Preparation of functional geopolymers from municipal solid waste incineration fly ash: An approach combining experimental and computational simulation studies.

This study aims to evaluate the feasibility and safety of using municipal solid waste incineration fly ash (MSW-IFA) in the development of geopolymer-based solidification/stabilization (S/S) treatments. Geopolymers have garnered attention as a sustainable alternative to traditional cement, owing to their high strength, stability, and minimal CO2 emissions. In this study, a combination of experimental and simulation calculations was used to investigate the setting time, mechanical properties, environmental risks, hydration mechanisms and processes of municipal solid waste incineration fly ash-based polymeric functional cementitious materials (GFCM). The results demonstrate that the mechanical properties of GFCM are related to the changes in the mineral phases and the degree of compactness. Quantum chemical calculations indicate that the hydration products may be [Si(OH)4], [Al(OH)3(OH2)] and [Al(OH)4]-. It is possible that the heavy metals are embedded in the hydrated silica-aluminate by electrostatic interaction or chemisorption. Heavy metals may be embedded in hydrated silica-aluminate by electrostatic action or chemisorption. This study provides a feasible method for resource utilization and heavy metal stabilization mechanism of MSW-IFA.

Genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus.

X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.

Workplace-based primary prevention intervention reduces incidence of hypertension: a post hoc analysis of cluster randomized controlled study.

BACKGROUND: A workplace-based primary prevention intervention be an effective approach to reducing the incidence of hypertension (HTN). However, few studies to date have addressed the effect among the Chinese working population. We assessed the effect of a workplace-based multicomponent prevention interventions program for cardiovascular disease on reducing the occurrence of HTN through encouraging employees to adopt a healthy lifestyle. METHODS: In this post hoc analysis of cluster randomized controlled study, 60 workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20). All employees in each workplace were asked to complete a baseline survey after randomization for obtaining sociodemographic information, health status, lifestyle, etc. Employees in the intervention group were given a 2-year workplace-based primary prevention intervention program for improving their cardiovascular health, including (1) cardiovascular health education, (2) a reasonable diet, (3) tobacco cessation, (4) physical environment promotion, (5) physical activity, (6) stress management, and (7) health screening. The primary outcome was the incidence of HTN, and the secondary outcomes were improvements of blood pressure (BP) levels and lifestyle factors from baseline to 24 months. A mix effect model was used to assess the intervention effect at the end of the intervention in the two groups. RESULTS: Overall, 24,396 participants (18,170 in the intervention group and 6,226 in the control group) were included (mean [standard deviation] age, 39.3 [9.1] years; 14,727 men [60.4%]). After 24 months of the intervention, the incidence of HTN was 8.0% in the intervention groups and 9.6% in the control groups [relative risk (RR) = 0.66, 95% CI, 0.58 ~ 0.76, P < 0.001]. The intervention effect was significant on systolic BP (SBP) level (ß = - 0.7 mm Hg, 95% CI, - 1.06 ~ - 0.35; P < 0.001) and on diastolic BP (DBP) level (ß = - 1.0 mm Hg, 95% CI, - 1.31 ~ - 0.76; P < 0.001). Moreover, greater improvements were reported in the rates of regular exercise [odd ratio (OR) = 1.39, 95% CI, 1.28 ~ 1.50; P < 0.001], excessive intake of fatty food (OR = 0.54, 95% CI, 0.50 ~ 0.59; P < 0.001), and restrictive use of salt (OR = 1.22, 95% CI, 1.09 ~ 1.36; P = 0.001) in intervention groups. People with a deteriorating lifestyle had higher rates of developing HTN than those with the same or improved lifestyle. Subgroup analysis showed that the intervention effect of BP on employees with educational attainment of high school above (SBP: ß = - 1.38/ - 0.76 mm Hg, P < 0.05; DBP: ß = - 2.26/ - 0.75 mm Hg, P < 0.001), manual labor workers and administrative worker (SBP: ß = - 1.04/ - 1.66 mm Hg, P < 0.05; DBP: ß = - 1.85/ - 0.40 mm Hg, P < 0.05), and employees from a workplace with an affiliated hospital (SBP: ß = - 2.63 mm Hg, P < 0.001; DBP: ß = - 1.93 mm Hg, P < 0.001) were significantly in the intervention group. CONCLUSIONS: This post hoc analysis found that workplace-based primary prevention interventions program for cardiovascular disease were effective in promoting healthy lifestyle and reducing the incidence of HTN among employees. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer.

