Recurrence of left ventricular systolic dysfunction and its risk factors in heart failure with improved ejection fraction patients receiving guideline-directed medical therapy: A trajectory analysis based on echocardiography.

BACKGROUND: Despite the better prognosis of heart failure (HF) with improved ejection fraction (HFimpEF), remnant cardiovascular risks, including cardiovascular death, rehospitalization, and future deterioration of left ventricular (LV) systolic function, remain in HFimpEF. However, for HFimpEF patients, especially for those receiving guideline-directed medical therapy (GDMT), the recurrent LV systolic dysfunction and its risk factors is still unclear. METHODS: A total of 1098 HF patients under HF follow-up management system were initially screened. Echocardiography was re-evaluated at 3-, 6-, and 12-month follow-up. After exclusion, a total of 203 HFimpEF patients on GDMT were enrolled in our final analysis. Cox regression analysis was conducted to select risk factors. RESULTS: During the 1-year follow-up, a total of 28 (13.8%) patients had recurrent LV systolic dysfunction. The trajectory analysis of echocardiographic parameters illustrated that persistent decline of left ventricular ejection fraction (LVEF) and worsening LV remodeling was observed in patients with recurrent LV systolic dysfunction. Multivariable Cox regression analysis identified that ischemic cardiomyopathy, atrial fibrillation, higher left ventricular end-diastolic diameter index (LVEDDI), elevated serum potassium, and a lack of sodium-glucose co-transporter-2 inhibitors (SGLT2i) treatment were confirmed as independent risk factors for recurrent LV systolic dysfunction. Recurrent LV systolic dysfunction was associated with higher rehospitalization rate. CONCLUSION: In our longitudinal cohort study, almost 14% HFimpEF receiving GDMT suffered recurrent LV systolic dysfunction. Ischemic cardiomyopathy, atrial fibrillation, higher LVEDDI, higher serum potassium, and a lack of SGLT2i therapy were tightly associated with recurrence of LV systolic dysfunction. Relapse of LV systolic dysfunction correlated with poor prognosis.

Correlation of BUB1 and BUB1B with the development and prognosis of endometrial cancer.

This study aimed to evaluate the expression and clinical significance of budding uninhibited by benzimidazole 1 (BUB1) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) in endometrial carcinoma (EC). BUB1 and BUBIB expressions were evaluated by bioinformatics. Protein expression, clinical features, prognosis and immune cell infiltration were explored in 20 EC tumors. siRNA was used to evaluate BUB1 and BUBIB function in EC cells. BUB1 and BUBIB were highly expressed in 26 cancers. BUB1 was associated with overall survival (OS) in eight cancers and disease-free survival in ten; BUB1B was associated with OS in nine cancers and DFS in eleven. BUB1 and BUBIB exhibited high frequencies of gene changes (mainly mutations, > 5%) in cancer. BUB1 was negatively correlated and BUB1B was positively correlated with cancer-associated fibroblasts and endothelial cell infiltration. BUB1 and BUBIB knockdown decreased migration and invasion in EC cells. High BUB1 expression correlated with tumor malignant phenotypes (P < 0.05). High BUB1 mRNA expression reduced OS (P = 0.00036) and recurrence-free survival (P = 0.0011). High BUB1B mRNA expression reduced OS (P = 0.0024). BUB1/BUB1B correlated with activated CD8 + T and CD4 + T cell infiltration. BUB1 and BUBIB are highly expressed and correlated with clinicopathological characteristics in EC. BUB1 and BUBIB are potential prognosis markers and immunotherapy targets.

Activating peroxymonosulfate with MOF-derived NiO-NiCo2O4/titanium membrane for water treatment: A non-radical dominated oxidation mechanism.

