Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis.

OBJECTIVE: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data were conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI. DATA SOURCES: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using Medline, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases. REVIEW METHODS: Meta-analyses of the reported relative risks (RR) or mean differences (MD) were conducted. Subgroup analyses determined the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed. RESULTS: Seven studies (n = 655) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% CI 1.30 - 3.04; p = .015) than patients treated with placebo. The HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at the 3 month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence), or all-cause mortality (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle-brachial index at 6 months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved 3 month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence). CONCLUSION: Hepatocyte growth factor treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts.

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

Drug-coated balloon for treatment of non-atherosclerotic renal artery stenosis-a multi-center study.

INTRODUCTION: Renal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment. METHODS AND ANALYSIS: This will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate. TRIAL REGISTRATION: ClinicalTrials.gov (number NCT05858190). Protocol version V.4 (3 May 2023).

Ant-Neointimal Formation Effects of SLC6A6 in Preventing Vascular Smooth Muscle Cell Proliferation and Migration via Wnt/ß-Catenin Signaling.

Vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of vascular remolding, such as atherosclerosis and restenosis. Solute carrier family 6 member 6 (SLC6A6) is a transmembrane transporter that maintains a variety of physiological functions and is highly expressed in VSMCs. However, its role on VSMCs during neointimal formation remains unknown. In this study, mRNA and protein levels of SLC6A6 were examined using models of VSMC phenotype switching in vivo and in vitro and human artery samples with or without atherosclerosis. SLC6A6 gain- and loss-of-function approaches were performed by adenovirus infection or small interfering RNA (siRNA) transfection, respectively. Reactive oxygen species (ROS), proliferation, migration, and phenotype-related proteins of VSMCs were measured. Vascular stenosis rate and related genes were assessed in a rat vascular balloon injury model overexpressing SLC6A6. SLC6A6 was downregulated in dedifferentiated VSMCs, atherosclerotic vascular tissues, and injured vascular tissues. SLC6A6 suppressed VSMC proliferation and migration, while increasing contractile VSMC proteins. Mechanistically, SLC6A6 overexpression reduced ROS production and inhibited the Wnt/ß-catenin pathway. Furthermore, SLC6A6 overexpression suppressed neointimal formation in vivo. Collectively, overexpression of SLC6A6 suppresses neointimal formation by inhibiting VSMC proliferation and migration via Wnt/ß-catenin signaling and maintaining the VSMC contractile phenotype.

[Clinical Efficacy of Haplo-HSCT of ATG Combined with PTCy for Children with Myelodysplastic Syndrome].

OBJECTIVE: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）. METHODS: From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed. RESULTS: Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%. CONCLUSION: Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.

Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring.

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4-16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II-III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

C-reactive Protein, Free Fatty Acid, and Uric Acid as Predictors of Adverse Events after Endovascular Revascularization of Arterial Femoropopliteal Occlusion Lesions.

OBJECTIVES: This study aimed to investigate the relationship between pre-procedure high-sensitivity C-reactive protein (hsCRP), free fatty acid (FFA), and uric acid (UA) levels and post-procedure mortality and morbidity of endovascular revascularization of arterial femoropopliteal occlusion lesions. METHODS: This was a retrospective review of clinical data retrieved from a prospectively held database in Peking Union Medical College Hospital. A total of 71 Patients who underwent endovascular treatment (EVT) for femoropopliteal occlusive disease between January 1, 2014 and November 1, 2017, were included in this study. Endpoints were defined as major adverse limb events (MALE; target vessel revascularization, amputation, or disease progression) and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or all-cause death) during the entire follow-up period. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship of elevated biomarker levels (hsCRP, FFA and UA, measured by immunoturbidimetry assay, enzymatic assay and enzymatic assay, respectively) to MALE and MACE outcomes. RESULTS: Seventy-one patients (72 limbs) with sufficient follow-up information were included in the analysis. The mean age was 69.7 ± 8.6 years; 21.1% were female. The Rutherford class of target limbs were ≥ 3. The median follow-up was 36 (range 18-59 months). Univariate analyses revealed that patients with elevated hsCRP levels had an increased risk of MALE (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.281-5.617, P = 0.009). High FFA levels were associated with an increased risk of MALE (HR, 2.658; 95% CI, 1.075-6.573; P = 0.034). Multivariate analyses demonstrated that elevated hsCRP values (HR, 4.015; 95% CI, 1.628-10.551; P = 0.003) and FFA value (HR, 3.034; 95% CI, 1.102-8.354; P = 0.032) were both significantly associated with increased MALE. Elevated UA levels predicted MACE in the presence of confounders (HR, 11.446; 95% CI, 1.367-95.801 P = 0.023). CONCLUSION: Pre-procedure hsCRP and FFA levels could serve as predictors of adverse events after EVT in patients with arterial femoropopliteal occlusive disease. The role of UA in MACE may warrant further investigation, because the correlation is not as powerful as the other two in the study.

