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BackgroundPrevious studies, in which the data were collected about half a century ago, suggested that elevated low density lipoprotein cholesterol (LDL-C) is not associated with increased risk of cardiovascular disease (CVD) in patients over 70 years old. However, what is the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years has not been well examined in China.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative study. In this analysis, participants of CHARLS who did not taking statins and did not have heart disease and stroke at 2011 were include and were followed up to 2018. The outcome of this analysis was occurrence of CVD at follow up, which include heart disease and stroke. Cox regression was used to assess the harmful effect of LDL-C on CVD occurrence. We calculated e-values to quantify the effect of unmeasured confounding on our results.ResultsOf the 9,631 participants, 15.2% (N=1,463) were aged over 70 years and 52.5% (N=5,060) were female. During the 7 years follow-up, 1,437 participants had a first CVD attack. Risk of CVD occurrence increased 8% with each 10 mg/mL elevation in LDL-C in whole participants (adjusted HR, 1.08; 95% CI, 1.06-1.10) and age groups of ≥70 years, 60-69years and ConclusionsIn contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old as in the relatively younger participants. These results should strengthen guideline recommendations for the use of lipid lowering therapies in those elderly.

Ischemic stroke is a serious cerebral disease that often induces death and long-term disability. As a currently available therapy for recanalization after ischemic stroke, thrombolysis, including intravenous thrombolysis and endovascular therapy, still cannot be applicable to all patients due to the narrow time window. Mesenchymal stem cell (MSC) transplantation therapy, which can trigger neuronal regeneration and repair, has been considered as a significant advance in treatment of ischemic stroke. MSC transplantation therapy has exhibited its potential to improve the neurological function in ischemic stroke. Our review describes the current progress and future perspective of MSC transplantation therapy in ischemic stroke treatment, including cell types, transplantation approaches, therapeutic mechanisms, and preliminary clinical trials of MSC transplantation, for providing us an update role of MSC transplantation in ischemic stroke treatment.

Background Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival. Methods We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed. Results Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue. Conclusions SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.

Osteoporosis is a widely distributed disease that may cause complications such as accelerated tooth movement, bone resorption, and tooth loss during orthodontic treatment. Promoting bone formation and reducing bone resorption are strategies for controlling these complications. For several decades, the autophagy inducer lithium chloride (LiCl) has been explored for bipolar . In this study, we investigated the autophagy-promoting effect of LiCl on bone remodeling under osteoporotic conditions during tooth movement. Ovariectomy was used to induce osteoporosis status in vivo. The results showed that LiCl rejuvenated autophagy, decreased apoptosis, and promoted bone formation, thus protecting tooth movement in osteoporotic mice. Furthermore, in vitro experiments showed that LiCl reversed the effects of ovariectomy on bone marrow-derived mesenchymal stem cells (BMSCs) extracted from ovariectomized mice, promoting osteogenesis and suppressing apoptosis by positively regulating autophagy. These findings suggest that LiCl can significantly decrease adverse effects of osteoporosis on bone remodeling, and that it has great potential significance in the field of bone formation during tooth movement in osteoporosis patients., Graphical abstract Image 1, Highlights • Lithium chloride was shown for the first time to promotes bone formation in ovariectomized mice during orthodontic tooth movement. • The osteogenesis of lithium chloride in orthodontic tooth movement is through promoting autophagy and inhibiting apoptosis. • The effect of lithium chloride on autophagy and osteogenesis could be blocked by 3-MA. • Our study provides a clue and cue for effective OTM in patients with osteoporosis.

To investigate the influence of epileptogenic cortex (Rolandic areas) with executive functions in Rolandic epilepsy using structural covariance analysis of structural magnetic resonance imaging (MRI). Structural MRI data of drug-naive patients with Rolandic epilepsy (n = 70) and typically developing children as healthy controls (n = 83) were analyzed using voxel-based morphometry. Gray matter volumes in the patients were compared with those of healthy controls, and were further correlated with epilepsy duration and cognitive score of executive function, respectively. By applying Granger causal analysis to the sequenced morphometric data according to disease progression information, causal network of structural covariance was constructed to assess the causal influence of structural changes from Rolandic cortices to the regions engaging executive function in the patients. Compared with healthy controls, epilepsy patients showed increased gray matter volume in the Rolandic regions, and also the regions engaging in executive function. Covariance network analyses showed that along with disease progression, the Rolandic regions imposed positive causal influence on the regions engaging in executive function. In the patients with Rolandic epilepsy, epileptogenic regions have causal influence on the structural changes in the regions of executive function, implicating damaging effects of Rolandic epilepsy on human brain.

Premise: The effects of proton pump inhibitors (PPI) depend on metabolic enzyme CYP2C19 that has different activity due to gene polymorphism. The purpose of this meta-analysis is to determine the potential effects of CYP2C19 polymorphism on the efficiency of PPI-based treatment. Materials & methods: The PubMed, EMBASE, Cochrane Library, etc. were searched for relevant articles published in English or Chinese from inception to 31 May 2020. Finally, 26 randomized controlled trials and 15 cohort studies met the inclusion criteria and used for the meta-analysis via STATA version 15. Results: Poor metabolizer (PM) genotype Helicobacter pylori eradication rates were highest for Asian individuals receiving triple or quadruple first-line therapy based on PPIs (p

Acute myocardial infarction (AMI) in patients with acute kidney injury (AKI) is associated with poor long-term outcome. However, the short-term prognosis of AKI in patients with ST-elevation AMI (STEMI) needs to be explored further. We assessed this relationship between these patients and short-term mortality in relation to AKI and chronic kidney disease (CKD). All data were extracted from the Medical Information Mart for Intensive Care III database. The primary outcome was 28-day mortality. Kaplan-Meier curves, logistic regression models, and propensity score matching analysis were used to evaluate the associations between AKI in patients with STEMI and outcomes. A total of 1031 patients with STEMI met the inclusion criteria. For 28-day mortality, in the multivariable logistic regression models, the odds ratio (95% CI) of group 2 (AKI but no CKD) and group 3 (AKI in the presence of CKD) were 3.24 (1.46-7.18) and 4.57 (1.83-11.37), respectively, compared with group 1 (no AKI and no CKD). Comorbid AKI increased the risk of short-term mortality among patients with STEMI, especially for those with AKI in the presence of CKD.