Traditional peroxymonosulfate (PMS) catalytic membranes dominated by radical pathways often face interference from complex components in water bodies. Herein, we employed a controlled electro-deposition technique to coat a Ni-Co metal-organic framework (MOF) precursor onto titanium hollow fiber membrane (THFM), followed by high-temperature calcination to synthesize a MOF-derived NiO-NiCo2O4/THFM (M-NNCO-THFM) PMS catalytic membrane. Then, the M-NNCO-THFM filtration integrated with PMS activation (MFPA process) for water treatment. Experimental results demonstrated that the M-NNCO-THFM MFPA process successfully achieved complete phenol (PE) removal via a non-radical-dominated degradation pathway, involving singlet oxygen (1O2) and electron transfer, while exhibiting wide pH adaptability and exceptional stability in complex water matrices. Mechanism analysis revealed that the electron transfer process was significantly enhanced by the MOF-derived heterojunction structure, which increased the flat-band potential from 0.39 eV to 0.56 eV, thereby facilitating efficient electron transfer for PE removal. The non-radical 1O2 pathway was primarily due to the cycling of metal valence states (Ni2+/Co3+), leading to the reduction of Co2+ and its reaction with PMS, resulting in the generation of reactive species. Furthermore, electrochemical measurements indicated that the M-NNCO-THFM exhibited lower charge transfer resistance and enhanced charge transfer efficiency compared to non-MOF-derived NNCO-THFM, corresponding to the superior catalytic performance and electrochemically active surface area of M-NNCO-THFM.

Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF). METHOD: 427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification. CONCLUSION: Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.

Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

Establishment and Validation of a Mouse Bacterial Vaginosis Model.

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal infection without a reliable animal model. To establish a novel mouse BV model, we evaluated multiple parameters of various identified bacteria-infected mice, including Staphylococcus aureus (SA), Escherichia coli (EC), Streptococcus agalactiae, ß-Hemolytic streptococcus, and Gardnerella vaginalis (GV). METHODS: Mature female KM mice were randomly allocated to a vehicle group (group A, without any treatment) and experimental groups. After vaginal secretions were harvested, experimental groups were divided into phosphate buffer solution group (PBS, group B), control group including SA, and EC with a 1:1 ratio (group C), SA, EC, and Streptococcus agalactiae with a 1:2:1 ratio group (group D), SA, EC, and ß-Hemolytic streptococcus with a 1:2:1 ratio group (group E), and GV group (group F). The vaginal secretions of experimental mice were collected by flushing with 100 mL sterile PBS on days 2, 4, and 6. Vaginal secretions were examined by Gram staining, sialidase assay, ammonia test, and pH value measurement. IL-6 and IL-10 levels in mouse serum were detected by enzyme-linked immunosorbent assay. Hematoxylineosin staining and mouse cervicovaginal tissue histopathological scores were observed. The diagnostic test results were analyzed by logistic regression analysis and receiver operating characteristic curves. The Shapiro-Wilk analysis of variance, or rank-sum test, was used for normal distribution analysis. Pearson's correlation and chi-squared test determined the correlation and comparison data expressed as a percentage or frequency. RESULTS: There was less severe vaginal morphology in GV-infected mice compared to other bacteria-infected mice. The sialidase assay, the ammonia test, and the pH values of vaginal secretions showed significant differences between GV-infected and uninfected mice. Serum IL-6 and IL-10 levels and vaginal histological scoring increased in other bacteria-infected mice, but GV-infected mice showed only a mildly increasing trend of IL-10 levels and vaginal histological scoring compared to control mice. CONCLUSIONS: GV-infected mice showed clinical features similar to human BV infection, including vaginal anatomical and pathological indices, and biochemical and immune parameters. Serum IL-10 level has potential for use in BV diagnosis.

In silico design of a lipid-like compound targeting KRAS4B-G12D through non-covalent bonds.

One of the most common drivers in human cancer is the peripheral membrane protein KRAS4B, able to promote oncogenic signalling. To signal, oncogenic KRAS4B not only requires a sufficient nucleotide exchange, but also needs to recruit effectors by exposing its effector-binding sites while anchoring to the phospholipid bilayer where KRAS4B-mediated signalling events occur. The enzyme phosphodiesterase-δ plays an important role in sequestering KRAS4B from the cytoplasm and targeting it to cellular membranes of different cell species. In this work, we present an in silico design of a lipid-like compound that has the remarkable feature of being able to target both an oncogenic KRAS4B-G12D mutant and the phosphodiesterase-δ enzyme. This double action is accomplished by adding a lipid tail (analogous to the farnesyl group of the KRAS4B protein) to an previously known active compound (2H-1,2,4-benzothiadiazine, 3,4-dihydro-,1,1-dioxide). The proposed lipid-like molecule was found to lock KRAS4B-G12D in its GDP-bound state by adjusting the effector-binding domain to be blocked by the interface of the lipid bilayer. Meanwhile, it can tune GTP-bound KRAS4B-G12D to shift from the active orientation state to the inactive state. The proposed compound is also observed to stably accommodate itself in the prenyl-binding pocket of phosphodiesterase-δ, which impairs KRAS4B enrichment at the lipid bilayer, potentially reducing the proliferation of KRAS4B inside the cytoplasm and its anchoring at the bilayer. In conclusion, we report a potential inhibitor of KRAS4B-G12D with a lipid tail attached to a specific warhead, a compound which has not yet been considered for drugs targeting RAS mutants. Our work provides new ways to target KRAS4B-G12D and can also foster drug discovery efforts for the targeting of oncogenes of the RAS family and beyond.

