The independent prediction study of the effect of heart-type fatty acid binding protein on the severity and long-term cardiac function in Covid-19 patients.

The study was conducted to assess the predictive ability of the heart-type fatty acid binding protein (HFABP) on the severity and long-term cardiac function of Covid-19 infected persons. In the case of negative HsTn-T, we determined whether HFABP was related to the severity of Covid-19 or it was the long-term impact of cardiac function. Chi-square test and t-test were used to evaluate whether HFABP level was an independent predictor of myocardial injury and whether it was related to the severity of Covid-19 and the long-term impact of cardiac function. Among the 20 patients in each of the two groups (mild and severe), 27.5% of all had elevated HFABP. Two were HFABP positive in the mild group, and nine were HFABP positive in the severe group, with a significant difference between the two groups (P=0.013). The mean serum level of HFABP in the mild group was 3.96 ±1.80, compared with 6.70±3.77 in the severe group, with a significant difference between the two groups (P=0.003). In addition, after two years of follow-up, there was a statistically significant difference in the changes of cardiac function between the HFABP-positive group and the HFABP-negative group (P=0.037). These data indicate that among HsTn-T-negative Covid-19 patients, HFABP is a more sensitive and independent predictor of myocardial damage, and it is useful for distinguishing mild and severe Covid-19. The level of HFABP has a significant effect on the long-term changes of heart function in Covid-19 patients.

NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes caused by oxidative stress, inflammation, insulin resistance, myocardial fibrosis, and lipotoxicity; its nature is insidious, complex and difficult to treat. NLRP3 inflammasome triggers the maturation and release of pro-inflammatory cytokines, participates in pathophysiological processes such as insulin resistance and myocardial fibrosis, in addition to being closely related to the development and progression of diabetic cardiomyopathy. The development of inhibitors targeting specific aspects of inflammation suggests that NLRP3 inflammasome can be used to treat diabetic cardiomyopathy. This paper aims to summarize NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy, and to provide new suggestions for the treatment of this disease.

La cardiomiopatía diabética es una complicación grave de la diabetes causada por estrés oxidativo, inflamación, resistencia a la insulina, fibrosis miocárdica y lipotoxicidad. Se trata de un padecimiento insidioso, complejo y difícil de tratar. El inflamasoma NLRP3 desencadena la maduración y liberación de citoquinas proinflamatorias, participa en procesos fisiopatológicos como la resistencia a la insulina y la fibrosis miocárdica, además de estar estrechamente relacionado con la aparición y progresión de la cardiomiopatía diabética. El desarrollo de inhibidores dirigidos a aspectos específicos de la inflamación sugiere que el inflamasoma NLRP3 puede utilizarse para tratar la cardiomiopatía diabética. Este artículo pretende resumir el mecanismo y las dianas terapéuticas del inflamasoma NLRP3 en la cardiomiopatía diabética, así como aportar nuevas sugerencias para el tratamiento de esta enfermedad.

Mecanismos y dianas terapéuticas del inflamasoma NLRP3 en la miocardiopatía diabética / NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy

Resumen La cardiomiopatía diabética es una complicación grave de la diabetes causada por estrés oxidativo, inflamación, resistencia a la insulina, fibrosis miocárdica y lipotoxicidad. Se trata de un padecimiento insidioso, complejo y difícil de tratar. El inflamasoma NLRP3 desencadena la maduración y liberación de citoquinas proinflamatorias, participa en procesos fisiopatológicos como la resistencia a la insulina y la fibrosis miocárdica, además de estar estrechamente relacionado con la aparición y progresión de la cardiomiopatía diabética. El desarrollo de inhibidores dirigidos a aspectos específicos de la inflamación sugiere que el inflamasoma NLRP3 puede utilizarse para tratar la cardiomiopatía diabética. Este artículo pretende resumir el mecanismo y las dianas terapéuticas del inflamasoma NLRP3 en la cardiomiopatía diabética, así como aportar nuevas sugerencias para el tratamiento de esta enfermedad.

Abstract Diabetic cardiomyopathy (DCM) is a serious complication of diabetes caused by oxidative stress, inflammation, insulin resistance, myocardial fibrosis, and lipotoxicity; its nature is insidious, complex and difficult to treat. NLRP3 inflammasome triggers the maturation and release of pro-inflammatory cytokines, participates in pathophysiological processes such as insulin resistance and myocardial fibrosis, in addition to being closely related to the development and progression of diabetic cardiomyopathy. The development of inhibitors targeting specific aspects of inflammation suggests that NLRP3 inflammasome can be used to treat diabetic cardiomyopathy. This paper aims to summarize NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy, and to provide new suggestions for the treatment of this disease.

