Percutaneous Ventricular Restoration Prevents Left Ventricular Remodeling Post Myocardial Infarction: One-Year Evaluation of the Heartech First-in-man Study.

BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, P = .001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, P = .002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, P = .003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, P = .01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).

Preparation of a zeolite imidazole skeleton-silica hybrid monolithic column for amino acid analysis via capillary electrochromatography.

We developed a novel, convenient and low-cost one-pot strategy for preparing a zeolitic imidazolate framework-8 (ZIF-8)-silica hybrid monolithic column by adding ZIF-8 directly to a polymer solution of the silica matrix. The simulated stationary phase and monolithic column prepared under optimal conditions were characterized using X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis nitrogen physisorption and zeta potential. The results obtained confirmed the successful introduction of ZIF-8 into the silica monolithic column, and the prepared monolithic column exhibited good permeability and physicochemical stability. A capillary electrochromatography method was developed based on a ZIF-8-silica hybrid monolithic column through which 15 mixed amino acids, 4 neutral compounds, 4 nipagin esters and 2 chlorinated fungicides were separated in 14, 5, 7 and 6 min, respectively, under optimal conditions. The relative standard deviations retention times and column efficiencies in run-to-run, day-to-day and column-to-column varied in the ranges of 1.90%-2.21%, 2.13%-2.51% and 3.08%-6.65%, respectively, which demonstrated that ZIF-8-silica hybrid monolithic column exhibited satisfactory reproducibility and stability. The incorporation of ZIF-8 into a silica monolithic column is a promising method for preparing novel monolithic columns composed of a metal-organic framework.

One-pot synthesis of a novel chiral Zr-based metal-organic framework for capillary electrochromatographic enantioseparation.

A novel chiral stationary phase (CSP) of Zr-based metal-organic framework, l-Cys-PCN-224, was prepared by one-pot method and applied for the enantioseparation by capillary electrochromatography. The CSP was characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, Fourier-transform infrared spectra, nitrogen adsorption/desorption, circular dichroism spectrum, zeta-potential, and so on. The results revealed that the CSP had good crystallinity, high specific surface area (2580 m2 /g), and good thermal stability. Meanwhile, the cross-section of l-Cys-PCN-224-bonded open-tubular (OT) column was observed by a scanning electron microscope, which proved the successful bonding of l-Cys-PCN-224 particles to the inner wall. Relative standard deviations of the column efficiencies were 3.87%-9.14%, and not obviously changed after 200 runs, which indicated that l-Cys-PCN-224-bonded OT column had the better stability and reproducibility. Excellent chiral separation performance was verified with nine kinds of natural amino acids including acidic, neutral, and basic as the analytes. All amino acids studied achieved good separation with the resolution of 1.38-13.9 and selector factor of 1.11-3.71. These results demonstrated that the CSP had an excellent potential in the chiral separation field.

ß-Cyclodextrin-modified covalent organic framework as chiral stationary phase for the separation of amino acids and ß-blockers by capillary electrochromatography.

Covalent organic frameworks (COFs) as a novel stationary phase have attracted much attention in the field of chromatography owing to their permanent nanoscale porosity, higher surface area, and exceptional stabilities. Here, a novel isocyanate-ß-cyclodextrin-modified COF (MDI-ß-CD-modified COF) was synthesized using isocyanate-ß-cyclodextrin as the chiral selector and imine-based TpPa-1 COF as the matrix by a bottom-up strategy. The reaction condition and the structure of MDI-ß-CD-modified COF were optimized and characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectra, nitrogen adsorption/desorption (Brunauer-Emmett-Teller [BET]), and thermogravimetric analysis (TGA). And then the coated open-tubular column (OT column) was prepared using MDI-ß-CD-modified COF as chiral stationary phase (CSP) by in situ growth approach, which exhibited excellent stability and repeatability. For seven consecutive runs, the intraday and interday relative standard deviations (RSDs) were in range from 0.35% to 2.21% for the migration time of histidine. The column-to-column reproducibility ranged from 2.39% to 3.08%. Meanwhile, the separation of eight compounds including four amino acids and four ß-blockers by capillary electrochromatography sufficiently verified the favorable chiral resolution properties of the MDI-ß-CD-modified COF-coated OT column. This strategy of fabricating MDI-ß-CD-modified COF-coated OT column expanded the application of imine-based COFs in chromatographic analytical fields.

