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OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS: Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.

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ETHNOPHARMACOLOGICAL RELEVANCE: Dehydrocorydaline (DHC), an active component of Corydalis yanhusuo (Y.H. Chou & Chun C. Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu (Papaveraceae), exhibits protective and pain-relieving effects on coronary heart disease, but the underlying mechanism still remains unknown. AIM OF THE STUDY: Network pharmacology and experimental validation both in vivo and in vitro were applied to assess whether DHC can treat myocardial ischemia-reperfusion injury (MIRI) by regulating the forkhead box O (FoxO) signalling pathway to inhibit apoptosis. MATERIALS AND METHODS: DHC and MIRI targets were retrieved from various databases. Molecular docking and microscale thermophoresis (MST) determined potential binding affinity. An in vivo mouse model of MIRI was established by ligating the left anterior descending coronary artery. C57BL/6N mice were divided into sham, MIRI, and DHC (intraperitoneal injection of 5 mg/kg DHC) groups. Haematoxylin and eosin, Masson, and immunohistochemical stainings verified DHC treatment effects and the involved signalling pathways. In vitro, H9c2 cells were incubated with DHC and underwent hypoxia/reoxygenation. TUNEL, JC-1, and reactive oxygen species stainings and western blots were used to explore the protective effects of DHC and the underlying mechanisms. RESULTS: Venny analysis identified 120 common targets from 121 DHC and 23,354 MIRI targets. DHC exhibited high affinity for CCND1, CDK2, and MDM2 (<-7 kcal/mol). In vivo, DHC attenuated decreases in left ventricular ejection fraction and fractional shortening, reduced infarct sizes, and decreased cTnI and lactate dehydrogenase levels. In vitro, DHC alleviated apoptosis and oxidative stress in the hypoxia/reoxygenation model by attenuating ΔΨm disruption; reducing the production of reactive oxygen species; upregulating Bax and CCND1 via the FoxO signalling pathway, as well as cleaved-caspase 8; downregulating the apoptosis-associated proteins Bcl-2, Bid, cleaved-caspase 3, and cleaved-caspase 9; and promoting the phosphorylation of FOXO1A and MDM2. CONCLUSION: By upregulating the FoxO signaling pathway to inhibit apoptosis, DHC exerts a cardioprotective effect, which could serve as a potential therapeutic option for MIRI.

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Natural biomaterials have been showing extensive potential in wound healing; attempts therefore focus on productions achieving both antimicrobial and tissue regenerative abilities. Here, we construct a decellularized human colon tumor (DHCT)-derived scaffold for wound remolding via microfluidic bioprinting. The DHCT retains a series of growth factors, fibrin, and the collagen configuration, that favor tissue repair and reconstruction. Specifically, the scaffold shows superior abilities in cell migration and angiogenesis. The biocompatible scaffold is also imparted with tissue adhesion ability and photothermal effect due to the coating of biologically derived polydopamine on the surface. The strong photothermal effect under near-infrared irradiation also present the scaffold with an antibacterial rate exceeding 90%. Furthermore, in vivo experiments convinced that the polydopamine-integrated DHCT scaffold can markedly expedite the healing process of acute extensive wounds. These findings indicate that composite materials derived from natural tumors have substantial potential in pertinent clinical applications.

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BACKGROUND: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. METHODS: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. RESULTS: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines' use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62-2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18-3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100-25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80-2105.83]) by network meta-analysis. CONCLUSIONS: Our findings show a significant association between anthracyclines' use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.

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Chemotherapy alone or in combination with allogeneic stem cell transplantation has been the standard of care for acute myeloid leukemia (AML) for decades. Leukemia relapse with limited treatment options remains the main cause of treatment failure. Therefore, an effective and safe approach to improve treatment outcomes is urgently needed for most AML patients. Mesenchymal stem cells (MSCs) have been reported to efficiently induce apoptosis and shape the fate of acute myeloid leukemia cells. Here, we identified LG190155 as a potent compound that enhances the antileukemia efficiency of MSCs. Pretreatment of MSCs with LG190155 significantly provoked differentiation in both AML patient-derived primary leukemia cells and AML cell lines and reduced the tumor burden in the AML mouse model. Using the quantitative proteomic technique, we discovered a pivotal mechanism that mediates AML cell differentiation, in which autocrine bone morphogenetic protein 6 (BMP6) in MSCs boosted IL-6 secretion and further acted on leukemic cells to trigger differentiation. Furthermore, the activity of the BMP6-IL6 axis was dramatically enhanced by activating vitamin D receptor (VDR) in MSCs. Our data illustrated an effective preactivated approach to reinforcing the antileukemia effect of MSCs, which could serve as an effective therapeutic strategy for AML.