Context Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. Objective This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. Methods We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Results This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. Conclusion This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Background. High power shorter duration (HPSD) ablation may lead to safe and rapid lesion formation. However, the optimal radio frequency power to achieve the desired ablation index (AI) or lesion size index (LSI) is insubstantial. This analysis aimed to appraise the clinical safety and efficacy of HPSD guided by AI or LSI (HPSD-AI or LSI) in patients with atrial fibrillation (AF). Methods. The Medline, PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to November 2020 were searched for studies comparing HPSD-AI or LSI and low power longer duration (LPLD) ablation. Results. Seven trials with 1013 patients were included in the analysis. The analyses verified that HPSD-AI or LSI revealed benefits of first-pass pulmonary vein isolation (PVI) (RR: 1.28; 95% CI: 1.05–1.56, P = 0.01) and acute pulmonary vein reconnection (PVR) (RR: 0.65; 95% CI: 0.48–0.88, P = 0.005) compared with LPLD. HPSD-AI or LSI showed higher freedom from atrial tachyarrhythmia (AT) (RR = 1.32, 95% CI: 1.14–1.53, P = 0.0002) in the subgroup analysis of studies with PVI ± (with or without additional ablation beyond PVI). HPSD-AI or LSI could short procedural time (WMD: −22.81; 95% CI, −35.03 to −10.60, P = 0.0003), ablation time (WMD: −10.80; 95% CI: −13.14 to −8.46, P

Although Rolandic epilepsy (RE) has been regarded as a brain developmental disorder, neuroimaging studies have not yet ascertained whether RE has brain developmental delay. This study employed deep learning–based neuroanatomic biomarker to measure the changed feature of “brain age” in RE. The study constructed a 3D-CNN brain age prediction model through 1155 cases of typically developing children’s morphometric brain MRI from open-source datasets and further applied to a local dataset of 167 RE patients and 107 typically developing children. The brain-predicted age difference was measured to quantitatively estimate brain age changes in RE and further investigated the relevancies with cognitive and clinical variables. The brain age estimation network model presented a good performance for brain age prediction in typically developing children. The children with RE showed a 0.45-year delay of brain age by contrast with typically developing children. Delayed brain age was associated with neuroanatomic changes in the Rolandic regions and also associated with cognitive dysfunction of attention. This study provided neuroimaging evidence to support the notion that RE has delayed brain development. • The children with Rolandic epilepsy showed imaging phenotypes of delayed brain development with increased GM volume and decreased WM volume in the Rolandic regions. • The children with Rolandic epilepsy had a 0.45-year delay of brain-predicted age by comparing with typically developing children, using 3D-CNN-based brain age prediction model. • The delayed brain age was associated with morphometric changes in the Rolandic regions and attentional deficit in Rolandic epilepsy.

Prehypertension is a risk factor for cardiovascular disease (CVD) and all‐cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all‐cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all‐cause mortality was different among individuals with or without diabetes. In the prospective community‐based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. The outcomes were CVD and all‐cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all‐cause mortality by diabetes status. During a median follow‐up of 11.03 years, 2981 CVD events and 4655 all‐cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all‐cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38–1.71] and 1.27 [1.17–1.38]), but not in participants with diabetes (1.20 [0.93–1.56] and 0.88 [0.73–1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all‐cause mortality were all significant (all p

OBJECTIVE Among the risk factors of stroke, hypertension was one of the most important and modifiable factors. The current study aimed to assess whether antihypertensive treatment to ideal levels of blood pressure can eliminate stroke risk in a prospective cohort study. METHODS The Kailuan study was a prospective longitudinal cohort study on stroke risk factors and events. We analyzed association of baseline antihypertensive treatment efficacy with the risk of stroke during 11.0-year follow-up, and further evaluated association of newly antihypertensive treatment efficacy at 4-year follow-up with subsequent stroke. Multivariate Cox proportion models were used to calculated hazard ratios and their 95% confidence intervals (CIs) for stroke. RESULTS A total of 97 772 participants (median age: 51.65 years) without previous stroke were included. At baseline, 55 518 participants had normotension, 2339 treated and controlled, 32 331 untreated hypertension and 7584 treated but uncontrolled. Compared with normotension, individuals with treated and controlled, untreated hypertension and treated but uncontrolled, had 83, 97 and 162% higher risk of developing total stroke after adjusting for potential stroke risk factors, respectively (hazard ratio 1.83 [95% CI 1.56-2.15], 1.97 [95% CI 1.85-2.11] and 2.62 [95% CI 2.40-2.86]; all P

Jia Yu,1,* Hongyan Sun,2,* Jinhua Zhu,3,* Xintong Wei,1 Hongfei Shi,2 Bin Shen,3 Liyun Ren,1 Yan He,1 Rongyan Zhang,3 Mingzhi Zhang,1 Hao Peng1,4 1Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Center for Disease Prevention and Control of Tianning District, Changzhou, People’s Republic of China; 3Center for Disease Prevention and Control of Wujiang District, Suzhou, People’s Republic of China; 4Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao PengDepartment of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of ChinaTel +86 512 6588 0078Fax +86 512 6588 0052Email penghao@suda.edu.cnObjective: The relationship between obesity and hyperuricemia has been demonstrated by many studies. However, whether or to what extent metabolic condition influents the association between obesity and hyperuricemia was not clear. Here, we aimed to examine the association between obese-metabolic phenotype and hyperuricemia in a large sample of Chinese adults.Methods: According to BMI and metabolic syndrome, obese-metabolic phenotype was defined as metabolically unhealthy obesity (MUO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically healthy non-obesity (MHNO)in the Tianning cohort (N=5072). We conducted a cross-sectional analysis between obese-metabolic phenotype and hyperuricemia, followed by a Mendelian Randomization analysis using GWAS summary data to confirm the causality between uric acid and BMI.Results: The average level of serum UA showed 41.87-higher μmol/L in participants with MHO (β=41.87, P< 0.001) and 63.18-higher μmol/L in participants with MUO (β=63.18, P< 0.001), compared to those with MHNO. Compared to participants with MHNO, those with MUO had the highest likelihood to have hyperuricemia (OR=4.56, P< 0.001), followed by those with MHO (OR=3.32, P< 0.001). Mendelian randomization analysis indicated that uric acid was more likely to be a consequence of BMI (β=0.059, P=6.54× 10− 154).Conclusion: MUO, in comparison with MHO, was significantly associated with hyperuricemia in Chinese adults.Keywords: metabolic syndrome, obesity, serum uric acid, hyperuricemia

To explore the incidence, severity, and risk factors of multidimensional fatigue in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). This prospective study included 79 patients with NPC in Guangzhou (China) from June 2015 to July 2018. Data were collected before and after CCRT, including demographic and clinical characteristics, nutritional parameters, and fatigue scores, based on completion of the Multiple Dimensional Inventory-20 Questionnaire, with five subscales: General Fatigue, Mental Fatigue, Physical Fatigue, Reduced Activity, and Reduced Motivation. Increased general fatigue was found to be associated with lower lymphocyte count and body mass index 42 years. Higher scores for reduced activity were associated with age > 42 years, female sex, and lower serum sodium. Increased mental fatigue was related with lower lymphocyte count and unemployment; and increased total fatigue was associated with lower lymphocyte count, age > 42 years, and 3–6 courses of treatment. Furthermore, 3–6 courses of treatment was an independent predictor of severe general fatigue, while age >42 years was an independent predictor of severe physical fatigue. Importantly, cancer stage IVB and 3–6 courses of treatment could predict severe total fatigue. Our data demonstrate that fatigue is increased in all dimensions in NPC patients following CCRT, and that the predictors differ for each fatigue dimension. These results could guide the development of targeted interventions that may reduce the impact of cancer-related fatigue in patients with NPC.

