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Evidence suggests that enolase-phosphatase 1 (ENOPH1) is involved in the progression of some certain types of cancers and acts as an oncogenic factor in tumor progression. The present study aimed to identify the central role of ENOPH1 in the progression of breast cancer (BC), a highly proliferative and aggressive disease.ENOPH1 expression in BC tissues was explored based on the online resource and 40 paired fresh BC and para-carcinoma samples. Functional assays were performed to evaluate the biological effect of ENOPH1 on cell proliferation and migration in ENOPH1-silenced or overexpressing BC cell lines. Blockade of NF-κB by BAY11-7082 was performed to evaluate whether ENOPH1 exerted tumor-promoting properties via regulating the NF-κB signaling pathway. Results of the present study demonstrated that ENOPH1 expression was profoundly upregulated in BC tissues compared with adjacent breast tissues, and ENOPH1 expression was associated with cancer stage, node metastasis status, and overall survival. Functional assays demonstrated that ENOPH1 overexpression significantly accelerated BC cell proliferation, migration, and invasion, while genetic knockdown of ENOPH1 yielded the opposite effects. Mechanistically, ENOPH1 activated the NF-κB pathway, as evidenced by increased expression of NF-κB downstream genes and enhanced NF-κB p65 nuclear translocation. Furthermore, the oncogenic properties of ENOPH1 in proliferation, migration, and invasion were restrained following inhibition of the NF-κB signaling pathway.These findings indicated the significance of ENOPH1 in promoting cell proliferation and invasion, mainly through activating the NF-κB pathway, suggesting that ENOPH1 might be an attractive prognostic factor and a potential target for BC therapy.

This study aims to establish an optimization procedure to define the cut-offs of quantitative assays for acetylcholine receptor antibody (AChRAb), evaluate their diagnostic performance in myasthenia gravis (MG), and explore the association with clinical features.Samples from a representative cohort of 77 MG patients, 80 healthy controls (HC) and 80 other autoimmune diseases (OAD) patients were tested using competitive inhibition ELISA and RIA. Raw values (OD and cpm) and processed values (inhibition rate, binding rate and concentration) were used to define the cut-offs with statistical methods, a rough method, and receiver operating characteristic (ROC) curve. Optimal cut-offs were selected by comparing false positive rates in HC and OAD individuals. The diagnostic performance was evaluated in whole MG cohort and subgroups. Agreement between ELISA and RIA for AChRAb positivity were examined with Kappa test and McNemar test. Clinical association with AChRAb was explored by comparison among subgroups and with Spearman rank correlation.The optimal cut-offs for AChRAb positivity were determined as OD ≤ 1.79 for ELISA and cpm ≥ 1234.12 for RIA, which derived from statistical method and performed better than those derived from ROC curves. The sensitivity and specificity were 74.03%, 100% for ELISA, and 74.03%, 99.37% for RIA. There was good agreement between ELISA and RIA for AChRAb positivity in whole cohort and subgroups (weighted к ≥ 0.71, p 0.01; McNemar test, p 0.05). Levels of AChRAb were different in MG subgroups (p 0.01). Correlation between Quantitative Myasthenia Gravis scores and AChRAb levels was moderate for ELISA and RIA (rThe raw testing values of ELISA and RIA were found as optimal quantitative measures of AChRAb levels. There are good agreements on diagnostic performance between two assays. Quantitative values are more informative than positivity in association with clinical features.

Aerobic exercises could improve the sperm motility of obese individuals. However, the underlying mechanism has not been fully elucidated, especially the possible involvement of the epididymis in which sperm acquire their fertilizing capacity. This study aims to investigate the benefit effect of aerobic exercises on the epididymal luminal milieu of obese rats. Sprague–Dawley male rats were fed on a normal or high-fat diet (HFD) for ten weeks and then subjected to aerobic exercises for 12 weeks. We verified that TRPA1 was located in the epididymal epithelium. Notably, aerobic exercises reversed the down-regulated TRPA1 in the epididymis of HFD-induced obese rats, thus improving sperm fertilizing capacity and Cl− concentration in epididymal milieu. Ussing chamber experiments showed that cinnamaldehyd (CIN), agonist of TRPA1, stimulated an increase of the short-circuit current (ISC) in rat cauda epididymal epithelium, which was subsequently abolished by removing the ambient Cl− and HCO3−. In vivo data revealed that aerobic exercises increased the CIN-stimulated Cl− secretion rate of epididymal epithelium in obese rats. Pharmacological experiments revealed that blocking cystic fibrosis transmembrane regulator (CFTR) and Ca2+-activated Cl− channel (CaCC) suppressed the CIN-stimulated anion secretion. Moreover, CIN application in rat cauda epididymal epithelial cells elevated intracellular Ca2+ level, and thus activate CACC. Interfering with the PGHS2-PGE2-EP2/EP4-cAMP pathway suppressed CFTR-mediated anion secretion. This study demonstrates that TRPA1 activation can stimulate anion secretion via CFTR and CaCC, which potentially forming an appropriate microenvironment essential for sperm maturation, and aerobic exercises can reverse the down-regulation of TRPA1 in the epididymal epithelium of obese rats.

