Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice.

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

Single-cell RNA sequencing reveals new subtypes of lens superficial tissue in humans.

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.

Pentraxin 3 in Circulating Microvesicles: a Potential Biomarker for Acute Heart Failure After Cardiac Surgery with Cardiopulmonary Bypass.

The aim of this study was to investigate whether pentraxin 3 (PTX3) in microvesicles (MVs) can be a valuable biomarker for the prediction of acute heart failure (AHF) after cardiac surgery with cardiopulmonary bypass (CPB). One hundred and twenty-four patients undergoing cardiac surgery with CPB were included and analyzed (29 with AHF and 95 without AHF). The concentrations of PTX3 in MVs isolated from plasma were measured by ELISA kits before, 12 h, and 3 days after surgery. Patients' demographics, medical history, surgical data, and laboratory results were collected. The levels of PTX3 in MVs were significantly elevated during perioperative surgery, which was increased more in the AHF group. The concentrations of PTX3 in MVs at postoperative 12 h were independent risk factors for AHF with the area under the ROC curve of 0.920. The concentration of PTX3 in MVs may be a novel biomarker for prediction of AHF after cardiac surgery.

Size Distribution of Microparticles: A New Parameter to Predict Acute Lung Injury After Cardiac Surgery With Cardiopulmonary Bypass.

Background: Acute lung injury (ALI) is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). No precise way, however, is currently available to predict its occurrence. We and others have demonstrated that microparticles (MPs) can induce ALI and were increased in patients with ALI. However, whether MPs can be used to predict ALI after cardiac surgery with CPB remains unknown. Methods: In this prospective study, 103 patients undergoing cardiac surgery with CPB and 53 healthy subjects were enrolled. MPs were isolated from the plasma before, 12 h after, and 3 d after surgery. The size distributions of MPs were measured by the LitesizerTM 500 Particle Analyzer. The patients were divided into two subgroups (ALI and non-ALI) according to the diagnosis of ALI. Descriptive and correlational analyzes were conducted between the size distribution of MPs and clinical data. Results: Compared to the non-ALI group, the size at peak and interquartile range (IQR) of MPs in patients with ALI were smaller, but the peak intensity of MPs is higher. Multivariate logistic regression analysis indicated that the size at peak of MPs at postoperative 12 h was an independent risk factor for ALI. The area under the curve (AUC) of peak diameter at postoperative 12 h was 0.803. The best cutoff value of peak diameter to diagnose ALI was 223.05 nm with a sensitivity of 88.0% and a negative predictive value of 94.5%. The AUC of IQR at postoperative 12 h was 0.717. The best cutoff value of IQR to diagnose ALI was 132.65 nm with a sensitivity of 88.0% and a negative predictive value of 92.5%. Combining these two parameters, the sensitivity reached 92% and the negative predictive value was 96%. Conclusions: Our findings suggested that the size distribution of MPs could be a novel biomarker to predict and exclude ALI after cardiac surgery with CPB.

MicroRNA-328-3p facilitates the progression of gastric cancer via KEAP1/NRF2 axis.

Gastric cancer is a common lethal malignancy and causes great cancer-related mortality worldwide. MicroRNA (miR)-328-3p is implicated in the progression of various human cancers; however, its role and mechanism in the progression of gastric cancer remain unclear.Human gastric cancer cells were incubated with miR-328-3p mimic, inhibitor or the matched negative control. Cell viability, colony formation, migrative and invasive capacity, cell apoptosis and oxidative stress were measured. To clarify the involvement of nuclear factor-E2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1), small interfering RNA was used. miR-328-3p was upregulated in human gastric cancer cells and tissues, and its level positively correlated with the progression of gastric cancer. miR-328-3p promoted cell viability, colony formation, migration and invasion, thereby facilitating the progression of gastric cancer. miR-328-3p mimic reduced, while miR-328-3p inhibitor increased apoptosis and oxidative stress of human gastric cancer cells. Mechanistically, miR-328-3p upregulated NRF2 via targeting KEAP1to attenuate excessive free radical production and cell apoptosis. miR-328-3p functions as an oncogenic gene and inhibiting miR-328-3p may help to develop novel therapeutic strategies of human gastric cancer.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Organocatalytic enantioselective SN1-type dehydrative nucleophilic substitution: access to bis(indolyl)methanes bearing quaternary carbon stereocenters.