First-in-man study of Heartech® percutaneous left ventricular partitioning device for treatment of heart failure postmyocardial infarction.

OBJECTIVE: This first-in-man (FIM) study aimed to determine the safety and efficacy of the Heartech® left ventricular partitioning device (LVPD) in patients with chronic heart failure (HF) postmyocardial infarction. METHODS: Sixteen patients were enrolled from three cardiac intervention centers in China. All patients underwent percutaneous ventricular restoration (PVR) procedures with implantation of the Heartech® LVPD. Safety and immediate success rates were recorded. Major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause mortality, myocardial infarction, stroke, emergent or selective surgery or interventional therapy, renal failure requiring hemodialysis, and major bleeding were recorded. Efficacy features included functional status, echocardiographic characteristics, life quality characteristics including peak oxygen consumption of cardiopulmonary exercise testing (CPET), European five-dimensional health scale (EQ-5D), 6-min walk test (6MWT) at baseline and during follow-up (NCT02938637). RESULTS: The device success rate was 93.75% (15 successes in 16 patients) with 100% safety. During follow-up of 36 ± 4.5 days, no MACCEs were found. The left ventricular end-systolic volume index decreased significantly (LVESVi, 72.47 ± 22.77 mL/m2 vs. 50.13 ± 13.36 mL/m2 , p < .001) as did left ventricular end diastolic volume index (LVEDVi, 106.27 ± 28.01 mL/m2 vs. 83.20 ± 16.87 mL/m2 , p = .001). Left ventricular ejection fraction (LVEF, 32.47 ± 6.98% vs. 40.41 ± 6.15, p < .001), 6MWT (383.13 ± 108.70 vs. 453.47 ± 88.24, p < 0.001) and EQ-5D (65.93 ± 11.25 vs. 78.67 ± 8.35, p < .001) improved significantly. CONCLUSIONS: Heartech® LVPD appeared to be safe and effective for treatment of HF postmyocardial infarction.

Epidemiological trends and virological traits of hepatitis B virus infection in pregnant women and neonates.

In infants, hepatitis B virus (HBV) infections are mainly acquired by mother-to-child transmission (MTCT). Current tests for the presence of HBV markers at birth can neither confirm nor exclude MTCT. The aim of this study was to find an early diagnostic marker of HBV MTCT. From 2011 to 2016, we studied a total of 5999 pregnant women who gave birth at our hospital in Shenzhen City, China. HBsAg-positive mothers and their offspring (n=386 pairs) were tested at birth for HBV markers, and 207 infants were followed up at 7-12 months after birth. The HBsAg-seropositive rate of the pregnant women was 12.5%. Additionally, 28.0%, 36.0%, 98.5% and 6.6% of umbilical cord (UC) blood samples of neonates were found to be positive for HBsAg, HBeAg, anti-HBc and HBV-DNA, respectively, whereas for neonatal femoral venous (FV) blood, the percentages were 16.2%, 38.0%, 98.8% and 2.6%, respectively. Mothers with high HBV DNA loads and those who were HBeAg positive were the most likely to have HBV-positive offspring. Immunoprophylaxis failed in five infants: the difference in median HBV DNA titer between UC blood from infants with and without HBV MTCT was statistically significant, and there was no significant difference in HBV DNA titer between UC blood and in peripheral blood of infants with HBV MTCT. In conclusion, we found that HBeAg positivity and high HBV loads are strong risk factors for MTCT of HBV and that the HBV DNA titer in the UC is a good predictor for HBV MTCT.

Pleural IFN-γ release assay combined with biomarkers distinguished effectively tuberculosis from malignant pleural effusion.

BACKGROUND: Tuberculosis (TB) remains a major public health concern on a global scale, especially in developing nations. So far, no formal guidelines are available for the diagnosis and treatment of tuberculosis pleurisy. The diagnosis of TB is worsened by the immense difficulty in differential determination of tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE). The purpose of this investigation is to assess the differential diagnostic efficiencies of the pleural IFN-γ release assay (IGRA) and widely-used biochemical parameters in the distinction analysis of TPE and MPE. METHODS: A cohort of 222 patients with pleural effusion was examined, comprising of 143 TPE and 58 MPE patients. The patients were examined with IGRA, and the widely-used biomarkers in the pleural effusion and peripheral blood. RESULTS: Our results show that the TPE patients have significantly higher M. tuberculosis (Mtb) antigen-specific IFN-γ responses to ESAT-6 protein and peptide pool in the blood compared to MPE patients. TPE patients were also shown to have enriched Mtb antigen-specific IFN-γ responses in pleural effusion than in peripheral blood. Among the widely-used biomarkers, the adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) in pleural effusion were better biomarkers with high sensitivity and specificity to discriminate TPE and MPE. In addition, pleural IGRA could not be affected by the pleural adhesion, and the applications of the pleural IGRA together with ADA and CEA provide a promising approach for the TPE and MPE differential identification. CONCLUSIONS: Our study proposes that the integration of pleural IGRA and ADA, CEA detection could add to more effective diagnosis stratagems in the discernment between TPE and MPE.

Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography.

In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-ß-cyclodextrin [AI-ß-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-ß-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-ß-CD-coated column were optimized with the orthogonal experiment design L9 (34 ). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-ß-CD-coated columns was about 0.2 to 0.5 µm. The AI-ß-CD content in stationary phase based on the EA was approximately 2.77 mmol·m-2 . The AI-ß-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-ß-CD, has a great potential for enantioseparation in OT-CEC.

MicroRNA-638 inhibits cell proliferation by targeting suppress PIM1 expression in human osteosarcoma.

MicroRNAs (miRNAs) are a type of small noncoding RNAs that often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the functions and the mechanism of miR-638 in osteosarcoma (OS). The expression of miR-638 in OS and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by CCK8 assay. Different assays, including bioinformatics algorithms, luciferase report assay, and Western blotting, were used to identify the target gene proviral integration site for Moloney murine leukemia virus 1 (PIM1) of miR-638 in OS. The expression of PIM1 in clinical OS tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in OS tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in OS than in NCTs, which may induce the corresponding downregulation of miR-638 in OS. Ectopic expression of miR-638 inhibited OS cell growth in vitro. Subsequently, we identified that PIM1 is the downstream target gene of miR-638 in OS cells, and silencing PIM1 expression phenocopied the inhibitory effect of miR-638 on OS cell proliferation. Furthermore, we observed that PIM1 was overexpressed in OS tissues, and high expression of PIM1 in OS predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor through inhibiting PIM1 expression in OS.

A double defects-dominated flexible TiO2 matrix for in-situ SERS sensing of antibiotic residues in aquatic ecosystem (fish & fishpond water) and their on-site degradation in flowing water.

High-performance flexible semiconductor material can be used as an excellent multifunctional matrix for in-situ ultrasensitive surface-enhanced Raman scattering (SERS) detection and synchronous photocatalytic degradation of antibiotic residues in aquatic ecosystem. Here, a calcium-doped TiO2 flexible matrix with double defects (surface oxygen vacancy defect and Ti3+ energy level defect) was developed by its "in-situ one-step" hydrothermal synthesis on cotton fabric for the above purposes. Due to the joint contribution of double defects, a multi-channel charge transfer mode and a high-efficiency carrier separation are achieved, which endows flexible cotton fabric/Ca-doped TiO2 (Cot/Ca-TiO2) substrate with the greatly boosted SERS effect for in-situ detection of antibiotic residues on fish body surface and in fishpond water by a simple wiping or dipping sampling method, even for simultaneous identification of multi-component residues. The detection limits of three antibiotic residues (enrofloxacin, ciprofloxacin and enoxacin) are as low as 10-9 M, which are far lower than the EU standard. More meaningfully, the flexible Cot/Ca-TiO2 can be used as a multifunctional filter-membrane type photocatalyst for efficient on-site degradation of antibiotic residues in flowing fishpond water by a multi-grade photocatalysis means. Moreover, the flexible matrix exhibits good recyclability in both actual detection and photocatalysis.

Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants.

OBJECTIVE: Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination. METHODS: A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. RESULTS: Neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals. CONCLUSIONS: Our results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

Non-pharmacological interventions for community-dwelling older adults with possible sarcopenia or sarcopenia: a scoping review.