Background and aims The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041). Conclusions This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.

Immunotherapy, in particular immune checkpoint blockade (ICB) therapy targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, has remarkably revolutionized cancer treatment in the clinic. Anti-PD-1/PD-L1 therapy is designed to restore the antitumor response of cytotoxic T cells (CTLs) by blocking the interaction between PD-L1 on tumour cells and PD-1 on CTLs. Nevertheless, current anti-PD-1/PD-L1 therapy suffers from poor therapeutic outcomes in a large variety of solid tumours due to insufficient tumour specificity, severe cytotoxic effects, and the occurrence of immune resistance. In recent years, nanosized drug delivery systems (NDDSs), endowed with highly efficient tumour targeting and versatility for combination therapy, have paved a new avenue for cancer immunotherapy. In this review article, we summarized the recent advances in NDDSs for anti-PD-1/PD-L1 therapy. We then discussed the challenges and further provided perspectives to promote the clinical application of NDDS-based anti-PD-1/PD-L1 therapy.

Objective Type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus. Methods Medline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness. Results A total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): −6.02%, confidence interval (CI): −10.37% to −1.67%] and SGLT2 inhibitors (MD: −2.60%, CI: −4.87% to −0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: −0.06, CI: −0.10 to −0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein. Conclusion Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.

Lithium argyrodite-type electrolytes are regarded as promising electrolytes due to their high ionic conductivity and good processability. Chemical modifications to increase ionic conductivity have already been demonstrated, but the influence of these modifications on interfacial stability remains so far unknown. In this work, we study Li 6 PS 5 Cl and Li 5.5 PS 4.5 Cl 1.5 to investigate the influence of halogenation on the electrochemical decomposition of the solid electrolyte and the chemical degradation mechanism at the cathode interface in depth. Electrochemical measurements, gas analysis and time-of-flight secondary ion mass spectrometry indicate that the Li 5.5 PS 4.5 Cl 1.5 shows pronounced electrochemical decomposition at lower potentials. The chemical reaction at higher voltages leads to more gaseous degradation products, but a lower fraction of solid oxygenated phosphorous and sulfur species. This in turn leads to a decreased interfacial resistance and thus a higher cell performance.

Background Subclavian steal syndrome (SSS) caused by Sjogren's syndrome is rare, especially for elderly patients with risk factors for atherosclerosis. The current report presents the uncommon etiology and treatment of SSS, aiming to improve doctor's clinical experience. Case summary A 69-year-old man was diagnosed with hypertension and acute cerebral infarction presenting with left upper limb weakness and pain even gradually aggravating to left limb hemiplegia 30 years ago. He was managed with antihypertensive and antithrombotic therapy; however, his condition was recurrent, and he never had any further examination. It was found that the difference of the bilateral upper arm systolic pressure was over 20 mmHg, and Doppler examination showed that the blood flow of the left vertebral artery was reversed, suggesting SSS. Further tests revealed a benign lymphoepithelial lesion in salivary gland tissue, confirming the Sjogren's syndrome. Conclusion The patient was found to have hypertension when he was 33 years old, and the blood pressure of both sides was asymmetric, which was ignored. The patient's symptoms of dizziness and upper limb weakness were misdiagnosed as general cerebral infarction. It is necessary to test the aorta computed tomography angiography to prove secondary hypertension factors such as Sjogren's syndrome.

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.

