A retrospective study on the effect of Chinese patent medicine combined with conventional treatment on the survival outcomes of 313 patients with stage II-III NSCLC.

PURPOSE: We aim to explore the effect of Chinese Patent Medicine (CPM), including Huisheng oral solution (HSOS) on the 4-year survival rate of patients with stage II and III non-small cell lung cancer, and assess the association between blood coagulation indicators and survival outcomes. MATERIALS AND METHODS: 313 patients diagnosed with stage II and III NSCLC were collected during 2015-2016. Kaplan-Meier method and Cox proportional hazard model were applied to analyze the factors affecting the 4-year survival rate of patients. RESULTS: According to the effect of CPM, the medicine prescribed in this study could be classified into two types. The proportion of patients who received "Fuzheng Quyu" CPM for more than three months was higher than the proportion of patients who received other two types of CPM for more than three months. Medical records of 313 patients with NSCLC were analyzed. 4-year survival rate for patients received CPM more than 6 months and 3 months were higher than those received CPM less than 3 months (P = 0.028 and P = 0.021 respectively. In addition, 4-year survival rate for patients who received HSOS for more than 3 months was higher than those who received HSOS for less than 3 months (P = 0.041). Patients with elevated preoperative fibrinogen (FIB) level and those without surgery had an increased mortality risk (HR = 1.98, P < 0.01, and HR = 2.76, P < 0.01 respectively). CONCLUSION: The medium and long-term use of CPM/HSOS was positively associated with higher survival rate in NSCLC patients. Patients with high-level preoperative FIB level and those without surgery might have a poor prognosis in the following years.

[Application Value of Plasma vWF and ADAMTS-13 in Evaluating Postoprative Vascular Endothelial Injury and Prognosis in Children with VSD].

OBJECTIVE: To dynamically observe the levels and activities of von Willebrand factor (vWF) and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in plasma of children with congenital ventricular septal defect (VSD) during perioperative period, and explore the value of plasma vWF antigen (vWF:Ag) and ADAMTS-13 activity (ADAMTS-13: AC) in evaluating vascular endothelial injury and prognosis in children with VSD. METHODS: In this cross-sectional study, a total of 74 children with VSD who underwent surgical treatment in TEDA International Cardiovascular Hospital from September 2018 to March 2019 were enrolled in the observation group. Among them, there were 28 cases of pure VSD, 32 cases of VSD combined with pulmonary hypertension, and 14 cases of VSD combined with valvular heart disease. 31 healthy children who underwent physical examination in Tianjin Children's Hospital during the same period were collected as the control group. The biochemical indexes of the children at admission were recorded. Peripheral plasma was collected at admission, postsurgery day 0 and day 1, respectively, and the levels of vWF activity (vWF:AC), vWF:Ag, ADAMTS-13 antigen (ADAMTS-13:Ag) and ADAMTS-13:AC were detected. RESULTS: The level of plasma vWF:Ag and vWF:AC in the observation group before surgery were significantly lower than those in the control group (P<0.001), and increased continuously, on postsurgery day 0 and day 1 (P<0.001). The level of ADAMTS-13:Ag in the observation group before surgery was significantly higher than that in the control group (P<0.001), which decreased significantly on postsurgery day 0 (P<0.001), and increased significantly on postsurgery day 1 compared with postsurgery day 0 (P=0.033). The level of ADAMTS-13:AC in the observation group before surgery was significantly lower than that in the control group (P=0.015), which decreased significantly on postsurgery day 0 (P=0.037), and increased on postsurgery day 1, but the difference was not statistically significant (P=0.051). The changes of vWF and ADAMTS-13 in the three subgroups were basically similar to the observation group. vWF: Ag/ADAMTS-13: AC ratio on postsurgery day 0 and day 1 had high diagnostic value in vascular endothelial injury (AUC=0.80, P<0.001; AUC=0.93, P<0.001). Preoperative vWF and ADAMTS-13 levels, and related baseline indicators were not correlated with postoperative infection, bleeding, thrombosis,etc. CONCLUSION: Preoperative vWF: Ag, vWF: AC and ADAMTS-13: AC levels in children with VSD are low, while the level of ADAMTS-13: Ag is high. After surgery, the levels of vWF: Ag and vWF: AC are increased and the level of ADAMTS-13: Ag is decreased. The postoperative vWF: Ag/ADAMTS-13: AC ratio shows high diagnostic value in evaluating vascular endothelial injury. There is no correlation between preoperative vWF and ADAMTS-13 levels with perioperative clinical events.