BACKGROUND To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. METHODS Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. RESULTS Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p

Objectives: Furin has been associated with hypertension through unclear underlying mechanisms. FURIN promoter methylation may participate in the underlying mechanisms, but no evidence supports this possibility. Here, we performed a prospective analysis to study the association between FURIN promoter methylation and incident hypertension. Methods: DNA methylation levels in the FURIN promoter were quantified by target bisulfite sequencing using peripheral blood from 1043 participants in the Gusu cohort (mean age: 50 years, 30% men) who were free of hypertension at baseline. After an average of 4 years of follow-up, 149 (14.3%) participants developed hypertension. Multiple testing was controlled for by measuring the false-discovery rate. Results: Of the eight CpG loci assayed, DNA methylation levels at Chr15: 91416118 were significantly associated with incident hypertension after adjusting for covariates and multiple testing (hazard ratio [HR] = 1.38, 95% confidence interval [CI]: 1.17–1.64, q = 0.001). The weighted truncated-product method, which combines single CpG associations, revealed that DNA methylation at multiple CpG sites was jointly associated with incident hypertension (P < 0.001). Using the average methylation level of all CpG sites as a surrogate for FURIN promoter methylation revealed a similar association (HR = 1.36, 95% CI: 1.08–1.72, P = 0.009). Almost all CpG methylations negatively correlated with serum furin levels, which mediated approximately 29.44% of the association between FURIN promoter methylation and incident hypertension. Conclusions: These results suggest that FURIN promoter hypermethylation is associated with an increased risk for hypertension in Chinese adults, partially through suppressing furin expression or excretion.

Objectives Since DHZCP had significant inhibitory effects on liver and kidney fibrosis, we hypothesize that DHZCP could also inhibit pulmonary fibrosis. Therefore, the aim of this study is to examine the effect of DHZCP on silicosis, a type of pulmonary fibrosis caused by silica dust, and its underlying mechanism. Methods Pulmonary fibrosis was induced by inhalation of silica (SiO2) dust in mice which were then randomly divided into 5 groups: pulmonary fibrosis model group, high-dose DHZCP group, medium-dose DHZCP group, low-dose DHZCP group and Tetrandrine group. The normal control group mice were not exposed to SiO2 dust. After 28 days of continuous intragastric administration of DHZCP, the mice were sacrificed. The histopathology of lungs, the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and hydroxyproline (HYP) in serum. Besides, the expression of transforming growth factor‑β1 (TGF-β1), α-smooth muscle actin (α-SMA), Smad2, Smad3 and Smad7 in lung tissue were examined. Results The mice with silicosis was generated with an observed inflamed lung tissues and elevated inflammatory cytokines. DHZCP significantly reduced serum levels of TNF-α, IL-6, IL-1β and HYP in mice with lung fibrosis. DHZCP treatment remarkably downregulated mRNA and protein levels of TGF-β1, α-SMA, Smad2 and Smad3 in lung tissue, while increased the protein level of Smad7. Conclusions These results demonstrated that DHZCP could alleviate pulmonary fibrosis induced by SiO2. The anti-fibrotic effects of DHZCP are conferred by decreasing inflammation and pulmonary fibrosis, which may be related to the TGF-β1/Smad pathway.

BACKGROUND: Most previous studies of the family doctor contract services (FDCS) evaluated its quality by using residents’ signing rates, awareness, and satisfaction. We hypothesize that renewal willingness could be another important indicator to examine the quality of FDCS. OBJECTIVE: To measure residents’ willingness to maintain contracts with family doctors and examine the influencing factors. DESIGN: Cross-sectional study. PARTICIPANTS: 11,250 residents in 31 provincial administrative regions across China. MAIN METHODS: A multistage stratified random sampling method was used to recruit participants. Univariate analysis, mixed-effect regression model analysis, and stepwise multivariate logistic regression analysis were performed to determine the influencing factors of residents’ willingness to maintain contracts with family doctors. KEY RESULTS: About 71.3% participants who contracted with and received healthcare services from family doctors were willing to maintain contracts with family doctors in China. Residents registering as local households (OR = 1.192, 95% CI = 1.039–1.368), enrolled in medical insurance (OR = 1.299, 95% CI = 1.011–1.668), reporting better health (OR = 1.246, 95% CI = 1.100–1.413), with shorter walking time to the nearest healthcare center (compared with > 30 min walking time

Purpose The objective of this study was to investigate the association of abnormal glycemic phenotypes with microvascular complications in type 2 diabetes patients. Participants and methods A total of 24,266 participants who were from the multicenter cross-sectional survey of China National HbA1c Surveillance System across China were included in the present study. Diabetes patients with abnormal glucose were divided into three groups according to phenotype: isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH), or combined hyperglycemia (CH). The main outcomes were isolated diabetic retinopathy, isolated diabetic nephropathy, and combined diabetic retinopathy with nephropathy. Multivariate logistic regression was used to assess the association of abnormal glycemic phenotypes with microvascular complications. Results The CH phenotype had the highest prevalence of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy, followed by IPH. Multivariate analysis showed that the CH phenotype was associated with the highest risk of isolated diabetic retinopathy (OR: 1.20, 95% CI: 1.02-1.41), isolated diabetic nephropathy (OR: 1.59, 95% CI: 1.27-2.01) and combined diabetic retinopathy with nephropathy (OR: 1.93, 95% CI: 1.44-2.59). More importantly, participants with IPH phenotype also showed significantly higher risks of isolated diabetic retinopathy (OR: 1.16, 95% CI: 1.05-1.28), isolated diabetic nephropathy (OR: 1.37, 95% CI: 1.09-1.37) and combined diabetic retinopathy with nephropathy (OR:1.64, 95% CI: 1.21-2.21) compared to the IFH phenotype. After stratifying by age, sex, diabetes duration and BMI, the higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy were confirmed in IPH phenotype group, compared to the IFH phenotype group. Conclusion Diabetic patients with IPH phenotype had higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy compared with the participants phenotype of IFH, but lower than the phenotype of CH.

Objective To compare the survival outcomes of local ablation (LA) and partial nephrectomy (PN) for T1N0M0 renal cell carcinoma (RCC). Method We identified 38,155 T1N0M0 RCC patients treated with PN or LA in 2004‐2016 from the retrospective Surveillance, Epidemiology, and End Results databases. Among them, there were 4656 LA and 33,499 PN. A Cox proportional hazards regression model, cause‐specific Cox regression and Fine and Gray sub‐distribution hazard ratio (sHR) with inverse probability of treatment weighting (IPTW) adjusting was utilized to compare the effects of LA vs PN on all‐, RCC‐, and non‐RCC–caused mortality. Results Within the IPTW analysis, patients who underwent PN experienced a better overall survival (OS) (HR, 1.56; 95% CI, 1.40‐1.74; P 85 years (HR, 1.14; 95% CI, 0.73‐1.79, P = .577), chromophobe RCC (HR, 1.68; 95% CI, 0.94‐3.00, P = .078), and tumor size 85 years (sHR, 0.89; 95% CI, 0.52‐1.27, P = .520) and tumor size 85), small RCC (, To compare the prognosis of local ablation (LA) and partial nephrectomy (PN) for T1N0M0 renal cell carcinoma (RCC) in the era of active surveillance and minimally invasive PN. Overall, PN showed a better OS and CSS than LA in T1N0M0 RCC treatment, but for elder age (>85 years), small tumors (

