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The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm.This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed.A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P 0.01), shorter hospital stays (P 0.01), and lower cost (P 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P 0.01).Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.

Background. Chronological age (CA) is not a perfect proxy for the true biological aging status of the body. A new biological aging measure, phenotypic age (PhenoAge), has been shown to capture morbidity and mortality risk in the general US population and diverse subpopulations. This study was aimed at evaluating the association between PhenoAge and long-term outcome of patients with multivessel coronary artery disease (CAD). Methods. A total of 609 multivessel CAD patients who received PCI attempt and with follow-up were enrolled. The clinical outcome was all-cause mortality on follow-up. PhenoAge was calculated using an equation constructed from CA and 9 clinical biomarkers. Cox proportional hazards regression models and receiver operating characteristic (ROC) curves were performed to evaluate the association between PhenoAge and mortality. Results. Overall, patients with more diseases had older PhenoAge and phenotypic age acceleration (PhenoAgeAccel). After a median follow-up of 33.5 months, those with positive PhenoAgeAccel had a significantly higher incidence of all-cause mortality ( P = 0.001 ). After adjusting for CA, Cox proportional hazards models showed that both PhenoAge and PhenoAgeAccel were significantly associated with all-cause mortality. Even after further adjusting for confounding factors, each 10-year increase in PhenoAge was also associated with a 51% increased mortality risk. ROC curves revealed that PhenoAge, with an area under the curve of 0.705, significantly outperformed CA, the individual clinical chemistry measure, and other risk factors. When reexamining the ROC curves using various combinations of variables, we found that PhenoAge provides additional predictive power to all models. Conclusions. In conclusion, PhenoAge was strongly associated with all-cause mortality even after adjusting for CA. Our findings suggest that PhenoAge measure may be complementary in predicting mortality risk for patients with multivessel CAD.

Agomelatine was a novel and melatonergic antidepressant. The present study was conducted to find out whether age was an important factor for agomelatine in treating depressed type 2 diabetes mellitus (T2DM) patients. In total, 193 depressed T2DM patients were included. There were 84 patients ranged from 27 years old to 49 years old (age phase I) (n = 44 receiving agomelatine, n = 40 receiving paroxetine or fluoxetine), and 109 patients ranged from 50 years old to 70 years old (age phase II) (n = 56 receiving agomelatine, n = 53 receiving paroxetine or fluoxetine). The Hamilton Depression Rating Scale (HDRS) score, Hamilton Anxiety Rating Scale (HARS) score, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) level and body mass index (BMI) were assessed after 12 weeks treatment. After treatment, we found that among patients in age phase I, there were no significant differences in final average HDRS score, HARS score, FPG, HbA1c level, BMI, response rate and remission rate between the two groups. However, among patients in age phase II, compared to patients receiving paroxetine or fluoxetine, patients receiving agomelatine had the significantly lower average HDRS score, HARS score, HbA1c level and BMI, and significantly higher response rate and remission rate. The incidence of treatment-related adverse events was similar between the two groups in both age phases. These results suggested that age was an important factor for agomelatine in treating depressed T2DM patients. Compared to paroxetine/fluoxetine, agomelatine might be more appropriate for elderly depressed T2DM patients.

Background A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN. Methods This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN. Results The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92–8.27) and three times (OR, 2.931; 95% CI, 1.91–4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups. Conclusion Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study’s findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.

(1) Background and Objectives: The COVID-19 pandemic has considerably affected clinical systems, especially the emergency department (ED). A decreased number of pediatric patients and changes in disease patterns at the ED have been noted in recent research. This study investigates the real effect of the pandemic on the pediatric ED comprehensively by performing a systematic review of relevant published articles. (2) Materials and Methods: A systematic review was conducted based on a predesigned protocol. We searched PubMed and EMBASE databases for relevant articles published until 30 November 2021. Two independent reviewers extracted data by using a customized form, and any conflicts were resolved through discussion with another independent reviewer. The aggregated data were summarized and analyzed. (3) Results: A total of 25 articles discussing the impact of COVID-19 on pediatric emergencies were included after full-text evaluation. Geographic distribution analysis indicated that the majority of studies from the European continent were conducted in Italy (32%, 8/25), whereas the majority of the studies from North America were conducted in the United States (24%, 6/25). The majority of the studies included a study period of less than 6 months and mostly focused on the first half of 2020. All of the articles revealed a decline in the number of pediatric patients in the ED (100%, 25/25), and most articles mentioned a decline in infectious disease cases (56%, 14/25) and trauma cases (52%, 13/25). (4) Conclusions: The COVID-19 pandemic resulted in a decline in the number of pediatric patients in the ED, especially in the low-acuity patient group. Medical behavior changes, anti-epidemic policies, increased telemedicine use, and family financial hardship were possible factors. A decline in common pediatric infectious diseases and pediatric trauma cases was noted. Researchers should focus on potential child abuse and mental health problems during the pandemic.