Liposome fusogenic enzyme-free circuit enables high-fidelity determination of single exosomal RNA.

Accurate determination of single exosomal inclusions in situ presents a significant challenge due to their extremely low abundance as well sub-100 nm vesicle dimensions. Here, we created a Liposome Fusogenic Enzyme-free circuit (LIFE) approach for the high-fidelity identification of exosome-encapsulated cargoes without destroying the vesicle integrity. The probe-loaded cationic fusogenic liposome could capture and fuse with a single target exosome, enabling probes delivery and target biomolecule-initiated cascaded signal amplification in situ. Then the DNAzyme probe encountered conformal change upon exosomal microRNA activation, and generated a convex DNAzyme structure to cleave the RNA site of substrate probe. After that, the target microRNA could be released to introduce a cleavage cycle to yield amplified fluorescence readout. Therefore, trace cargoes in a single exosome could be accurately determined by elaborately controlling the ratio of introduced LIFE probe, paving the way toward the exploration of a universal sensing platform for the assessment of exosomal cargoes to facilitate early disease diagnosis and personalized treatment.

Long-term prognosis of culotte versus different crush strategies in management of unprotected left main bifurcation coronary lesions: A meta-analysis.

OBJECTIVE: To assess the long-term clinical effects of Culotte and different Crush techniques in the treatment of unprotected left main bifurcation coronary lesions to determine the best percutaneous coronary intervention strategy. METHODS: The systematic review and meta-analysis comprised search on PubMed, Embase, Cochrane Library, WanFang Data and the China National Knowledge Infrastructure literature databases to locate randomised controlled trials and cohort studies published in Chinese and/or English language till June 2021 and comprised application of Culotte and Crush stenting techniques for percutaneous coronary intervention in patients with unprotected left main bifurcation coronary lesions. The selected studies were analysed for quality, publication bias and heterogeneity. RESULTS: Of the 197 studies located, 8(4.06%) were subjected to meta-analysis. The incidence of major adverse cardiac events in the Mixed-Crush group was higher than the Culotte group (p=0.02), which, in turn, was higher than the Double Kiss Crush group (p<0.0001), The incidence of target lesion revascularisation in the Culotte group was significantly higher than Double Kiss Crush group (p<0.001). The incidence of myocardial infarction in the Culotte group was higher than the Double Kiss Crush group (p=0.04). The incidence of cardiogenic death in the Double Kiss Crush group was similar to that in the Culotte group (p=0.32). CONCLUSIONS: Patients in the Double Kiss Crush group had the most long-term benefits, while those receivingg Mixed Crush had the least long-term benefits.

Antibodies Can Last for More Than 1 Year After SARS-CoV-2 Infection: A Follow-Up Study From Survivors of COVID-19.

Background: COVID-19 is a global pandemic. The prevention of SARS-CoV-2 infection and the rehabilitation of survivors are currently the most urgent tasks. However, after patients with COVID-19 are discharged from the hospital, how long the antibodies persist, whether the lung lesions can be completely absorbed, and whether cardiopulmonary abnormalities exist remain unclear. Methods: A total of 56 COVID-19 survivors were followed up for 12 months, with examinations including serum virus-specific antibodies, chest CT, and cardiopulmonary exercise testing. Results: The IgG titer of the COVID-19 survivors decreased gradually, especially in the first 6 months after discharge. At 6 and 12 months after discharge, the IgG titer decreased by 68.9 and 86.0%, respectively. The IgG titer in patients with severe disease was higher than that in patients with non-severe disease at each time point, but the difference did not reach statistical significance. Among the patients, 11.8% were IgG negative up to 12 months after discharge. Chest CT scans showed that at 3 and 10 months after discharge, the lung opacity had decreased by 91.9 and 95.5%, respectively, as compared with that at admission. 10 months after discharge, 12.5% of the patients had an opacity percentage >1%, and 18.8% of patients had pulmonary fibrosis (38.5% in the severe group and 5.3% in the non-severe group, P < 0.001). Cardiopulmonary exercise testing showed that 22.9% of patients had FEV1/FVC%Pred <92%, 17.1% of patients had FEV1%Pred <80%, 20.0% of patients had a VO2 AT <14 mlO2/kg/min, and 22.9% of patients had a VE/VCO2 slope >30%. Conclusions: IgG antibodies in most patients with COVID-19 can last for at least 12 months after discharge. The IgG titers decreased significantly in the first 6 months and remained stable in the following 6 months. The lung lesions of most patients with COVID-19 can be absorbed without sequelae, and a few patients in severe condition are more likely to develop pulmonary fibrosis. Approximately one-fifth of the patients had cardiopulmonary dysfunction 6 months after discharge.