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The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

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ReNiO3 (Re = Pr, Sm, Eu) solid electrolytes were prepared by the sol-gel method, which were sintered in a pure oxygen atmosphere of 20 MPa at 1000 °C for 24 hours. The DC resistivities of the three materials in air and in a hydrogen-containing atmosphere were tested respectively. The resistivities in the hydrogen-containing atmosphere were about 102, 104, and 105 times higher than those in air and XPS analysis showed that after 10%H2-Ar treatment, the proportion of Ni2+ of PrNiO3, SmNiO3 and EuNiO3 increased successively. The proton transport number of PrNiO3 was lower than 0.5 at 50-500 °C, and SmNiO3 and EuNiO3 were almost pure proton conductors below 200 °C. The conductivities of SmNiO3 and EuNiO3 were 1.08 × 10-4 S cm-1 and 1.83 × 10-5 S cm-1 at 200 °C in 5%H2-Ar. The hydrogen sensing properties of SmNiO3 and EuNiO3 show that the measurement results of the two materials were accurate in the range of 0.5-10% H2.

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Myocardial ischemia-reperfusion (MI/R) injury is a complication in vascular reperfusion therapy for MI, occurring in approximately 60% of patients. Ferroptosis is an important process in the development of MI/R cardiac lesions. Transferrin receptor 1 (TfR1), a marker of ferroptosis, corresponds to the changes in MI/R cardiac lesions and is expected to be a biomarker for detecting MI/R-induced ferroptosis. However, the noninvasive in vivo visualization of ferroptosis in MI/R is a big challenge. Thus, this study aimed to develop a novel multimodal imaging platform to identify markers of MI/R cardiac lesions in vivo through targeting TfR1. Methods: Magnetic particle imaging (MPI) modality for ferroptosis based on superparamagnetic cubic-iron oxide nanoparticles (SCIO NPs), named feMPI, has been developed. FeMPI used TfR1 as a typical biomarker. The feMPI probe (SCIO-ICG-CRT-CPPs NPs, CCI NPs) consists of SCIO NPs, TfR1-targeting peptides (CRT), cell-penetrating peptides (CPPs), and indocyanine green (ICG). The specificity and sensitivity of CCI NPs in the MI/R mouse model were evaluated by MPI, magnetic resonance imaging (MRI), and near-infrared (NIR) fluorescent imaging. Results: The intensity of the MPI signal correlates linearly with the percentage of infarct area in MI/R stained by TTC, enabling a quantitative assessment of the extent of cardiac lesions. Notably, these findings are consistent with the standard clinical biochemical indicators in MI/R within the first 24 h. FeMPI detects cardiac injury approximately 48 h prior to the current clinical imaging detection methods of MI/R. Conclusion: The feMPI strategy can be a powerful tool for studying the process of MI/R-induced ferroptosis in vivo, providing clues for molecular imaging and drug development of ferroptosis-related treatments.

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BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

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Background: It remains controversial regarding the association between weight change and cardiovascular disease risk in older adults (aged ≥60 years). This study aimed to evaluate the association between weight change and the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risks in older adults. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Older adults aged 60-79 years who were free of self-reported ASCVD at the time of the NHANES interview were included. Data were collected from January 1999 to December 2018 and analyzed in March 2022. We focused on the associations between weight change and the 10-year ASCVD risks with the percentage change in weight during short-term (1 year) and long-term (10 years), which categorized as moderate to high weight loss (≥10%), small weight loss (5.1-9.9%), stable weight (±5%), small weight gain (5.1-9.9%), and moderate to high weight gain (≥10%). Results: The number of participants was 1,867 (mean age 67.49 years; 42.10% female) for the long-term interval (10 years) in our analysis, and 1894 for the short-term interval (1 years). We only observed an inverse association between long-term weight loss and the 10-year ASCVD risk in fully adjusted model (loss ≥ 10%: ß = 2.52, 95%CI = 0.98, 4.05; loss 5.1% ~ 9.9%: ß = 2.99, 95% CI = 1.30, 4.68), but all intervals of weight gain ≥5% were not significant associated with higher risk than stable weight. However, in the subgroup analyses, the association between long-term weight loss and the 10-year ASCVD risk was not significant in old-old (aged 75-79), obesity (BMI ≥ 35 kg/m2), intentional weight loss, moderate physical activity and diabetics. Conclusion: Older adults (aged 60-79 years) with weight loss >5% over the past 10 years have excess predicted 10-year ASCVD risk. Our study supports the benefits of stable weight in promoting cardiovascular health in older adults.