Background Health-related quality of life (HRQOL) has become an important part of the evaluation of clinical efficacy and prognosis in gastric cancer. This study aimed to assess the HRQOL of patients with gastric cancer using the a five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and explore the factors influencing patients' perceived quality of life. For those significant factors, we can take appropriate measures to intervene to extend patient survival and improve the quality of life. Methods A cross-sectional questionnaire survey was administered to 243 patients with gastric cancer in the First Affiliated Hospital of Suzhou University from December 2018 to December 2020. HRQOL was measured by the Chinese version of the EQ-5D-5L. Nonparametric test analyses and a Tobit regression model were used to identify the independent variables associated with the EQ-5D-5L utility scores. Results In this research, the mean score was 0.810, and the median was 0.893. Approximately 25% of patients reported no problems at all in any of the five dimensions. Problems in pain and discomfort were the most frequently reported (64.2%). Nonparametric test analyses showed that patients who did not have health insurance, or who had a history of alcohol use, a family history of cancer, had received surgery only, or had an interval of less than 1 week between taking this survey and their last treatment, demonstrated lower EQ-5D-5L scores. The Tobit regression model confirmed that health insurance, family history, and treatment were significantly associated with EQ-5D-5L scores. Conclusions The HRQOL of gastric cancer patients can be measured by EQ-5D-5L, and the results may provide a guide for choosing an appropriate individualized treatment plan.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

The prevalence of chronic kidney disease(CKD) increases year by year and has become a highly prevalent disease, seriously affecting the quality of life of patients and bringing heavy family burden. There are many diseases causing CKD, including va-rious primary and secondary glomerulonephritis, renal tubular injury, and renal vascular lesions. Although routine medical treatment for CKD can alleviate the clinical symptoms to a certain extent, it is sometimes difficult to prevent the progression of CKD. Traditional Chinese medicine(TCM) is advantageous in high safety, few adverse reactions, and definite clinical efficacy in the treatment of CKD. The active components contained can play a synergistic effect through multiple pathways and multiple targets to delay disease progression, but its mechanism of action has not been fully elucidated. As revealed by the literature in this field in China and abroad, abnormal mitophagy is a common feature of the pathogenesis of CKD of different types. In recent years, a large number of studies have proved that the regulation of mitophagy through the PINK1/Parkin signaling pathway and mitophagy receptor pathway could delay the progression of CKD and protect renal function. Therefore, the regulation of mitophagy by TCM in the prevention and treatment of CKD through related pathways has become a potential therapeutic target in recent years. This paper reviewed the research articles on the definite efficacy of TCM in preventing and treating CKD by regulating mitophagy through relevant pathways to provide new targets and stra-tegies for preventing and treating CKD and delaying their entry into end-stage renal diseases.

Background socioeconomic inequity in mortality and life expectancy remains inconclusive in low- and middle-income countries, and to what extent the associations are mediated or modified by lifestyles remains debatable. Methods we included 21,133 adults from China Health and Nutrition Survey (1991–2011) and constructed three parameters to reflect participants’ overall individual- (synthesising income, education and occupation) and area-level (urbanisation index) socioeconomic status (SES) and lifestyles (counting the number of smoking, physical inactivity and unhealthy diet and bodyweight). HRs for mortality and life expectancy were estimated by time-dependent Cox model and life table method, respectively. Results during a median follow-up of 15.2 years, 1,352 deaths were recorded. HRs (95% CIs) for mortality comparing low versus high individual- and area-level SES were 2.38 (1.75–3.24) and 1.84 (1.51–2.24), respectively, corresponding to 5.7 (2.7–8.6) and 5.0 (3.6–6.3) life-year lost at age 50. Lifestyles explained ≤11.5% of socioeconomic disparity in mortality. Higher lifestyle risk scores were associated with higher mortality across all socioeconomic groups. HR (95% CI) for mortality comparing adults with low individual-level SES and 3–4 lifestyle risk factors versus those with high SES and 0–1 lifestyle risk factors was 7.06 (3.47–14.36), corresponding to 19.1 (2.6–35.7) life-year lost at age 50. Conclusion this is the first nationwide cohort study reporting that disadvantaged SES was associated with higher mortality and shorter life expectancy in China, which was slightly mediated by lifestyles. Risk lifestyles were related to higher mortality across all socioeconomic groups, and those with risk lifestyles and disadvantaged SES had much higher mortality risks.