Nano-Silver Medical Antibacterial Dressing Combined with High-Flow Oxygen Therapy Facilitates Ulcer Wound Healing of Superficial Malignant Tumors.

BACKGROUND: Due to the poor healing of superficial malignant tumor ulcer wounds, patients suffer great pain and significantly reduced quality of life. Related research shows that oxygen therapy can reduce wound bleeding and promote wound healing. OBJECTIVE: This study aims to explore the therapeutic effect of nano-silver antibacterial dressing combined with high-flow oxygen therapy on surface malignant tumor ulcers. METHODS: In this retrospective analysis, 64 patients with superficial malignant tumors and ulcer infection were included and divided into the research group and the control group, with 32 cases in each group. After conventional debridement, the control group was treated with vaseline dressing, while the research group was treated with nano-silver medical antibacterial dressing combined with high-flow oxygen therapy. Both groups were treated for 7 days. The frequency of dressing change and the number of times of blood oozing between the two groups after treatment were recorded. The pain, clinical efficacy, and levels of procalcitonin (PCT) and C-reactive protein (CRP) were compared between the two groups before and after treatment. RESULTS: The dressing changes and blood oozing were less frequent in the research group compared with the control group. The pain score and the levels of PCT and CRP in the research group were lower than those in the control group. The overall response rate was significantly higher in the research group as compared to the control group. All the above differences were statistically significant (P<0.05). CONCLUSION: Nano-silver medical antibacterial dressing combined with high-flow oxygen therapy can reduce the frequency of dressing changes in patients, relieve pain, reduce inflammation, and accelerate the healing of superficial malignant tumor ulcer wounds.

Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells.

Substantial evidence suggests that the effects of smoking in atherosclerosis are associated with inflammation mediated by endothelial cells. However, the mechanisms and potential drug therapies for smoking-induced atherosclerosis remain to be clarified. Considering that melatonin exerts beneficial effects in cardiovascular diseases, we examined its effects on cigarette smoke-induced vascular injury. We found that cigarette smoke extract (CSE) treatment induced NLRP3-related pyroptosis in human aortic endothelial cells (HAECs). CSE also induced ROS generation and upregulated the Nrf2 pathway in HAECs. Furthermore, pretreatment of HAECs with Nrf2-specific siRNA and an Nrf2 activator revealed that Nrf2 can inhibit CSE-induced ROS/NLRP3 activation. Nrf2 also improved cell viability and the expression of VEGF and eNOS in CSE-treated HAECs. In balloon-induced carotid artery injury model rats exposed to cigarette smoke, melatonin treatment reduced intimal hyperplasia in the carotid artery. Mechanistic studies revealed that compared with the control group, Nrf2 activation was increased in the melatonin group, whereas ROS levels and the NLRP3 inflammasome pathway were inhibited. These results reveal that melatonin might effectively protect against smoking-induced vascular injury and atherosclerosis through the Nrf2/ROS/NLRP3 signaling pathway. Overall, these observations provide compelling evidence for the clinical use of melatonin to reduce smoking-related inflammatory vascular injury and atherosclerosis.

A systematic review and meta-analysis on the association between C-reactive protein levels and adverse limb events after revascularization in patients with peripheral arterial disease.