BACKGROUND: Sarcopenia is a progressive, age-related muscle disease that, if left untreated, imposes significant personal, social, and economic burdens. OBJECTIVE: To compile and document the nature and extent of existing studies exploring non-pharmacological interventions as a strategy to prevent or treat possible sarcopenia or sarcopenia in community-dwelling older adults. METHOD: Thirteen databases were searched up from January 2010 to March 2023 and filters were limited to English and Chinese language. Studies with older adults (≥60 y) in the community were included. The review was conducted and reported according to the PRISMA-ScR guidance and seven stages of methodology framework. A descriptive synthesis of trial characteristics and effectiveness was conducted. RESULTS: A total of 59 studies were included in the analysis. Most studies were RCTs. Few studies enrolled older adults with possible sarcopenia. The 70-79 age group has been studied more than any other age group. Six intervention types were identified, including exercise-only, nutrition-only, health education-only, traditional Chinese medicine-only, multicomponent intervention and control type. Majority of exercise-only interventions received resistance-based exercise. In nutrition-only category, overall food intervention or nutrients intervention was more than dietary pattern. Moreover, exercise plus nutrition was the main sub-type in multicomponent interventions. Health education-only and traditional Chinese medicine-only interventions were less frequently identified. Most studies had high and moderate compliance. CONCLUSION: There is evidence for the effectiveness of exercise and exercise plus nutrition interventions in improving muscle strength and physical performance, whereas the effectiveness of other intervention types or their combinations requires additional research. SCOPING REVIEW REGISTRATION: Open Science Framework (OSF) Registration DOI 10.17605/OSF.IO/RK3TE.

Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial.

Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of SIM0417 plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750 mg SIM0417 plus 100 mg ritonavir, 300 mg SIM0417 plus 100 mg ritonavir or placebo every 12 h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676. Findings: Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n = 12), low dose group (n = 12) or placebo (n = 8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of -2.16 ± 0.761 log10 copies/mL (p = 0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR = 3.08, 95% CI 0.968-9.818). SIM0417 plus ritonavir were well tolerated with all adverse events in grade 1. Interpretation: SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose-response relationship, and the 750 mg SIM0417 plus 100 mg ritonavir was selected as the recommended clinical dose. Funding: The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.

Synthesis and structure of the ß-carboline derivatives and their binding intensity with cyclin-dependent kinase 2.

Series of 3-substituted of 6-aminosulfonyl-ß-carbolines were designed and synthesized. In addition, the binding mode of these ß-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. The results showed that replacement of 3-cyclohexylmethoxy group will increase the hydrophobic binding interaction with the deep hydrophobic pocket of CDK2 correlate to the higher binding intensity.

Quality of Life in Lower-Limb Amputees 10 Years After the 2008 Sichuan Earthquake: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to investigate the long-term outcome of quality of life (QOL) in the lower-limb amputees 10 years after the 2008 Sichuan earthquake. METHODS: In the cross-sectional study, 66 lower-limb amputees were recruited. The prosthetics-related QOL was assessed using the Prosthetic Evaluation Questionnaire (PEQ) in terms of the scales of utility, appearance, sounds, residual limb health, perceived response, frustration, social burden, ambulation, and well-being. The score of each PEQ subscale was calculated and compared among the cohorts with different demographic characteristics. RESULTS: The PEQ scores showed that the scales of sounds, residual limb health, and frustration were still low in the lower-limb amputees 10 years after the 2008 Sichuan earthquake. The comparison of PEQ scales among cohorts with different demographic characteristics indicated that the potential demographic risk factors, namely, age, marital status, educational level, living independence, and comorbidity, were associated with prosthesis-related QOL. CONCLUSIONS: The prosthesis-related QOL of the lower-limb amputees 10 years after the 2008 Sichuan earthquake has been partly documented in this study. The potential demographic risk factors associated with QOL of amputees were also identified. These findings could enhance the understanding of prosthesis-related QOL of lower-limb amputees sustained in an earthquake and facilitate the optimization of post-disaster rehabilitation strategies.

Insights into the Unique Lung Microbiota Profile of Pulmonary Tuberculosis Patients Using Metagenomic Next-Generation Sequencing.