Background The role of serum uric acid (SUA) in development of myocardial infarction (MI) is controversial. The current study aimed to investigate the association between both baseline SUA and changes in SUA and the risk of MI. Methods The current study included 71,449 Chinese participants (mean age, 50.9 years) free of MI during the time of follow-up. Participants were divided into 4 categories according to the SUA levels between baseline and the second follow-up: stable low, elevated, reduced and stable high. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs) for MI. Results During a median follow-up of 8.96 years, 837 MI cases were identified. After adjustment for potential confounders, MI risk was only associated with stable high SUA, the HR was 1.42 (95%CI: 1.02–1.92, p = 0.03), compared with those with stable low SUA. However, there was no association between hyperuricemia at baseline and MI, the HR was 1.14 (95%CI: 0.91–1.42, p = 0.19) compared with those with normal SUA. Subgroup analyses stratified by age, sex, hypertension, diabetes and estimated glomerular filtration rate were also confirmed no significant difference (p-interaction >0.05 for all). Furthermore, mediation analyses revealed 14.14% of association was mediated by hypertension. Conclusions Only stable high SUA was associated with increased higher risk of MI. Changes in SUA levels in any other direction or high SUA levels at baseline were not associated with risk of MI.

The natriuretic peptides (NPs) system, and mainly atrial natriuretic peptide (ANP), plays a key role in human metabolism and cardiometabolic disorders. Due to differences in NP levels and in prevalence of metabolic syndrome (MetS) between men and women, we aimed to explore the gender difference of association between N-terminal pro-atrial natriuretic peptide (NT-proANP) and MetS in a general population in China. Participants’ weight, height, waist circumference, blood pressure, plasma NT-proANP, and other traditional biomarkers were measured. Multivariate logistic regression models were used to determine the association between plasma NT-proANP and MetS, and the odds ratio (OR) and 95% confidence interval (CI) were calculated for men and women, respectively. Among 2203 participants, 1361 (61.78%) were women, 687(30.77%) participants had MetS, and the average age was 53 years. Women had a higher level of NT-proANP than men. However, adjusted logistic regression demonstrated that men in the upper quartile group of NT-proANP had 0.60 (95% CI 0.39–0.92) times the risk of having MetS, while women in the upper quartile group had 1.10 (95% CI 0.77–1.56) times the risk of having MetS compared to the lower quartile group. Furthermore, with the increase of the level of NT-proANP, the ORs showed a declining trend in men (P = 0.017), but it was not statistically significant among women (P = 0.700). There are gender differences in the relationship between NT-proANP and MetS, while an inverse association between plasma NT-proANP and MetS in men suggests that higher levels of NT-proANP may be a protective factor for MetS.

Background. Helicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP. Methods. We searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I2) statistic. Results. A total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29–0.47). The combined estimate is I2 = 57% (P

Background The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota–originating short‐chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities. Methods We used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90‐day poor functional outcomes were evaluated by logistic regression models. Results We found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs‐producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity. The SCFAs levels were negatively correlated with stroke severity and prognosis. Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90‐day poor functional outcomes even after adjustments. Conclusions Dysbiosis of SCFAs‐producing bacteria and SCFAs in AIS patients increased the subsequent risk for poor functional outcomes, indicating that SCFAs could be potential prognostic markers and therapeutic targets for stroke.

Background More than two thirds of new of nasopharyngeal carcinoma (NPC) cases occurring in the east and southeast parts of Asia. As a consequence, the development of intervention programs that can educate and assist patients of NPC in adopting and maintaining long-term behavioral changes to prevent further progression of the disease and improve quality of life represents a continuing need. Methods Patients diagnosed with NPC (n=141) completed chronic disease self-management questionnaires (CDSMP) before, immediately after, and 3, 6, and 12 months after receiving primary cancer treatment. An independent-samples T test was used to compare mean changes in chronic disease self-management (CDSM) items between the intervention group and control group. Results There was no difference between the two groups at baseline. Patients who received an intervention demonstrated a significant improvement in fatigue and shortness of breath after treatment. They also demonstrated significant improvements in weekly minutes of aerobic exercise and stretching/strengthening exercise. These advantages lessened slightly with elapsed time. Conclusions For NPC patients, nutrition counseling combined with head and neck rehabilitation exercises can greatly reduce fatigue and shortness of breath and greatly increase the use of stretching/strengthening and aerobic exercise 3 months after intensity-modulated radiotherapy (IMRT).

Background The objective of this population-based study was to examine whether there was association of hand grip strength (HGS) with cardiopulmonary function in population without cardiopulmonary disease. Methods Data were derived from an ongoing cross-sectional survey of the National Physique and Health in Shanxi Province. There were 908 participants with the cardiac function tests and 380 participants with the pulmonary function tests. Multiple linear regression analysis was used to assess the association of HGS with cardiopulmonary function. Results Among participants with the cardiac function tests, HGS was positively associated with left ventricular end diastolic diameter in both genders (male: b = 0.010 (0.005, 0.015), P

Background. The catheter-tissue contact force (CF) is one of the significant determinants of lesion size and thus has a considerable impact on the effectiveness of ablation procedures. This study aimed to evaluate the impact of CF on the lesion size during right ventricular outflow tract (RVOT) ablation in a swine model. Methods. Twelve Guangxi Bama miniature male pigs weighing 40 to 50 kg were studied. After general anesthesia, a ThermoCool SmartTouch contact-sensing ablation catheter was introduced to the RVOT via the femoral vein under the guidance of the CARTO 3 system. The local ventricular voltage amplitude and impedance were measured using different CF levels. We randomly divided the animals into the following four groups according to the different CF levels: group A (3–9 g); group B (10–19 g); group C (20–29 g); and group D (30–39 g). Radiofrequency ablations were performed at three points in the free wall and septum of the RVOT in power control mode at 30 W for 30 s while maintaining the saline irrigation rate at 17 mL/min. At the end of the procedures, the maximum depth, surface diameter, and lesion volume were measured and recorded. A linear regression analysis was performed to determine the relationship between continuous variables. Results. A total of 72 ablation lesions were created in the RVOT of the 12 Bama pigs. The maximum depth, surface diameter, and volume of the lesions measured were well correlated with the CF (free wall: β = 0.105, β = 0.162, β = 3.355, respectively, P

Background and aims Although serum lipids are widely accepted as independent predictors of myocardial infarction (MI), there is insufficient evidence for associations of changes in lipid levels with MI. The present study aimed at investigating the associations between changes in lipids and incidence of MI in people without lipid-lowering therapy. Methods 64,031 Chinese participants (mean age: 53.42 ± 11.95 years) without previous MI were enrolled in the study. The participants were divided into four categories based on quartiles of lipid changes. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for MI. Results During a median follow-up of 7.03 years, 599 individuals developed MI. After adjustment for covariates, increased total cholesterol (TC), increased low-density lipoprotein cholesterol (LDL-C), increased non-high-density lipoprotein cholesterol (non-HDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) were associated with elevated risk of MI, with HRs (95% CIs) in the highest quartile group compared with the lowest quartile group of 1.56 (1.21–2.01), 1.96 (1.49–2.57), 1.95 (1.52–2.50), and 0.69 (0.53–0.90), respectively. However, changes in triglyceride (TG) were not associated with MI risk (p = 0.8030). Conclusions Changes in levels of TC, LDL-C, non-HDL-C, and HDL-C, but not TG, were associated with risk of MI. Early detection and control of lipid levels may be beneficial and necessary for young people and those with healthy lipid levels at baseline.