Background and aimsThe global prevalence of non-alcoholic fatty liver disease (NAFLD) is expected to rise continuously. Furthermore, emerging evidence has also shown the potential for concomitant depression in NAFLD. This study aims to examine the prevalence, risk factors, and adverse events of depression in NAFLD and evaluate whether treated depression can reverse the increased risks of adverse outcomes.Materials and methodsThis study analyses the 2000–2018 cycles of NHANES that examined liver steatosis with fatty liver index (FLI). The relationship between NAFLD and depression was assessed with a generalized linear mix model and a sensitivity analysis was conducted in the no depression, treated depression, and untreated depression groups. Survival analysis was conducted with cox regression and fine gray sub-distribution model.ResultsA total of 21,414 patients were included and 6,726 were diagnosed with NAFLD. The risk of depression in NAFLD was 12% higher compared to non-NAFLD individuals (RR: 1.12, CI: 1.00–1.26, p = 0.04). NAFLD individuals with depression were more likely to be older, females, Hispanics or Caucasians, diabetic, and have higher BMI. Individuals with depression have high risk for cardiovascular diseases (CVD) (RR: 1.40, CI: 1.25–1.58, p < 0.01), stroke (RR: 1.71, CI: 1.27–2.23, p < 0.01), all-cause mortality (HR: 1.50, CI: 1.25–1.81, p < 0.01), and cancer-related mortality (SHR: 1.43, CI: 1.14–1.80, p = 0.002) compared to NAFLD individuals without depression. The risk of CVD, stroke, all-cause mortality, and cancer-related mortality in NAFLD individuals with treated depression and depression with untreated treatment was higher compared to individuals without depression.ConclusionThis study shows that concomitant depression in NAFLD patients can increase the risk of adverse outcomes. Early screening of depression in high-risk individuals should be encouraged to improve the wellbeing of NAFLD patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United States National Health and Nutrition Examination Survey (NHANES) 2011–2018, multivariate logistic regression and marginal analysis were conducted according to quartiles of regional fat percentages, stratified by gender. A total of 23,752 individuals were analysed. Males generally showed a larger increase in marginal probabilities of NAFLD development than females, except in head fat, which had the highest predictive probabilities of non-obese NAFLD in females (13.81%, 95%CI: 10.82–16.79) but the lowest in males (21.89%, 95%CI: 20.12–23.60). Increased percent of trunk fat was the strongest predictor of both non-obese (OR: 46.61, 95%CI: 33.55–64.76, p < 0.001) and obese NAFLD (OR: 2.93, 95%CI: 2.07–4.15, p < 0.001), whereas raised percent gynoid and leg fat were the weakest predictors. Ectopic fat deposits are increased in patients with non-obese NAFLD, with greater increases in truncal fat over gynoid fat. As increased fat deposits in all body regions can increase odds of NAFLD, therapeutic intervention to decrease ectopic fat, particularly truncal fat, may decrease NAFLD risk.

BACKGROUND Endoscopic submucosal dissection (ESD) has shown to be effective in management of colorectal neoplasm in the Asian countries, while its implementation in Western countries where endoscopic mucosal resection (EMR) is preferred is still debatable. AIM To compare the surgical, histological, and oncological outcomes between ESD and EMR in the treatment of colorectal polyps, with subgroup analysis comparing the efficacy of ESD and EMR between Japan and the rest of the world. METHODS Embase and Medline databases were searched from inception to October 2020 in accordance with PRISMA guidelines for studies comparing en bloc, complete resection, margin involvement, resection time, need for additional surgery, complications, and recurrence rate of ESD with EMR. RESULTS Of 281344 colorectal polyps from 21 studies were included. When compared to EMR, the pooled analysis revealed ESD was associated with higher en bloc and complete resection rate, and lower lateral margin involvement and recurrence. ESD led to increased procedural time, need for additional surgery, and perforation risk. No significant difference in bleeding risk was found between the two groups. Meta-regression analysis suggested only right colonic polyps correlated with an increased perforation risk in ESD. Confounders including polyp size and invasion depth did not significantly influence the en bloc and complete resection rate, bleeding risk and recurrence. In subgroup analysis, Japan performed better than the rest of the world in both ESD and EMR with perforation risk of 4% and 0.0002%, respectively, as compared to perforation risk of 8% and 1%, respectively, in reports coming from rest of the world. CONCLUSION ESD resulted in better resection outcomes and lower recurrence compared to EMR. With appropriate training, ESD is preferred over EMR as the first-line therapy for resection of colorectal polyps, without restricting to lesions greater than 20 mm and those with high suspicion of submucosal invasion.

Large quantities of lead/zinc (Pb/Zn) mine tailings were deposited at tailings impoundments without proper management, which have posed considerable risks to the local ecosystem and residents in mining areas worldwide. Therefore, the geochemical behaviors of potentially toxic elements (PTEs) in tailings were in-depth investigated in this study by a coupled use of batch kinetic tests, statistical analysis and mineralogical characterization. The results indicated that among these studied PTEs, Cd concentration fluctuated within a wide range of 0.83-6.91 mg/kg, and showed the highest spatial heterogeneity. The mean Cd concentrations generally increased with depth. Cd were mainly partitioned in the exchangeable and carbonate fractions. The release potential of PTEs from tailings was ranged as: Cd Mn Zn Pb As, Cd Pb Zn Mn As and Cd Pb Mn Zn As, respectively, under the assumed environmental scenarios, i.e. acid rain, vegetation restoration, human gastrointestinal digestion. The results from mineralogical characterization indicated that quartz, sericite, calcite and pyrite were typical minerals, cumulatively accounting for over 80% of the tailings. Sulfides (arsenopyrite, galena, and sphalerite), carbonates (calcite, dolomite, cerussite and kutnahorite), oxides (limonite) were identified as the most relevant PTEs-bearing phases, which significantly contributed to PTEs release from tailings. A combined result of statistical, geochemical and mineralogical approaches would be provided valuable information for the alteration characteristics and contaminant release of Pb/Zn mine tailings.