Stimulator of interferon genes promotes diabetic sarcopenia by targeting peroxisome proliferator activated receptors γ degradation and inhibiting fatty acid oxidation.

BACKGROUND: Declined skeletal muscle mass and function are inevitable consequences of long-term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia. METHODS: Wild-type and STINGgt/gt C57BL/6J mice and C2C12 myotubes were used to study the role of STING in the regulation of diabetic sarcopenia and the underlying mechanisms. RESULTS: STING was abnormally activated in diabetic muscles and in PA-treated myotubes (P < 0.01 for all parameters). The diabetic mice demonstrated decreased forelimb grip strength, lean mass, muscle weight and hanging impulse, which were improved by STING deficiency due to alleviated muscle fibre atrophy and interstitial fibrosis (P < 0.05 for all parameters). STING deficiency alleviated muscle fibre atrophy through the following mechanisms. Firstly, STING deficiency or inhibition increased the contents of pDRP1Ser616 , PINK1, Parkin and LC3-II, decreased p62 content, and increased the amount of mito-Keima fluorescent dots at 578 nm in diabetic state (P < 0.05 for all parameters), suggesting improved mitofission and mitophagy. Secondly, STING deficiency or inhibition increased the expression of pAKTSer473 and GLUT4 post-insulin change in diabetic state (P < 0.05 for all), indicating alleviated insulin resistance (IR). Mechanically, STING deficiency or inhibition increased peroxisome proliferator activated receptors γ (PPARγ) protein content by reducing the degradation of ubiquitinated PPARγ through the proteasome pathway and thus increased the expression of fatty acid oxidation (FAO)-related proteins in diabetic state (P < 0.05 for all parameters). Decreased expression of FAO-related proteins caused by PPARγ inhibition abolished the improvements in mitofission, mitophagy and IR achieved by STING inhibition in PA-treated myotubes and thus promoted muscle fibre atrophy (P < 0.05 for all parameters). STING deficiency alleviated interstitial fibrosis by decreasing TGFß1 expression in diabetic state and TGFß1 promoted the fibrogenic differentiation of fibro-adipogenic progenitors (P < 0.05 for all parameters). PPARγ inhibition abolished the effect of STING inhibition on reducing TGFß1 content in PA-treated myotubes (P < 0.01). CONCLUSIONS: STING deficiency exerted protective effects in diabetic sarcopenia by inhibiting the degradation of ubiquitinated PPARγ through the proteasome pathway and enhancing PPARγ-mediated FAO, which alleviated muscle fibre atrophy by promoting mitophagy and ameliorating IR, and alleviated interstitial fibrosis by reducing TGFß1 production and suppressing the fibrogenic differentiation of fibro-adipogenic progenitors.

LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.

LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: autophagy related 14; AVSF: autophagic vacuoles with unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: chaperone-mediated autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript 4; ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem cells; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/ß-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma stem cells; HCC: hepatocellular carcinoma; HD: Huntington disease; HSCs: hematopoietic stem cells; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; IL3: interleukin 3; IR: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase 2; MA: macroautophagy; MHC: major histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver disease; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NLRP3: NLR family pyrin domain containing 3; PARK7: Parkinsonism associated deglycase; PD: Parkinson disease; PEA15/PED: proliferation and apoptosis adaptor protein 15; PKM/PKM2: pyruvate kinase M1/2; RA: rheumatoid arthritis; RARA: retinoic acid receptor alpha; RCAN1: regulator of calcineurin 1; RCC: renal cell carcinoma; RDA: RNautophagy and DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase 3; SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin C-terminal hydrolase L1; VAMP8: vesicle associated membrane protein 8.