Background Induction chemotherapy followed by concurrent chemoradiotherapy is one of the standards of care for patients with nasopharyngeal carcinoma, but the optimal number of induction cycles is unclear. Here we compared survival data from patients treated with 2 to 4 cycles. Methods Patients with nasopharyngeal carcinoma at West China Hospital of Sichuan University between January 2009 and December 2015 were retrospectively analyzed. Results Six hundred and seventy three patients met eligibility criteria. After a median follow-up of 53 months (interquartile range, 38-74), there was no difference between 2 and 3 cycles in overall survival (88.14% vs 91.24%). But four cycles were associated with worse overall survival (79.12%) and higher incidence of treatment-related toxicities. Multivariate analysis showed that the number of induction cycles and lymph node classification were prognostic factors. Conclusions Two and three cycles of induction chemotherapy are associated with similar survival, while four cycles reduce survival and increase treatment-related toxicity in endemic regions.

BACKGROUND To investigate the clinical efficacy and mechanism of laparoscopic sleeve gastrectomy (LSG) in improving renal function in obese patients. METHODS We retrospectively reviewed the anthropometric indices (waist circumference, hip circumference and body mass index (BMI)), renal function indices (serum creatinine, urea and urinary albumin:creatinine ratio (UACR)), serum inflammatory indices (C-reactive protein, interleukin-6 and tumour necrosis factor-α) and an adipose factor (leptin) in 50 patients with obesity (BMI ≥32.5 kg/m2 ) who underwent LSG in our hospital from January 2018 to January 2019. RESULTS Patients constituted 23 men and 27 women, with an average age of 32.5 ± 8.7 years and BMI of 43.99 ± 8.29 kg/m2 . Body weight and BMI 1 month post-operatively were significantly lower than preoperatively (P

Background As a key enzyme of natriuretic peptides system playing an integral role in energy homeostasis, furin may be a potential contributor to obesity. However, the association between furin and obesity has been scarcely studied. This study aims to examine the prospective association between serum furin and abdominal obesity. Methods Waist circumference (WC) was measured twice 4 years apart for a total of 892 Chinese adults free of abdominal obesity at baseline. Abdominal obesity was defined as WC over 85 cm for men and as WC over 80 cm for women. A Cox proportional hazard model was constructed to examine the association of baseline serum furin with incident abdominal obesity. Results After an average 4 years of follow-up, 184 participants developed new abdominal obesity. Baseline serum furin was significantly associated with dynamic body weight during follow-up (β=−0.593, p=0.003). Participants with a higher level of serum furin at baseline were less likely to develop new abdominal obesity compared with those with a lower level of serum furin (HR=0.81, 95% CI 0.67 to 0.97). Conclusions A lower level of serum furin predicts a higher risk of developing future abdominal obesity in Chinese adults. Furin deficiency may be a contributor to abdominal obesity but still needs further investigations.

Purpose To evaluate the value of ultrasound (US)-guided vacuum-assisted excisional biopsy (VAB) in treating benign phyllodes tumors (PTs) of the breasts and to investigate the lesion characteristics that could affect the local recurrence rate. Patient and Methods From December 2008 to February 2018, 93 patients with PTs diagnosed on histology underwent US-guided, 7-gauge VAB. The recurrence rate of benign PT and complications of VAB were evaluated on follow-up US every three to six months. The lesion characteristics were analyzed to identify the factors affecting the recurrence rate. Results Of the 87 patients, local recurrence was found in 15 patients (17%) in a mean follow-up period of 35.8 months, and the rate of complete excision was 82.8% (72/87). PTs with a largest diameter less than 3.3 cm had a significantly lower recurrence rate than PTs with a largest diameter larger than 3.3 cm (P Conclusions In conclusion, US-guided VAB is an effective method to treat benign PT, especially in lesions with a diameter less than 3.3 cm.

Objectives. One reason for the high recurrence and metastatic rates of tumors such as hepatocellular carcinoma (HCC) treated by microwave ablation (MWA) is the presence of residual foci in the tumor due to heat sink effect. Microbubble-enhanced ultrasound (MEUS) can noninvasively disrupt and block the tumor blood perfusion and has the potential to overcome the heat sink effect and enhance the therapeutic effect of MWA. The study aimed at evaluating the potential additional benefit of microbubble-enhanced ultrasound (MEUS) in hepatocellular carcinoma (HCC) treated by microwave ablation (MWA). Methods. In this study, a new strategy of combining MWA with MEUS for treating HCC was proposed. Twenty-four rabbits with VX2 tumors in livers were randomly divided into MEUS + MWA, MEUS alone, MWA alone, and blank control groups, respectively (n = 6). In the MEUS group, the tumors were directly exposed to therapeutic ultrasound for 5 min with a concurrent intravenous injection of microbubbles (0.1 ml/kg diluted into 5 ml saline). In the MWA group, the tumors were treated by MWA for 1 min. In the MEUS + MWA group, tumors were ablated by MWA for 1 min after ultrasound cavitation enhanced by microbubbles as in the MEUS group. In the blank control group, the tumors received probe sham and intravenous saline. Contrast-enhanced ultrasound (CEUS) was performed before treatment and immediately after treatment to display the size, shape, and contour of the tumors. Throughout the treatment process, the local temperature of the treatment area was detected by a temperature needle punctured into the tumor. The blood samples of animals were obtained after treatment for evaluating the liver function. Tumor cell necrosis and apoptotic rates were observed after treatment by histological examination. Results. CEUS showed that although perfusion defects appeared in all the treatment groups, especially in the MEUS + MWA group, there was no significant difference between the two groups on the volumes of perfusion defects, which were 1.78 ± 0.31 (cm3) in the MWA group and 1.84 ± 0.20 (cm3) in the combined group P<0.01. The time to reach the peak temperature of the treatment area was 21.7 ± 5.0 (s) in the MWA group and 10.3 ± 5.0 (s) in the MEUS + MWA group P<0.01. The peak temperature (PT) of the two groups were 100.9 ± 5.0 (°C) and 134.1 ± 6.0 (°C), respectively P<0.01. This showed that the local temperature of the treatment area was sharply increased to a higher PT using MEUS + MWA. Histological examination results showed that the apoptosis rate and necrosis rate in the MEUS + MWA group were 23.6 ± 4.6% and 60.5 ± 9.7%, respectively, which are significantly higher than those in the MWA group (17.9 ± 4.5% and 37.6 ± 3.4%) and those in the MEUS group (18.2 ± 1.0% and 37.6 ± 3.4%). They are all higher than those in the control group (3.85 ± 1.72% and 5.3 ± 1.1%). Hematological examination showed no significant differences between treatment groups on liver function. Conclusions. These results suggested MEUS treatment alone may significantly reduce tumor blood perfusion and led to a sharp rise in the local temperature of the treatment area to a higher PT using MEUS + MWA with higher rates of necrosis and apoptosis of cancer cells without severe liver function damage, which might be a safe strategy for treating HCC.

