A pan-cancer analysis of anti-proliferative protein family genes for therapeutic targets in cancer.

The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and BTG4. The APRO family is reportedly associated with the initiation and progression of cancers. This study aims to undertake a comprehensive investigation of the APRO family of proteins as a prognostic biomarker in various human tumors. We performed a pan-cancer analysis of the APRO family based on The Cancer Genome Atlas (TCGA). With the bioinformatics methods, we explored the prognostic value of the APRO family and the correlation between APRO family expression and tumor mutation burden (TMB), microsatellite instability (MSI), drug sensitivity, and immunotherapy in numerous cancers. Our results show that the APRO family was primarily down-regulated in cancer samples. The expression of APRO family members was linked with patient prognosis. In addition, APRO family genes showed significant association with immune infiltrate subtypes, tumor microenvironment, and tumor cell stemness. Finally, our study also demonstrated the relationship between APRO family genes and drug sensitivity. This study provides comprehensive information to understand the APRO family's role as an oncogene and predictor of survival in some tumor types.

Bacterial lipopolysaccharide related genes signature as potential biomarker for prognosis and immune treatment in gastric cancer.

The composition of microbial microenvironment is an important factor affecting the development of tumor diseases. However, due to the limitations of current technological levels, we are still unable to fully study and elucidate the depth and breadth of the impact of microorganisms on tumors, especially whether microorganisms have an impact on cancer. Therefore, the purpose of this study is to conduct in-depth research on the role and mechanism of prostate microbiome in gastric cancer (GC) based on the related genes of bacterial lipopolysaccharide (LPS) by using bioinformatics methods. Through comparison in the Toxin Genomics Database (CTD), we can find and screen out the bacterial LPS related genes. In the study, Venn plots and lasso analysis were used to obtain differentially expressed LPS related hub genes (LRHG). Afterwards, in order to establish a prognostic risk score model and column chart in LRHG features, we used univariate and multivariate Cox regression analysis for modeling and composition. In addition, we also conducted in-depth research on the clinical role of immunotherapy with TMB, MSI, KRAS mutants, and TIDE scores. We screened 9 LRHGs in the database. We constructed a prognostic risk score and column chart based on LRHG, indicating that low risk scores have a protective effect on patients. We particularly found that low risk scores are beneficial for immunotherapy through TIDE score evaluation. Based on LPS related hub genes, we established a LRHG signature, which can help predict immunotherapy and prognosis for GC patients. Bacterial lipopolysaccharide related genes can also be biomarkers to predict progression free survival in GC patients.

Succinylation-associated lncRNA signature to predict the prognosis of colon cancer based on integrative bioinformatics analysis.

Colon cancer (CC) has a poor 5-year survival rate though the treatment techniques and strategies have been improved. Succinylation and long noncoding RNAs (lncRNAs) have prognostic value for CC patients. We analyzed and obtained succinylation-related lncRNA by co-expression in CC. A novel succinylation-related lncRNA model was developed by univariate and Least absolute shrinkage and selection operator (Lasso) regression analysis and we used principal component analysis (PCA), functional enrichment annotation, tumor immune environment, drug sensitivity and nomogram to verify the model, respectively. Six succinylation-related lncRNAs in our model were finally confirmed to distinguish the survival status of CC and showed statistically significant differences in training set, testing set, and entire set. The prognosis of with this model was associated with age, gender, M0 stage, N2 stage, T3 + T4 stage and Stage III + IV. The high-risk group showed a higher mutation rate than the low-risk group. We constructed a model to predict overall survival for 1-, 3-, and 5-year with AUCs of 0.694, 0.729, and 0.802, respectively. The high-risk group was sensitive to Cisplatin and Temozolomide compounds. Our study provided novel insights into the value of the succinylation-related lncRNA signature as a predictor of prognosis, which had high clinical application value in the future.

Ultrasound-guided Multiple Nerve Blocks: A Safe and Effective Anesthetic Modality in Geriatric Hip Fracture Patients.