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The semiconductor manufacturing industry relies heavily on wafer surface defect detection for yield enhancement. Machine learning and digital image processing technologies have been used in the development of various detection algorithms. However, most wafer surface inspection algorithms are not be applied in industrial environments due to the difficulty in obtaining training samples, high computational requirements, and poor generalization. In order to overcome these difficulties, this paper introduces a full-flow inspection method based on machine vision to detect wafer surface defects. Starting with the die image segmentation stage, where a die segmentation algorithm based on candidate frame fitting and coordinate interpolation is proposed for die sample missing matching segmentation. The method can segment all the dies in the wafer, avoiding the problem of missing dies splitting. After that, in the defect detection stage, we propose a die defect anomaly detection method based on defect feature clustering by region, which can reduce the impact of noise in other regions when extracting defect features in a single region. The experiments show that the proposed inspection method can precisely position and segment die images, and find defective dies with an accuracy of more than 97%. The defect detection method proposed in this paper can be applied to inspect wafer manufacturing.

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Background: Depression is an independent factor to predict the hospitalization and mortality in the chronic HF patients. Citalopram is known as an effective drug for depression treatment. Currently, there is no specific recommendation in the HF guidelines for the treatment of psychological comorbidity. In recent years, many studies have shown that the citalopram may be safe in treating of chronic HF with depression. Objective: To evaluate the efficacy and safety of the citalopram in the treatment of elderly chronic HF combined with depression. Methods: PubMed, EMBASE, Cochrane, Web of Science, CNKI, VIP, CBM, and Wanfang were searched from their inception to May 2022. In the treatment of elderly chronic HF combined with depression, randomized controlled studies of the citalopram were included. Independent screening and extraction of data information were conducted by two researchers, and the quality was assessed by the Cochrane bias risk assessment tool. Review manager 5.4.1 was employed for statistical analysis. Results: The results of meta-analysis prove that the citalopram treatment for depressed patients with chronic HF has a benefit for HAMD-24 (MD: -8.51, 95% CI: -10.15 to -6.88) and LVEF (MD: 2.42, 95% CI: 0.51 to 4.33). Moreover, the score of GDS decreases, and NT-proBNP (MD: -537.78, 95% CI: -718.03 to -357.54) is improved. However, the comparison with the control group indicates that there is no good effect on HAMD-17 (MD: -5.14, 95% CI: -11.60 to 1.32), MADRS (MD: -1.57, 95% CI: -3.47 to 0.32) and LVEDD (MD: -1.45, 95% CI: -3.65 to -0.76). No obvious adverse drug reactions were observed. Conclusion: Citalopram treatment for depressed patients with chronic HF has a positive effect on LVEF and NT-proBNP. It can alleviate HAMD-24 and GDS, but the relative benefits for LVEDD, HAMD-17 and MADRS still need to be verified.Systematic Review Registration: PROSPERO [CRD42021289917].

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The ferrite process has been developed to purify wastewater containing heavy metal ions and recycle valuable metals by forming chromium ferrite. However, organic matter has an important influence on the crystallization behavior and stability of chromite synthesized from chromium-containing wastewater. We focused on the influence and effect mechanism of two typical organic acid salts (citrate (CA) and tartrate (TA)) on the process of chromium mineralization. It was found that the presence of organic matter leads to the increase of the residual content of Cr in CA system (0.50 mmol/L) and TA system (0.61 mmol/L) in the solution, and the removal of chromium was mainly due to the surface adsorption of Fe(III) hydrolysate. The decreased crystallinity of mineralized products is ascribed to the completion of organic compounds with Fe(II) and Fe(III), which hinders the formation of ferrite precursors. There was bidentate and monodentate chelation between -COO- and metal ions in the CA system and TA system respectively, which resulted in a stronger affinity between CA and iron. This study provides the underlying mechanism for Cr(III) solid oxidation by the ferrite method in an organic matter environment and is of great significance to prevent and control chromium pollution in the environment.