To explore the application and effect of the "one disease, one product" project to the nursing care of patients who have undergone pituitary tumour surgery using the nasal sphenoid approach.This is a prospective research study. In a standard treatment control study, 132 patients undergoing transnasal pituitary tumour surgery were divided into the control group (n = 71) and the observation group (n = 61). The control group was given routine pituitary tumor care, and the "one disease, one product" nursing model was used on the experimental group. The anxiety level of patients, the incidence of postoperative complications, postoperative hospitalization, and levels of satisfaction and capability of group members were measured between the control and experimental groups.There was no difference in the level of anxiety between the 2 groups before admission (P = 0.634). The anxiety level of the patients in the observation group decreased after the "one disease, one product" nursing intervention (P = 0.012), but in the control group, it did not decrease significantly (P = 0.149), and the anxiety level in the control group was significantly higher than in the observation group on day 1 preoperatively (P0.001)."One disease, one product" nursing can reduce the preoperative anxiety and postoperative satisfaction of pituitary adenoma surgery patients through the sphenoid sinus approach. It is worthy of popularization and application in pituitary adenoma resection through the sphenoid sinus approach.

Background Internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer (BC) patients with chemotherapy. Previous studies focused on complications between these different approaches and ignored patient comfort. In this study, we aim to compare patient comfort between IJV and AxV/SCV approaches, as well as surgery duration and complications. Methods This is a single-center prospective randomized controlled clinical trial. A total of 200 patients diagnosed with invasive BC will be enrolled in this study. After signing written informed consent, patients schedule to undergo IVAP implantation will be randomized at a 1:1 ratio to receive central venous catheters (CVC) with either IJV or AxV/SCV approaches. Baseline as well as demographic data and procedure time of port implantation will be recorded. All patients will receive assessment of comfort with a comfort scale table at days 1, 2 and 7 after implantation surgery. Patients will be followed up and complications will be recorded until devices are removed at the end of the treatment period, or in case of complications. Patient comfort, procedure time of implantation and complications will be compared and analyzed between these two arms. Discussion To the best of our knowledge, this is the first study to compare patient comfort as primary outcome measure between IJV and AxV/SCV puncture. This study will further confirm the benefits of ultrasound guidance and may provide a better choice of IVAP implantation for BC patients. Trial registration This study has been registered at Chinese Clinical Trial Registry (ChiCTR, www. chictr.org.cn) and Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR2000034986).

Various bone substitutes have been applied in sinus augmentation (SA) to overcome insufficient bone height at the posterior maxilla region caused by pneumatized sinus and severe alveolar bone resorption after teeth loss. However, their effectiveness in SA needs to be further elucidated. In this study, strontium-doped brushite (Sr-DCPD), a new bone substitute, together with bovine-derived hydroxyapatite (bHA) and synthetic hydroxyapatite (sHA) was used in rabbit maxillary SA with simultaneous implant installation. The sinus space-keeping capacity, resorption rate, osteoconductivity, and mechanical properties of regenerated bone, were evaluated by micro-computed tomography (CT), histological analysis, and mechanical testing. Sr-DCPD exhibited the best osteoconductivity and new bone formation (

Introduction: Cognitive impairment is a core feature of schizophrenia. The effects of atypical antipsychotics on the cognitive functions of patients with first-episode schizophrenia have not been c...

Microtubule‐depolymerizing agents can selectively disrupt tumor vessels via inducing endothelial membrane blebbing. However, the mechanism regulating blebbing is largely unknown. IMB5046 is a newly discovered microtubule‐depolymerizing agent. Here, the functions of focal adhesion kinase (FAK) during IMB5046‐induced blebbing and the relevant mechanism are studied. We found that IMB5046 induced membrane blebbing and reassembly of focal adhesions in human vascular endothelial cells. Both FAK inhibitor and knock‐down expression of FAK inhibited IMB5046‐induced blebbing. Mechanism study revealed that IMB5046 induced the activation of FAK via GEF‐H1/ Rho/ ROCK/ MLC2 pathway. cRGD peptide, a ligand of integrin, also blocked IMB5046‐induced blebbing. After activation, FAK further promoted the phosphorylation of MLC2. This positive feedback loop caused more intensive actomyosin contraction and continuous membrane blebbing. FAK inhibitor blocked membrane blebbing via inhibiting actomyosin contraction, and stimulated stress fibre formation via promoting the phosphorylation of HSP27. Conclusively, these results demonstrate that FAK is a molecular switch controlling endothelial blebbing and stress fibre formation. Our study provides a new molecular mechanism for microtubule‐depolymerizing agents to be used as vascular disrupting agents.

Background and aims Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese. Methods 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008–2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate Results Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24–1.70) for TG, 1.26 (1.08–1.46) for nonHDL-c, 2.21 (1.91–2.57) for TC:HDL-c ratio, 2.14 (1.83–2.51) for TG:HDL-c ratio, and 0.47 (0.40–0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0–10%) higher risk of CKD. Conclusions Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only.