There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them.Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss - and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time.A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%).Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs.This research did not receive additional support from organizations beyond the authors' academic institutions.

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1

BackgroundNon-alcoholic fatty liver disease (NAFLD) is prevalent amongst overweight and obese individuals, and weight loss remains the main mode of treatment for NAFLD patients. Weight perception plays a key role in the efficacy of such treatment. The current study aims to investigate the prevalence, associating factors and implications of poor weight perception amongst such individuals.MethodsAn analysis was done on data collected from NHANES between 1999 and 2018. Comparison was made between NAFLD individuals with and without poor weight perception in terms of prevalence, associated characteristics, and clinical outcomes. Multivariate analysis was used to compare effect size of adverse events associated with NAFLD individuals with poor weight perception.ResultsOf the 12,170 NAFLD patients, 19.2% (CI: 18.5 to 19.9%) had poor weight perception. Poor weight perception was significantly associated with lower education levels, reduced levels of exercise and unhealthier lipid profiles. There was an increased risk in all-cause mortality (HR: 1.18, CI: 1.00 to 1.38, p = 0.047), cardiovascular disease mortality (SHR: 1.33, CI: 1.03 to 1.71, p = 0.026), major adverse cardiovascular events (OR: 1.21 CI: 1.10 to 1.32, p < 0.001), and advanced fibrosis (OR: 1.30, CI: 1.03 to 1.64, p = 0.025) for individuals with poor weight perception.ConclusionThis study highlights the positive association between appropriate weight perception and better outcomes in individuals with NAFLD. Poor weight perception increased the risk of adverse events and decreased inclination toward seeking weight loss treatment. Greater emphasis should be placed on dealing with weight perception in individuals with NAFLD for better treatment outcomes.

To explore the association between male infertility and hypertension risk, a meta-analysis and systematic review was conducted. Observational studies were sought in Medline, PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure up to April 30, 2021. Two independent reviewers selected available studies and extracted the data. The association between male infertility and hypertension risk was estimated by calculating the relative risk (RR) and 95% confidence interval (95% CI) using Stata12.0 statistical software. A total of seven studies were included in this meta-analysis, including 102,152 patients and 636,645 healthy individuals. The results demonstrated that male infertility was significantly associated with increased hypertension incidence (RR = 1.08; 95% CI 1.02-1.14; p = 0.004), with moderate-quality evidence. A subgroup analysis based on region showed that a positive association was observed in Europe but not the United States or Asia. This positive association was further confirmed in a cohort study, but not in a case-control study. After adjusting for potential confounders, male infertility was still significantly associated with hypertension risk (RR = 1.06, 95% CI 1.03-1.09). In conclusion, our findings suggest that male infertility increases the risk of hypertension incidence. However, further studies are needed to provide more conclusive evidence.

Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in Zkscan3 knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagic genes in human cancer and non-cancer cells, we generated ZKSCAN3 knockout HK-2 (non-cancer) and Hela (cancer) cells via the CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, western blot and transcriptome sequencing, with special attention to the differences in expression of autophagic and lysosomal genes. We found that ZKSCAN3 may be a cancer-related gene involved in cancer progression, but not an essential transcriptional repressor of autophagic or lysosomal genes, as the lacking of ZKSCAN3 cannot significantly promote the expression of autophagic and lysosomal genes.

BackgroundMalnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030.MethodsUsing data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed.FindingsIn 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507–895) per 100,000 population. DALY rates decreased from 2000 to 2019 (−2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277–2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. BACKGROUND: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030.METHODS: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m 2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. FINDINGS: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries.INTERPRETATION: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further.FUNDING: None.