OBJECTIVE: Patients with peripheral arterial disease (PAD) are predisposed to postprocedure adverse limb events (ALE). Previous single-center studies investigating the relationship between baseline C-reactive protein (CRP) levels and postprocedure ALE have reported inconsistent results. Therefore, we performed a systematic review and meta-analysis of reported data to determine the association between CRP levels and the occurrence of postprocedure ALE in patients with PAD. METHODS: Studies investigating the association between the CRP levels and postprocedure ALE (ie, target vessel revascularization, amputation, restenosis, disease progression, composite endpoint of any of these ALE) were identified in the Medline, EMBASE, and Cochrane databases. Meta-analyses of the reported hazard ratios (HRs) were conducted using an inverse variance-weighted random effects model. Subgroup analyses were performed to determine the differences in outcomes between open surgery and endovascular treatment. Pooled estimates are reported as HRs to compare higher and lower CRP levels and odds ratio or relative risk per unit increase in logeCRP (natural logarithm C-reactive protein). RESULTS: A total of eight studies involving 1460 participants were included in our meta-analysis. Patients with higher baseline CRP levels had a greater risk of ALE (HR, 1.09; 95% confidence interval, 1.00-1.18; P = .04) compared with those with lower baseline CRP levels. The pooled estimate of odds ratio and relative risk for ALE was 2.25 (95% confidence interval, 1.49-3.41; P < .01) per unit increase in logeCRP. Subgroup analyses found no significant differences in the pooled estimates in studies of open surgery vs endovascular treatment. CONCLUSIONS: Our results have demonstrated that high baseline CRP levels are predictive of ALE in patients with PAD after lower limb revascularization.

Cigarette smoke extract stimulates PCSK9 production in HepG2 cells via ROS/NF­κB signaling.

Cigarette smoke (CS) exposure is a risk factor for dyslipidemia and atherosclerosis. Reduced expression of low­density lipoprotein receptor (LDLR) in hepatocytes may be one of the underlying mechanisms for these disorders. The aim of the present study was to investigate the molecular mechanism underlying the regulatory effect of CS extract (CSE) on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low LDLR expression in HepG2 cells. PCSK9 and LDLR mRNA and protein expression levels in HepG2 cells were evaluated after CSE treatment via reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. In addition, total intracellular reactive oxygen species (ROS) production was determined via 2,7­dichlorofluorescein diacetate fluorescence. CSE significantly increased PCSK9 expression and inhibited LDLR expression in a time­ and concentration­dependent manner. Furthermore, CSE significantly induced ROS production and nuclear factor κB (NF­κB) activation. However, pretreatment with a ROS scavenger or an NF­κB inhibitor significantly attenuated the CSE­induced changes in PCSK9 and LDLR expression. In addition, pretreatment with melatonin markedly reduced ROS production, NF­κB activation and PCSK9 expression, and increased LDLR expression in the CSE­treated cells. These data suggest that melatonin inhibits CSE­regulated PCSK9 and LDLR production in HepG2 cells via ROS/NF­κB signaling.

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis.

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation.

An indirect comparison by Bayesian network meta-analysis of drug-coated devices versus saphenous vein graft bypass in femoropopliteal arterial occlusive disease.

OBJECTIVE: To compare the efficacy and safety between drug-coated devices (DCDs) and bypass surgery with saphenous vein graft (BSV) in femoropopliteal arterial occlusive disease. METHODS: A Bayesian network meta-analysis and indirect comparison were performed. Randomized controlled trials of BSV, bypass surgery with prosthetic graft, bare metal stents, endoluminal bypass (covered stent), percutaneous transluminal angioplasty, and DCDs treating femoropopliteal arterial occlusive disease were collected. The primary end point was target lesion revascularization/target vessel revascularization, and secondary end points were all-cause mortality, limb salvage, and early complications (PROSPERO registry number: CRD42019136530). RESULTS: Forty-two trials and 6867 patients were included. The comparison of DCDs and BSV revealed no significant difference in the 1-year target lesion revascularization/target vessel revascularization (DCDs vs BSV: odds ratio [OR], 0.60; 95% credible interval [CrI], 0.16-2.39). Total early complications from BSV were significantly higher than those from DCDs (DCDs vs BSV: OR, 0.14; 95% CrI, 0.05-0.45), and the main complications of BSV were not death related. There was also no significant difference in systemic early complications (DCDs vs BSV: OR, 0.19; 95% CrI, 0.00-7.82) and 1-year amputation rate (DCDs vs BSV: OR, 2.81; 95% CrI, 0.16-89.53). The 30-day (DCDs vs BSV: OR, 0.38; 95% CrI, 0.00-110.46), 1-year (DCDs vs BSV: OR, 0.96; 95% CrI, 0.24-3.29), 2-year (DCDs vs BSV: OR, 1.60; 95% CrI, 0.64-4.95), and 5-year all-cause mortality rates (DCDs vs BSV: OR, 2.05; 95% CrI, 0.92-4.39) showed no significant differences between DCDs and BSV, although there was a noticeable tendency toward significant results of a higher 5-year mortality rate. CONCLUSIONS: There is no significant difference between DCDs and BSV in short-term efficacy or short- and long-term mortality. Despite traditional BSV remaining the gold standard, DCDs provide a reasonable alternative therapy. In addition, the DCDs have a lower short-term morbidity associated with the procedure at the cost of the possible risk of higher long-term mortality. Clinical trials with more validity are required for a direct comparison between BSV and DCDs.

