BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Objective: To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) . Methods: We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD). Results: CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 ^-18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 ² CFU/g. Conclusion The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.
CRISPR-Cas Systems ; Nucleic Acid Amplification Techniques/methods* ; Recombinases/genetics* ; Vibrio parahaemolyticus/genetics*

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective:To evaluate the effectiveness of single modal and multimodal exercise interventions on sarcopenia in the elderly. Methods:Randomized controlled trials about the effects of single modal and multimodal exercises on the improvement of sarcopenia in the elderly were retrieved from seven databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wanfang data) from the establishment of the databases to July, 2021. Two researchers selected the literatures independently, and evaluated the quality of methodology. The meta-analysis was performed with RevMan 5.3. Results:A total of 15 studies were incorporated, including 816 cases of sarcopenia. Compared to the blank control group, the skeletal muscle mass index improved little with single (MD = -0.05, 95%CI -0.14 to 0.04, P > 0.05) and multiple (MD = 0.15, 95%CI -0.01 to 0.31, P > 0.05) exercises. The maximum grip force improved with both single (MD = 2.06, 95%CI 0.25 to 3.87, P < 0.05) and multiple (MD = 2.36, 95%CI 1.10 to 3.63, P < 0.001) exercises. The knee extensors strength (SMD = 0.49, 95%CI 0.26 to 0.73, P < 0.001) and the walking speed (MD = 0.24, 95% CI 0.19 to 0.29, P < 0.001) improved with multimodal exercises. Conclusion:Single modal exercise may improve maximal grip strength in the elderly with sarcopenia, and multimodal exercise may be effective on maximal grip strength, knee extensors strength and walking speed.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1 METHODS: 55 cases of paediatric TCF3-PBX1 RESULTS: Among the 55 children with TCF3-PBX1 CONCLUSION The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.
Adolescent ; Bone Marrow ; Child ; Child, Preschool ; Female ; Humans ; Male ; Neoplasm, Residual ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.