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Aim: This study was designed to systematically evaluate the effects of growth factor (GF) for therapeutic angiogenesis on ischemic heart disease (IHD) by pooling the results of randomized controlled trials (RCTs). Methods and Results: PubMed, EMBASE, and CENTRAL databases were searched from inception to October 2022. RCTs, investigating the effects of GF therapy on IHD, were included. The risk bias of included study was assessed according to Cochrane tool. Weighted mean difference (WMD), calculated with fixed effect model or random effect model, was used to evaluate the effects of GF therapy on left ventricular ejection fraction (LVEF) and Canadian Cardiovascular Society (CCS) angina class. Relative risk (RR) was used to evaluate the effects of GF therapy on all-cause mortality, major adverse cardiovascular events (MACE) and revascularization. Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 15.1 software. Twenty-nine studies involving 2899 IHD patients (1,577 patients in GF group and 1,322 patients in control group) were included. Compared with the control group, GF therapy did not reduce all-cause mortality (RR: 0.82; 95% CI: 0.54-1.24; p = 0.341), MACE [(RR: 0.83; 95% CI: 0.61-1.12; p = 0.227), revascularization (RR: 1.27, 95% CI: 0.82-1.96, p = 0.290) and CCS angina class (WMD: -0.08, 95% CI: -0.36 to 0.20, p = 0.560). However, GF therapy could increase LVEF during short-term follow-up (<1 year). Conclusion: GF for therapeutic angiogenesis was beneficial for increasing LVEF during short-term follow-up (<1 year), however, the therapy was not efficacious in decreasing all-cause mortality, MACE and revascularization.

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BACKGROUND: The prevention and control of hypertension should be an effective way to reduce deaths and it has been a high priority in China. In 2013, the Chinese government increased the subsidy standard for the National Essential Public Health Services Package (NEPHSP) from RMB 15 to RMB 30 per person, which was expected to cover 70 million hypertensions. This study explored the influence of increasing NEPHSP subsidy on outpatient and inpatient expenditure among patients with hypertension. METHODS: Data were mined from the 2011-2015 Harmonized China Health and Retirement Longitudinal Study. The study sample included 3192 hypertensive patients who were not lost to follow-up from 2011 to 2015. Hypertensive patients who covered by NEPHSP from 2011 to 2015 were defined as the treatment group, otherwise defined as the comparison group. The policy intervention was the increase of NEPHSP subsidy in 2013, and the years before and after 2013 were respectively considered as pre- (2011) and post-intervention (2015). The primary outcomes variables were the outpatient and inpatient expenditure of patients with hypertension, based on direct spending of outpatients and inpatients separately reported by patients with hypertension. Using propensity score matching (PSM) to match the individual characteristics of hypertension in the treatment group and the comparison group, difference-in-differences (DID) were used to analyze the outcomes. RESULTS: The patients with hypertension' outpatient and inpatient expenditure patterns in the treatment and control group show an increasing trend from 2011 to 2015. After PSM, of the 1 956 hypertensive participants, 369 covered by the NEPHSP before and after 2013. A DID estimate of the increased NEPHSP subsidy was associated with a significant decrease of 1 251.35 RMB (t = 2.13, P = 0.034) in hypertension related inpatient expenditure, no significant change (t = 0.61, P = 0.544) among outpatient expenditure. CONCLUSIONS: The NEPHSP may reduce inpatient expenditure among hypertension. Further strengthening of the NEPHSP may reduce their burden.