Systematic review and meta-analysis of the prevalence of venous thromboembolic events in novel coronavirus disease-2019 patients.

BACKGROUND: Emerging clinical evidence has shown that patients with the novel coronavirus disease-2019 (COVID-19) have complications that include venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE). The prevalence of VTE in patients hospitalized with COVID-19 is unclear. METHODS: Eligible studies on COVID-19 were collected from PubMed, Web of Science, and Embase. Patient characteristics and information were extracted for three categories of patients: consecutive, ICU, and non-ICU group. All PEs and DVTs were diagnosed by computed tomographic pulmonary arteriography and duplex ultrasound examination, respectively. A subgroup analysis of testing strategies in ICU and non-ICU patients for PE and DVT was also performed. RESULTS: Forty clinical studies involving 7966 patients hospitalized with COVID-19 were included. Pooled VTE prevalence was 13% in consecutive patients (95% confidence interval [CI], 0.05-0.24; I2 = 97%), 7% in non-ICU patients (95% CI, 0.01-0.18; I2 = 93%), and 31% in ICU patients (95% CI, 0.22-0.42; I2 = 91%). ICU patients had the highest prevalence of PE among the three groups (17% [95% CI, 0.12-0.23] vs 8% in consecutive patients [95% CI, 0.04-0.13], 4% in non-ICU patients [95% CI, 0.01-0.08]). ICU patients also had the highest DVT prevalence (25% [95% CI, 0.14-0.37] vs 7% in consecutive patients [95% CI, 0.03-0.14], and 7% in non-ICU [95% CI, 0.02-0.14]). The subgroup analysis showed a three-fold improvement in the PE and DVT detection rates in both ICU and non-ICU patients with COVID-19 when the screening test for VTE was applied. In the settings of screening tests for VTE, ICU patients have a significantly higher prevalence of PE (37% vs 10%; P < .0001) and DVT (40% vs 12%; P = .0065) compared with non-ICU patients. CONCLUSIONS: VTE is common in patients hospitalized with COVID-19, especially among ICU patients. Screening tests for PE and DVT may significantly improve detection rates in both ICU and non-ICU patients with COVID-19 than tests based on clinical suspicion.

Cigarette smoke exposure impairs lipid metabolism by decreasing low-density lipoprotein receptor expression in hepatocytes.

BACKGROUND: Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear. METHODS: In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%. RESULTS: The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 µM melatonin. CONCLUSIONS: In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers.

Endovascular Aortic Repair Is a Viable Strategy for Treatment of Primary Infected Abdominal Aortic Aneurysm.

BACKGROUND: Infected abdominal aortic aneurysm (IAAA) is rare, and information is limited whether endovascular aortic repair (EVAR) can be considered a permanent treatment or is a temporary fix preceding open surgery. This retrospective study reviewed the short- and long-term outcomes of open surgery, emergent EVAR, and elective EVAR in the treatment of primary IAAA. METHODS: Between January 2008 and January 2017, 16 men and 3 women (aged 60.7 y; range 30-76 y) with IAAA were treated with emergent open repair, emergent EVAR, or elective EVAR, after adjunctive antibiotic therapy. Demographics, aneurysm anatomy, clinical presentations, laboratory tests, details of aneurysm repair, morbidity, mortality, and postoperative outcomes of these patients were reviewed. RESULTS: Positive microbial cultures were obtained in 12 patients. Six and 3 patients underwent emergent EVAR and open repair, respectively. Ten patients who completed the full antibiotic regimen received elective EVAR. The mean follow-up duration was 28.8 mo (range, 1.5-96 mo). The 30-day mortality rates of the emergent EVAR, open repair, and elective EVAR groups were 16.7% (1/6), 0%, and 0%, respectively; the 1-year survival rates were 16.7% (1/6), 100% (1/1), and 88.9% (8/9). Reduction in the blood erythrocyte sedimentation rate (ESR) during the first week of antibiotic treatment was inversely related to aneurysm rupture and correlated with patients' post-EVAR survival time. CONCLUSIONS: Elective EVAR for IAAA had acceptable short- and long-term outcomes. Patients' response to initial antibiotic treatment may help facilitate management. Less than 0.130 reduction in ESR during the first week of antibiotic treatment may indicate risk of aneurysm rupture.