BACKGROUND Central nervous system graft-vs-host disease (CNS-GVHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation. Currently, establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out. CASE SUMMARY Here, we present two patients with CNS-GVHD. Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes, and had abnormal cerebrospinal fluid (CSF) studies as determined by CSF and blood immune biomarker examinations, suggestive of suspected CNS-GVHD. Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients, we did not attempt to perform a brain biopsy, but prompted the initiation of empirical immunosuppressive therapy. In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings, a final diagnosis of CNS-GVHD was made. CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNS-GVHD, which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

Apatinib, a competitive inhibitor of VEGFR2, has anti-angiogenesis and anticancer activities through different mechanisms, but it still cannot fully explain the drug efficacy of apatinib. Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in cancer biology, however, the exact role of ferroptosis in apatinib-mediating anticancer treatment are still not clear. The effects of (1S, 3R)-RSL3 and apatinib were evaluated in different GC cell lines and in normal human gastric epithelial cells. Further, the effects of apatinib and inhibition of antioxidant defense enzyme glutathione peroxidase (GPX4) on cell viability, cell death, glutathione (GSH) levels, lipid ROS production, cellular malondialdehyde (MDA) levels and protein expression were evaluated in vitro as well as in a mouse tumor xenograft model. The expression level of GPX4 in GC tissues and paracancerous tissues was measured by immunohistochemistry. (1S, 3R)-RSL3 selectively killed GC cells, but not normal cells. Apatinib induced ferroptosis in GC cells by decreasing cellular GSH levels and increasing lipid peroxidation levels. This effect was blocked by co-incubation with ferrostatin-1, liproxstatin-1, GSH, or vitamin E. Further investigation revealed that apatinib down-regulated GPX4 expression via inhibition of the transcription factors Sterol regulatory element-binding protein-1a (SREBP-1a). Besides, we found that multi-drug resistant GC cells were vulnerable to apatinib-induced GPX4 inhibition. In summary, we show that apatinib could induce the lipid peroxidation through GPX4 mediated by SREBP-1a, then negatively regulate the GC cell, even the multi-drug-resistant GC cell, ferroptosis.

Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo. BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo, CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

Background:. Although endovascular therapy has been widely used for focal aortoiliac occlusive disease (AIOD), its performance for extensive AIOD (EAIOD) is not fully evaluated. We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency. Methods:. Between January 2008 and June 2018, patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II (TASC II) C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled. Demographic, diagnosis, procedure characteristics, and follow-up information were reviewed. Univariate analysis was used to identify the correlation between the variables and the primary patency. A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency. Five- and 10-year primary and secondary patency, as well as survival rates, were calculated by Kaplan-Meier analysis. Results:. A total of 148 patients underwent endovascular treatment in our center. Of these, 39.2% were classified as having TASC II C lesions and 60.8% as having TASC II D lesions. The technical success rate was 88.5%. The mean follow-up time was 79.2 ± 29.2 months. Primary and secondary patency was 82.1% and 89.4% at 5 years, and 74.8% and 83.1% at 10 years, respectively. The 5-year survival rate was 84.2%. Compared with patients without loss of primary patency, patients with this condition showed significant differences in age, TASC II classification, infrainguinal lesions, critical limb ischemia (CLI), and smoking. Multivariate logistic regression analysis showed age

Orostachys cartilaginous is a traditional herbal medicine and its cell cultures contain large amounts of polysaccharides. To utilize the cultured O. cartilaginous cells, this study purified the crude polysaccharides of O. cartilaginous cells by macroporous resin absorption and optimized the purification process in the experiment of orthogonal design with four factors (sample concentration and volume, and eluent concentration and volume) and three levels; the antibacterial and anti-cancer effects of the purified polysaccharides (OTP) were further examined. The results showed that polysaccharide purity reached 95 % in the optimized group, i. e., 1.6 mg/mL of sample (crude polysaccharides) concentration, 3.0 bed volume (BV) of sample volume, 65 % eluent (ethanol) concentration, and 3.0 BV of eluent volume. In the antibacterial experiment, the growth of three bacterial species, i. e., Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was inhibited by OTP, whereas that of Escherichia coli was not affected; the largest diameter of the inhibitory zone was found on B. subtilis; the extracellular alkaline phosphatase activity and the electrical conductivity, nucleic acid, and protein levels of B. subtilis increased after OTP treatment, indicating that the inhibition of B. subtilis growth was caused by the leakage of cell contents. In the anti-cancer experiment, OTP decreased the cell viabilities of the tested human cancer cells, i. e., AGS (gastric cancer), HCT116 (colon cancer), HepG2 (liver cancer), and HeLa (cervical cancer), and the highest inhibitory effect was on HCT116. OTP promoted HCT116 apoptosis and affected the expression of apoptosis-related proteins, i. e., the expression of B-cell lymphoma-2 decreased and that of bcl-2 associated X protein, cytochrome c, caspase 9 and caspase 3 increased. The findings of the present study suggest that O. cartilaginous cell cultures have a potential application in food or drug production.