Association Between Epicardial Adipose Tissue and Left Atrial and Ventricular Function in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Existing evidence suggested that the role of epicardial adipose tissue (EAT) in heart failure with reduced and preserved ejection fraction (HFrEF/HFpEF) might be divergent. Here, we conducted a systematic review and meta-analysis to evaluate the association between EAT and HF. Several databases were searched from their inception to January 20, 2023. We calculated the standard mean difference (SMD) in EAT between the HF and control groups, as well as the correlation coefficient between EAT and left atrial (LA) and left ventricular (LV) function. This meta-analysis included 23 studies, involving 1563 HFrEF and 1351 HFpEF patients. Our findings indicated that EAT was significantly higher in HFpEF patients (SMD: 0.61, 95% CI: 0.27-0.94), but not in total HF or HFrEF patients compared to controls. In HFrEF, EAT was positively correlated with LVEF, LV end-diastolic volume index (LVEDVI), LA global longitudinal strain (LAGLS), and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-ProBNP). However, no significant relationship existed between EAT and LV mass index (LVMI) or LVGLS. For HFpEF, EAT correlated positively with LVMI, LVEDVI, LV end-systolic volume index (LVESVI), LA volume index (LAVI), cardiac troponin T, and extracellular volume (ECV), but negatively with LVGLS and LAGLS. EAT was shown to be higher in HFpEF, but not in HFrEF. Less EAT was linked with worse LA function but not worse LV function in HFrEF, while more EAT was associated with worse LA/LV function in HFpEF.

Comparisons of Two-dimensional Echocardiographic Aortic Dimensions between Chinese, Japanese, and Europeans.

PURPOSE: We aimed to investigate the impacts of age, gender, and race on aortic dimensions in healthy adults. METHODS: We analyzed data from 3 large population-based sample studies, including Chinese Echocardiographic Measurements in Normal Chinese Adults, Japanese the Normal Values for Echocardiographic Measurements Project, and European Normal Reference Ranges for Echocardiography, to compare the two-dimensional echocardiography-derived aortic diameters at different levels and to explore the effects of age, gender, and race on aortic measurements. We also compared the values corrected by body surface area (BSA) or height. RESULTS: The results are as follows: (1) Aortic diameters showed positive correlations with age (r=0.12-0.42, P<0.05), and there were significant inter-age group differences before and after indexing to BSA (P<0.05); (2) Men had greater measurements of aortic diameters than women, with the differences being the same when indexed to height. However, indexing to BSA reversed the differences; (3) The aortic diameters at annulus (Ao-a) and sinus (Ao-s) levels were very close with minor differences between the Chinese and Japanese regardless of whether BSA was used for correction; and (4) The aortic measurements at Ao-s and proximal ascending aorta (Ao-asc) levels in the Chinese were significantly lower than in the Europeans for both genders, with the differences remaining the same even after indexing to BSA or height (P<0.05). CONCLUSION: Aortic dimensions vary with age and gender, and there are significant differences between races or ethnicities even when stratified by gender and age. The indexation by BSA or height cannot eliminate these differences. Therefore, age-specific, gender-specific, race-specific, and nationality-specific reference values may be more appropriate at present for clinical practice to avoid misdiagnosis and misclassification of aortic dilation.

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.

Aberrant serum and tissue levels of Beclin1 and mechanistic target of rapamycin (mTOR) proteins in epithelial ovarian cancer.

Beclin1 and mechanistic target of rapamycin (mTOR) can be used as tumor markers of epithelial ovarian cancer. This study aimed to assess the association of Beclin1 and mTOR expression with clinicopathological and prognostic data in epithelial ovarian cancer patients. Serum and tissue samples from 45 epithelial ovarian cancer patients and 20 controls were analyzed by enzyme-linked immunosorbent assay and immunohistochemistry for Beclin1 and mTOR expression. The online datasets from gene expression profiling interactive analysis (n = 426), Kaplan-Meier plotter (n = 398), cBioPortal (n = 585), and UALCAN (n = 302) were also analyzed. Beclin1 expression was associated with low-grade differentiation (P = .003), earlier clinical stage (P = .013), fewer local lymph node metastases (P = .02) and lower serum Beclin1 level (P = .001). mTOR expression was associated with high-grade differentiation (P = .013), advanced clinical stage (P = .021), ascites (P = .028), and higher serum mTOR level (P = .001). The online datasets showed that a high mTOR expression level (HR = 1.44; 95% CI = 1.08-1.92; P = .013) was associated with a poor overall survival of 426 patients. Beclin1 was mutated in 1.8% and mTOR was mutated in 5% of epithelial ovarian cancer patients. Serum Beclin1 and mTOR levels were able to predict tumor differentiation, clinical stage, lymph node metastasis, and ascites in epithelial ovarian cancer patients.