Ischemia-modified Albumin to Evaluate Short-term Prognostic of Patients with Acute Coronary Syndrome.

In patients with acute coronary syndrome (ACS), the predicted short-term result of ischemic modified albumin (IMA) is still not recognised now. The above have been searched in PubMed, Embase, Medline, Cochrane Library databases, and Wanfang databases from the beginning to June 2020. The study explored that patients with positive of IMA had differences in short-term results compared to negative of IMA. Odds ratios for each study was compiled and conducted for heterogeneity assessment, quality review, publication bias. A total of 684 patients (405 positive patients; 279 negative patients) were included in four studies. Comprehensive analysis found that compared with the negative of IMA in patients with ACS, the positive of IMA in patients with ACS had a high incidence of major cardiovascular adverse events (MACE) (HR 1.85; p=0.03), but there was no significant difference in the occurrence of cardiac death (HR 4.40; p = 0.16).  It was concluded that the positive of IMA in patients with ACS is associated with an increased incidence of MACE, but there was no statistically significant difference in incidence of cardiac death. Due to the limited data coming from different research groups in different countries, the diagnostic criteria for the IMA cut-off may be different. Future large randomised controlled trials will be certainly needed to confirm these findings. Key Words: Acute coronary syndrome, Ischemia-modified albumin, Meta-analysis, MACE, Cardiac death.

High incidence and mortality of pneumothorax in critically Ill patients with COVID-19.

BACKGROUND: The clinical characteristics of the patients with COVID-19 complicated by pneumothorax have not been clarified. OBJECTIVES: To determine the epidemiology and risks of pneumothorax in the critically ill patients with COVID-19. METHODS: Retrospectively collecting and analysing medical records, laboratory findings, chest X-ray and CT images of 5 patients complicated by pneumothorax. RESULTS: The incidence of pneumothorax was 10% (5/49) in patients with ARDS, 24% (5/21) in patients receiving mechanical ventilation, and 56% (5/9) in patients requiring invasive mechanical ventilation, with 80% (4/5) patients died. All the 5 patients were male and aged ranging from 54 to 79 years old. Pneumothorax was most likely to occur 2 weeks after the beginning of dyspnea and associated with reduction of neuromuscular blockers, recruitment maneuver, severe cough, changes of lung structure and function. CONCLUSIONS: Pneumothorax is a frequent and fatal complication of critically ill patients with COVID-19.

Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing.

Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO2 /FiO2 ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3-6.0). Pulmonary inflammation index, platelet counts, sodium, C-reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7-0.8). And potassium, creatinine, temperature, and D-dimer showed mild distinguishing power (each AUC between 0.6-0.7). In addition, higher C-reactive protein was associated with shorter time to progress to severe cases (r = -0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID-19.

Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study.

BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23-8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.

"Five-Early" Model: The Magic Weapon against COVID-19.

BACKGROUND: COVID-19(2019 novel coronavirus disease)has brought tremendous pressure to the prevention and control of the national epidemic due to its concealed onset, strong infectivity and fast transmission speed. METHODS: In this retrospective study, 226 patients diagnosed with 2019 novel coronavirus pneumonia (NCP) in the Chongqing University Three Gorges Hospital were included. The patients' clinical data, including general information, initial symptoms at the onset, time of disease diagnosis, time to treatment in hospital, time of nucleic acid conversion to negative, disease classification, total time of hospitalization were collected. The clinical data of the mild and severe patients were compared. RESULTS: Fever, cough, sore throat, poor appetite andfatigue were the main symptoms of the diagnosed patients. The time of diagnosis was significantly shorter in the mild patients (4.96 ± 4.10 days) than severe patients (7.63 ± 9.17 days) (P=0.004). Mild patients had shorter time to treatment in hospital (6.09 ± 4.47 vs. 8.71 ± 9.04 days) and less time of nucleic acid conversion to negative (7.58 ± 2.51 vs. 11.6 ± 4.67 days) compared to the severe patients. CONCLUSION: The above results can be used as a quantitative basis for the "five-early"(early detection, early screening, early diagnosis, early isolation treatment, and early recovery) model. The government, the masses, and the hospitals' joint prevention and optimization of the "five-early" model will provide important scientific reference for further prevention and control of the epidemics.

Epidemiological and Clinical Characteristics of COVID-19 in Adolescents and Young Adults.

