Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

The Synergistic Effect in CdS/g-C3N4 Nanoheterojunctions Improves Visible Light Photocatalytic Performance for Hydrogen Evolution Reactions.

This study focuses on the development of heterojunction photocatalysts for the efficient utilization of solar energy to address the energy crisis and reduce environmental pollution. Cadmium sulfide (CdS)/graphite-type carbon nitride (g-C3N4) nanocomposites were synthesized using a hydrothermal method, and their photoelectrochemical properties and photocatalytic performance for hydrogen evolution reaction (HER) were characterized. Scanning electron microscope images showed the intimate interface and caviar-like nanoheterojunction of the CdS nanoparticles on g-C3N4 nanospheres, suggesting their potential involvement in the photocatalytic process. Electrochemical and spectroscopic analyses were conducted to confirm the roles of CdS in the nanoheterojunction. The results showed that 10 wt% CdS/g-C3N4 nanospheres exhibited higher photocatalytic activity than pure g-C3N4 under visible light irradiation. A HER rate of 655.5 µmol/g/h was achieved after three photocatalytic cycles, signifying good photocatalytic stability. The synergistic effect of the Z-scheme heterojunction formed by g-C3N4 and CdS was identified as the main factor responsible for the enhanced photocatalytic performance and stability. The interface engineering effect of CdS/g-C3N4 facilitated the separation of photogenerated electrons and holes. This study provides insights into the design and fabrication of efficient HER photocatalysts.

Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis.

BACKGROUND: This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin. METHODS: PubMed, the Cochrane Library database, clinicaltrial.gov , and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH). RESULTS: Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03-1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15-20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36-7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68-4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25-4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different. CONCLUSIONS: The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.

The prognostic value of MELD-XI in elderly patients with ST-segment elevation myocardial infarction: an observational study.

BACKGROUND: The model for end-stage liver disease excluding international normalized ratio (MELD-XI) is a simple score for risk assessment. However, the prognostic role of MELD-XI and its additional value to current risk assessment in elderly patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is uncertain. METHODS: In all, 1029 elderly patients with STEMI undergoing PCI were consecutively included and classified into three groups according to the TIMI risk score: low-risk (≤ 3, n = 251); moderate-risk (4-6, n = 509); and high-risk (≥ 7, n = 269) groups. Multivariate analysis was performed to identify risk factors for adverse events. RESULTS: The overall in-hospital mortality was 5.3% and was significantly higher in the high-risk group (1.2% vs. 3.3% vs. 13.0%, p < 0.001). The optimal cut-off of the TIMI risk score and MELD-XI for in-hospital death was 7 and 13, respectively. MELD-XI was associated with in-hospital (adjusted odds ratio = 1.09, 95% CI = 1.04-1.14, p = 0.001) and one-year (adjusted hazard ratio = 1.05, 95% CI = 1.01-1.08, p = 0.005) mortality independently of the TIMI risk score. Combining TIMI risk score and MELD-XI exhibited better predictive power for in-hospital death than TIMI risk score (area under the curve [AUC] = 0.810 vs. 0.753, p = 0.008) or MELD-XI alone (AUC = 0.810 vs. 0.750, p = 0.018). Patients with TIMI risk score ≥ 7 and MELD-XI ≥ 13 had the worst prognosis. CONCLUSION: MELD-XI could be considered as a risk-stratified tool for elderly patients with STEMI undergoing PCI. It had an additive prognostic value to TIMI risk score.

Identification and functional study of immortalized mouse thymic epithelial cells.

As the key cells in a three-dimensional scaffold within the thymus, Thymic epithelial cells (TECs) play critical roles in the homing, migration and differentiation of T cell precursors through adhesive interactions and the release of various cytokines. In this study, primary cultures of mouse TECs were isolated and identified with TEC-specific antibodies CK5 and CK8. These TECs were immortalized by retroviral transduction of simian virus (SV) 40 large T antigen. We then compared the functions of TECs and immortalized TECs (iTECs). Cell morphology and the proliferative capacity of TECs and iTECs were observed by inverted microscope photography and crystal violet assay after passage. A soft agar assay was then performed to observe their clone formation ability. The expression levels of epithelial cell related factors, such as IL-7, Lptin, Pax-9, Sema3A and et al., were detected by IF and qPCR. TECs were co-cultured with human acute monocytic leukemia cells (THP-1), and the effect of TECs on promoting THP-1 proliferation was observed with flow cytometry and CFSE labeling. Senescence-associated ß-galactosidase assay was measured to detect the anti-aging capabilities of the cells. Cell cycle distribution was analyzed by propidium iodide (PI) staining, and paclitaxel (PTX)-induced apoptosis was detected by Annexin V-PI staining to evaluate the anti-apoptotic ability of the cells. Throughout, we found that the immortalized TECs still retain the characteristics of primary TECs, such as the morphology, function and epithelial characteristics; however, iTECs have stronger capabilities in proliferation and anti-aging. Our research suggests that the iTECs were successfully immortalized by SV40 large T antigen, and that the biological characteristics and functions of iTECs were similar to the original TECs. This immortalized cell can be used as an efficient cell model in functional research of the thymus substituting primary TECs with iTECs.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure: A Network Meta-Analysis.