Extensive prediction of drug response in mutation-subtype-specific LUAD with machine learning approach.

Background: Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide. Therapeutic failure in lung cancer (LUAD) is heavily influenced by drug resistance. This challenge stems from the diverse cell populations within the tumor, each having unique genetic, epigenetic, and phenotypic profiles. Such variations lead to varied therapeutic responses, thereby contributing to tumor relapse and disease progression. Methods: The Genomics of Drug Sensitivity in Cancer (GDSC) database was used in this investigation to obtain the mRNA expression dataset, genomic mutation profile, and drug sensitivity information of NSCLS. Machine Learning (ML) methods, including Random Forest (RF), Artificial Neurol Network (ANN), and Support Vector Machine (SVM), were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods. The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods, and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype. Finally, the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets. Results: Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs. Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response (area under the curve [AUC] 0.875) using CIT, GAS2L3, STAG3L3, ATP2B4-mut, and IL15RA-mut as molecular features. Furthermore, the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance (AUC 0.780) in Gefitinib with CCL23-mut. Conclusion: This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.

Comparison of Improvement in 2-Year Survival Rate of Patients with Stage II-III Non-Small Cell Lung Cancer Treated with Different Durations of Chinese Patent Medicine: A Retrospective Cohort Study.

Background: Chinese patent medicine is widely used among patients with malignant tumors, and current studies have shown that long-term treatment with Chinese patent medicine is related to improved outcomes of patients. Huisheng Oral Liquid is a kind of Chinese patent medicine with the effects of curing dispersion-thirst and dissipating blood stasis. However, little is known about how it affects the survival rate of patients. Thus, patients with stage II-III NSCLC (non-small-cell lung cancer) were chosen to participate in a retrospective cohort study, which was conducted to preliminarily investigate the effects of using Chinese patent medicine and Huisheng Oral Liquid for different treatment durations on patients' 2-year survival rate and explore the prognostic factors affecting the 2-year survival rate of those patients. Purpose: This work compares the effect of different durations of treatment with Chinese patent medicine and Huisheng Oral Liquid on the 2-year survival rate of patients with stage II-III NSCLC and explores the prognostic factors of the patients' 2-year survival rate. Methods: This retrospective cohort study included patients with non-small cell lung cancer stage II-III according to the 2015 NCCN Guidelines: Non-Small Cell Lung Cancer. The Kaplan-Meier method was used to compare the 2-year survival rate of patients treated with different durations of Chinese medicine and Huisheng Oral Liquid. The relationship between different treatment durations and degree of improvement of 2-year survival rate was explored using the Cochran-Armitage trend test. The Cox proportional-hazards regression models were used to explore factors affecting the 2-year survival rate of patients. Results: A total of 614 patients with stage II-III NSCLC diagnosed from January 2015 to December 2018 were included in this study. Patients treated with Chinese patent medicine were divided into three groups by treatment durations: < 3 months, ≥ 3 months, and ≥6 months, and those treated with Huisheng Oral Liquid were divided into < 3 months and ≥3 and ≥6 months. The results showed that ① the 2-year survival rate of patients treated with Chinese patent medicine for ≥3 months and ≥6 months was higher than that of patients treated for <3 months and the difference was statistically significant (p < 0.05). Further analysis of Huisheng Oral Liquid treatment revealed that ② the 2-year survival rate of patients treated with Huisheng Oral Liquid for ≥3 months was higher than that of patients treated for <3 months (p < 0.05). Because the total number of patients treated with Huisheng Oral Liquid for ≥6 months and the number of patients with improved outcomes were too small, there was no statistically significant difference in the 2-year survival rate between the two groups (p > 0.05). The results of the Cochran-Armitage trend test showed that the 2-year survival rate tended to increase with the duration of Huisheng Oral Liquid treatment (p < 0.05). ③ The Cox proportional -hazards regression model revealed that among all 614 patients, surgery [HR = 0.48, 95% CI = (0.34, 0.68)], chemotherapy [HR = 0.46, 95% CI = (0.31,0.67)], and treatment with Huisheng Oral Liquid for ≥3 months were protective factors [HR = 0.48, 95%CI = (0.27,0.88)], whereas male gender [HR = 1.59, 95% CI = (1.01, 2.50)] and FIB ≥4 g/L [HR = 1.95, 95% CI = (1.37, 2.77)] were risk factors. Conclusion: Chinese patent medicine treatment for ≥3 months showed an improvement in the 2-year survival rate of patients with stage II-III NSCLC. Patients treated with Huisheng Oral liquid for ≥3 months also showed an improvement in the 2-year survival rate, and the 2-year survival rate tended to increase as the treatment duration increased. Finally, male and FIB ≥ 4 g/L were risk factors for prognosis.

Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p.

Rationale: Cardiac fibrosis is an important feature of cardiac remodeling and is a hallmark of heart failure. Recent studies indicate that elevated IgE plays a causal role in pathological cardiac remodeling. However, the underlying mechanism of how IgE promotes cardiac fibrosis has not been fully elucidated. Methods and Results: To explore the function of IgE in cardiac fibrosis, we stimulated mouse primary cardiac fibroblasts (CFs) with IgE and found that both IgE receptor (FcεR1) and fibrosis related proteins were increased after IgE stimulation. Specific deletion of FcεR1 in CFs alleviated angiotensin II (Ang II)-induced cardiac fibrosis in mice. To investigate the mechanisms underlying the IgE-mediated cardiac fibrosis, deep miRNA-seq was performed. Bioinformatics and signaling pathway analysis revealed that IgE upregulated Col1a1 and Col3a1 expression in CFs by repressing miR-486a-5p, with Smad1 participating downstream of miR-486a-5p in this process. Lentivirus-mediated overexpression of miR-486a-5p was found to alleviate Ang II-induced myocardial interstitial fibrosis in mice. Moreover, miR-486-5p serum levels were lower in patients with heart failure than in healthy controls, and were negatively correlated with NT-proBNP levels. Conclusions: Our study demonstrates that elevated IgE promotes pathological cardiac fibrosis by modulating miR-486a-5p and downstream factors, such as Smad1. These findings suggest new targets for pathological cardiac fibrosis intervention.

miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2.

Aerobic glycolysis was closely associated with the malignant transformation and prognosis of tumours. miR-206 was found to be downregulated in several cancers. However, whether miR-206 functions in non-small-cell lung cancers (NSCLCs) via the process of aerobic glycolysis remains poorly characterized. Quantitative real-time PCR was performed to detect miR-206 level in NSCLC cells and tissues. The effect of miR-206 on hexokinase 2 (HK2) expression was examined through miR-206 overexpression or miR-206 knockdown. CCK-8 assay and colony formation assay were carried out to explore the role of miR-206 on cell proliferation and colony formation, respectively. The relationship between miR-206 and HK2 was measured by dual-luciferase reporter assay. Glucose consumption, lactate production assay and ATP generation were performed in NSCLC cells following miR-206 and HK2 overexpression. We found that miR-206 was downregulated in NSCLC tissues and cells. miR-206 overexpression downregulated the expression of HK2 via targeting HK2 3'UTR in NSCLC cells. In addition, miR-206 decreased the cell viability and colony formation in NSCLC cells. Furthermore, miR-206 reduced glucose uptake, lactate production and ATP generation in NSCLC cells via HK2 repression. In conclusion, these findings suggested that miR-206 regulated NSCLC cell aerobic glycolysis by targeting HK2.

Risk factors and clinical significance of acute kidney injury after on-pump or off-pump coronary artery bypass grafting: a propensity score-matched study.

OBJECTIVES: Our goal was to investigate risk factors for acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and the impact of AKI on short-term outcomes. METHODS: Data on 1395 patients (1261 who had isolated CABG and 134 with other operations) who underwent non-emergent CABG from January 2013 to March 2016 were retrospectively collected from a single centre. Logistic regression was performed to analyse risk factors. Cox regression was used to analyse the impact of AKI on the postoperative 30-day death rate. A 1:1 propensity score matching was performed to balance the baseline characteristics. RESULTS: The incidence of AKI with on-pump and off-pump coronary artery bypass was 10.4% and 3.5%, respectively. With logistic regression, duration of surgery was a risk factor for AKI (stage ≥2); previous hypertension, preoperative renal function insufficiency and the presence of cardiopulmonary bypass (CPB) were risk factors for mild AKI (stage ≥1). CPB time >207.5 min could be used to predict AKI (sensitivity 79.2%, specificity 78.6%) in the combined group. After adjusting for the duration of the operation, postoperative AKI (stage ≥1) was a risk factor for 30-day death and there was no difference in the 30-day death rate between on-pump and off-pump CABG. CONCLUSIONS: The use of CPB was a risk factor for mild AKI that did not affect the 30-day death rate of CABG whereas moderate to severe AKI caused by prolonged CPB time associated with surgical complexity affected the 30-day death rate. AKI may indicate surgical injury. The decision to use the on- or off-pump technique does not affect the 30-day death rate of CABG.