Impaired antibody response to inactivated COVID-19 vaccines in hospitalized patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) are at an increased risk of morbidity and mortality of coronavirus disease 2019 (COVID-19). Data on the antibody response to COVID-19 vaccines in T2D patients are less studied. This study aimed to evaluate IgG antibody response to inactivated COVID-19 vaccines in hospitalized T2D patients. Hospitalized patients with no history of COVID-19 and received two doses of inactivated COVID-19 vaccines (Sinopharm or CoronaVac) were included in this study from March to October 2021. SARS-CoV-2 specific IgG antibodies were measured 14-60 days after the second vaccine dose. A total of 209 participants, 96 with T2D and 113 non-diabetes patients, were included. The positive rate and median titer of IgG antibody against receptor-binding domain (anti-RBD) of spike (S) protein of SARS-CoV-2 in T2D group were lower than in control group (67.7% vs 83.2%, p = .009; 12.93 vs 17.42 AU/ml, p = .014) respectively. Similarly, seropositivity and median titers of IgG antibody against the nucleocapsid (N) and S proteins of SARS-CoV-2 (anti-N/S) in T2D group were lower than in control group (68.8% vs 83.2%, p = .032; 18.81 vs 29.57 AU/mL, p = .012) respectively. After adjustment for age, sex, BMI, vaccine type, days after the second vaccine dose, hypertension, kidney disease, and heart disease, T2D was identified as an independent risk factor for negative anti-RBD and anti-N/S seropositivity, odd ratio 0.42 (95% confidence interval 0.19, 0.89) and 0.42 (95% CI 0.20, 0.91), respectively. T2D is associated with impaired antibody response to inactivated COVID-19 vaccine.

Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study.

AIMS: The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. METHODS AND RESULTS: This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P < 0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P < 0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P < 0.001] during 12 month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P < 0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up. CONCLUSIONS: Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Highly-efficient degradation of organic pollutants by oxalic acid modified sludge biochar: Mechanism and pathways.

The application of sludge biochar (SC) materials as efficient catalysts for organic pollutants mineralization via advanced oxidation process meets the good strategy of "make waste profitable". The catalytic oxidations of methyl orange (MO) and pyrene by oxalic acid modified sludge biochar (SC-OA) with and without H2O2 were carried out. The analysis of Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), electronic paramagnetic resonance spectrometer (EPR) and free radical quenching experiment were performed and the definite relationships between persistent free radicals (PFRs) type and specific reactive oxygen species (ROS) were made clear. It is suggested for the first time that carbon-centered type PFRs in SC-OA without H2O2 could form O2•- and •OH from COOH groups, while oxygen-centered type PFRs induced H2O2 to produce •OH. The degradation intermediates of MO and pyrene were identified and the transformation pathways were proposed. SC-OA, possessing good sustainable utilization and clean catalytic property, is expected to be popularized and applied in the mineralization of organic pollutants, especially in the in-situ remediation of contaminated soil where is no continuous supply of H2O2.

Association between visceral adiposity index and heart failure: A cross-sectional study.

BACKGROUND: Obesity is an important risk factor for heart failure (HF). HYPOTHESIS: Visceral adiposity index (VAI) is a simple metric for assessing obesity; however, the association between VAI and risk for HF has not been studied. METHODS: A cross-sectional study involving 28 764 participants ≥18 years of age from the National Health and Nutrition Examination Survey (NHANES), 2009-2018, in the United States was performed. VAI was calculated using body mass index (BMI), waist circumference (WC), triglycerides (TG), and high-density lipoprotein cholesterol. VAI was analyzed as a continuous and categorical variable to examine its association with HF. Subgroup analysis was also performed. RESULTS: The highest VAI (fourth quartile [Q4]) was found among males, BMI, systolic and diastolic blood pressure, WC, hypertension, diabetes, liver disease, coronary heart disease, smoking, total cholesterol, and TG. More participants in Q4 took ß-receptor blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor-neprilysin inhibitor, calcium channel blockers, and antidiabetic and antihyperlipidemic medications. Participants with HF exhibited greater VAI. A per-unit increase in VAI resulted in a 4% increased risk for HF (odds ratio [OR] 1.04 [95% confidence interval (CI) 1.02-1.05]). After multivariable adjustment, compared with the lowest quartile, the OR for Q3 was 1.55 (95% CI 1.24-1.94). Subgroup analysis revealed no significant interactions between VAI and specific subgroups. CONCLUSION: VAI was independently associated with the risk for HF. As a noninvasive index of visceral adiposity, VAI could be used for a "one shot" assessment of HF risk and may serve as a novel marker.