Objective: To evaluate the prognostic value of conversion of high-risk human papillomavirus (HR-HPV) status after treatment for cervical cancer. Methods: A total of 112 cervical cancer patients with HR-HPV positivity without distant metastasis treated with surgery or radical concurrent radiochemotherapy were enrolled. HR-HPV status was analyzed before and after treatment and at the time point of recurrence or metastasis. Log-rank tests and Cox proportional hazard models were used to evaluate the association between conversion of HR-HPV status after treatment and survival. Results: Eighty-four (75%) patients had negative conversion HR-HPV (ncHR-HPV) after treatment and twenty-eight (25%) were persistent positive HR-HPV (ppHR-HPV). The negative conversion rate was 75.8% in patients who received surgical treatment and 71.4% in patients who received radical concurrent radiochemotherapy. There was no significant difference between the two groups (χ2=0.000, P=1.000). There was no significant correlation between HR-HPV conversion after treatment with age (χ2=0.616, P=0.252), FIGO stage (χ2=0.051, P=0.823) and pathological type (χ2=0.000, P=1.000). Univariate analysis showed that treatment regimen and ncHR-HPV was closely related to progression-free survival (PFS) and overall survival (OS) of cervical cancer patients. Multivariate COX regression model showed that treatment regimen (HR=3.57, 95% CI: 1.57-8.11, P=0.002) and ncHR-HPV (HR=5.14, 95% CI: 2.32-11.46, P

Due to the limitations in autogenous nerve grafting or Schwann cell transplantation, large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit. Cell based therapies provide a novel treatment for peripheral nerve injuries. In this study, we first experimented an optimal scaffold material synthesis protocol, from where we selected the 10% GFD formula (10% GelMA hydrogel, recombinant human basic fibroblast growth factor and dental pulp stem cells (DPSCs)) to fill a cellulose/soy protein isolate composite membrane (CSM) tube to construct a third generation of nerve regeneration conduit, CSM-GFD. Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model. After 12 week post implant surgery, at histologic level, we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers. At physical level, CSM-GFD achieved functional recovery assessed by a sciatic functional index study. In both levels, CSM-GFD performed like what gold standard, the nerve autograft, could do. Further, we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD. In conclusion, we claimed that this third-generation nerve regeneration conduit, CSM-GFD, could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.

The incidence of diabetes mellitus (DM) and its complications have increased considerably worldwide. Diabetic keratopathy is the major complication of the cornea characterized by delayed corneal wound healing, decreasing corneal epithelial sensitivity, and recurrent corneal ulcers. There is accumulating evidence that diabetic keratopathy is correlated with the hyperglycemic state. Different corneal components may produce different alterations under hyperglycemia. In addition, diabetic nerve alteration may become a novel biomarker of early-stage DM. Abnormalities of the corneal nerve plexus have been associated with diabetic inflammatory states. There is rapidly growing evidence based on investigations of diabetic corneal nerves through in vivo confocal microscopy. Understanding the molecular pathogenesis caused by hyperglycemia may assist in the identification of novel biomarkers, as well as therapeutic targets for early treatment. This review mainly summarizes recent findings on corneal alteration and pathogenesis in DM.

Background Although energy devices and botulinum toxin A (BTX-A) can alleviate age-related laxity, ptosis, and platysmal bands, they have limited efficacy on horizontal neck lines. Objectives The purpose of this study was to investigate the efficacy, safety, and subject satisfaction of a combined treatment of non–cross-linked hyaluronic acid (HA) compound filling plus mesotherapy for the correction of horizontal neck lines, in comparison with BTX-A. Methods This multicenter, randomized, evaluator-blinded, prospective study enrolled female patients with moderate-to-severe horizontal neck lines corrected with either 2 or 3 sessions of of non–cross-linked HA compound filling plus mesotherapy or 1 session of BTX-A injection. Improvement of the neck lines grades, Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and adverse events (AEs) were evaluated and compared at 1, 3, 6, and 10 months after the final treatment. Results Twenty-five patients received HA filling plus mesotherapy and 23 received BTX-A injection. Compared with BTX-A, the HA compound filling plus mesotherapy significantly improved the horizontal neck lines grades on all follow-up visits (P = 0.000). Cases of different baseline grades (2, 2.5, and 3) demonstrated similar outcomes. The GAIS and patients’ satisfaction ratings were significantly higher for the HA filling plus mesotherapy treatment group (P = 0.000). Significantly higher pain ratings, higher incidence, and longer recovery of AEs (erythema, edema, and ecchymosis) were noticed in the combined treatment group (P Conclusions Compared with BTX-A, combined treatment with HA compound filling plus mesotherapy significantly improved moderate-to-severe horizontal neck lines and achieved a high level of patient satisfaction. Level of Evidence: 4

The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.

Introduction: Glomerular hyperfiltration (GHF) is an early kidney injury. We investigated whether GHF is associated with arterial stiffness expressed by increase of brachial–ankle pulse wave velocity (baPWV) and pulse pressure (PP), and whether the coexistence of GHF and abnormal metabolism increases the risk of arterial stiffness.Methods: In this prospective cohort study, 2,133 non-chronic kidney disease (CKD) participants aged ≥40 years were followed for a mean period of 3.3 years. The extent of arterial stiffness was expressed by measures of baPWV and PP. GHF was defined as eGFR exceeding the age- and sex-specific 90th percentile. Multivariate logistic regression models were used to assess the association between GHF/abnormal metabolism and increased baPWV/PP. The interaction indexes of GHF and abnormal metabolism on arterial stiffness were calculated based on the OR in a multivariate logistic regression model.Results: GHF alone was not associated with increased baPWV or PP in all participants in this study. However, when GHF coexisted with abnormal metabolism, the risk of increased PP increased 3.23-fold [OR = 3.23(1.47–7.13)] compared with participants with normal filtration and normal metabolism, in which the interaction accounted for 55.1% of the total effect and 79.8% of the effect from GHF and abnormal metabolism. After subtracting the independent effects of GHF and abnormal metabolism, their combined effect still resulted in a 1.78-fold increase in PP.Conclusion: GHF could interact with abnormal metabolism to significantly enhance arterial stiffness. Since abnormal metabolism commonly exists in the general population, even slight changes in renal function should be distinguished to prevent arterial stiffness risk.

BackgroundIt is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass (non-high-density lipoprotein cholesterol [non-HDL-C]) or particle concentration (apolipoprotein B [Apo B]) more accurately reflects risk of incident cardiovascular disease (CVD). We evaluated CVD risk among China population in whom these markers where discordant.MethodsIn total, 7,117 initially healthy participants from the China Health and Nutrition Survey were included. Logistic regressions among Apo B, non-HDL-C, and LDL-C, respectively, were used to examined CVD risk by categories of concordant and discordant values defined by residual differences. Mediation analysis was performed to explore the intermediary effect of Apo B between the obesity and the risk of CVD.ResultsAlthough all 3 biomarkers were correlated (r ≥ 0.81), discordance occurred in approximately 16% of China participants. Participants with discordant high Apo B were more likely to have higher proportion of traditional risk factors and dyslipidemia. During a follow-up of 6 years, 207 CVD cases were identified. High LDL-C, non-HDL-C and Apo B were associated with increased risk of CVD. Participants with discordant high Apo B relative to LDL-C or non-HDL-C had increased CVD risk compared with concordant levels, odds ratios were 1.38 (95% CI: 1.01 to 1.87), 1.40 (95% CI: 1.01 to 1.94), respectively. Furthermore, mediation analyses revealed 16.67% of association between obesity with CVD was mediated by Apo B.ConclusionsDiscordance analysis demonstrates that Apo B is a more accurate marker of CVD risk in China healthy participants than LDL-C and non-HDL-C. Direct measurement of lipoprotein particle concentration might help better inform clinical risk assessment and guide clinical decision making.