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis.

Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 µM) + Niv (20 µM), Esc (75 µM) + Niv (5 µM), and Esc (75 µM) + Niv (20 µM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 µM) + Niv (20 µM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.

Treatment outcomes and prognosis of patients with primary and acquired BRAF-mutated non-small cell lung cancer: A multicenter retrospective study.

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.

The prognostic impact of mild and severe immune-related adverse events in non-small cell lung cancer treated with immune checkpoint inhibitors: a multicenter retrospective study.

Patients treated with immune checkpoint inhibitors (ICIs) often experience unique immune-related adverse events (irAEs), and the previous studies demonstrated an association between irAEs and better outcomes in patients with ICI treatment for advanced non-small cell lung cancer (NSCLC). However, the correlation between the occurrence of mild and severe irAEs and prognosis remains unclear. Additionally, little is known regarding the association between the timing of mild and severe irAEs and clinical outcomes. We retrospectively conducted a multicenter study of advanced NSCLC patients treated with ICI monotherapy. Of the 222 patients, 79 patients (35.6%) experienced at least one irAE, and most were of grade 1 or 2 (mild) (26.6%). The most common irAEs were pneumonitis (n = 21, 9.5%) and skin-related adverse reactions (n = 19, 8.6%). The median progression-free survival of all patients treated with ICIs was 3.2 months. Patients experiencing irAEs had a better prognosis than those without such events (6.5 vs. 2.6 months, p = 0.004), and mild irAEs were associated with the best prognosis. The difference in overall survival between mild and severe irAEs was significant (34.3 vs. 17.3 months, p = 0.021). We further analyzed differences between patients with irAEs occurring at 3 or 6 weeks, and found that the earlier the occurrence of mild irAEs, the better the prognosis; however, the opposite was true for severe irAEs. In summary, patients with early occurring mild irAEs showed better clinical outcomes, whereas those with early severe irAEs tended to show poorer clinical outcomes.

Efficacy and safety of maintenance immune checkpoint inhibitors with or without pemetrexed in advanced non-squamous non-small cell lung cancer: a retrospective study.

BACKGROUND: Advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients without driver gene mutations are usually treated with immune checkpoint inhibitors (ICIs) plus pemetrexed as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum. Some patients in the real world receive ICIs monotherapy as maintenance therapy. No clinical study has compared the efficacy and safety of ICIs with or without pemetrexed as maintenance therapy. METHODS: We performed a retrospective study analyzing clinical data of patients with NS-NSCLC who were diagnosed in Zhejiang Cancer Hospital from September 2018 to May 2021 and received maintenance therapy after 4-6 cycles of ICIs plus pemetrexed/platinum. Patients were divided into ICIs plus pemetrexed group and ICIs monotherapy group. Progression Free Survival 1 (PFS1) and PFS2, defined as the interval from the date of initial treatment and maintenance therapy to the date of systemic progression/death or the last follow-up, respectively. RESULTS: A total of 120 patients received ICIs with or without pemetrexed as maintenance therapy. Eighty-two patients received ICIs plus pemetrexed as maintenance therapy, and 38 patients received ICIs monotherapy. There were no statistically significant difference in median PFS1 between the ICIs monotherapy group and ICIs plus pemetrexed group (12.00 months vs. 12.07 months, P = 0.979). Among patients with PD-L1 TPS < 1%, the median PFS1 was worse with ICIs monotherapy (9.50 months vs. 14.20 months, P = 0.039). Among patients with PD-L1 TPS ≥50% or 1-49%, the median PFS1 in both groups was not statistically significant (P = 0.866, P = 0.589, respectively). Results for median PFS2 were similar to median PFS1, with statistically significantly different only in patients with PD-L1 TPS < 1% (P = 0.008). The 2-year survival rates of the two groups were similar (66.7% vs. 69.5%, P = 0.812). The incidence of fatigue was significantly higher in the ICIs plus pemetrexed group (P = 0.023). CONCLUSIONS: ICIs with or without pemetrexed can be used as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum in patients with advanced NS-NSCLC based on PD-L1 expression.

Metal-Organic Frameworks Functionalized Separators for Lithium-Sulfur Batteries.