BACKGROUND: Adolescents and young adults might play a key role in the worldwide spread of Coronavirus Disease 2019 (COVID-19) because they are more likely to be involved in overseas study, business, work, and travel. However, the epidemiological and clinical characteristics remain unknown. METHODS: We collected demographic, epidemiological, and clinical data from 46 confirmed COVID-19 patients aged 10 to 35 years from the Chongqing Three Gorges Central Hospital. Several key epidemiological parameters, asymptomatic cases, transmission to family members, and clinical characteristics at admission and during treatment were summarized. RESULTS: Of 46 confirmed patients, 14 patients (30.4%) were aged between 10 and 24 years, and 24 (52.2%) patients were male. The estimated mean incubation period was 6.6 days (95% confidence interval [CI] 4.4-9.6). The median serial interval was 1.9 days (95% CI 0.4-6.2). Three of the asymptomatic cases showed transmission to their family members. Only one patient was identified as a severe case at admission. The common symptoms at admission were dry cough (34, 81.0%) and fever (29, 69.1%). Nearly 60% of the patients showed ground-glass opacity on chest computed tomography. Three patients developed acute kidney injury during treatment. Most of the patients (78.3%) recovered and were discharged by the end of the follow-up. CONCLUSIONS: This single-center study with a relatively small sample size showed that adolescent and young adult patients with COVID-19 had a long incubation period and a short serial interval. The transmission occurred from asymptomatic cases to family members. Fewer patients developed complications during treatment.

Circulating complement-1q tumor necrosis factor-α-related protein isoform 5 levels are low in type 2 diabetes patients and reduced by dapagliflozin.

AIMS/INTRODUCTION: As a member of the tumor necrosis factor-α-related protein family, complement-1q tumor necrosis factor-α-related protein isoform 5 (CTRP5) has been found to be associated with obesity and insulin resistance (IR). Previous studies in humans and animals have reported contradictory results related to the association between CTRP5 and IR. The purpose of the present study was to explore the relationship between CTRP5 and IR through a cross-sectional study and drug intervention study of type 2 diabetes patients. MATERIALS AND METHODS: A cross-sectional study was carried out with 118 newly diagnosed patients with type 2 diabetes and 116 healthy adults. In an interventional study, 78 individuals with newly diagnosed type 2 diabetes received sodium-glucose cotransporter 2 inhibitor (dapagliflozin) treatment for 3 months. Circulating CTRP5 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Serum CTRP5 concentrations were markedly reduced in patients with type 2 diabetes when compared with those of healthy individuals (P < 0.01). When considering the study population as a whole, individuals with IR (homeostasis model of assessment of IR ≥2.78) had lower CTRP5 concentrations than the individuals without IR (homeostasis model of assessment of IR <2.78; P < 0.01). Serum CTRP5 negatively correlated with age, body mass index, waist-to-hip ratio, Systolic blood pressure, triglyceride, total cholesterol, glycated hemoglobin, fasting blood glucose, 2-h blood glucose, fasting insulin and homeostasis model of assessment of IR. After 12 weeks of sodium-glucose cotransporter 2 inhibitor treatment, serum CTRP5 levels in type 2 diabetes patients were significantly reduced accompanied with ameliorated glycometabolism and IR compared with before treatment (P < 0.01). CONCLUSIONS: CTRP5 is likely a marker for type 2 diabetes in humans.

Effect of Pre-Hospital Ticagrelor in Primary Percutaneous Coronary Intervention on Patients with ST-Segment Elevation Myocardial Infarction: A systematic review and meta-analysis.

OBJECTIVE: To determine the therapeutic effects of pre-admission ticagrelor in acute ST elevation myocardial infarction after primary percutaneous coronary intervention. METHODS: The meta analysis was conducted at the period from the establishment of the database to the February 2018 period, and comprised earlier studies that were selected after comprehensive search of PubMed, Medline, Excerpta Medica dataBASE and Cochrane databases. The studies compared the pre-treatment group (pre-hospital ticagrelor) with the control group (in-hospital ticagrelor) and found differences in primary percutaneous coronary intervention outcomes for sick individuals suffering from acute ST elevation myocardial infarction. RESULTS: The two studies selected together had 1915 subjects. The rate of stent thrombosis in the control group was higher than in the pre-treatment group (p<0.01), but there were no significant differences in all-cause mortality (p=0.88), myocardial infarction (p=0.17) and stroke (p=0.49). CONCLUSIONS: Pre-hospital ticagrelor decreased the incidence of stent thrombosis in patients with acute ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance.

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic-hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.