The microbiota plays an important role in human health and disease development. The lung microbiota profile in pulmonary tuberculosis (TB) patients and the effects of anti-TB treatment on the profile need to be determined thoroughly and comprehensively. This study primarily aimed to determine the lung microbiota profile associated with pulmonary TB and characterize the longitudinal changes during anti-TB treatment. A total of 53 participants, comprising 8 healthy individuals, 12 untreated pulmonary TB patients, 15 treated pulmonary TB patients, 11 cured pulmonary TB patients, and 7 lung cancer patients, were recruited in the present study. Bronchioalveolar lavage fluid (BALF) samples were collected from the above participants, and throat swabs were taken from healthy individuals. Microbiomes in the samples were examined using metagenomic next-generation sequencing (mNGS). Differences in microbiota profiles were determined through a comparison of the indicated groups. Our findings indicated that the BALF samples displayed decreased richness and diversity of the microbiota compared to those of the throat swab samples, and these two kinds of samples exhibited obvious separation on principal-coordinate analysis (PCoA) plots. Untreated pulmonary TB patients displayed a unique lung microbiota signature distinct from that of healthy individuals and lung cancer patients. Our data first demonstrated that anti-TB treatment with first-line drugs increases alpha diversity and significantly affects the beta diversity of the lung microbiota, while it also induces antibiotic resistance genes (ARGs). IMPORTANCE Characterization of the lung microbiota could lead to a better understanding of the pathogenesis of pulmonary TB. Here, we applied the metagenomic shotgun sequencing instead of 16S rRNA sequencing method to characterize the lung microbiota using the BALF samples instead of sputum. We found that alterations in the lung microbiota are associated with TB infection and that anti-TB treatment significantly affects the alpha and beta diversity of the lung microbiota in pulmonary TB patients. These findings could help us better understand TB pathogenesis.

Clinical efficacy of aspirin combination treatment in the treatment of coronary heart disease and its effect on inflammatory factors: a systematic review and meta-analysis.

BACKGROUND: As the mainstay treatment for coronary heart disease (CHD), aspirin alone is reported to be less effective than in combination when treating CHD. The aim of this analysis was to systematically evaluate the efficacy and safety of aspirin in combination with other drugs for the treatment of CHD, as well as its effect on the levels of inflammatory factors. METHODS: Electronic databases were searched from 2011 to 2021 and randomized controlled trials (RCTs) on aspirin in CHD patients were included in our study. Data was statistically analyzed using Stata 16.0 (StataCorp). RESULTS: A total of 13 RCTs were included, with a total of 1,442 patients. Compared with control group (aspirin alone) group, the response rate in the treatment group (aspirin in combination with other drugs) was significantly improved [odds ratio (OR) =5.11; 95% confidence interval (CI): 3.56-7.35], while the incidence of adverse reactions was markedly decreased (OR =0.36; 95% CI: 0.25-0.53). Before treatment, no significant differences were identified in the levels of inflammatory factors between the groups The inflammatory factors included C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). After treatment, CRP and TNF-α levels were significantly lower in both groups compared with those before treatment. However, there was no statistically significant difference in IL-6 levels after treatment between the groups. DISCUSSION: Aspirin is effective in the treatment of CHD, both alone and in combination. However, the latter has higher clinical efficacy and safety, and can significantly reduce the level of inflammatory factors in CHD patients.

LncRNA SNHG12 regulates ox-LDL-induced endothelial cell injury by the miR-218-5p/IGF2 axis in atherosclerosis.

Atherosclerosis (AS) is a cardiovascular disorder accompanied by endothelial dysfunction. Extensive evidence demonstrates the regulatory functions of long noncoding RNAs (lncRNAs) in cardiovascular disease, including AS. Here, the function of lncRNA small nucleolar RNA host gene 12 (SNHG12) in AS progression was investigated. A cell model of AS was established in human umbilical endothelial cells (HUVECs) using oxidative low-density lipoprotein (ox-LDL). CCK-8, flow cytometry, TUNEL, ELISA, and western blotting analyses were performed. Apolipoprotein E-deficient (apoE-/-) mice fed a Western diet were used as in vivo models of AS. RT-qPCR determined the levels of SNHG12, microRNA-218-5p (miR-218-5p) and insulin-like growth factor-II (IGF2). The molecular mechanisms were investigated using luciferase reporter and RNA pull-down assays. We found that SNHG12 and IGF2 expression levels were high and miR-218-5p expression levels were low in AS patients and ox-LDL-treated HUVECs. SNHG12 depletion attenuated ox-LDL-induced injury in HUVECs, whereas miR-218-5p suppression partially abated this effect. Moreover, IGF2 overexpression prevented the alleviative role of miR-218-5p in ox-LDL-treated HUVECs. SNHG12 upregulated IGF2 expression by sponging miR-218-5p. More importantly, SNHG12 increased proinflammatory cytokine production and augmented atherosclerotic lesions in vivo. Overall, SNHG12 promotes the development of AS by the miR-218-5p/IGF2 axis.