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via enantioconvergent dehydrative nucleophilic substitution. A broad range of 3,3'-, 3,2'- and 3,1'-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99 : 1 er). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C-H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product. Mechanistic studies suggest a formal SN1-type pathway enabled by chiral phosphoric acid catalysis. The practicability of the obtained enantioenriched BIMs was further demonstrated by versatile transformation and high antimicrobial activities (3al, MIC: 1 µg mL-1).

Impaired immune and coagulation systems may be early risk factors for COVID-19 patients: A retrospective study of 118 inpatients from Wuhan, China.

The coronavirus disease 2019 (COVID-19) outbreak has become a global health threat and will likely be one of the greatest global challenges in the near future. The battle between clinicians and the COVID-19 outbreak may be a "protracted war."The objective of this study was to investigate the risk factors for in-hospital mortality in patients with COVID-19, so as to provide a reference for the early diagnosis and treatment.This study retrospectively enrolled 118 patients diagnosed with COVID-19, who were admitted to Eastern District of Renmin Hospital of Wuhan University from February 04, 2020 to March 04, 2020. The demographics and laboratory data were collected and compared between survivors and nonsurvivors. The risk factors of in-hospital mortality were explored by univariable and multivariable logistic regression to construct a clinical prediction model, the prediction efficiency of which was verified by receiver-operating characteristic (ROC) curve.A total of 118 patients (49 males and 69 females) were included in this study; the results revealed that the following factors associated with in-hospital mortality: older age (odds ratio [OR] 1.175, 95% confidence interval [CI] 1.073-1.287, P = .001), neutrophil count greater than 6.3 × 10 cells/L (OR 7.174, (95% CI 2.295-22.432, P = .001), lymphocytopenia (OR 0.069, 95% CI 0.007-0.722, P = .026), prothrombin time >13 seconds (OR 11.869, 95% CI 1.433-98.278, P = .022), D-dimer >1 mg/L (OR 22.811, 95% CI 2.224-233.910, P = .008) and procalcitonin (PCT) >0.1 ng/mL (OR 23.022, 95% CI 3.108-170.532, P = .002). The area under the ROC curve (AUC) of the above indicators for predicting in-hospital mortality were 0.808 (95% CI 0.715-0.901), 0.809 (95% CI 0.710-0.907), 0.811 (95% CI 0.724-0.898), 0.745 (95% CI 0.643-0.847), 0.872 (95% CI 0.804-0.940), 0.881 (95% CI 0.809-0.953), respectively. The AUC of combined diagnosis of these aforementioned factors were 0.992 (95% CI 0.981-1.000).In conclusion, older age, increased neutrophil count, prothrombin time, D-dimer, PCT, and decreased lymphocyte count at admission were risk factors associated with in-hospital mortality of COVID-19. The prediction model combined of these factors could improve the early identification of mortality risk in COVID-19 patients.

[Intervention of Qingshen Granule for Immune Inflammation of Chronic Renal Failure Patients with Damp-heat Syndrome].

Objective To observe the effect of Qingshen Granule (QG) on the immune function of chronic renal failure (CRF) patients with damp-heat syndrome (DHS). Methods A total of 162 CRF patients were assigned to the treated group and the control group by random digit table, 81 in each group. All patients were treated with conventional Western medical therapy. Those in the treated group addition- ally took QG, one package each time (10 g) , thrice per day. The therapeutic course for all was 12 weeks. The clinical efficacy was observed in the two groups. The contents of peripheral blood CD4 ⁺ T cells, CD8 ⁺ T cells, Thl7 cells, and nuclear factor-κB p65 (NF-κBp65) activity were detected using flow cy- tometry. Expressions of serum IL-17, tumor necrosis factor receptor-associated factor 6 (TRAF6), ma- trix metalloproteinase-9 (MMP-9) , matrix metalloproteinase inhibitor-I (TIMP-1 ) , collagen N (Col-V) were detected using ELISA. Results Finally 156 patients completed the trial (77 cases in the treated group and 79 cases in the control group). The total clinical curative effective rate was significantly higher in the treated group (80. 52%, 62/77) than in the control group (68. 35%, 54/79) with statistical differ- ences between the two groups (x² = 54. 849, P <0. 05). Compared with before treatment in the same group, the levels of peripheral blood CD4 ⁺ /CD8 ⁺ , Thl7 cell content, NF-κB p65 activity, serum levels of IL-17, TRAF6, and TIMP-1 , TIMP-1/MMP-9 ratio, Col-IV level all decreased in the treated group after treat- ment (P <0. 05) ; serum MMP-9 level decreased .(P <0. 05) and TIMP-1 /MMP-9 ratio increased (P <0. 05) in the control group. Compared with the control group, CD4⁺/CD8 ⁺ T cell ratio, Th17 cell content, NF-κB p65 activity decreased more obviously in the treated group after treatment (P <0. 05). Serum levels of IL- 17, TRAF6, TIMP-1, TIMP-1/MMP-9 ratio, and Col-IV all decreased (P <0.05) and MMP-9 level increased (P <0. 05) in the treated group (P <0. 05). Conclusion QG could adjust immune dysfunction and disar- ranged immunity mediated inflammatory response, and attenuate renal fibrosis in CKD patients with DHS.