BACKGROUND: Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments. METHODS: A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF. RESULTS: Fifty randomized controlled trials were identified. Relative to placebo, no increased risk of HF events was seen for vildagliptin (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.25-1.68), sitagliptin (RR 0.86; CI 0.43-1.57), or saxagliptin (RR 0.84; 95% CI 0.33-1.61), but alogliptin was associated with a higher risk of HF (RR 2.13; 95% CI 1.06-6.26). Vildagliptin and sitagliptin were associated with a significantly decreased risk of HF compared with alogliptin. Vildagliptin had the highest probability to be the safest option with regard to the risk of HF (49.18%), followed by saxagliptin (26.56%), sitagliptin (20.76%), linagliptin (0.25%), and alogliptin (0.12%). A statistically significant inconsistency was noted in some comparisons. CONCLUSIONS: The risk of HF needs to be taken into account when prescribing DPP-4 inhibitors. Evidence suggests that vildagliptin may be the least harmful agent with regard to the risk of HF. However, a statistically significant inconsistency was identified in the Bayesian network meta-analysis. Therefore, further studies are warranted to evaluate the cardiovascular safety of DPP-4 inhibitors.

Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials.

BACKGROUND: The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. METHODS: PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. RESULTS: Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03-1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06, 95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION: In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.

Measles Outbreak among Previously Immunized Adult Healthcare Workers, China, 2015.

Measles is caused by measles virus belonging to genus Morbillivirus of the family Paramyxoviridae. Vaccination has played a critical role in controlling measles infection worldwide. However, in the recent years, outbreaks of measles infection still occur in many developing countries. Here, we report an outbreak of measles among healthcare workers and among the 60 measles infected patients 50 were healthcare workers including doctors, nurses, staff, and medics. Fifty-one patients (85%) tested positive for IgM antibodies against the measles virus and 50 patients (83.3%) tested positive for measles virus RNA. Surprisingly, 73.3% of the infected individuals had been previously immunized against measles. Since there is no infection division in our hospital, the fever clinics are located in the Emergency Division. In addition, the fever and rash were not recognized as measles symptoms at the beginning of the outbreak. These factors result in delay in isolation and early confirmation of the suspected patients and eventually a measles outbreak in the hospital. Our report highlights the importance of following a two-dose measles vaccine program in people including the healthcare workers. In addition, vigilant attention should be paid to medical staff with clinical fever and rash symptoms to avoid a possible nosocomial transmission of measles infection.

Relationship between the health poverty vulnerability and multimorbidity patterns identified with latent class analysis aged 45 years or more adults in Northwestern China: A cross-section study.

This study aims to identify multimorbidity patterns and examine whether health poverty vulnerability (HPV) varies among adults aged 45 years or more. Data from 4338 participants were extracted from a Chinese cross-sectional study. Latent class analysis was used to identify multimorbidity patterns based on 11 self-reported chronic diseases. A 3-stage feasible generalized least-squares method was used to measure the HPV. The associations and influencing factors were analyzed using the Tobit model. The mean HPV values were 0.105 ±â€…0.225 and 0.329 ±â€…0.357, based on extreme poverty and those of low- and middle-income countries' poverty line, respectively. Four latent multimorbidity patterns were identified, comprising hypertension (57.33%), cardiovascular diseases (19.94%), the musculoskeletal system (13.09%), and spine (9.64%). The HPV value from hypertension (coefficient [Coef] =0.03, 95% confidence interval (CI) = 0.00-0.05) was significantly higher than that of the musculoskeletal system based on extreme poverty. In addition, the HPV values for hypertension (Coef =0.08, 95% CI = 0.05-0.11), spine (Coef =0.06, 95% CI = 0.02-0.11), and cardiovascular diseases (Coef =0.07, 95% CI = 0.03-0.11) were significantly high based on low- and middle-income countries' poverty line. Age ≥75 years, registered poor households, catastrophic medical expenditure, and toilet style were major risk factors. Although the multimorbidity pattern-induced HPV has been significant improved on extreme poverty, it still poses a very serious challenge with regard to low- to middle-income countries' poverty line. The sensitivity analysis proved the robustness of the results. Policymakers should focus on adults with 3 multimorbidity patterns, namely, registered poor households, age ≥75 years, and catastrophic health expenditure, to adopt targeted interventions to prevent and eliminate HPV.

