiss1/GPR54 in pubertal goat Leydig cells was detected through reverse transcriptase PCR (RT-PCR), and its protein expression in Leydig cells or the testis was examined by immunohistochemistry and Western blot analysis. Isolated and cultured Leydig cells were treated with different concentration of kisspeptin (0, 1, 10 and 100 μM) and kisspeptin antagonist for 4, 24 or 72 h. The direct effect of kisspeptin on testosterone secretion and Kiss1/GPR54 mRNA expression was evaluated by ELISA and RT-PCR. Kiss1/GPR54 mRNA and protein were expressed in Leydig cells and spermatids, and GPR54 were expressed in Sertoli cells. Kisspeptin treatment significantly stimulated testosterone secretion in Leydig cells, with the highest levels found under 24 h of treatment with 10 μM kisspeptin. Treatment with kisspeptin + kisspeptin antagonist significantly reduced the kisspeptin-stimulated testosterone secretion in Leydig cells. Kisspeptin treatment significantly enhanced the expression of Kiss1/GPR54 mRNA in Leydig cells. These data suggest the local expressions of Kiss1/GPR54 in goats' testes and its autocrine role in Leydig cells, which is helpful in understanding the regulation role of kisspeptin/GPR54 system in other peripheral tissues.

Kisspeptin, encoded by the KISS1 gene, and its receptor GPR54 are essential in puberty onset and male fertility due to their central regulatory roles. However, the roles of KISS1/GPR54 in peripheral tissues remain unclear. This study aimed to investigate the temporal expression patterns of KISS1/GPR54 in goat testes and epididymides and its spatial expression patterns in pubertal goats. Immunohistochemical analysis revealed that kisspeptin/GPR54 were localized in Leydig, Sertoli, and germ cells of pubertal goats' testis, as well as in principal and basal cells of the epididymis. RT-PCR revealed a marked variation in the KISS1/GPR54 expressions in the testes and epididymides from the age of first week to adulthood. KISS1 and GPR54 mRNA levels in testes decreased from the age of first week to two months and then increased from two months to puberty and adulthood. The KISS1 and GPR54 mRNA levels in Leydig cells decreased from the age of one week to two months and increased from two months to puberty, and then decreased from puberty to adulthood. Only GPR54 mRNA levels in the epididymides increased from the age of one week to two months and puberty, and then decreased from puberty to adulthood. RT-PCR analysis showed the different spatial expression patterns of KISS1/GPR54 in pubertal goat tissues. The KISS1 mRNA level was high in the hypothalamus, moderate in pancreas, liver, epididymis and testis; and low in the other tissues. The GPR54 expression was high in the pancreas and testis; moderate in pituitary, hypothalamus and mesenteric lymph node; and low in the other tissues. In conclusion, the KISS1/GPR54 system possessed distinct temporal expression profiles in goats' testes and epididymides, as well as different spatial expression patterns in pubertal goat tissues, which implied the possible local role of this system in goats' testes, epididymides, and other peripheral tissues.

// Jiayuan Wu 1, * , Caixia Liang 2 , Manyu Chen 2 , Wenmei Su 2, * 1 Nutritional Department, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China 2 Department of Oncology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China * These authors have contributed equally to this work Correspondence to: Jiayuan Wu, email: 87537665@qq.com Wenmei Su, email: 455822394@qq.com Keywords: tumor-stroma ratio, prognosis, clinicopathological features, solid tumors, meta-analysis Received: June 30, 2016 Accepted: September 05, 2016 Published: September 20, 2016 ABSTRACT Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor–stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle–Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