Risk factors for intracardiac thrombus in peripartum cardiomyopathy: a retrospective study in China.

AIMS: Peripartum cardiomyopathy (PPCM) are more vulnerable to intracardiac thrombus than other types of cardiomyopathies, although explicit anticoagulant strategy is not sure. Too aggressive anticoagulation therapy can lead to severe bleeding events. Hence, we want to construct a risk stratification model for intracardiac thrombus in PPCM patients. METHODS AND RESULTS: A total of 159 suspected PPCM cases were initially screened, whereas 123 confirmed cases were enrolled in the final analysis. The study population was randomly assigned as derivation group (N = 83) and validation group (N = 40). The derivation cohort was utilized to develop the model, and the validation cohort was used to internal validate the discriminatory ability of the model. Formation of intracardiac thrombus was detected in 22 patients. After adjusted by multivariable logistic regression analysis, left ventricle ejection fraction (LVEF, OR 0.772, 95% CI 0.665-0.897, P = 0.001), haemoglobin levels (OR 1.050, 95% CI 1.003-1.099, P = 0.038), and thrombocyte counts (OR 1.018, 95% CI 1.006-1.029, P = 0.003) were identified as risk factors independently associated with intracardiac thrombus and were finally included in the tentative risk stratification model with a C-indexes of 0.916 (95% CI: 0.850-0.982, P < 0.001). A score of ≤7 was regarded as low risk, 8-10 defined intermediate risk, and ≥11 defined high risk in our model. Internal validation showed good discriminatory ability of the model with a C-indexes of 0.790 (95% CI: 0.644-0.936, P = 0.017). CONCLUSIONS: In our retrospective study, impaired LVEF, elevated haemoglobin levels, and high thrombocyte counts were regarded as independent risk factors for intracardiac thrombus in PPCM. A risk stratification model derived from these risk factors, which was economic and easily applicable in clinical practice, could rapidly and accurately identify PPCM patients with higher-risk of intracardiac thrombus.

Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension.

BACKGROUND: It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure (HF) with reduced ejection fraction (HFrEF) and low systolic blood pressure (SBP). This study aimed to investigate the efficacy and tolerability of sacubitril/valsartan in HFrEF patients with SBP < 100 mmHg. METHODS & RESULTS: An observational study was conducted on 117 patients, 40.2% of whom had SBP < 100 mmHg without symptomatic hypotension, and 59.8% of whom had SBP ≥ 100 mmHg in an optimized HF follow-up management system. At the 6-month follow-up, 52.4% of patients with SBP < 100 mmHg and 70.0% of those with SBP ≥ 100 mmHg successfully reached the target dosages of sacubitril/valsartan. A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP < 100 mmHg and SBP ≥ 100 mmHg (1627.5 pg/mL and 1340.1 pg/mL, respectively; P = 0.75). The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories, with a 10.8% increase in patients with SBP < 100 mmHg (P < 0.001) and a 14.0% increase in patients with SBP ≥ 100 mmHg (P < 0.001). The effects of sacubitril/valsartan on SBP were statistically significant and inverse across both SBP categories (P = 0.001), with an increase of 7.5 mmHg in patients with SBP < 100 mmHg and a decrease of 11.5 mmHg in patients with SBP ≥ 100 mmHg. No statistically significant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension, deteriorating renal function, hyperkalemia, angioedema, or stroke. CONCLUSIONS: Within an optimized HF follow-up management system, sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

Case report: Heart failure secondary to myocardial infarction in a fertile woman with woven coronary artery.

A 42-year-old female was hospitalized with 2-day history of fever, dyspnea, and chest tightness. Four years ago, she had similar symptoms at the eighth week of gestation. Computed tomography coronary angiography only suggested moderate stenosis, but cardiac MRI indicated myocardial infarction. The coronary angiography demonstrated a woven coronary artery. She underwent successful coronary artery bypass grafting surgery and took medication regularly. Finally, the prognosis was favorable. Cardiovascular events seldom happen in fertile women because of the protection of estrogen, but once it occurs, the potential cause, such as coronary anomaly and other risk factors, should not be overlooked.