Introduction Congenital proximal radioulnar synostosis (CPRUS) is a relatively rare forearm deformity that is characterized by a fixed pronated forearm of varying severity. The osseous synostosis between the proximal part of the ulna and the radius can be seen on the X-ray images in most cases. Many researchers have attempted to identify methods to measure the disease severity to guide in the treatment of CPRUS. However, to describe the overall deformity, the use of multiple indicators is essential, and some of these measurements require special software or need to be conducted on cadavers. Objective The aim of the current study was to introduce the radius pronation angle (RPA), a novel radiological evaluation index of CPRUS, and analyze the relationship between the RPA and the severity of the deformity. Methods Three-dimensional models of 43 CPRUS forearms (19 left forearms and 24 right forearms) of 32 patients (23 males and 9 females; average age was 6 years 8 months; range, from 1.5 to 27 years) treated at Beijing Ji Shui Tan Hospital during 2016 to 2019 were reconstructed using a computer-assisted technique. The special flexed posterior-anterior views of the X-ray image (the f-PA view) of the forearms were obtained, and the forearm rotation angle and the ulnar inner rotation angle were measured on each forearm. The RPA was measured on the f-PA view, and the lengths of the osseous synostosis, ulna, and the radial head were measured on the computed tomography scan images using the multiplanar reconstruction function. The Pearson index was analyzed between the RPA and the other measurements. Results The RPAs were correlated with the forearm rotation angle, ulnar inner rotation angle, relative length of the osseous synostosis, and the relative length of the radial head (P Conclusions The RPA can be measured quickly and easily on the f-PA view of the X-ray image and can be used as a reliable indicator of the severity of CPRUS.

BACKGROUND The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

BackgroundCancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.MethodsEMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.ResultsThe HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.ConclusionsAdopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

Objective: To explore the effect of long-term antipsychotics use on the strength of functional connectivity (FC) in the brains of patients with chronic schizophrenia. Method: We collected resting-state functional magnetic resonance imaging from 15 patients with continuously treated chronic schizophrenia (TCS), 19 patients with minimally TCS (MTCS), and 20 healthy controls (HCs). Then, we evaluated and compared the whole-brain FC strength (FCS; including full-range, short-range, and long-range FCS) among patients with TCS, MTCS, and HCs. Results: Patients with TCS and MTCS showed reduced full-/short-range FC compared with the HCs. No significant differences in the whole-brain FCS (including full-range, short-range, and long-range FCS) or clinical characteristics were identified between patients with TCS and MTCS. Additionally, the FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus negatively correlated with the duration of illness and positively correlated with onset age across all patients with chronic schizophrenia. Conclusions: Regardless of the long-term use of antipsychotics, patients with chronic schizophrenia show decreased FC compared with healthy individuals. For some patients with chronic schizophrenia, the influence of long-term and minimal/short-term antipsychotic exposure on resting-state FC was similar. The decreased full- and short-range FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus may be an ongoing pathological process that is not altered by antipsychotic interventions in patients with chronic schizophrenia. Large-sample, long-term follow-up studies are still needed for further exploration.

Background Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. Patients and methods Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. Results OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3β, we verified GSK3β was over-activated in OLA1-KO cell lines. Conclusion OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3β.

OBJECTIVE Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. RESEARCH DESIGN AND METHODS We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. RESULTS Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7–11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59–2.16), heart failure (HR 4.40; 95% CI 3.67–5.28), CKD (HR 1.68; 95% CI 1.41–2.01), all-cause mortality (HR 2.91; 95% CI 2.53–3.34), and CVD mortality (HR 3.75; 95% CI 2.93–4.80) compared with those without incident AF. CONCLUSIONS Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.

The abuse of antibiotics would seriously affect human health and has become of worldwide critical concern, thus it is urgent to develop an environmentally friendly and nontoxic fluorescent probe for antibiotics sensing. In this work, a lead-free Cs

To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020.A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses.The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Background Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. Methods Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. Results Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P P P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). Conclusions Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.

Purpose Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis. Methods The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein–protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR. Results A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR. Conclusions Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH.