Lithium sulfur batteries (LSBs) have attracted tremendous attention owing to their high theoretical specific capacity and specific energy. However, their practical applications are hindered by poor cyclic life, mainly caused by polysulfide shuttling. The development of advanced materials to mitigate the polysulfide shuttling effect is urgently demanded. Metal-organic frameworks (MOFs) have been exploited as multifunctional materials for the decoration of separators owing to their high surface area, structural diversity, tunable pore size, and easy tailor ability. In this review, we aim to present the state-of-the-art MOF-based separators for LSBs. Particular attention is paid to the rational design (pore aperture, metal node, functionality, and dimension) of MOFs with enhanced ability for anchoring polysulfides and facilitating Li+ transportation. Finally, the challenges and perspectives are provided regarding to the future design MOF-based separators for high-performance LSBs.

Efficacy and safety of anlotinib with and without EGFR-TKIs or immunotherapy in the treatment of elder patients with non-small-cell lung cancer: a retrospective study.

BACKGROUND: Anlotinib is a multitarget tyrosine kinase inhibitor for treating patients with advanced non-small cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of anlotinib in elder patients with advanced NSCLC. METHODS: Elder patients with advanced NSCLC who received anlotinib were enrolled. They were all age ≥ 65 years and with demonstrated records of EGFR gene status. All patients had received treatment with anlotinib or immune checkpoint inhibitors (ICIs)/EGFR-TKIs. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors (RECIST 1.1). Common Adverse Events Evaluation Criteria (CTCAE 4.03) were used to evaluate adverse drug reactions. RESULTS: A total of 91 patients were included in this study. We divided the patients into two groups (EGFR wild type: 60 patients; EGFR mutation: 31 patients). Among EGFR negative patients, the progression-free survival (PFS) for anlotinib monotherapy and anlotinib combination ICI therapy was 3.2 months and 5.0 months, respectively (P = 0.012). The difference in overall survival (OS) between monotherapy and combination therapy was also significant (9.5 vs. 18.4 months, respectively P = 0.010). Interestingly, we further analyzed differences between patients with hypertension and without hypertension, and found that hypertension was associated with better prognosis (5.7 vs. 1.4 months, P < 0.0001). In the EGFR mutation group, the PFS for anlotinib and EGFR-TKI combination treatment indicated better efficacy than that of anlotinib monotherapy (1.83 months vs. 7.03 months, respectively, P = 0.001). The median OS for monotherapy and combination therapy in the EGFR mutation group showed no statistical difference (28.34 months vs. 31.37 months, P = 0.223). The most common adverse reactions were hypertension, fatigue, and hand-foot syndrome, mainly of grade 1 or 2. No significant increase in adverse reactions was observed in patients ≥ 70 years of age. CONCLUSIONS: Anlotinib treatment and combination regimens resulted in good efficacy and controllable adverse reactions in elder patients with advanced NSCLC.

The prevalence and characteristics of metabolic syndrome according to different definitions in China: a nationwide cross-sectional study, 2012-2015.

BACKGROUND: Metabolic syndrome (MetS) is characterized by a cluster of signs of metabolic disturbance and has caused a huge burden on the health system. The study aims to explore the prevalence and characteristics of MetS defined by different criteria in the Chinese population. METHODS: Using the data of the China Hypertension Survey (CHS), a nationally representative cross-sectional study from October 2012 to December 2015, a total of 28,717 participants aged 35 years and above were included in the analysis. The MetS definitions of the International Diabetes Federation (IDF), the updated US National Cholesterol Education Program Adult Treatment Panel III (the revised ATP III), and the Joint Committee for Developing Chinese Guidelines (JCDCG) on Prevention and Treatment of Dyslipidemia in Adults were used. Multivariable logistic regression was used to identify factors associated with MetS. RESULTS: The prevalence of MetS diagnosed according to the definitions of IDF, the revised ATP III, and JCCDS was 26.4%, 32.3%, and 21.5%, respectively. The MetS prevalence in men was lower than in women by IDF definition (22.2% vs. 30.3%) and by the revised ATP III definition (29.2% vs. 35.4%), but the opposite was true by JCDCG (24.4%vs 18.5%) definition. The consistency between the three definitions for men and the revised ATP III definition and IDF definition for women was relatively good, with kappa values ranging from 0.77 to 0.89, but the consistency between the JCDCG definition and IDF definition (kappa = 0.58) and revised ATP III definition (kappa = 0.58) was poor. Multivariable logistic regression showed that although the impact and correlation intensity varied with gender and definition, area, age, education, smoking, alcohol use, and family history of cardiovascular disease were factors related to MetS. CONCLUSIONS: The prevalence and characteristics of the MetS vary with the definition used in the Chinese population. The three MetS definitions are more consistent in men but relatively poor in women. On the other hand, even if estimated according to the definition of the lowest prevalence, MetS is common in China.