Jiawei Taohe Chengqi Decoction attenuates CCl4 induced hepatic fibrosis by inhibiting HSCs activation via TGF-ß1/CUGBP1 and IFN-γ/Smad7 pathway.

BACKGROUND: Hepatic fibrosis (HF) is an essential stage in the progression of different chronic liver conditions to cirrhosis and even hepatocellular carcinoma. The activation of hepatic stellate cells (HSCs) plays a crucial role in the progression of HF. IFN- γ/Smad7 pathway can inhibit HSCs activation, while TGF-ß1/CUGBP1 pathway can inhibit IFN-γ/Smad7 pathway transduction and promote HSCs activation. Thus, inhibiting the TGF-ß1/CUGBP1 pathway and activating the IFN-γ/Smad7 pathway reverses HSCs activation and inhibits HF. Jiawei Taohe Chengqi Decoction (JTCD) was derived from the Taohe Chengqi Tang in the ancient Chinese medical text titled "Treatise on Febrile Diseases". We found several anti-HF components in JTCD including ginsenoside Rb1 and others, but the specific mechanism of anti-HF in JTCD is not clear. PURPOSE: To elucidate the specific mechanism by which JTCD reverses HF by inhibiting the activation of HSCs, and to establish a scientific foundation for treating HF with Traditional Chinese medicine (TCM). METHODS: We constructed a CCl4-induced mice HF model in vivo and activated human hepatic stellate cell line (LX-2) with TGF-ß1 in vitro, after which they were treated with JTCD and the corresponding inhibitors. We examined the expression of pivotal molecules in the two pathways mentioned above by immunofluorescence staining, Western blotting and RT-PCR. RESULTS: JTCD attenuated liver injury and reduced serum ALT and AST levels in mice. In addition, JTCD attenuated CCl4-induced HF by decreasing the expression of α-SMA, COL1A1 and other markers of HSCs activation in mice liver tissue. Moreover, JTCD effectively suppressed the levels of TGF-ß1, p-Smad3, p-p38MAPK, p-ATF2, and CUGBP1 in vivo and in vitro and upregulated the levels of IFN-γ, p-STAT1, and Smad7. Mechanically, after using the inhibitors of both pathways in vitro, we found that JTCD inhibited the activation of HSCs by restoring the balance of the TGF-ß1/CUGBP1 and IFN-γ/Smad7 pathways. CONCLUSION: We demonstrated that JTCD inhibited HSCs activation and reversed HF by inhibiting the TGF-ß1/CUGBP1 signalling pathway and upregulating the IFN-γ/Smad7 signalling pathway. Moreover, we have identified specific links where JTCD interferes with both pathways to inhibit HSCs activation. JTCD is an effective candidate for the clinical treatment of HF.

Housing conditions, cooking fuels, and health-related quality of life among rural middle-aged and elderly in northwest China: A ten-year balanced panel study.

To investigate the impacts of improving housing conditions and transitioning to clean cooking fuels on health-related quality of life (HRQOL) among middle-aged and elderly populations in rural China. METHODS: Using a 10-year longitudinal follow-up study, we examined changes in housing conditions, cooking fuel use, and HRQOL among 690 Chinese adults aged 45 above in rural areas. HRQOL was assessed using the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. Generalized estimating equations were utilized to analyze correlations between variables. RESULTS: Using four-period balanced panel data of 10 years, there were significant differences in the self-reporting of mobility, self-care, usual activities, pain / discomfort and anxiety / depression in rural middle-aged and elderly people (p < 0.05). In terms of the EQ-5D index score and EQ-VAS score, showed a decreasing trend (p < 0.05). The housing area, housing material type, utilization of sanitary toilets, separation of housing and kitchen were separated and non-solid fuels used as cooking fuel were significantly associated with high HRQOL (p < 0.05). CONCLUSIONS: This study found that good housing conditions and the use of non-solid cooking fuel had positive effects on health-related quality of life of middle-aged and elderly people in rural areas of northwest China.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score­matched SEER database analysis.

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). AIM OF STUDY: The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. MATERIALS AND METHODS: Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. RESULTS: Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. CONCLUSION: In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.