Accurate surveillance of diabetes is crucial for establishing relevant policies of diabetes prevention and control. Previous studies estimated the trends in diabetes among adults in the U.S.; however, many did not consider results of the oral glucose tolerance test (OGTT) (1), and those studies that included the OGTT results reported a higher prevalence of undiagnosed diabetes (2). Capitalizing on the OGTT data since 2005–2006 in the National Health and Nutrition Examination Survey (NHANES), we assessed the trends in diagnosed and undiagnosed diabetes among adults in the U.S. from 2005 to 2016. NHANES is a cross-sectional survey with a stratified, multistage probability design to assess the health status of the noninstitutionalized civilian population in the U.S. (3). A household interview was conducted to collect health-related information including demographic characteristics and medical history. A subset of participants was randomly selected to provide a fasting blood sample and take an OGTT at the mobile examination center. Sample weights were constructed to account for nonresponse and oversampling. The survey was approved by the research ethics review board of the National Center for Health Statistics. Written informed consent was obtained from each participant. This investigation included nonpregnant participants aged 20 years or older, recruited from 2005–2006 to 2015–2016 cycles, who had information on self-reported diagnosed diabetes or laboratory results of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and 2-h plasma glucose (2-h PG). We calibrated plasma glucose measurements to …

In line with the Healthy China strategy, new requirements for medical education have been raised. Medical education against the background of a new model of medicine demands an effective response to its inherent complex elements concerning the rule of law. During the course of the implementation of the new medicine strategy, in face of the widening scope of medical risks, the growing awareness of patient rights, and the conventional logic of medical education, elements concerning the rule of law should be incorporated in medical education in the early stage so as to help medical practitioners develop the appropriate legal literacy and rely on ideas of rules, equality and ethical bottomlines to analyze and solve problems. Thus, medical practitioners would be better equiped to effectively respond to the legal problems they encounter in their medical practice. Legal education is the route of choice in response to the transformation in the mode of medical education and the attempt to solve complicated problems through medicine and the rule of law. Through legal education, the risks of technology embeddedness could be avoided, the relationship between patients and medical practitioners could be regulated in a standardized way, and the medical humanistic environment could be reshaped, thereby improving the quality and level of new medical education.

To investigate the relationship ofWe screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients withAmong the 1015 eligible children and adolescents, the overallIn children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of

To evaluate the safety and clinical efficiency of holmium laser enucleation of the prostate (HoLEP) in the treatment of small-volume BPH (SBPH) complicated by severe lower urinary tract symptoms (LUTS).We retrospectively analyzed the clinical data on 82 cases of SBPH with severe LUTS treated by HoLEP from January 2017 to December 2018. The patients were aged (65.5 ± 7.6) years, with a mean prostate volume of40 ml, a total IPSS of 24.8 ± 4.6, a QOL score of 5.2 ± 0.8, the maximum urinary flow rate (Qmax) of (7.6 ± 3.7) ml/s, and a mean PSA level of (1.8 ± 1.4) μg/L.All the operations were successfully completed, the mean operation time averaging (30.2 ± 5.0) min, enucleation time (26.7 ± 5.6) min and comminution time (3.5 ± 1.1) min, and the enucleated tissue weighing (20.3 ± 4.9) g. After surgery, the bladders were irrigated for (3.5 ± 1.9) h, with (3.0 ± 1.7) L of rinse solution, and catheterization lasted (24.8 ± 9.7) h. Histopathology revealed moderate or severe lymphocytic infiltration in 69 cases (84.1%). At 6 months after operation, significant improvement was observed in the IPSS, QOL, Qmax and PSA level compared with the baseline (P0.05). To date, no urethral stricture-related reoperation was ever necessitated.HoLEP is safe and effective for the treatment of SBPH complicated by severe LUTS and can be employed after adequate preoperative evaluation of the patient.《.

Limited studies had investigated the potential benefits of workplace-based hypertension management programs on long-term blood pressure (BP) control and health outcomes. This study used the propensity score matching to examine the effectiveness of a workplace-based hypertension management program on BP control and risks of major adverse cardiovascular events and all-cause mortality. Within the Kailuan study, a workplace-based hypertension management program was initiated in 2009 among men with hypertension, which included regular BP measuring (twice a month), free antihypertensive medications, and individualized health consultation. Participants were followed until loss to follow-up, death, or December 31, 2019. Among 17 724 male hypertensives aged 18 to 60 years, 6400 participated in the program. The propensity score matching yielded 6120 participants in the management group and 6120 participants in the control group. Both systolic and diastolic BPs were significantly lower in the management group than in the control group over follow-up, and the mean between-group difference at the 10th year was −7.83 (95% CI, −9.06 to −6.62) mm Hg for systolic BP and −4.72 (95% CI, −5.46 to −3.97) mm Hg for diastolic BP. Participants in the program were more likely to achieve BP control (odds ratio, 1.70 [95% CI, 1.41–2.06]) and had significantly lower risks of major adverse cardiovascular events (hazard ratio, 0.83 [95% CI, 0.72–0.94]) and all-cause mortality (hazard ratio, 0.71 [95% CI, 0.58–0.86]), compared with those who were not in the program. A workplace-based hypertension management program was related to reduced BP levels and lower risks of major adverse cardiovascular events and mortality in Chinese men with hypertension.

