The associations between single nucleotide polymorphisms and diabetic retinopathy risk: an umbrella review.

This umbrella review was conducted aiming to assess the association between genetic variations and the development of diabetic retinopathy (DR) by collecting and evaluating available systematic reviews and meta-analysis results. We evaluated the methodological quality using the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2.0, estimated the summary effect size by using the random effects model and calculated the 95% prediction intervals (PIs). Evidence from the included meta-analyses was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. This umbrella review included 32 meta-analyses of 52 candidate SNPs. The 12 selected meta-analyses were rated as "high," 2 studies were rated as "moderate," 11 studies were graded as "low," and the remaining 7 studies were graded as "critically low" in terms of methodological quality. Carriers of specific genotypes and alleles of the transcription Factor 7-like 2 C/T (TCF7L2 C/T) polymorphism (rs7903146, p < 0.001) might be more susceptible to the occurrence of DR in the homozygous and recessive models, and these associations were supported by "convincing" evidence. Significant associations were also found between interleukin-6 (IL-6) -174 G/C (rs1800795; p < 0.05) or vascular endothelial growth factor (VEGF) polymorphisms (rs2010963, rs699947, rs1570360, rs2010963, rs699947, rs2146323; all p values <0.05) and DR risk, but these associations were supported by "weak" evidence. The TCF7L2 C/T variant could be identified as a definitive genetic risk factor for the development and progression of DR. Data from additional in-depth studies are needed to establish robust evidence for the associations between polymorphisms of IL-6 or VEGF and DR.

Impact of sex on treatment-related adverse effects and prognosis in nasopharyngeal carcinoma.

BACKGROUND: In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. METHODS: Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. RESULTS: Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. CONCLUSIONS: Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis.

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

Trends of Mortality in End-Stage Liver Disease - China, 2008-2020.

Introduction: Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases. Methods: Data were obtained from China's Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC). Results: In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer. Conclusions: The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.

Laryngeal contact granuloma after radiotherapy in patients with nasopharyngeal carcinoma: a case series.

Background: Laryngeal contact granuloma (LCG) is a benign hypertrophic lesion and phonatory injury after abnormal vocal behavior is regarded as its major etiology. Patients receiving radiation for non-laryngeal head and neck tumors are troubled by persistent voice impairment. The occurrence of LCG after radiotherapy for nasopharyngeal carcinoma (NPC) in our practice has implored us to re-exam their underlying etiology. We hypothesize that a proportion of LCG results from voice change caused by non-laryngeal head and neck cancer radiotherapy and firstly describe a distinct LCG population originated after radiotherapy for NPC with respect to the clinical profile, presentation, prognosis and response to treatment of patients. Methods: We retrospectively reviewed the laryngoscopic examination and tumor study findings to elucidate the common clinical features of patients who presented with LCG after radiotherapy for NPC. All patients were regularly monitored with telescopic examination until lesions disappeared. Data on age, sex, clinical presentation, telescopic findings, management, latency time of lesion formation, remission time and clinical outcome were reviewed. Results: The medical review identified 27 cases of LCG secondary to radiotherapy for NPC. All lesions had been diagnosed during routine endoscopy following radiation. The interval between radiation onset and endoscopic diagnosis was 3.77 months (range, 0.67-11 months). 20 cases were resolved through simple observation, 4 cases were resolved with the administration of proton pump inhibitors (PPIs), and 3 cases with a poor response to PPI therapy required subsequent surgical resection. The mean remission time in the observation and PPI groups was 4.42 months (range, 0.73-18.9 months) and 5.78 months (range, 2.17-14.63 months), respectively. All patients recovered completely and none experienced recurrence during a mean follow-up of 32.44 months (range, 5.6-71.67 months). Conclusions: Iatrogenic granulomas of vocal process are presenting after radiation for non-laryngeal head and neck cancers. In contrast with spontaneous granulomas, these granulomas can be cured at high remission rates and low recurrence trend without specific intervention. Thus, simple observation may be sufficient for radiation-induced LCG.

Association between Periodontitis and Aortic Calcification: A Cohort Study.

The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.

Educational level differences in the primary and secondary prevention of stroke.