Background: Both baseline blood pressure (BP) and cumulative BP have been used to estimate cardiovascular event (CVE) risk of higher BP, but which one is more reliable for recommendation to routine clinical practice is unclear.Methods: In this prospective study, conducted in the Kailuan community of Tanshan City, China, a total of 95,702 participants free of CVEs at baseline (2006–2007) were included and followed up until 2017. Time-weighted cumulative BP that expresses the extent of cumulative BP exposure is defined as the sum of the mean of two consecutive systolic or diastolic BP times the interval between the two determinations, then normalized by the total follow-up duration. Incident CVEs during 2006–2017 were confirmed by review of medical records. We performed a competing risk regression analysis to assess CVE risk of the different durations of higher BP exposure. ROC analysis was performed to assess the predictive value of higher BP on CVE occurrence.Results: We found that when the risk of higher BP on CVE occurrence was estimated based on time-weighted cumulative BP, the hazard ratios (HRs) increased with the increase in duration of higher BP exposure in each of the four BP groups: Conclusions: Baseline BP remains a useful indicator for predicting future occurrence of CVEs. Nevertheless, time-weighted cumulative BP could more reliably estimate the CVE risk of higher BP exposure than baseline BP.

Immune checkpoint inhibitors (ICIs), especially pembrolizumab, have improved outcomes in patients with advanced or metastatic gastric cancer (GC). However, there are no reliable markers for the evaluation of its efficacy. GC samples from the UCSC Xena Browser and Gene Expression Omnibus (GEO) databases were performed by bioinformatics analysis. The single sample gene set enrichment (ssGSEA) algorithm was used to calculate the prognostic genes expression differences score (ssGSEA score) for each sample. Weighted gene co-expression network analysis (WGCNA) was applied to identify the score-related key model. The hub gene was identified based on the intersection between tumor-related transcription factors (TFs) and the key module. The predictive ability for pembrolizumab response of the hub gene was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). The correlations between the hub gene and immune infiltration in GC were investigated by the CIBERSORT algorithm. According to the ssGSEA score, patients with GC were divided into the high- and low-score group. RUNX1T1 was the hub gene of the ICIs treatment in GC. Its high expression was related to the low-score group, which indicated low sensitivity to pembrolizumab and poor prognosis. RUNX1T1 showed good predictive power for pembrolizumab response (AUC = 0.742). The CIBERSORT analysis showed that a high expression for RUNX1T1 weakened the anti-tumor immune response by affecting the immune cell infiltration.Runx1T1 may be a potential predictor of pembrolizumab efficacy in GC and be a prognostic marker for GC.

Background and PurposeIdentifying risks of stroke-associated pneumonia (SAP) is important for clinical management. We aimed to evaluate the association between gut microbiome composition and SAP in patients with acute ischemic stroke (AIS).MethodsA prospective observational study was conducted, and 188 AIS patients were enrolled as the training cohort. Fecal and serum samples were collected at admission. SAP was diagnosed by specialized physicians, and disease severity scores were recorded. Fecal samples were subjected to 16S rRNA V4 tag sequencing and analysed with QIIME and LEfSe. Associations between the most relevant taxa and SAP were analysed and validated with an independent cohort. Fecal short-chain fatty acid (SCFA), serum D-lactate (D-LA), intestinal fatty acid-binding protein (iFABP) and lipopolysaccharide binding protein (LBP) levels were measured.ResultsOverall, 52 patients (27.7%) had SAP in the training cohort. The gut microbiome differed between SAP and non-SAP patients; specifically,Roseburiadepletion and opportunistic pathogen enrichment were noted in SAP patients, as confirmed in the validation cohort (n=144, 28 SAP [19.4%]). Based on multivariate analysis,Roseburiawas identified as a protective factor against SAP in both cohorts (training, aOR 0.52; 95% CI, 0.30-0.90; validation, aOR 0.44; 95% CI, 0.23-0.85). The combination of these taxa into a microbial dysbiosis index (MDI) revealed that dysbiosis increased nearly 2 times risk of SAP (training, aOR 1.95; 95% CI, 1.19-3.20; validation, aOR 2.22; 95% CI, 1.15-4.26). Lower fecal SCFA levels and higher serum D-LA levels were observed in SAP patients. Furthermore, SAP was an independent risk factor of 30-day death and 90-day unfavorable outcome.ConclusionWe demonstrate that a microbial community with depletedRoseburiaand enriched opportunistic pathogens is associated with increased risk of SAP among AIS patients. Gut microbiota screening might be useful for identifying patients at high risk for SAP and provide clues for stroke treatment.

Shujing Huang,1,&ast; Hongyan Sun,2,&ast; Jia Yu,3 Hongfei Shi,2 Liyun Ren,3 Yan He,3 Mingzhi Zhang,3 Hao Peng,3,4 Heng Guo1 1Department of Public Health, School of Medicine, Shihezi University, Shihezi, People’s Republic of China; 2Center for Disease Prevention and Control of Tianning District, Changzhou, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People’s Republic of China; 4Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heng GuoDepartment of Public Health, School of Medicine, Shihezi University, North 2nd Road, Shihezi, 832000, People’s Republic of ChinaTel +86 993 205 7153Email shzuguoheng@foxmail.comHao PengDepartment of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of ChinaTel +86 512 6588 0078Fax +86 512 6588 0052Email penghao@suda.edu.cnPurpose: Sleep duration was associated with large artery atherosclerosis, but its association with atherosclerosis in lower extremity arteries was not well studied. Together with sleep, physical activity constitutes main component of our daily life and influences sleep. Here, we aimed to examine the independent and joint associations of sleep duration and physical activity with peripheral artery disease (PAD) in Chinese adults.Patients and Methods: In Tianning cohort, night-time sleep duration and physical activity were assessed by the Pittsburgh Sleep Quality Index and the Global Physical Activity Questionnaire, respectively, for 5130 participants (51.0± 15.6 years, 58.7% female). PAD was defined as ankle-brachial index (ABI) < 0.9. General linear, and logistic regression models were used to assess the associations of sleep duration and physical activity with PAD. The biological interaction between sleep duration and physical activity on PAD was examined using additive model.Results: Compared to participants sleeping 6– 8.9 h, those sleeping ≥ 9 h had a 0.02 lower ABI (β=− 0.02, P=0.007) and 38% higher odds of PAD (OR=1.38, P=0.035). Compared to physically active participants sleeping 6– 8.9 h, among ≥ 9 h group, physically inactive individuals had significantly increased odds of PAD (OR=2.40, P< 0.001), whereas physically active individuals did not (OR=1.15, P=0.472). On additive scale, attributable proportion due to interaction (0.40, 95% CI: 0.07, 0.73) indicated a significant interaction between sleep duration and physical activity on PAD.Conclusion: Being physically active may attenuate the detrimental association between prolonged sleep duration and PAD. Moreover, we found a significant interaction between prolonged sleep duration and physical inactivity in the prevalence of PAD.Keywords: lower extremity disease, Tianning cohort, sleep duration, joint association, physical activity