Background Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

IMB5046 is a nitrobenzoate microtubule inhibitor we reported previously. During screening of its structural analogues, we identified a novel compound IMB5476 with increased aqueous solubility. Here, its antitumor activity and the underlying mechanism were investigated. IMB5476 disrupted microtubule networks in cells and arrested cell cycle at G2/M phase. It inhibited purified tubulin polymerization in vitro. Competition assay indicated that it bound to tubulin at the colchicine pocket. Further experiments proved that it induced cell death by mitotic catastrophe and apoptosis. Notably, it was a poor substrate of P-glycoprotein and exhibited potent cytotoxicity against drug-resistant tumor cells. In addition, IMB5476 could inhibit angiogenesis in vitro. IMB5476 also inhibited the growth of drug-resistant KB

Inflammatory bowel disease (IBD) is a life-threatening and chronic inflammatory disease of gastrointestinal tissue, with complex pathogenesis. Current research on IBD has mainly focused on bacteria; however, the role of fungi in IBD is largely unknown due to the incomplete annotation of fungi in current genomic databases. With the development of molecular techniques, the gut mycobiome has been found to have great diversity. In addition, increasing evidence has shown intestinal mycobiome plays an important role in the physiological and pathological processes of IBD. In this review, we will systemically introduce the recent knowledge about multi-dimensional fungal dysbiosis associated with IBD, the interactions between fungus and bacteria, the role of fungi in inflammation in IBD, and highlight recent advances in the potential therapeutic role of fungus in IBD, which may hold the keys to develop new predictive, therapeutic or prognostic approaches in IBD.

This research was designed to detect the function of low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) in breast cancer (BC). Our results revealed that LRP8 was highly expressed in BC tissues and cell lines compared with human normal breast tissues. The poor prognosis of patients with BC was associated with the up-regulation of LRP8 while inversely connected with overexpression of miR-1262. Functionally, LRP8 depletion in BC cells impaired the proliferative, clonogenic, invasive, and migratory capabilities, which was consistent with the effects of upregulated miR-1262. Bioinformatics prediction and luciferase reporter assay confirmed that miR-1262 was an upstream factor for LRP8 and negatively regulated the expression of LRP8. Further experiments illustrated that the co-transfection of miR-1262 antamir and si-LRP8 could significantly suppress the promoting impacts caused by the transfection of miR-1262 antamir alone. These findings highlighted that LRP8 accelerated the BC development by contributing cellular aggressiveness, which was modulated by miR-1262.

Gemcitabine (Gem) is currently used as the first-line therapy for liver and pancreatic cancer but has limited efficacy in most cases. Dexamethasone (Dex) have been applied as a chemoprotectant and chemosensitizer in cancer chemotherapy. This study further explored the potential of combination of Gem and Dex and tested the hypothesis that glucocorticoid receptor signaling is essential for the synergistic antitumor activity. In the HepG2 and AsPC-1 xenograft models, the combination treatment showed a significantly synergistic antitumor activity. Immunohistochemistry of post-treatment tumors showed a significant decrease in proliferation and angiogenesis as compared to either of the treatments alone. Dex alone and the combination with Gem inhibited the expression of glucocorticoid receptor. The combination of Dex and Gem showed synergistic cytotoxicity in cell lines in vitro. The antiproliferative synergism is prevented by used glucocorticoid receptor (GR) small interfering RNA, demonstrating that the glucocorticoid receptor is required for the antiproliferative synergism of Gem and Dex. The inhibition of glucocorticoid receptor signaling pathway and induction of apoptosis via activation of caspases 3, 8 and 9, PARP, contributed to the synergistic effect of this combination therapy. These results demonstrate that Dex could potentiate the antitumor efficacy of Gem. The synergistic antitumor activity of the combination of Dex and Gem was through glucocorticoid receptor signaling. Taken together, a combination of Dex and Gem shows a significant synergistic antitumor activity and lesser toxicity both in vitro and in vivo and could be a combination chemotherapy for the treatment of highly expression of glucocorticoid receptor patients.

Showing anti-proliferation activity against MCF7 cells better than cisplatin, a platinum(ii) complex, [PtL(DMSO)Cl], was found to potently and selectively inhibit protein tyrosine phosphatase 1B (PTP1B), a putative target for anticancer agents, suggesting a new possible anticancer strategy based on platinum drugs.