Metastatic low-grade endometrial stromal sarcoma with sex cord and smooth muscle differentiation: A case report.

BACKGROUND: Metastatic low-grade endometrial stromal sarcoma (LG-ESS) with sex cord-like and smooth muscle-like differentiation is rare. This article reports such a case with multiple recurrences and with extensive pelvic and abdominal metastasis. CASE SUMMARY: A 47-year-old female patient was diagnosed with multiple cystic masses in the pelvic cavity by magnetic resonance imaging examination. Based on the postoperative pathological and immunohistochemical analyses of the surgical specimen, she was diagnosed with a metastatic low-grade endometrial stromal sarcoma with sex cord and smooth muscle differentiation. CONCLUSION: LG-ESS is a low-grade malignant tumor with a high recurrence rate and metastasis probability. It is easily misdiagnosed initially. It is essential to distinguish LG-ESS with sex cord-like differentiation from uterine tumour resembling ovarian sex cord tumour.

[Genomics-based Biomarkers for Diseases:A Bibliometric Analysis Based on Web of Science].

Objective To analyze the research hotspots and trends of biomarkers for diseases based on genomics and thus provide basis for the future studies in this field. Method Based on the Web of Science,we analyzed the genomics-based biomarkers for diseases in literature published between 2006 and 2018 in terms of country and institutions,knowledge base,research hotspots,and trends by using bibliometric methods and CiteSpace software. Results A total of 998 articles were retrieved.The total number of articles has shown an upward trend and reached a peak of 112 in 2017 and 2018.Most articles(n=477)were from the United States,follwed by China(n=93).Nature,P Natl Acad Sci USA,PLoS One,Science,and New Engl J Med are core journals in this field.Keywords co-occurrence analysis identified four research hotspots:disease research,research method and technology,research level,and application purpose. Conclusion Research in functional genomics,cancer immunotherapy,genome-wide association and multi-omics techniques,personalized medicine,and precision medicine are research hotspots and frontiers in this field.

Remodeling the endoplasmic reticulum proteostasis network restores proteostasis of pathogenic GABAA receptors.

Biogenesis of membrane proteins is controlled by the protein homeostasis (proteostasis) network. We have been focusing on protein quality control of γ-aminobutyric acid type A (GABAA) receptors, the major inhibitory neurotransmitter-gated ion channels in mammalian central nervous system. Proteostasis deficiency in GABAA receptors causes loss of their surface expression and thus function on the plasma membrane, leading to epilepsy and other neurological diseases. One well-characterized example is the A322D mutation in the α1 subunit that causes its extensive misfolding and expedited degradation in the endoplasmic reticulum (ER), resulting in autosomal dominant juvenile myoclonic epilepsy. We aimed to correct misfolding of the α1(A322D) subunits in the ER as an approach to restore their functional surface expression. Here, we showed that application of BIX, a specific, potent ER resident HSP70 family protein BiP activator, significantly increases the surface expression of the mutant receptors in human HEK293T cells and neuronal SH-SY5Y cells. BIX attenuates the degradation of α1(A322D) and enhances their forward trafficking and function. Furthermore, because BiP is one major target of the two unfolded protein response (UPR) pathways: ATF6 and IRE1, we continued to demonstrate that modest activations of the ATF6 pathway and IRE1 pathway genetically enhance the plasma membrane trafficking of the α1(A322D) protein in HEK293T cells. Our results underlie the potential of regulating the ER proteostasis network to correct loss-of-function protein conformational diseases.