This research was designed to develop a nasopharyngeal cancer (NPC) scale based on quality of life (QOL) instruments for cancer patients (QLICP-NA). This scale was developed by using a modular approach and was evaluated by classical test and generalizability theories. Programmed decision procedures and theories on instrument development were applied to create QLICP-NA V2.0. A total of 121 NPC inpatients were assessed using QLICP-NA V2.0 to measure their QOL data from hospital admission until discharge. Scale validity, reliability, and responsiveness were evaluated by correlation, factor, parallel, multi-trait scaling, and t test analyses, as well as by generalizability (G) and decision (D) studies of the generalizability theory. Results of multi-trait scaling, correlation, factor, and parallel analyses indicated that QLICP-NA V2.0 exhibited good construct validity. The significant difference of QOL between the treated and untreated NPC patients indicated a good clinical validity of the questionnaire. The internal consistency (α) and test–retest reliability coefficients (intra-class correlations) of each domain, as well as the overall scale, were all >0.70. Ceiling effects were not found in all domains and most facets, except for common side effects (24.8 %) in the domain of common symptoms and side effects, tumor early symptoms (27.3 %) and therapeutic side effects (23.2 %) in specific domain, whereas floor effects did not exist in each domain/facet. The overall changes in the physical and social domains were significantly different between pre- and post-treatments with a moderate effective size (standard response mean) ranging from 0.21 to 0.27 (p

In the penumbra after focal cerebral ischemia, an increase of protease Omi is linked to a decrease of Hs1-associated protein X-1 (Hax-1), a protein belonging to the Bcl-2 family. In this study we investigated the mechanisms underlying the regulation of Hax-1 by protease Omi in cerebral ischemia/reperfusion (I/R) injury. Mouse neuroblastoma N2a cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R); cell viability was assessed with MTT assay. Mice underwent 2-h middle cerebral artery occlusion (MCAO) and reperfusion, and the infarct volume was determined with TTC staining. The expression of Omi and Hax-1 was detected using immunoblot and immunofluorescence assays. The mitochondrial membrane potential was measured using TMRM staining. In the brains of MCAO mice, the protein level of Omi was significantly increased, while the protein level of Hax-1 was decreased. Similar changes were observed in OGD/R-treated N2a cells, but the mRNA level of Hax-1 was not changed. Furthermore, in OGD/R-treated N2a cells, knockdown of Omi significantly increased Hax-1 protein level. Immunofluorescence assay showed that Omi and Hax-1 were co-localized in mitochondria of N2a cells. OGD/R caused marked mitochondrial damage and apoptosis in N2a cells, while inhibition of Omi protease activity with UCF-101 (10 μmol/L) or overexpression of Hax-1 could restore the mitochondrial membrane potential and attenuate cell apoptosis. Moreover, pretreatment of MCAO mice with UCF-101 (7.15 mg/kg, ip) could restore Hax-1 expression, inhibit caspase activation, and significantly reduce the infarct volume. Protease Omi impairs mitochondrial function by cleaving Hax-1, which induces apoptosis in OGD/R-treated N2a cells and causes I/R injury in MCAO mice.

We aimed to develop a nomogram based on a population-based cohort to estimate the individualized overall survival (OS) for patients with nasopharyngeal carcinoma (NPC) and compare its predictive value with that of the traditional staging system. Data for 3693 patients with NPC were extracted from the Surveillance, Epidemiology, and End Results dataset and randomly divided into two sets: training (n = 2585) and validation (n = 1108). On the basis of multivariate Cox regression analysis, a nomogram was constructed to predict the 3-, 5-, and 10-year survival probability for a patient. The performance of the nomogram was quantified with respect to discrimination, calibration, and clinical utility. In the training set, age, sex, race, marital status, histological type, T stage, N stage, M stage, radiotherapy, and chemotherapy were selected to develop a nomogram for predicting the OS probability based on the multivariate Cox regression model. The nomogram was generally more discriminative compared with the American Joint Committee on Cancer 7th staging system. Calibration plots exhibited an excellent consistency between the observed probability and the nomogram's prediction. Categorical net classification improvement and integrated discrimination improvement suggested that the predictive accuracy of the nomogram exceeded that of the classic staging system. With respect to decision curve analyses, the nomogram exhibited preferable net benefit gains than the staging system across a wide range of threshold probabilities. This proposed nomogram exhibits an excellent performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and thus can be used as a convenient and reliable tool for prognosis prediction in patients with NPC.

Cypermethrin (CYP), an insecticide, has deleterious effects on male reproductive function. The objective was to identify whether the effects of beta-CYP on male reproductive organs were associated with oxidative stress. Three doses of beta-CYP (1, 10, and 20mg/kg) were administered to male mice for 35 d, with or without vitamin E (20mg/kg). The moderate (10mg/kg) and high (20mg/kg) doses of beta-CYP not only decreased body weight and the weight of the testes, epididymides, seminal vesicles, and prostate (P