The aim of this study is to estimate the educational level differences in the primary and secondary prevention of stroke among the Chinese population. Data were obtained from the China Kadoorie Biobank (CKB) survey of 512,891 people aged 30-79 years in 10 geographic regions of China, which was conducted from 2002 to 2008. The Prediction for Atherosclerotic Cardiovascular Disease Risk in China model was used to identify individuals with a high estimated 10-year stroke risk. A total of 8884 participants (1.7%) had established stroke and 218,972 (42.7%) had a high stroke risk. In both primary and secondary prevention, the participants' educational level was positively associated with the control of smoking, blood pressure, consuming a healthy diet, and the use of antiplatelet, BP-lowering medications but negatively associated with higher physical activity levels (all Ptrend < 0.001). In addition, the positive associations were observed with the control of drinking and use of anti-hyperglycaemia medication for primary prevention (all Ptrend < 0.001) and with the use of lipid-lowering medication for secondary prevention (Ptrend = 0.019). The results of the interaction between education level and prevention level showed that, compared with participants in primary prevention, educational level disparities in those with secondary prevention had significantly higher use of antiplatelets and lipid-lowering drugs, achieving the physical activity goal and non-current drinker (all Pfor interaction < 0.05). A higher education level was associated with an increased acceptance of primary and secondary prevention strategies (not smoking or drinking, consuming a healthier diet) except for engaging in a suitable level of physical activity.

Translation and validation of the Chinese version of the orthorexia nervosa assessment questionnaires among college students.

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA.

BACKGROUND: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA. METHODS: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test. RESULTS: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters. CONCLUSIONS: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

Global, Regional, and National Burden of Cancer in Children Younger Than 5 Years, 1990-2019: Analysis of the Global Burden of Disease Study 2019.

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.

The global burden and associated factors of ovarian cancer in 1990-2019: findings from the Global Burden of Disease Study 2019.

BACKGROUND: Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide over the past 30 years. METHOD: Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI). RESULTS: Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990-2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index. CONCLUSIONS: Although the age-standardized rates of ovarian cancer didn't significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.

Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China.

Background: Oxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, and SOD2 rs11968525) and skeletal fluorosis, and examined potential gene-environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake. Methods: A cross-sectional study was conducted in the Zhijin County, Guizhou Province of China. Skeletal fluorosis was identified according to the Chinese Diagnostic Criteria of Endemic Skeletal Fluorosis. Dietary information was assessed through face-to-face interviews by trained interviewers using a 75-item food frequency questionnaire. The genotype was detected by high throughput TaqMan-MGB RT-PCR technology. Odds ratios (ORs) and 95% CIs were calculated using an unconditional logistic regression model. Results: Intake of vitamin E, zinc, and selenium was found to be inversely associated with the risk of skeletal fluorosis. The multivariable-adjusted ORs were 0.438 (95% CI: 0.268 to 0.715, P-trend < 0.001) for vitamin E, 0.490 (95% CI: 0.298 to 0.805, P-trend = 0.001) for zinc, and 0.532 (95% CI: 0.324 to 0.873, P-trend = 0.010) for selenium when comparing the highest with the lowest quartile. The relationship for vitamin C was not observed after adjustment for risk factors. Furthermore, participants with PON1 rs662 AA genotype had a significantly decreased risk of skeletal fluorosis compared with those with the GG genotype (OR = 0.438, 95% CI: 0.231 to 0.830). GG + AG genotype carriers were 2.212 times more likely to have skeletal fluorosis than AA carriers (OR = 2.212, 95% CI: 1.197 to 4.090). Compared with AA carriers, AG carriers had a 2.182 times higher risk of skeletal fluorosis (OR = 2.182, 95% CI: 1.143 to 4.163). Although we observed the risk of skeletal fluorosis was higher with a lower intake of antioxidant nutrients, the potential interactions between nutrient intake and genetic polymorphisms were not observed. Conclusion: Participants with a higher intake of vitamin E, zinc, and selenium have a lower likelihood of skeletal fluorosis. In addition, the PON1 rs662 polymorphism is related to skeletal fluorosis.

Non-alcoholic Fatty Liver Disease Is Associated With Aortic Calcification: A Cohort Study With Propensity Score Matching.

Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis. Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort. Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes. Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.

Greater Adherence to Dietary Guidelines Associated with Reduced Risk of Cardiovascular Diseases in Chinese Patients with Type 2 Diabetes.