Background Estimation of incidence and prognosis of melanomas with brain metastases (MBM) at initial diagnosis based on a large cohort is lacking in current research. This study aims to construct an effective prognostic nomogram for newly diagnosed MBM. Materials and Methods Patients diagnosed with melanomas from Surveillance, Epidemiology, and End Results program between 2010 and 2014 were enrolled in our study. Risk factors predicting brain metastases (BM) were identified using logistic regression analysis. Cox regression analysis was performed to identify prognostic factors of overall survival (OS). Nomogram for estimating 6‐, 9‐, and 12‐month OS was established based on Cox regression analysis. The discriminative ability and calibration of the nomogram were tested using C statistics, calibration plots, and Kaplan‐Meier curves. Results Sixty‐two thousand three hundred and sixty‐nine melanoma patients were enrolled, including 928 with BM. Sex, marital status, insurance status, subsite, surgery of primary sites, radiation, chemotherapy, bone metastases, liver metastases, and lung metastases were associated with MBM at initial diagnosis. On multivariable Cox regression, the following eight variables were incorporated in the prediction of OS: age, unmarried status, absence of surgery to primary sites or unknown, absence of radiation or unknown, absence of chemotherapy or unknown, with bone metastases, with liver metastases, and with lung metastases. The nomogram showed good predictive ability as indicated by discriminative ability and calibration, with the C statistics of 0.716 (95% CI, 0.695‐0.737). Conclusions The incidence and prognosis of MBM patients were well estimated in this study based on a large cohort. The nomogram performed well and could be a useful tool to predict prognosis., This study provided population‐based estimates of the incidence and prognosis for patients of melanoma with brain metastases at initial diagnosis. The nomogram performed well and could be a useful tool to predict prognosis.

This study aims to compare the value of acute physiologic and chronic health evaluation scoring systems (APACHE II and APACHE III) among patients with acute cerebral infarction. The APACHE II and APACHE III scores were determined in 399 patients with acute cerebral infarction within 24 h of admission in order to investigate their predictive value for prognosis in acute cerebral infarction. The area under the ROC curve was used to measure the ability of two scoring systems in predicting the prognosis of patients, and the area under the curve of the two scoring systems was compared. The APACHE II and APACHE III scoring systems demonstrated good predictive value for prognosis in acute cerebral infarction, and the areas under the receiver operating characteristic were 0.808 and 0.818, respectively. There was no significant difference in the area under the curve between these two scoring systems. Both the APACHE II and APACHE III scoring systems had good predictive value for prognosis in acute cerebral infarction, and there was no obvious difference between these two systems. Preference was suggested for APACHE II.

A healthy lifestyle has been widely recommended for the prevention and management of type 2 diabetes. However, no systematic review has summarised the relationship between combined lifestyle factors (including, but not limited to, smoking, alcohol drinking, physical activity, diet and being overweight or obese) and incident type 2 diabetes and risk of health outcomes among diabetic individuals. EMBASE and PubMed were searched up to April 2019 without language restrictions. References included in articles in relevant publications were also screened. Cohort studies investigating the combined associations of at least three lifestyle factors with incident type 2 diabetes and health outcomes among diabetic individuals were included. Reviewers were paired and independently screened studies, extracted data and evaluated study quality. Random-effects models were used to calculate summary HRs. Heterogeneity and publication bias tests were also conducted. Compared with participants considered to have the least-healthy lifestyle, those with the healthiest lifestyle had a 75% lower risk of incident diabetes (HR 0.25 [95% CI 0.18, 0.35]; 14 studies with approximately 1 million participants). The associations were largely consistent and significant among individuals from different socioeconomic backgrounds and baseline characteristics. Among individuals with type 2 diabetes (10 studies with 34,385 participants), the HRs (95% CIs) were 0.44 (0.33, 0.60) for all-cause death, 0.51 (0.30, 0.86) for cardiovascular death, 0.69 (0.47, 1.00) for cancer death and 0.48 (0.37, 0.63) for incident cardiovascular disease when comparing the healthiest lifestyle with the least-healthy lifestyle. Adoption of a healthy lifestyle is associated with substantial risk reduction in type 2 diabetes and long-term adverse outcomes among diabetic individuals. Tackling multiple risk factors, instead of concentrating on one certain lifestyle factor, should be the cornerstone for reducing the global burden of type 2 diabetes.

Purpose: We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.Methods: We searched Pubmed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events (including total CVD, CVD mortality, total coronary heart disease [CHD], fatal CHD, nonfatal myocardial infarction [MI] and stroke) and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.Results: Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR: 0.92; 95% CI: 0.84, 0.99; I2 = 0%; 4 studies), as well as menaquinone and total CHD (0.70; 95% CI: 0.53, 0.93; I2 = 32.1%; 2 studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI: 1.48, 2.28; I2 = 16.8%; 5 studies) and CVD mortality (1.96; 95% CI: 1.47, 2.61; I2 = 0%; 2 studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.Conclusions:Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.