Long noncoding RNA HEIH promotes the proliferation and metastasis of non-small cell lung cancer.

OBJECTIVES: This study is aimed to explore the functions of long noncoding RNA (lncRNA) HEIH on the proliferation as well as metastasis of non-small cell lung cancer (NSCLC). METHODS: HEIH was shown to be increased in NSCLC by a microarray study on lncRNA profiling. We detected the expression of HEIH in different human NSCLC lines and tissues by quantitative real-time PCR. After gain- and loss-of-function approaches in A549 and Calu-1 cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays and a colony formation assay were applied to test the proliferative activity of cells, and the apoptosis of cells was measured by flow cytometry. Western blot analysis was used to evaluate the protein expression, and the effects of lncRNA HEIH on cell migratory and invasive abilities of A549 and Calu-1 cells were evaluated using wound healing and transwell assays. RESULTS: In our study, we confirmed the elevated expression of HEIH in NSCLC tissues and cell lines compared with the normal ones. After constructing A549 and Calu-1 cells with altered HEIH expression by transient transfection, cell viability was found to be positively regulated by the HEIH level. Moreover, overexpression of HEIH accelerated the cell migrating rate and increased the invasive cell number according to the results of a wound healing assay and transwell assay. CONCLUSIONS: HEIH could accelerate the proliferation and metastasis of NSCLC, providing a novel therapeutic target for clinical treatment.

Clinical analysis of lectin-like oxidized low-density lipoprotein receptor-1 in patients with in-stent restenosis after percutaneous coronary intervention.

In-stent restenosis (ISR) is the most common complication associated with percutaneous coronary intervention (PCI). Although some studies have reported an association between lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and ISR, not enough clinical validation data are available to support this link. Here, we report our cross-sectional study aimed at exploring the feasibility of LOX-1 as a biomarker for the prognostic diagnosis of patients undergoing PCI.Three groups were included: ISR group, including 99 patients with ISR diagnosed with coronary arteriography (CAG) after PCI; lesion group, comprising 87 patients with coronary artery stenosis (<50%) diagnosed with CAG after PCI; and control group, consisting of 96 volunteers with no coronary artery disease. The levels of LOX-1 were measured in each patient by using an enzyme-linked immunosorbent assay, and their general information as well as laboratory parameters were recorded and followed up during a period of 2 years.LOX-1 levels gradually increased after PCI along with the progression of the lesion in the 3 groups. The levels of LOX-1 were significantly higher in the ISR group than in the other 2 groups (P < .001). LOX-1 levels were correlated with the levels of uric acid (UA) (r = 0.289, P = .007), creatinine (CREA) (r = .316, P = .003), and high-density lipoprotein cholesterol (HDL-C) (r = -0.271, P = .012), whereas no statistically significant correlation was detected with the Gensini score (r = 0.157, P = .141). The sensitivity and specificity of LOX-1 were 81.5% and 55.7%, respectively, with the most optimal threshold (5.04 µg/L). The area under curve (AUC) of the receiver operator characteristic (ROC) curve of LOX-1 was 0.720, and LOX-1 had the highest AUC compared with CREA, UA, and HDL-C, both individually and in combination.A high level of LOX-1 in the early period after PCI has a certain predictive power and diagnostic value for ISR. However, the level of LOX-1 is not related to the Gensini score of coronary artery after PCI, and CREA and UA, which are weakly related to LOX-1, have no obvious synergy in the diagnosis of ISR with LOX-1.

Diagnostic value of miR-30d-5p and miR-125b-5p in acute myocardial infarction.