The objective of this study is to investigate the dose-response relationship between antibiotic exposure in early life and the risk of subsequent overweight or obesity. Electronic databases were searched from inception to December 2020. Prospective studies that reported the odds ratios (ORs) of childhood overweight or obesity for three or more quantitative categories of antibiotic exposure were identified. A random-effect model was used to pool the ORs and 95% confidence intervals (CIs). Generalized least squares and restricted cubic splines were used to explore the dose-response association. A total of 12 sets of results from 10 articles involving 427,453 participants were included in this meta-analysis. The pooled OR for increased risk of overweight or obesity was 1.30 in high-level antibiotic exposure (95% CI: 1.20 to 1.41) and 1.06 in low-level antibiotic exposure (95% CI: 1.02 to 1.10), as compared with children who never exposed to antibiotics. There was a logarithmic-curve relationship between early-life antibiotic exposure and the risk of subsequent overweight or obesity. The OR was 1.08 (95% CI: 1.06 to 1.11) for one prescription, 1.16 (95% CI 1.11 to 1.21) for two prescriptions, 1.24 (95% CI: 1.16 to 1.32) for three prescriptions, 1.30 (95% CI: 1.20 to 1.41) for four prescriptions, and less than a 5% increase for more prescriptions. Early-life antibiotic exposure is associated with the risk of childhood overweight or obesity in a dose-response manner. Further studies are needed to confirm our results.

Background Vertebral augmentation (VA) techniques are used to treat acute osteoporotic vertebral compression fractures (OVCFs). However, the incidence of recurrent vertebral fractures after VA is controversial. Various factors have been discussed in the literature, but no convincing study on the quality of paraspinal muscles has been reported. The purposes of this study were to evaluate the changes in paraspinal muscles and discuss the relationship between paraspinal muscle degeneration and vertebral refractures after percutaneous kyphoplasty (PKP). Methods This retrospective study was conducted in patients who underwent PKP for an initial OVCF between July 2017 and August 2018. Patients were followed up and categorized in the refractured or non-refractured group. A final magnetic resonance imaging (MRI) scan and a preoperative MRI scan were used to determine the measurements. The paraspinal muscles at the mid-height level of the initial fractured vertebral body were measured using regions of interest (ROIs), including the cross-sectional area (CSA) and signal intensity (SI). The changes in the observed data were compared between the groups using rank-sum tests. Results Overall, 92 patients were enrolled in the study; 33 of them sustained vertebral refractures during the follow-up and the other 59 patients did not. There were no significant differences in terms of sex, age, preoperative bone mineral density, and body mass index between the groups (all, P > 0.05). The refractured group had a significantly higher decrease in the ROI-CSA and CSA/SI, and a higher increase in ROI-SI, compared with the preoperative data (all, P < 0.05). Conclusions The quality of paraspinal muscles significantly decreased in patients with new OVCFs after PKP. This brings a new perspective to the study of postoperative recurrent fractures; patients and physicians need to pay more attention to the efficacy of bed rest and bracing.

Background Septic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients. Methods Patients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes. Results Nine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22–2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22–3.42], MAKE (OR 1.80, 95% CI 1.04–2.63) and SRAE (OR 2.33, 95% CI 1.46–3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29–0.79) after adjustment for potential covariates. Conclusion Latent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.

Background Previous studies have shown that inflammation plays an important role in atherosclerosis and cardiovascular disease. Platelet to lymphocyte ratio (PLR) has been reported as a novel inflammatory marker. However, it is not clear whether PLR is associated with short‐term all‐cause mortality in critically ill patients with non‐ST‐segment elevation myocardial infarction (NSTEMI). Methods The data for the study is from the Medical Information Mart for Intensive Care III database. The primary outcome in our study was 28‐day mortality. Kapan‐Meier curve, lowess smoother curve, and multivariate Cox regression models were used to determine whether the association between PLR and 28‐day mortality of critically ill patients with NSTEMI. Results A total of 1273 critically ill patients with NSTEMI were included in this analysis. Kapan‐Meier curve and lowess smoother curve show that high PLR is associated with an increased risk of 28‐day all‐cause mortality. The study population is divided into two groups according to the cut‐off value of PLR level. In the Cox model, high PLR levels (PLR≥195.8) were significantly associated with increased 28‐day mortality (HR 1.54; 95%CI 1.09–2.18, p = .013). In quartile analyses, the HR (95% CI) for the third (183 ≤ PLR

Background: Circulating miRNAs have been identified as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC), but their efficacy in discovering early-stage ESCC is still unsatisfying. Esophageal squamous dysplasia (ESD) is the precursor lesion of ESCC. Notably, little is known about the role(s) of circulating miRNAs in identifying ESD. In this study, we, therefore, aimed to identify serum miRNAs as novel diagnostic markers for detecting ESD and ESCC. Methods: The genome-wide miRNA expression was profiled in 104 (52 ESCC and 52 controls) serum samples using microarray. Seven candidate miRNAs from the microarray assay were evaluated for their diagnostic performance in another cohort of 266 participants (96 ESCC, 92 ESD, and 78 healthy controls). Results: The serum levels of miR-16-5p, miR-197-5p, miR-451a, and miR-92a-3p were associated with ESCC; the biomarker based on the panel of these four miRNAs could efficiently distinguish patients with ESCC from the controls [AUC = 0.856; 95% confidence interval (CI), 0.794–0.905; P < 0.001]. The serum levels of miR-16-5p, miR-320c, miR-638, and miR-92a-3p were significantly higher in patients with ESD than in controls, and this four-miRNA signature could efficiently differentiate patients with ESD from the controls (AUC = 0.842; 95% CI, 0.778–0.893; P < 0.001). In addition, compared with serum carcinoembryonic antigen and carbohydrate antigen 199, miRNA-based panels had a better diagnostic performance in distinguishing patients with ESCC and ESD from healthy controls. Conclusions: Our study identified two novel panels of circulating miRNAs with high efficiency in detecting ESCC and ESD, suggesting that circulating miRNAs, in particular the combination of them, might serve as noninvasive biomarkers for the early detection of ESCC. Impact: This study suggests the feasibility of using circular miRNA-based blood tests to aid in the detection of ESD and ESCC.

Data on LA/LAA thrombus resolution after rivaroxaban treatment has not been established. The aim of the present study was to compare the efficacy and safety on the resolution of LA/LAA thrombus between rivaroxaban and warfarin in nonvalvular atrial fibrillation (AF) patients. 80 AF patients with LA/LAA thrombus between January 2013 and June 2016 were randomized divided into warfarin group (n = 40) and rivaroxaban group (n = 40). Compared to warfarin group, thrombin time (TT; p