Grass carp (Ctenopharyngodon idella) is the largest economic fish in freshwater culture in China, which is predisposed to infectious diseases under high temperature. Under the background of global warming, the industrialization of the Pearl River Delta region has led to aggravated thermal pollution, which has increasingly serious impacts on the aquatic ecological environment. This will result in more frequent exposure of grass carp to overheated water temperatures. Previous studies have only identified the regulatory genes of fish that respond to pathogens or temperature stress, but the transcriptional response to both is unknown. In this study, the histopathological analysis showed heat stress exacerbated spleen damage induced by Aeromonas hydrophila. The transcriptional responses of the spleens from A. hydrophila lipopolysaccharide (LPS) -injected grass carp undergoing heat stress and at normal temperatures for 6, 24, and 72 h were investigated by mRNA and microRNA sequencing. We identified 28, 20, and 141 differentially expressed (DE) miRNAs and 126, 383, and 4841 DE mRNAs between the two groups after 6, 24, and 72 h, respectively. There were 67 DE genes mainly involved in the cytochrome P450 pathway, antioxidant defense, inflammatory response, pathogen recognition pathway, antigen processing and presentation, and the ubiquitin-proteasome system. There were 5 DE miRNAs involved in regulating apoptosis and inflammation. We further verified 17 DE mRNAs and 5 DE miRNAs using quantitative real-time PCR. Based on miRNAs and mRNAs analysis, continuous heat stress will affect the antibacterial responses of grass carp spleens, resulting in aggravation of spleen injury. Together, these results provide data for further understanding of the decreased tolerance of fish to pathogen infection in persistent high-temperature environments.

Patients undergoing liver transplant (LTX) typically confront a challenging postoperative journey. A dysbiotic gut microbiome is associated with the development of complications, including post-LTX allograft rejection, metabolic diseases and de novo or recurrent cancer. A major explanation of this are the bipartite interactions between the gut microbiota and host immunity, which modulates the alloimmune response towards the liver allograft. Furthermore, bacterial translocation from dysbiosis causes pathogenic changes in the concentrations of microbial metabolites like lipopolysaccharides, short-chain fatty acids (SCFAs) and Trimethylamine-N-Oxide, with links to cardiovascular disease development and diabetes mellitus. Gut dysbiosis also disrupts bile acid metabolism, with implications for various post-LTX metabolic diseases. Certain taxonomy of microbiota such as lactobacilli, F.prausnitzii and Bacteroides appear to be associated with these undesired outcomes. As such, an interesting but as yet unproven hypothesis exists as to whether induction of a “beneficial” composition of gut microbiota may improve prognosis in LTX patients. Additionally, there are roles of the microbiome as predictive and prognostic indicators for clinicians in improving patient care. Hence, the gut microbiome represents an exceptionally exciting avenue for developing novel prognostic, predictive and therapeutic applications.

In China, Hyphantria cunea (Drury) is an invasive phytophagous pest; it attacks nearly all species of defoliated trees. To develop integrated pest management programs (IPM) for H. cunea, we need to ensure the availability of insects by mass-rearing them on artificial diets under laboratory conditions. This study compared the growth characteristics, nutritional indices, growth indices, and digestive enzyme activity of insects reared on Pterocarya stenoptera C.DC (Fagales: Juglandaceae), the Chinese wingnut, and an artificial diet. We also investigated the correlation between diet components and growth indices using principal components analysis and Pearson correlation analysis. We found that mass-rearing of H. cunea on an artificial diet was feasible. It led to a shorter developmental period, with heavier larvae and pupae than natural diets. The principal components analysis indicated that the growth indices and α-Amylase were significantly positively associated with PC1, which explained 82.45% of the total data variability. Pearson correlation analysis showed a significant correlation between digestion, absorption parameters, and growth. Developing a mass-rearing program to produce H. cunea on an artificial diet will be valuable for improving IPM strategies. Understanding the mechanism of the responses of phytophagous insect populations to anthropogenic diet regulation can provide new ideas and methods for pest control.

Introduction Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial. Methods We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case–control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations. Results Our case–control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06–3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17–1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03–1.51) and Asia (RR = 1.32, 95%CI 1.24–1.41). Conclusions The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.

Background Ankylosing spondylitis with Andersson lesions is not rare, but its potential pathogenesis and natural course remain unclear. Case description We describe a case of CT image changes in ankylosing spondylitis from fracture to Andersson lesions. A 40-year-old man with a 23-year history of ankylosing spondylitis presented with acute back pain after a slight fall, and the CT showed a T12 fracture; the patient refused surgery for 12 months. The process from fracture to Andersson lesions was characterized by CT, including the subsequent interbody bone graft with internal fixation and successful bone fusion at the last follow-up. Histopathologic analysis showed degenerative fibrocartilage tissue calcification, necrotic intervertebral disc tissue, fibrovascular hyperplasia, and focal accumulation of inflammatory cells. Conclusion Aseptic inflammation and persistent instability caused by a fracture contributed in the course from fracture to Andersson lesions in ankylosing spondylitis. CT can accurately track the pathological process, and interbody fusion via the posterior pedicle lateral approach can achieve satisfactory effectiveness, good fusion and kyphosis correction.