Deletion of Meg8-DMR Enhances Migration and Invasion of MLTC-1 Depending on the CTCF Binding Sites.

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. The first maternal methylation DMR discovered in this domain was the Meg8-DMR, the targets and biological function of which are still unknown. Here, using an enhancer-blocking assay, we first dissected the functional parts of the Meg8-DMR and showed that its insulator activity is dependent on the CCCTC-binding factor (CTCF) in MLTC-1. Results from RNA-seq showed that the deletion of the Meg8-DMR and its compartment CTCF binding sites, but not GGCG repeats, lead to the downregulation of numerous genes on chromosome 12, in particular the drastically reduced expression of Dlk1 and Rtl1 in the Dlk1-Dio3 domain, while differentially expressed genes are enriched in the MAPK pathway. In vitro assays revealed that the deletion of the Meg8-DMR and CTCF binding sites enhances cell migration and invasion by decreasing Dlk1 and activating the Notch1-Rhoc-MAPK/ERK pathway. These findings enhance research into gene regulation in the Dlk1-Dio3 domain by indicating that the Meg8-DMR functions as a long-range regulatory element which is dependent on CTCF binding sites and affects multiple genes in this domain.

Curcumin-mediated Photodynamic Therapy Inhibits the Phenotypic Transformation, Migration, and Foaming of Oxidized Low-density Lipoprotein-treated Vascular Smooth Muscle Cells by Promoting Autophagy.

ABSTRACT: Vascular smooth muscle cells (VSMCs) are becoming a hot spot and target of atherosclerosis research. This study aimed to observe the specific effects of curcumin (CUR)-mediated photodynamic therapy (CUR-PDT) on oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and confirm whether these effects are mediated by autophagy. In this study, the mouse aortic smooth muscle cell line and A7r5 cell lines were used for parallel experiments. VSMC viability was evaluated by Cell Counting Kit-8 assay. VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro. The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting. The migration ability of the cells was detected by using transwell assay. The presence of intracellular lipid droplets was detected by Oil Red O staining. The results showed that VSMCs transformed from the contraction phenotype to the synthetic phenotype when stimulated by ox-LDL, during which autophagy was inhibited. However, CUR-PDT treatment significantly promoted the level of autophagy and inhibited the process of phenotypic transformation induced by ox-LDL. In addition, ox-LDL significantly promoted VSMC migration and increased the number of lipid droplets, whereas CUR-PDT treatment significantly reduced the ox-LDL-induced increase in the migration ability of, and lipid droplet numbers in, VSMCs. When the VSMCs were pretreated with the autophagy inhibitor 3-methyladenine for 24 hours, the effects of CUR-PDT were reversed. Therefore, our study indicated that CUR-PDT can inhibit the phenotypic transformation, migration, and foaming of ox-LDL-treated VSMCs by inducing autophagy.

NPRL2 promotes docetaxel chemoresistance in castration resistant prostate cancer cells by regulating autophagy through the mTOR pathway.

Docetaxel-based chemotherapy is recommended for metastatic castration-resistant prostate cancer (mCRPC). However, chemoresistance is inevitable and eventually progresses after several rounds of chemotherapy. Therefore, exploration of new therapeutic targets and molecular mechanisms that contribute to chemoresistance remains necessary. Our previous study accidentally demonstrated that expression of nitrogen permease regulator-like 2 (NPRL2), which is defined as a tumor suppressor, is upregulated in prostate cancer (PCa) and linked to poor prognosis, particularly in CRPC. The aim of this study was to investigate the role of NPRL2 in the chemoresistant CRPC cells. We found that NPRL2 was significantly overexpressed in docetaxel-resistant CRPC cells, while autophagy was enhanced and mTOR signaling was inhibited. Inhibiting NPRL2 increased the sensitivity to docetaxel in docetaxel-resistant CRPC cells, enhanced apoptosis and inhibited autophagy, and the opposite trends were observed when the mTOR inhibitor torin 1 was added to NPRL2-silenced cells. We further found that NPRL2 silenced docetaxel-resistant CRPC cells were sensitive to docetaxel in vivo. Briefly, our research reveals that overexpression of NPRL2 promotes chemoresistance by regulating autophagy via mTOR signaling and inhibits apoptosis in CRPC cells.

PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS.

AIM: PCOS often showed abnormal follicular development. Previous studies have found that the increased apoptosis of granulosa cells (GCs) is one of the key factors leading to follicular dysplasia. It has been found that the decrease or deletion of PATL2 function can significantly inhibit the development and maturation of human oocytes. We found that PATL2 was also expressed in human ovarian GCs, suggesting that PATL2 may be involved in the regulation of related biological events in GCs. This study aims to explore the function of PATL2 on regulation of GCs apoptosis, and the potential role of PATL2 in the development of PCOS-related abnormal follicles. MATERIALS AND METHODS: The follicular GCs of PCOS patients and normal ovulating female patients were collected. Moreover, human granular cell line (KGN) was used for in vitro experiments. RESULTS: (1) The maturation rate and fertilization rate of oocytes in the PCOS group were significantly lower than those in the normal control group (p＜0.05). (2) Flow cytometry and TUNEL staining showed that the apoptosis level of GCs in the PCOS group was significantly increased. (3) Immunofluorescence and Western Blot showed that the PATL2 expression level of GCs in the PCOS group was significantly reduced. (4) Knocking down the expression of PATL2 by siRNA significantly prevented the apoptosis of GCs. CONCLUSIONS: Reduced PATL2 could resulted in the increased apoptosis level of ovarian GCs, which might be closely related to the occurrence and development of abnormal follicles in PCOS.

Clinical features of children with coronavirus disease 2019 caused by Delta variant infection. / 11例Deltaå˜å¼‚æ ªæ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥ç— ä¾‹çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the epidemiological and clinical features of children with coronavirus disease 2019 (COVID-19) caused by Delta variant infection and their differences from children with ordinary COVID-19 (non-Delta variant infection). METHODS: Eleven children aged <14 years, who were diagnosed with COVID-19 caused by Delta variant infection from August to September 2021 were enrolled (variant group). Five children aged <14 years who were diagnosed with ordinary COVID-19 from February to March 2020 served as the control group. The epidemiological data, clinical features, and laboratory examination results were compared between the two groups. RESULTS: There was no significant difference in the proportion of children with clinical symptoms between the two groups (P>0.05). There were no significant differences in white blood cell count, lymphocyte count, and platelet count between the two groups (P>0.05), while the variant group had a lower neutrophil count than the control group (P<0.05). Lymphocytopenia was not observed in either group. Compared with the control group, the variant group had a higher proportion of children with an increase in creatine kinase isoenzyme (P<0.05), while there were no significant differences in the proportion of children with an increase in lactate dehydrogenase, D-Dimer, C-reactive protein or interleukin-6 between the two groups (P>0.05). Among the 9 children in the variant group, 5 tested positive for IgM antibody at week 2 after admission, and all children tested positive for IgG antibody. At week 3 after admission, the level of IgM antibody tended to decrease in 9 children, and the level of IgG antibody tended to decrease in 8 children. CONCLUSIONS: Delta variant is more infectious. COVID-19 caused by Delta variant infection may cause more serious myocardial damage than ordinary COVID-19 in children. In children infected with Delta variant, IgG antibody appears at almost the same time as IgM antibody.

Rab27A promotes cellular apoptosis and ROS production by regulating the miRNA-124-3p/STAT3/RelA signalling pathway in ulcerative colitis.

