Prognostic factors for acute posterior circulation cerebral infarction patients after endovascular mechanical thrombectomy: A retrospective study

This article was to analyze the factors influencing the prognosis of posterior circulation cerebral infarction (PCCI) patients, retrospectively.One hundred forty five patients diagnosed with PCCI in Nanyang Central Hospital between June 25, 2016 and October 14, 2019 were included and underwent cerebral vascular mechanical thrombectomy. The clinical data of those patients were collected. The patients were followed up for 3 months to observe the prognostic efficacy and explore the influencing factors for poor prognosis. The potential prognostic factors for PCCI patients after emergency endovascular mechanical thrombectomy were analyzed by univariate and multivariable logistic regression. The thermodynamic diagram was drawn to explore the associations between the prognostic factors.The risk of poor prognosis in PCCI patients receiving emergency endovascular mechanical thrombectomy was reduced by 0.552 time with every 1-point increase of the Alberta Stroke Program Early CT in posterior circulation score (odds ratio [OR] = 0.448, 95% confidence interval [CI]: 0.276–0.727). The risk of poor prognosis was increased by 0.827 time for each additional grade in the digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading (OR = 1.827, 95% CI: 1.221–2.733, P = .003) and increased by 0.288 time for every 1-point increase in National Institutes of Health Stroke scale at 24 hours (OR = 1.288, 95% CI: 1.161–1.429). All P < .05.Alberta Stroke Program Early CT in posterior circulation score, digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading, National Institutes of Health Stroke scale score at 24 hours were factors affecting the prognosis of PCCI patients undergoing emergency endovascular mechanical thrombectomy, which might provide evidence for endovascular treatment of PCCI.     

One-year efficacy of tenofovir alafenamide in patients with chronic hepatitis B: An observational study

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.We aimed to explore the efficacy after 1-year TAF treatment.A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000–1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079–0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003–1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m², P = .004) after 1-year TAF treatment.One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.     

Effectiveness of therapeutic hypothermia for mild neonatal encephalopathy: A protocol for systematic review and meta-analysis

Background:Neonates with moderate to severe encephalopathy benefit significantly from therapeutic hypothermia, with reduced risk of death or disability. However, the need for therapeutic hypothermia for mild neonatal encephalopathy (NE) remains unclear. Therefore, we conducted a protocol for systematic review and meta-analysis to provide evidence supporting therapeutic hypothermia for term or near term neonates with mild NE, including findings of recent long-term outcome studies, as well as novel adjunctive therapies to augment neurodevelopmental outcomes for neonates with NE who receive therapeutic hypothermia.Methods:Two independent researchers performed a systematic literature search in different electronic databases including PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Medline, Ovid, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database without any restrictions of languages and date. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. Two reviewers will assess the risk of bias of the included studies by the “Risk of Bias Assessment Tool” of the Cochrane Handbook for randomized controlled trials. Statistical analysis will be performed with Review Manager software 5.3.Results:A synthesis of current evidence of therapeutic hypothermia for treating mild NE will be provided in this protocol.Conclusion:The results of this study will provide a theoretical basis for the clinical use of therapeutic hypothermia in mild NE.     

Characteristics and immune checkpoint inhibitor effects on non-smoking non-small cell lung cancer with KRAS mutation: A single center cohort (STROBE-compliant)

Kirsten rat sarcoma (KRAS) mutation (KRASm) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. We have aimed to survey NSCLC patients harboring KRASm in Taiwan, where never-smoking lung adenocarcinoma predominates, and analyze the immune checkpoint inhibitor effect on NSCLC harboring KRASm.NSCLC patients with KRASm were enrolled and tested on programmed death-ligand 1 (PD-L1) expression using available tissue. We analyzed their clinical features, PD-L1 status, responses to ICIs, and overall survival (OS).We studied 93 patients with a median age 66.0 years, 23.7% of whom were women, and 22.6% were never-smokers. The results showed that G12C (36.6%) was the most common KRASm. In 47 patients with available tissue for PD-L1 testing, PD-L1 expression was positive in 66.0% of patients, while PD-L1 ≥50% was higher in ever-smokers (P = .038). Among 23 patients receiving ICI treatment, those with PD-L1 ≥50% experience a 45.5% response rate to ICI. There were benefits from ICI treatment on OS compared with no ICI treatment (median OS 35.6 vs 9.8 months, P = .002) for all of our patients, and for patients with PD-L1 ≥50% (median OS not-reached vs 8.4 months, P = .008). There were no differences in survival across different KRAS subtypes (P = .666).Never-smokers composed more than one-fifth of KRASm in NSCLC in Taiwan. A high PD-L1 expression was related to smoking history and responded well to ICI. ICI treatment improved the OS in NSCLC patients with KRASm, particularly those with PD-L1 ≥50%.     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Clinical course and outcomes of COVID-19 patients with chronic obstructive pulmonary disease: A retrospective observational study in Wuhan,China