Verticillium dahliae is a widespread fungal pathogen that causes Verticillium wilt on many economically important crops and ornamentals worldwide. Populations of V. dahliae have been divided into two distinct races based upon differential host responses in tomato and lettuce. Recently, the contemporary race 2 isolates were further divided into an additional race in tomato. Herein, we provide a high-quality reference genome for the race 1 strain VdLs.16 isolated from lettuce in California, U.S.A. This resource will contribute to ongoing research that aims to elucidate the genetic basis of V. dahliae pathogenicity and population genomic diversity.

The capability to significantly shorten the synthetic period of a broad spectrum of open organic materials presents an enticing prospect for materials processing and applications. Herein we discovered 1,2,4‐triazolium poly(ionic liquid)s (PILs) could serve as a universal additive to accelerate by at least one order of magnitude the growth rate of representative imine‐linked crystalline open organics, including organic cages, covalent organic frameworks (COFs), and macrocycles. This phenomenon results from the active C5‐protons in poly(1,2,4‐triazolium)s that catalyze the formation of imine bonds, and the simultaneous salting‐out effect (induced precipitation by decreasing solubility) that PILs exert on these crystallizing species., 1,2,4‐Triazolium poly(ionic liquid) (PIL) is an additive to accelerate by at least one order of magnitude the crystallization rate of imine‐linked crystalline open organics (organic cages, covalent organic frameworks (COFs), and macrocycles). This acceleration effect stems from the active C5 protons in polytriazolium that catalyze formation of imine bonds and the salting‐out effect of PILs on these crystallizing species.

Background: Tumor cell-derived exosomes (TEXs) have been widely used to induce antitumor immune responses in animal models and clinical trials. Similarly, leukemia cell-derived exosomes (LEXs) can induce antileukemia immune responses in animal models. However, the antileukemia immunity induced by LEXs is less effective, which may be due to an inadequate costimulatory capacity.Methods: In this study, we transduced L1210 leukemia cells with a lentiviral vector encoding two B7 costimulatory molecules (CD80, CD86) and obtained LEXs that highly expressed CD80 and CD86. The antileukemia immune response derived from these LEXs was examined in vitro and in vivo in animal models.Results: We found that B7 gene-modified LEXs, including LEX-CD80, LEX-CD86, and LEX-8086, could significantly boost the expression of CD80 and CD86 in dendritic cells (DCs) and promote the secretion of functional cytokines such as TNF-α and IL-12. Moreover, these B7 gene-modified LEXs, particularly LEX-CD8086, could effectively induce CD4+ T cell proliferation, Th1 cytokine secretion, and an antigen-specific anti-leukemia cytotoxic T lymphocyte (CTL) response. Additional animal studies indicated that immunization with B7 gene-modified LEXs, in particular LEX-CD8086, could significantly retard tumor growth compared to the control LEXnull group.Conclusions: This study sheds light on the feasibility of obtaining LEXs that overexpress costimulatory molecules via genetically modified leukemia cells, thereby enhancing their anti-leukemia immunity and providing a potential therapeutic strategy that contributes to leukemia immunotherapy.

Background Protease-activated receptor-2 (PAR-2)-modulated tight junctions (TJs) have been suggested to be involved in the pathogenesis of chronic inflammatory diseases. However, immunopathogenesis remains to be investigated among patients with allergic rhinitis (AR). Objective This study sought to investigate the role of PAR-2 in the modulation of epithelial barrier function and the expression of TJs in the nasal mucosa of AR patients. Methods The expression of TJs and PAR-2 of the nasal mucosa in AR patients and control subjects by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. In vitro, Primary human nasal epithelial cells (pHNECs) of AR patients were stimulated by Der p1 to analyze the correlation between PAR-2 and TJs expression. Der p1-induced pHNECs were treated with the PAR-2 agonist SLIGRL-NH2 and antagonist FSLLRY-NH2. Fluorescein isothiocyanate–dextran 4 kDa detection was employed as an indicator of epithelial permeability. Results Lower expression levels of TJs in the nasal epithelium of AR patients were observed in comparison with that in control subjects. The PAR-2 level was markedly increased following treatment with 1,000 ng/mL of Der p1 for 24 hours in a cellular model of AR. The expression of PAR-2 was increased in Der p1-induced pHNECs of AR patients and correlated inversely with zonula occlidens (ZO)-1 and claudin-1. Treatment with Der p1 further downregulated TJs expression and promoted an increased epithelial permeability in Der p1-induced pHNECs. Conclusions PAR-2 could downregulate the expression of ZO-1 and claudin-1, which is involved in epithelial barrier dysfunction in AR.