Jiawei Taohe Chengqi Decoction attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Decoction (JTCD) is a Traditional Chinese Medicine (TCM) formula modified from Taohe Chengqi Decoction in the classic ancient literature of TCM "Treatise on Febrile Diseases". Clinical and pharmacological studies have shown that JTCD has a therapeutic effect on hepatic encephalopathy, non-alcoholic fatty liver, cirrhotic ascites, and can alleviate acute liver injury in rats. Our previous studies confirmed that JTCD could alleviate hepatic fibrosis and activation of hepatic stellate cells (HSCs). However, its mechanism remains unclear. AIM OF THE STUDY: This study aimed to elucidate the mechanism of Src Signal on hepatic fibrosis and HSCs activation, and whether JTCD inhibited hepatic fibrosis and HSCs activation through affecting Src Signal. MATERIALS AND METHODS: In vivo, sixty specific pathogen free male C57/BL6 mice were divided into following six groups: Control group, Model group, SARA group, JTCD low dose group, JTCD medium dose group and JTCD high dose group. Then we established a carbon tetrachloride (CCL4)-induced hepatic fibrosis mice model, each JTCD group was given the corresponding dose of JTCD by gavage, the SARA group was given Saracatinib and the control group was given saline, once a day for 4 consecutive weeks. UPLC-Q-TOF-MS analyzed chemical components of JTCD. Pathological examination including Hematoxylin and Eosin (H&E), Masson and Sirius red staining was used to observe the characteristic of hepatic fibrosis. Automatic biochemical analyzer detected the levels of alanine aminotransfease (ALT), and aspartate transaminase (AST) in serum. Western-blot and immunohistochemical staining (IHC) detected protein expression. In vitro, we used shRNA to knock down the expression of Src in immortalized human hepatic stellate cell line (LX-2), then intervened with ERK1/2 agonists/inhibitors and JTCD-containing serum after transforming growth factor ß1 (TGF-ß1) treatment. Immunofluorescence and western-blot detected protein expression. The migratory characteristic of HSCs was assessed by wound-healing assay. RESULTS: We identified 135 chemical components in the water extract of JTCD, and the water extract of JTCD contains a variety of anti-hepatic fibrosis components. Compared to the model group, hepatic fibrosis performance was significantly improved, the serum levels of ALT and AST were significantly decreased in JTCD groups and SARA group, IHC staining and western blot results indicated that JTCD decreased the expressions of α-smooth muscle actin (α-SMA), phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3. In vitro, JTCD-containing serum could significantly decrease the protein expressions of α-SMA, phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3 according to the results of western-blot and immunofluorescence, in addition, JTCD-containing serum inhibited the mobility and activation of LX-2. What's more, after intervening with Src-shRNA, ERK1/2 agonists/inhibitors and JTCD-containing serum, the western-blot results showed that Src/ERK/Smad3 signal has an important role in hepatic fibrosis and HSCs, and JTCD attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway. CONCLUSIONS: The results showed that Src kinase promoted hepatic fibrosis and HSCs activation through the ERK/Smad3 signal pathway. More importantly, the mechanism by which JTCD attenuated hepatic fibrosis and HSCs activation was by inhibiting the Src/ERK/Smad3 signal pathway.

New Perspectives on Chinese Medicine in Treating Hepatic Fibrosis: Lipid Droplets in Hepatic Stellate Cells.

Hepatic fibrosis (HF) is a wound healing response featuring excessive deposition of the extracellular matrix (ECM) and activation of hepatic stellate cells (HSCs) that occurs during chronic liver injury. As an initial stage of various liver diseases, HF is a reversible pathological process that, if left unchecked, can escalate into cirrhosis, liver failure, and liver cancer. HF is a life-threatening disease presenting morbidity and mortality challenges to healthcare systems worldwide. There is no specific and effective anti-HF therapy, and the toxic side effects of the available drugs also impose a heavy financial burden on patients. Therefore, it is significant to study the pathogenesis of HF and explore effective prevention and treatment measures. Formerly called adipocytes, or fat storage cells, HSCs regulate liver growth, immunity, and inflammation, as well as energy and nutrient homeostasis. HSCs in a quiescent state do not proliferate and store abundant lipid droplets (LDs). Catabolism of LDs is characteristic of the activation of HSCs and morphological transdifferentiation of cells into contractile and proliferative myofibroblasts, resulting in the deposition of ECM and the development of HF. Recent studies have revealed that various Chinese medicines (e.g., Artemisia annua, turmeric, Scutellaria baicalensis Georgi, etc.) are able to effectively reduce the degradation of LDs in HSCs. Therefore, this study takes the modification of LDs in HSCs as an entry point to elaborate on the process of Chinese medicine intervening in the loss of LDs in HSCs and the mechanism of action for the treatment of HF.