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OBJECTIVE: Diabetes mellitus is a common condition often associated with an ageing population. However, only few longitudinal studies in China have investigated the incidence of diabetes and identified its risk factors. Therefore, this study aimed to investigate the incidence and risk factors of diabetes in Chinese people aged ≥45 years using the harmonised China Health and Retirement Longitudinal Study (CHARLS) data. DESIGN: A dynamic cohort study. SETTING: The harmonised CHARLS 2011-2018. PARTICIPANTS: 19 988 adults aged ≥45 years. PRIMARY OUTCOME MEASURE: Incident diabetes from 2011 to 2018. RESULTS: The harmonised CHARLS is a representative longitudinal survey of people aged ≥45 years. Using data extracted from the harmonised CHARLS, we calculated the incidence of diabetes and used a competing risk model to determine risk factors of diabetes. In 2011-2013, 2013-2015, 2015-2018, the crude incidence of diabetes among middle-aged and older people in China was 1403.21 (1227.09 to 1604.19), 1673.22 (1485.73 to 1883.92) and 3919.83 (3646.01 to 4213.30) per 100 000 person-years, respectively, with a significant increasing trend. There were no geographical variations in the incidence of diabetes. Age, obesity and alcohol consumption were associated with an increased risk of incident diabetes. CONCLUSION: The incidence of diabetes increased annually, without any geographical differences. Age, obesity and alcohol consumption were found to be risk factors for incident diabetes.

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Microtubule-interacting and trafficking domain containing 1 (MITD1) is associated with abscission during cytokinesis. However, systematic investigation into its role in cancer is lacking. Therefore, we explored the pan-cancer role of MITD1 using multiple databases. Expression and clinical survival, immunological, and enrichment analyses were performed using R packages and online tools. For breast cancer, single-cell level analysis, immunochemistry, and in vitro experiments were performed to explore the mechanism of MITD1. A nomogram was established to predict the prognosis of patients with breast cancer and evaluate the immunotherapy biomarker based on two datasets. In some cancers, high MITD1 expression was associated with a more favorable prognosis. For instance, it inhibited tumor cell proliferation and migration in breast cancer. MITD1 may regulate cancer development by altering the tumor microenvironment, and MITD1 expression may predict the response to immune checkpoint blockade, platinum, and poly ADP-ribose polymerase inhibitor therapies. Our nomogram was used to determine the prognosis of patients with breast cancer. MITD1 can also predict the response to immunotherapy. Our first pan-cancer study of MITD1 has shown that it plays different roles in cancer development and therapy. In breast cancer, MITD1 inhibited cell proliferation and migration and serves as a new biomarker.

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INTRODUCTION: Hypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension. METHODS AND ANALYSIS: This trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences. DISCUSSION: We hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019.

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BACKGROUND: Hypertension is a prevalent and costly health condition in China. Little is known about variation of the inpatient and outpatient expenditures attributable to hypertension between prefecture-level administrative regions (PARs) and the drivers of such variation among China's middle-aged and elderly population. METHODS: We obtain data from China Health and Retirement Longitudinal Survey between 2011 and 2015, panel tobit models were used in our study to estimate differences across 122 PARs. Expenditure variation was explained by the characteristics of individuals and regions, including measures of healthcare supply. RESULTS: The cost of treatment for patients with hypertension varies greatly geographically, with the highest outpatient and inpatient costs being 77 and 102 times the lowest, respectively. After adjustment for the individual and PAR character, there are associations between expenditure and region bed density. CONCLUSION: There were significant regional differences in the outpatient and inpatient costs of middle-aged and elderly patients with hypertension in China, the difference between individuals may be an important reason, which has little to do with regional economic development differences, but is related to regional bed density.

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Enterovirus A (EV-A) species are the main agents responsible for hand, foot, and mouth disease (HFMD), a serious public health concern. Lack of appropriate reagents prevents the mechanistic study of these virus infections. 2C protein, a non-structural protein of Enterovirus, is crucial for viral replication and antiviral immunity. Here, preparation and testing of a monoclonal antibody by immunizing mice with Coxsackievirus A10 protein 2C (CVA10-2C) was reported. This antibody could identify most EV-A types, both conventional and unconventional groups. We also mapped the antibody epitope SLATGIIARA, which is highly conserved in EV-A species and located in the ATPase domain. Some key amino acids include G140, I141, I142, and R144. In conclusion, we generated a recombinant monoclonal antibody against multiple EVA types and confirmed its performance, which may facilitate the future study of Enterovirus A infection and many potential applications, such as the diagnosis of pathogen or the development of antiviral therapies.

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