The evidence regarding the impact of the scores on healthy eating indices on the risk of cardiovascular events among patients with type 2 diabetes (T2D) is limited. As such, in this study, we examined the associations of adherence to the Chinese and American dietary guidelines and the risk of cardiovascular disease (CVD) among Chinese individuals with T2D. We conducted a 1:1 age- and sex-matched case−control study based on a Chinese population. We used a structured questionnaire and a validated 79-item food-frequency questionnaire to collect general information and dietary intake information, and calculated the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015). As participants, we enrolled a total of 419 pairs of hospital-based CVD cases and controls, all of whom had T2D. We found a significant inverse association between diet quality scores on the CHEI and HEI-2015 and the risk of CVD. The adjusted odds ratios (95% confidence interval) per five-score increment were 0.68 (0.61, 0.76) in the CHEI and 0.60 (0.52, 0.70) in the HEI-2015. In stratified analyses, the protective associations remained significant in the subgroups of sex, BMI, smoking status, tea-drinking, hypertension state, dyslipidemia state, T2D duration, and medical nutrition therapy knowledge (all p < 0.05). These findings suggest that a higher CHEI or HEI-2015 score, representing a higher-quality diet relative to the most recent Chinese or American dietary guidelines, was associated with a decreased risk of CVD among Chinese patients with T2D.

TGF-ß1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma.

Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-ß1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. Functional assays showed that inhibition of TGF-ß1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-ß1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. Altogether, TGF-ß1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. As such, all these data suggested that targeting TGF-ß1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-ß1 pathways might elicit potent and superior antitumor activity relative to monotherapies.

Characteristics of Gut Microbiota in Patients with GH-Secreting Pituitary Adenoma.

Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA). Yet, no studies exist describing the state of gut microbiota at species level in GHPA. We performed a study using 16S rRNA amplicon sequencing in a cohort of patients with GH-secreting pituitary adenoma (GHPA, n = 28) and healthy controls (n = 67). Among them, 9 patients and 10 healthy controls were randomly chosen and enrolled in metagenomics shotgun sequencing, generating 280,426,512 reads after aligning to NCBI GenBank DataBase to acquire taxa information at the species level. Weighted UniFrac analysis revealed that microbial diversity was notably decreased in patients with GHPA, consistent with a previous study. With 16S rRNA sequencing, after correction for false-discovery rate (FDR), rank-sum test at the genus level revealed that the relative abundance of Oscillibacter and Enterobacter was remarkably increased in patients and Blautia and Romboutsia genera predominated in the controls, augmented by additional LEfSe (linear discriminant analysis effect size) analysis. As for further comparison at the species level with metagenomics sequencing, rank-sum test together with LEfSe analysis confirmed the enrichment of Alistipes shahii and Odoribacter splanchnicus in the patient group. Notably, LEfSe analysis with metagenomics also demonstrated that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND, derived from Enterobacter, were both significantly enriched in patients. Functional analysis showed that amino acid metabolism pathway was remarkably enriched in GHPA, while carbohydrate metabolism pathway was notably enriched in controls. Further, significant positive correlations were observed between Enterobacter and baseline insulin-like growth factor 1 (IGF-1), indicating that Enterobacter may be strongly associated with GH/IGF-1 axis in GHPA. Our data extend our insight into the GHPA microbiome, which may shed further light on GHPA pathogenesis and facilitate the exploration of novel therapeutic targets based on microbiota manipulation. IMPORTANCE Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extraintestinal diseases. Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of GH and IGF-1, causing increased morbidity and mortality. Researches have reported that the GH/IGF-1 axis exerts its own influence on the intestinal microflora. Here, the results showed that compared with healthy controls, GHPA patients not only decreased the alpha diversity of the intestinal flora but also significantly changed their beta diversity. Further, metagenomics shotgun sequencing in the present study exhibited that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND were enriched in patients. Also, we were pleasantly surprised to find that the Enterobacter genus was strongly positively correlated with baseline IGF-1 levels. Collectively, our work provides the first glimpse of the dysbiosis of the gut microbiota at species level, providing a better understanding of the pathophysiological process of GHPA.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

A qualitative study of the experience of returning to family life and the coping styles of patients after total laryngectomy.