[Research progress of survival predictive score in veno-arterial extracorporeal membrane oxygenation].

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal circulation technique that provides circulatory and oxygenation support, and it is currently used in the treatment of cardiogenic shock (CS), pulmonary embolism, cardiac arrest (CA), and other diseases. However, this technology is still associated with high complications and mortality. The use of predictive scores for risk stratification before VA-ECMO will be helpful to screen the optimal benefiting population, make optimal clinical decisions, and allocate medical resources reasonably. At present, there are few reports about predictive scores for VA-ECMO. This article systematically reviewed the predictive performance of various scoring tools [the survival after venoarterial ECMO (SAVE) score, prediction of cardiogenic shock outcome for acute myocardial infarction (AMI) patients salvaged by VA-ECMO (ENCOURAGE) score, model for end-stage liver disease (MELD-XI) score, post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) score, the predicting mortality in patients undergoing VA-ECMO after coronary artery bypass grafting (REMEMBER) score, predictors of mortality with VA-ECMO for acute massive pulmonary embolism, extracorporeal cardiopulmonary resuscitation (ECPR) score, the hypothermia outcome prediction after extracorporeal life support (HOPE) score] for patients receiving VA-ECMO to provide reference for clinical treatment.

Benefit of sodium-glucose cotransporter-2 inhibitors on survival outcome is related to the type of heart failure: A meta-analysis.

AIMS: This meta-analysis aimed to evaluate the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in different types of heart failure (HF). METHODS: Randomized controlled trials (RCTs) comparing SGLT-2 inhibitors with placebo in patients with HF were searched in PubMed, the Cochrane Library database, and clinicaltrials.gov. A random-effects model was used for evidence synthesis. The primary endpoint was cardiac death. RESULTS: We included 13 studies (12 RCTs). In patients with HF with preserved ejection fraction (HFpEF), SGLT-2 inhibitors reduced the composite endpoint of cardiac death or rehospitalization because of HF (HHF) (HR: 0.78, 95% CI: 0.70-0.87, I2 = 0%, P < 0.001) and that of HHF (HR: 0.74; 95% CI: 0.64-0.85, I2 = 0%, P < 0.001) but not that of cardiac death (HR: 1.01, 95% CI: 0.80-1.28, I2 = 23.9%, P = 0.943). In patients with HF with reduced EF (HFrEF), SGLT-2 inhibitors reduced the composite endpoint of cardiac death or HHF (HR: 0.75, 95% CI: 0.69-0.82, I2 = 0%, P < 0.001) and the individual endpoints of cardiac death (HR: 0.84, 95% CI: 0.75-0.95, I2 = 0%, P = 0.007) and HHF (HR: 0.69, 95% CI: 0.62-0.77, I2 = 0%, P < 0.001). CONCLUSIONS: SGLT-2 inhibitors reduced the risk of cardiac death in patients with HFrEF but not in those with HFpEF.

Comparative differences in the risk of major gastrointestinal bleeding among different direct oral anticoagulants: An updated traditional and Bayesian network meta-analysis.

Background: The most favorable gastrointestinal (GI) bleeding safety profile among different types of direct oral anticoagulants (DOACs) remains controversial. This meta-analysis includes the latest studies and aims to compare GI bleeding risk associated with the use of various DOACs. Methods: PubMed, Cochrane library, and clinicaltrial.gov were searched. Randomized control trials (RCTs) evaluating the safety of DOACs were identified. The primary endpoint assessed was major GI bleeding. Results: A total of 37 RCTs were included in the analyses. Based on the traditional meta-analysis, the major GI bleeding risk was different among various DOACs (interactive p-value <.10). Network meta-analysis findings showed that no DOACs increased the risk of major GI bleeding compared with conventional therapy. Furthermore, a 10 mg daily administration of apixaban reduced the major GI bleeding risk more than daily doses of 60 mg edoxaban, ≥15 mg rivaroxaban, and 300 mg dabigatran etexilate. No difference was observed between daily doses of 300 mg dabigatran etexilate, 60 mg edoxaban, and ≥15 mg rivaroxaban. The major GI bleeding risk associated with 30 mg daily dose of edoxaban was lower than with 10 mg daily rivaroxaban, and no differences between daily 5 mg apixaban, 30 mg edoxaban, and 220 mg dabigatran etexilate were observed. Conclusion: Differences in the major GI bleeding risk were observed when various DOACs were compared. Among standard-dose DOACs, apixaban was associated with the lowest degree of major GI risk. Among low-dose DOACs, edoxaban was associated with a lower major GI bleeding risk than rivaroxaban.