Rapid and accurate differential diagnosis of acute myocardial infarction (AMI) is crucial for timely interventions and the improvement of prognosis. However, this is difficult to achieve using current methods. Therefore, the present study aimed to evaluate the suitability of circulating microRNAs (miRNAs) as AMI biomarkers in patients with acute coronary syndrome (ACS). miRNA profiling in plasma samples from patients with AMI (n=3) and healthy controls (n=3) was performed using microarrays. Results were then validated in five patients and five healthy controls. miRNA-125b-5p and miR-30d-5p expression levels were quantified in plasma samples from 230 patients with ACS and 79 healthy controls using reverse transcription-quantitative polymerase chain reaction. Routine diagnostic parameters were assessed, including creatinine kinase MB, cardiac troponin I (cTnI) and myoglobin. A total of 33 miRNAs were differentially expressed in patients with AMI and healthy controls. Following validation based on the previously established roles for these miRNAs, six miRNAs were validated. miR­125b­5p and miR­30d­5p were selected for further investigation. Expression levels of miR­125b­5p and miR­30d­5p in plasma were higher in patients with ACS compared with the healthy controls (P<0.001). Receiver operating characteristic curve analysis revealed that the area under the curve of miR­30d­5p was higher than that of cTnI (0.915 and 0.899). miR­125b­5p (sensitivity, 0.808; specificity, 0.845) and miR­30d­5p (sensitivity, 0.855; specificity, 0.810) were suitable diagnostic predictors of AMI. Kaplan-Meier survival analysis indicated that miR-125b-5p levels were associated with 6 month cardiovascular events in patients with AMI, but not miR­30d­5p. miR-125b-5p and miR-30d-5p presented a diagnostic value for early diagnosis of AMI, and miR­30d­5p may have a higher diagnostic value than cTnI.

[In vivo evaluation of magnetic and hydrodynamic suspension centrifugal ventricular assist device].

OBJECTIVE: To verify the function of magnetic and hydrodynamic suspension centrifugal ventricular assist device in a sheep model. METHODS: The device was implanted into left ventricular apex on beating hearts. The outflow graft of each device was anastomosed to descending aorta in 11 animals. Hematologic, biochemical and blood clotting tests before and after surgery were performed. The data of pump functions were collected continuously. RESULTS: Among them, there were death from ventricular fibrillation (n = 3), acute pulmonary edema (n = 1) and left ventricular thrombus and molar cardiac muscle (n = 5). One animal survived for 75 days and died from bacterial infection after pumping for 59 hours. During assistance for 120 days, the flow rate was 3.0-3.4 L/min. All hematologic and biochemical parameters were within normal ranges in one sheep. The walking sheep wore the controller and lithium battery with a blood pump. Neither mechanical wearing nor thrombus formation was observed for inflow and outflow conduits or pump interior. CONCLUSIONS: The magnetic and hydrodynamic suspension centrifugal ventricular assist device demonstrates excellent hemocompatibility and reliability. And there is a great prospect of clinical success.

Identification of two novel mutations of the HOMEZ gene in Chinese patients with isolated ventricular septal defect.

OBJECTIVES: Ventricular septal defect (VSD) is the most common congenital heart disease (CHD). Genome-wide linkage analysis revealed a potential CHD susceptibility locus in the homeodomain leucine zipper-encoding (HOMEZ) gene in a South Indian population. The present study aimed to identify potential pathogenic mutations for HOMEZ and to provide insights into the etiology of isolated VSD in the Chinese population. METHODS: Case-control mutational analysis was performed in 400 patients with isolated VSD and 400 healthy controls. Protein-coding exton of HOMEZ and their flanking sequences were amplified by polymerase chain reaction and sequenced on an ABI3730 Automated Sequencer. CLC workbench software was used to compare the conservatism of the HOMEZ protein with other multiple species. The ExPASy-ProtScale online tool was used to predicate the alignment of the hydrophobic features. RESULTS: Two novel heterozygous missense mutations (c.116 C>T; c. 630T>A) were identified in HOMEZ gene exon-2. The two mutations lead to alanine to valine substitution at position 39 and serine to arginine at position 210, which are highly conserved among many species. The hydropathicity of the valine and arginine residue at the position 39 and 210 were significantly different from the wild type. CONCLUSIONS: We have identified two novel heterozygous missense mutations in HOMEZ gene exon-2 in isolated VSD patients in the Chinese population and have found that these two mutations resulted in alteration of the hydropathicity of the HOMEZ protein. Therefore, the two missense mutations of the HOMEZ gene are directly linked with the etiology of isolated VSD in the Chinese population.