Ulcerative colitis (UC) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of UC pathogenesis is associated with excessive cellular apoptosis and reactive oxygen species (ROS) production. However, their function and molecular mechanisms related to UC remain unknown. In this study, Rab27A mRNA and protein were proven to be overexpressed in intestinal epithelial cells of UC patients and DSS-induced colitis mice, compared with control (P < 0.05). And Rab27A silencing inhibits inflammatory process in DSS-induced colitis mice (P < 0.05). Then, it was shown that knockdown of Rab27A suppressed apoptosis and ROS production through modulation of miR-124-3p, whereas overexpression of Rab27A promoted apoptosis and ROS production in LPS-induced colonic cells. In addition, enhanced expression of miR-124-3p attenuated apoptosis and ROS production by targeting regulation of STAT3 in LPS-induced colonic cells. Mechanistically, we found Rab27A reduced the expression and activity of miR-124-3p to activate STAT3/RelA signalling pathway and promote apoptosis and ROS production in LPS-induced colonic cells, whereas overexpression of miR-124-3p abrogated these effects of Rab27A. More importantly, animal experiments illustrated that ectopic expression of Rab27A promoted the inflammatory process, whereas overexpression of miR-124-3p might interfere with the inflammatory effect in DSS-induced colitis mice. In summary, Rab27A might modulate the miR-124-3p/STAT3/RelA axis to promote apoptosis and ROS production in inflammatory colonic cells, suggesting that Rab27A as a novel therapeutic target for the prevention and treatment of UC patients.

Status of Hypertension in China: Results From the China Hypertension Survey, 2012-2015.

BACKGROUND: Although the prevalence of hypertension (HTN) continues to increase in developing countries, including China, recent data are lacking. A nationwide survey was conducted from October 2012 to December 2015 to assess the prevalence of HTN in China. METHODS: A stratified multistage random sampling method was used to obtain a nationally representative sample of 451 755 residents ≥18 years of age from 31 provinces in mainland China from October 2012 to December 2015. Blood pressure (BP) was measured after resting for 5 minutes by trained staff using a validated oscillometric BP monitor. HTN was defined as systolic BP (SBP) ≥140 mm Hg/or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medication within 2 weeks. Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg without antihypertensive medication. HTN control was defined as SBP <140 mm Hg and DBP<90 mm Hg. In addition, the prevalence of HTN (SBP ≥130 or DBP ≥80 mm Hg) and control rate (SBP <130 and DBP <80 mm Hg) of HTN were also estimated according to the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline. RESULTS: Overall, 23.2% (≈244.5 million) of the Chinese adult population ≥18 years of age had HTN, and another 41.3% (≈435.3 million) had pre-HTN according to the Chinese guideline. There were no significant differences of HTN prevalence between urban and rural residents (23.4% versus 23.1%, P=0.819). Among individuals with HTN, 46.9% were aware of their condition, 40.7% were taking prescribed antihypertensive medications, and 15.3% had controlled HTN. Calcium channel blockers were the most commonly used antihypertensive medication (46.5%) as monotherapy, and 31.7% of treated hypertensive patients used ≥2 medications. The prevalence of HTN based on the 2017 American College of Cardiology/American Heart Association guideline was twice as high as that based on 2010 Chinese guideline (46.4%), whereas the control rate fell to 3.0%. CONCLUSIONS: In China, there is a high prevalence of HTN and pre-HTN, and awareness, treatment, and control of HTN were low. Management of medical therapy for HTN needs to improve.

Impaired Tip60-mediated Foxp3 acetylation attenuates regulatory T cell development in rheumatoid arthritis.

In rheumatoid arthritis (RA), imbalanced T cells subsets play a critical role in sustaining chronic inflammatory responses in the synovium. Naïve T cells in RA patients undergo maldifferentiation, including an increase in the effector Th1/Th17 lineage and a reduction in regulatory T (Treg) cells. Upon stimulation, naïve CD4+CD45RO- T cells from RA patients exhibited insufficient expression of Foxp3, which induced a deficiency in Tregs production and an imbalance of Treg/Th17 differentiation. Further mechanistic study indicated that RA T cells failed to produce sufficient levels of the histone acetyltransferase Tip60, leading to reduced acetylation of Foxp3; this, in turn, decreased Foxp3 expression, impaired Treg commitment, and promoted Th17 production. Moreover, in human synovium chimeric mice, suppression of Tip60 activity in healthy T cells promoted tissue infiltration and arthritogenesis, while reconstitution of Tip60 in RA T cells suppressed synovitis and effector T cell infiltration. Our findings link T cell maldifferentiation and tissue infiltration with Tip60-mediated Foxp3 acetylation and identify Tip60 as a potential therapeutic target for suppression of tissue inflammation and autoimmunogenesis in RA.

Increased epoxyeicosatrienoic acids may be part of a protective mechanism in human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide hydrolase expression.

BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues (1.91 ±â€¯0.98 ng/mg vs. 0.96 ±â€¯0.77 ng/mg, mean ±â€¯SD, P < 0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (P < 0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (P > 0.05). CONCLUSION: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.