Information about coronavirus disease 2019 (COVID-19) patients with pre-existing chronic obstructive pulmonary disease (COPD) is still lacking. The aim of this study is to describe the clinical course and the outcome of COVID-19 patients with comorbid COPD.This retrospective study was performed at Wuhan Huoshenshan Hospital in China. Patients with a clear diagnosis of COVID-19 who had comorbid COPD (N = 78) were identified. COVID-19 patients without COPD were randomly selected and matched by age and sex to those with COPD. Clinical data were analyzed and compared between the two groups. The composite outcome was the onset of intensive care unit admission, use of mechanical ventilation, or death during hospitalization. Multivariable Cox regression analyses controlling for comorbidities were performed to explore the relationship between comorbid COPD and clinical outcome of COVID-19.Compared to age- and sex-matched COVID-19 patients without pre-existing COPD, patients with pre-existing COPD were more likely to present with dyspnea, necessitate expectorants, sedatives, and mechanical ventilation, suggesting the existence of acute exacerbations of COPD (AECOPD). Greater proportions of patients with COPD developed respiratory failure and yielded poor clinical outcomes. However, laboratory tests did not show severer infection, over-activated inflammatory responses, and multi-organ injury in patients with COPD. Kaplan–Meier analyses showed patients with COPD exhibited longer viral clearance time in the respiratory tract. Multifactor regression analysis showed COPD was independently correlated with poor clinical outcomes.COVID-19 patients with pre-existing COPD are more vulnerable to AECOPD and subsequent respiratory failure, which is the main culprit for unfavorable clinical outcomes. However, COPD pathophysiology itself is not associated with over-activated inflammation status seen in severe COVID-19.     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.     

Displaced proximal humerus fractures treated with ORIF via the deltoid interfascicular approach vs the deltopectoral approach: A prospective case-control study

Background:The purpose of this study was to evaluate the clinical outcomes and complications of displaced proximal humeral fractures treated with proximal humeral internal locking system (PHILOS) plate fixation via a deltoid interfascicular (DI) vs a deltopectoral (DP) approach.Methods:This prospective case-control study was conducted with patients admitted to our hospital from May 2015 to June 2018 who suffered from unilateral displaced proximal humerus fractures. Patients were treated with PHILOS plate fixation via a DI (DI group) or DP approach (DP group). The clinical outcomes and complication data were collected for comparison between the 2 groups. The patients were followed up at 3, 6, and 12 months; and every 6 months thereafter. The patients’ functional recoveries were evaluated according to the normalized Constant-Murley score, range of motion of the shoulder (flexion, abduction, external/internal rotation) and disabilities of the arm, shoulder and hand score.Results:A total of 77 patients, followed for an average of 15 ± 2.2months (range, 12–21), were enrolled (36 in DI group and 41 in DP group) for final analysis. No significant differences in age, sex, affected side, fracture type, injury mechanism or time from injury to operation were found between the 2 groups (all P > .05). The incision length, intra-operative blood loss, and duration of operation in the DI group were significantly less than those in the DP group, respectively (all P < .05). The functional outcomes assessed by the normalized Constant-Murley score and range of motion of flexion and internal rotation in the DI group were superior to those in the DP group at 3 and 6months after the operation (P < .05); however, no significant differences were observed at the 12-month and subsequent follow-ups (all P > .05). There was no significant difference in the range of shoulder external rotation and abduction during the postoperative follow-ups (P > .05). At the last follow-up, the mean disabilities of the arm, shoulder, and hand score was 14.0 (6.6) points in the DI group and 14.4 (6.9) points in the DP group (P = .793). Complications occurred in 1 patient in the DI group and 8 patients in the DP group (P = .049).Conclusion:The current study demonstrates that DI approach is a safe and effective alternative for the treatment displaced proximal humerus fractures. The DI approach rather than DP approach was recommended when lateral and posterior exposure of the proximal humerus is required, especially when fixed with PHILOS plate.     

Efficacy analysis of Cheng’s GIRAFFE reconstruction after proximal gastrectomy for adenocarcinoma of esophagogastric junction

ObjectiveReconstruction of the digestive tract for adenocarcinoma of esophagogastric junction (AEG) is in dispute. This study evaluated Cheng’s gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus (Cheng’s GIRAFFE anastomosis) in laparoscopic/open proximal gastrectomy for Siewert type II AEG, which was performed at Zhejiang Cancer Hospital and the First Affiliated Hospital of Zhejiang Chinese Medical University. Here, we discuss the preliminary results of gastric emptying and anti-reflux.MethodsFrom a retrospective database, 74 patients with advanced Siewert type II AEG underwent curative proximal gastrectomy with GIRAFFE anastomosis, and their gastric emptying and anti-reflux outcomes were evaluated by the Reflux Disease Questionnaire (RDQ) score, nuclide gastric emptying, 24-h impedance-pH monitoring and gastroscopy.ResultsSeventy-four patients successfully completed proximal partial gastrectomy with Cheng’s GIRAFFE esophagogastric anastomosis. RDQ score six months after the operation was 2.2±2.5. Results of nuclide gastric emptying examinations showed that the gastric half-emptying time was 67.0±21.5 min, the 1-h residual rate was (52.2±7.7)%, the 2-h residual rate was (36.4±5.1)%, and the 3-h residual rate was (28.8±3.6)%; 24-h impedance-pH monitoring revealed that the mean DeMeester score was 5.8±2.9. Reflux esophagitis was observed by gastroscopy in 7 patients six months after surgery.ConclusionsCheng’s GIRAFFE anastomosis is safe and feasible for Siewert type II AEG.