Accurate prediction of drug- and chemical-induced hepatotoxicity remains to be a problem for pharmaceutical companies as well as other industries and regulators. The goal of the current study was to develop an in vitro/in silico method for the rapid and accurate prediction of drug- and chemical-induced hepatocyte injury in humans. HepaRG cells were employed for high-throughput imaging in combination with phenotypic profiling. A reference set of 69 drugs and chemicals was screened at a range of 7 concentrations, and the cellular response values were used for training a supervised classifier and for determining assay performance by using tenfold cross-validation. The results showed that the best performing phenotypic features were related to nuclear translocation of RELA (RELA proto-oncogene, NF-kB subunit; also known as NF-kappa B p65), DNA organization, and the F-actin cytoskeleton. Using a subset of 30 phenotypic features, direct hepatocyte toxicity in humans could be predicted with a test sensitivity, specificity and balanced accuracy of 73%, 92%, and 83%, respectively. The method was applied to another set of 26 drugs and chemicals with unclear annotation and their hepatocyte toxicity in humans was predicted. The results also revealed that the identified discriminative phenotypic changes were related to cell death and cellular senescence. Whereas cell death-related endpoints are widely applied in in vitro toxicology, cellular senescence-related endpoints are not, although cellular senescence can be induced by various drugs and other small molecule compounds and plays an important role in liver injury and disease. These findings show how phenotypic profiling can reveal unexpected chemical-induced mechanisms in toxicology.

Backgroud To evaluate the relationship between omentin-1 and benign prostatic hyperplasia (BPH). BPH is the most common urological disease in elderly men worldwide. Lower serum omentin-1 levels were reported to be negatively associated with the incidence of inflammation, diabetes, obesity and metabolic syndrome, which all play a role in the development of BPH. To the best of our knowledge, the relationship between omentin-1 and BPH has not been investigated previously. Methods A total of 70 males participated in this study, including forty patients diagnosed with BPH and thirty healthy males. The anthropometric measurements and the biochemical parameters were measured in this study. We evaluated serum omentin-1 levels and the correlation with those data. We also test the gene expression of IL-8, IL-18 in BPH group using the TURP tissues. Results The serum omentin-1 levels were lower in the BPH patients than in the control group (27.95 ± 4.18 versus 32.03 ± 5.46, p p = 0.013) as well as the whole group (r = − 0.457, p Conclusion Omentin-1 may suppress the development of BPH and Lower serum omentin-1 levels in BPH patients might associated with higher prostate volume and higher IL-8 and IL-18 expression levels in their prostatic cells.

BACKGROUND: Apatinib is a small-molecule multitargeted tyrosine kinase inhibitor. Apatinib has demonstrated encouraging antitumor activities. This study aimed to observe the efficacy and safety of apatinib for the treatment of multiple brain micrometastases. CASE SUMMARY: We report two patients with multiple brain micrometastases after failure of second-line treatment. Both patients had extracerebral metastases. When the patients took 250 mg/d apatinib orally, the intracerebral lesions disappeared. The extracerebral lesions were partially alleviated. Both patients had a progression-free survival of more than 12 mo and were still stable. The safety was good. The main adverse events (AEs) were mild hypertension and proteinuria, which could be controlled. CONCLUSION: Apatinib has clear efficacy and good tolerance in patients with multiple brain micrometastases after failure of second-line treatment.

Objective To evaluate the feasibility and efficacy in selected T4a glottic cancer (thyroid cartilage invasion adherence to the anterior commissure) treated with frontolateral vertical partial laryngectomy (FLVPL) and laryngeal framework reconstruction using titanium mesh. Methods Six patients with the limited T4a glottic cancer with thyroid cartilage destruction adherence to the anterior commissure, underwent FLVPL from 2009 to 2016 in Sun Yat-Sen University Cancer Center. All patients were followed up postoperatively. Results All patients comprised radical tumor resection and favorable functional outcomes, and no aspiration and laryngeal stenosis were observed. According to postoperative pathology, four patients should go through postsurgical radiotherapy with a mean dose of 66 Gy. But one of them refused to undergo postoperative radiotherapy, who observed local recurrence in postcricoid area underwent total laryngectomy (TL) and ipsilateral selected neck dissection in post-surgery two year. During follow-up period, all patients were still alive, and five patients without local recurrence and distant metastases. Conclusion FLVPL and laryngeal framework reconstruction using titanium mesh is one viable surgical procedure to obtain adequate oncologic and functional outcomes.