Graphene family nanomaterials (GFNs) have attracted significant attention due to their unique characteristics and applications in the fields of biomedicine and nanotechnology. However, previous studies highlighted the in vitro and in vivo toxicity of GFNs with size and oxidation state differences are still elusive. Therefore, we prepared graphene (G) and graphene oxide (GO) of three different sizes (S-small, M-medium, and L-large), and characterized them using multiple surface-sensitive analytical techniques. In vitro assays using HEK 293T cells revealed that the small and large sizes of G and GO significantly reduced the cell viability and increased DNA damage, accompanying with activated reactive oxygen species (ROS) generation and induced various expressions of associated critical genetic markers. Moreover, the bacterial assays highlighted that G and GO caused strong acute toxicity on Tox2 bacteria. Effects of G were higher than GO and showed size dependent effect: L > M > S, while the medium size of GO induced mild genetic toxicity on RecA bacteria. In vivo assays revealed that exposure to G and GO caused the developmental toxicity, induced ROS generation, and activated related pathways (specifically GO) in zebrafish. Taken together, G showed stronger ability to decrease the survival rate and induce the acute toxicity, while GO showed obvious toxicity in terms of DNA damages, ROS generation, and abnormal gene expressions. Our findings highlighted that G and GO differentially induced toxicity based on their varying physical characteristics, especially sizes and oxidation state, and exposure concentrations and sensitivity of the employed in vitro and in vivo models. In short, this study provided deep insights on the negative effects of GFNs exposure.

China has the largest number of adults with diabetes. Although multiple metabolic risk factors (MRFs) are implicated in the development of diabetes, it remains unclear how they progress during the development of diabetes among Chinese. We examined trajectories of multiple MRFs among Chinese and identified the critical period when drastic changes occurred during the development of diabetes.This prospective cohort study included participants since 2006-2007 in the Kailuan study. People attended biennial examinations until 2017 with additions of new participants at each examination cycle. The time when a participant first completed the examination was served as the baseline. A total of 122,659 participants without prevalent diabetes at baseline and with complete follow-up data were included. MRFs were collected via biennial physical examinations and laboratory measures. Incident diabetes cases were identified via biennial fasting glucose tests and self-reported physician-diagnosis.During up to 12 years of follow-up, 14,922 incident diabetes cases were identified. Compared with participants who did not develop diabetes, those who developed diabetes had more adverse levels of most MRFs at baseline and during follow-up. Abrupt increases in multiple MRFs (including fasting glucose, surrogate insulin resistance indicators, lipids, systolic blood pressure, pulse pressure, heart rate, alanine aminotransferase, and C-reactive protein) were observed 3 years before the diagnosis of diabetes.We identified 3 years before diabetes diagnosis as a critical period when multiple MRFs experienced drastic changes. This would have implications for early monitoring and timely prevention for individuals who experience sudden adverse progression of multiple MRFs.

IMPORTANCE: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. OBJECTIVE: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. DESIGN, SETTING, AND PARTICIPANTS: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. INTERVENTIONS: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)–only control (n = 13 458); they received 2 intramuscular injections 21 days apart. MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. RESULTS: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase–polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P

Background Modular prosthesis fracture, especially distal femoral fracture, is a rare complication of total hip arthroplasty (THA). However, it is catastrophic, and may have a serious impact on the patients. A distal femoral prosthesis fracture in a patient with developmental dysplasia of the hip (DDH) with nonunion at the subtrochanteric osteotomy site has not yet been reported in any literature. This report presents the first such case, with a purpose of analyzing the causes of modular prosthesis fractures and nonunion of the osteotomy area, so as to provide orthopedic surgeons with experience and lessons. Case presentation We report the case of a 52-year-old woman with the distal femoral prosthesis fracture after THA and subtrochanteric osteotomy for Crowe type IV DDH. The patient had severe pain in the left thigh and her activities were limited. Plain radiographs revealed fracture of the left distal femoral prosthesis and nonunion in the subtrochanteric osteotomy region of the left femur. After a revision of the THA, the patient’s symptoms were resolved. Conclusions A prosthesis fracture combined with nonunion at the subtrochanteric osteotomy site is a rare complication. Modular THA combined with a subtrochanteric osteotomy in the treatment of Crowe type IV DDH should reduce the damage to blood supply and avoid further nonunion of the osteotomy area, which may otherwise lead to modular prosthesis fractures. A detailed preoperative plan and suitable rehabilitation program may help minimize the occurrence of subtrochanteric osteotomy nonunion and reduce complications, including femoral prosthesis fractures, in patients with DDH.

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid β peptide (Aβ) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu2+ from Aβ and become dimers upon Cu2+ coordination and show high efficiency for both Cu2+ elimination and Aβ assembly inhibition. Besides, these designed complexes can inhibit the production of Aβ-induced reactive oxygen species (ROS), protect mitochondria from damage, and improve the survival rate of neuron cells. Our work provides a new strategy to combine hydrophobic interaction and metal ion chelation to design amyloid inhibitors.