Outcomes of tricuspid annuloplasty with and without prosthetic rings: a retrospective follow-up study.

BACKGROUND: The efficacies of tricuspid valve repair, risk factors for treatment failure and postoperative quality of life have not been thoroughly evaluated in patients with tricuspid insufficiency associated with rheumatic heart disease (RHD). We therefore reviewed our experience with ring and non-ring tricuspid annuloplasty for the treatment of functional tricuspid insufficiency (TI) in RHD. METHODS: This retrospective, follow-up study involved 74 RHD patients who underwent either non-ring annuloplasty (De Vega procedure; 34 patients, 45.95 %) or ring annuloplasty (40 patients, 54.05 %) along with concurrent mitral or/and aortic valve replacement. Operation time, cardiopulmonary bypass time, aortic clamping time, intensive care unit stay and extubation time were recorded. Echocardiographic findings and Short Form (SF)-36 scores were compared between the two groups. RESULTS: In hospital mortality and complications were similar in the two study groups (P = 0.6755). At 1 week, 1 month, 6 months, 1 year, 2 years and even longer after the operation, the Kaplan-Meier curve of freedom from mild and above recurrent TI showed significantly better efficacy in the ring annuloplasty group than the De Vega procedure group (log rank P = 0.0377). Risk factors for recurrent TI included high pulmonary artery systolic pressure (PASP) and non-ring annuloplasty (PASP: hazard ratio = 1.52; non-ring: hazard ratio = 1.42). The mental component summary score at 1 year after the operation did not significantly differ between the two groups (P = 0.6446), but the physical component summary score was significantly better in the ring annuloplasty group (P = 0.0037). CONCLUSION: Compared with non-ring annuloplasty, ring annuloplasty was associated with improved survival, decreased TI recurrence and higher quality of life in RHD patients undergoing tricuspid valve repair combined with mitral and/or aortic valve replacement.

[Clinical study on intervention of liuwei dihuang pill on hormonotherapy in treating nephrotic syndrome].

OBJECTIVE: To observe the intervention of liuwei dihuang pill (LDP) on therapeutic effectiveness and adverse reaction of hormonotherapy in treating nephrotic syndrome. METHODS: Patients allocated in two groups were medicated with initial dose of prednisone 1 mg/kg once a day at 8 am in the morning. After being medicated for 8 to 12 weeks, the dose of prednisone was decreased by 5.0 mg every 2 weeks till 0.5 mg/kg per day. Then the medication was changed to that two days' dosage orally take once a day with the daily dose reduced by 5.0 mg/kg every 2 to 3 weeks, and maintained at 0.4 mg/kg once every two days. At same time, necessary symptomatic treatment was given. To the treated group oral administration of LDP 8 capsules was given additionally, 3 times per day until prednisone decreased to maintenance dose. RESULTS: Therapeutic effect in the treated group was significant better than that in the control group (P < 0.05). Urinary protein, plasma albumin, triglyceride (TG) and total cholesterol (TC) in both groups were obviously improved (P < 0.05 or P < 0.01). However, as compared with the control group, the improvement was better, and the recurrent rate was lower (P < 0.05) in the treated group. Scores of Yin-deficiency caused excessive Fire syndrome and incidence rate of adverse reaction in the treated group were lower than those in the control group (P < 0.05 or P < 0.01). CONCLUSION: LDP can markedly improve the therapeutic effectiveness and counteract the adverse reaction of hormonotherapy in treating nephrotic syndrome, and reduce the recurrence of the disease.