BACKGROUND: Total laryngectomy is the major treatment for stage III-IV laryngeal cancer, which prolongs patient's life; however, brings significant changes to physical function, mental health, and social life. As a result, patients must adopt various strategies to cope with these changes and challenges. Few studies have investigated the individual experiences of laryngectomized patients returning to home and society in China. Here we explored the living conditions and inner experiences of laryngectomized patients after discharge from the hospital, and identified the main difficulties they encountered and their coping strategies. METHODS: This study adopted a qualitative descriptive approach with a semi-structured interview. Purposive sampling helped to recruit 19 patients who had undergone total laryngectomy at a tertiary hospital. Patients were interviewed at their follow-up visits 6-12 months after discharge. The interview content was analyzed according to the Creswell steps. Similar descriptions of the patients' experiences were categorized into specific themes. RESULTS: Three major theme categories were extracted from the real-world experiences of patients following total laryngectomy to return to their former roles in family/social life and work-related activities: (I) impact of surgery on family life, including changes in physical function (e.g., decreased physical activities and functional impairment) and family roles (e.g., becoming a burden to the family and attempts to live as before); (II) impact of surgery on returning to society, including reduced social interaction and difficulty in social reintegration; and (III) the patients' coping styles, including negative coping (e.g., avoidance, compromise, and limited access to social resources) and positive coping (e.g., self-motivation and effective use of social resources). CONCLUSIONS: After total laryngectomy, patients face numerous challenges, and adopt different coping styles to deal with stressful situations. Care and support from family can help them adapt to the change in role and regain confidence in life. Actively seeking social support and using social resources effectively can help patients overcome adverse psychological effects and promote self-identity. Medical staff should provide personalized social support (including information, emotional support, and belonging), and strengthen the post-discharge follow-up and continuous management to promote the functional recovery of patients.

Association between serum prostate-specific antigen concentrations and the risk of developing type 2 diabetes mellitus in Chinese men: A cohort study.

AIMS/INTRODUCTION: The current literature suggests that men with diabetes have a lower prostate-specific antigen concentration than men without diabetes, but the causal association remains unclear. We aimed to investigate the association between serum prostate-specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. MATERIALS AND METHODS: We designed a cohort study that comprised 16,811 initially non-diabetic Chinese men who received annual health checkups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnosis, self-reportage, medication use, fasting glucose, 2-h post oral glucose or glycated hemoglobin measurements. Cox proportional hazards models were carried out to evaluate the association. RESULTS: During a median follow-up period of 3.8 years (interquartile range 1.91-5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate-specific antigen concentrations were inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate-specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2-4 were 0.84 (0.66-1.07), 0.75 (0.59-0.94) and 0.77 (0.62-0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). CONCLUSIONS: High serum prostate-specific antigen concentration was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are required to confirm these findings and investigate underlying mechanisms.

The Association between Interleukin-6 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus: A Meta-analysis with Trial Sequential Analysis.

BACKGROUND: Molecular epidemiological studies have sought associations between interleukin-6 (IL-6) polymorphisms and the risk of systemic lupus erythematosus (SLE); however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations. METHODS: Published literatures reporting the relationships of two IL-6 polymorphisms (G-174C and G-572C) and SLE risk were retrieved from electronic databases such as PubMed and EMBASE. The most appropriate genetic model was chosen for each polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was introduced to assess the information size and the positive results. RESULTS: With 17 studies (2780 cases and 3100 controls) included, a dominant association (CC+GC vs. GG) was suggested for G-174C polymorphism, and compared with the GG genotype, the CC+GC genotype of G-174C was associated with a decreased SLE risk (OR = 0.71; 95% CI = 0.56-0.88, P =.02). No association was found for G-572C under all genetic models (e.g. OR and 95%CI for CC+GC vs. GG: 0.89, 0.73-1.08, P =.22). Subgroup analyses indicated that SLE risk decreased in G-174C polymorphism by subgroups of Caucasian population, publications after 2010, studies with high quality, and studies complied with Hardy-Weinberg equilibrium (HWE). TSA suggested that the sample sizes used for G-572C were insufficient. CONCLUSION: We found that the minor allele C of IL6G-174C polymorphism is a protective factor in SLE. Further studies with a larger sample size are needed to confirm the null association for G-572C.