OBJECTIVES: The aim was to compare the feasibility of ultrasound-guided multiple nerve blocks (fascia iliaca compartment block+sacral plexus block+superior cluneal nerve block) with general anesthesia in geriatric hip fracture patients. METHODS: Ninety-four patients were randomly divided into 2 groups: group N received ultrasound-guided multiple nerve blocks and group G received general anesthesia. Primary outcome measures included perioperative Pain Threshold Index (PTI) and Numerical Rating Scale. Secondary outcome measures comprised the following: (1) perioperative Delirium Index and Short Portable Mental Status Questionnaire; (2) perioperative Comfort Index; (3) perioperative opioid consumption (within 72 hours postoperatively); and (4) postoperative side effects (within 72 h postoperatively). RESULTS: Eighty-seven patients completed the study. Baseline PTI was comparable between the groups. However, intraoperative PTI was significantly lower in group N than in group G. Preoperative and postoperative Comfort Index scores were comparable between the groups. Moderate delirium (24 to 72 h postoperatively) was significantly higher than the baseline in group G. Early moderate delirium (24 h postoperatively) was significantly higher in group G than in group N. Severe delirium was comparable between the groups and within each group. High intraoperative PTI was associated with high opioid consumption. The intravenous sufentanil dose in group G was twice of that in group N. Incidence of nausea and vomiting was similar between the groups. DISCUSSION: Ultrasound-guided multiple nerve blockade may be an alternative to the common anesthetic procedures used for geriatric hip fracture patients. It provided satisfactory intraoperative pain management and reduced early postoperative cognitive disorders.

The association of diabetes mellitus with neointimal formation following deployment of second-generation drug-eluting stents: an optical coherence tomographic study.

OBJECTIVES: The purpose of this study was to evaluate the association of diabetes mellitus (DM) with neointimal formation after implantation of second-generation drug-eluting stent (DES) visualized by optical coherence tomography (OCT). METHODS: Patients with single de novo coronary artery disease treated with second-generation DES between June 2014 and June 2017 in our department underwent OCT examination at 1-year follow-up and were enrolled in this retrospective study. The primary end point was in-stent mean neointimal thickness (MNT), and secondary end points included uncovered stent strut, minimal lumen area (MLA), neointimal burden, neointimal hyperplasia (NIH) patterns and stent thrombosis (ST) after 1 year of OCT follow-up. RESULTS: A total of 68 patents with DM (DM group) and 216 patients without DM (non-DM group) were enrolled. At 1-year follow-up, the DM group compared with the non-DM group, showed: MNT [160 (85-245) µm vs. 120 (60-220) µm, P = 0.038] and neointimal burden [21.4 (8.3-30.1)% vs. 14.0 (5.7-26.1)%, P = 0.023] to be significantly increased. Concurrently, MLA [4.60 (3.53-6.06) mm vs. 5.76 (4.28-7.20) mm2, P = 0. 0.002] was significantly reduced. Interestingly, the degree of uncovered struts (7.3 ± 7.1% vs. 7.7 ± 6.7%, P = 0.704), NIH patterns (P = 0.984), and ST (7.9% vs. 7.4%, P = 0.88) were comparable between the two groups. After propensity score matching, the MNT [160 (90-240) µm vs. 110 (60-220) µm, P = 0.048] and neointimal burden [21.4 (8.3-30.1)% vs. 15.4 (5.6-26.3)%, P = 0.044] remained significantly different in the DM compared to the non-DM group. CONCLUSION: DM leads to significant increase in MNT and neointimal burden even with second-generation DES, nevertheless stent strut coverage, ST and NIH characteristics remained comparable among the cohorts at 1-year.

Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. METHODS: In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. RESULTS: A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2-2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1-6.3, P <  0.001), cough (OR = 1.7, 95% CI: 1.0-2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1-10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0-3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2-5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19-40 years [OR = 12.7, 95% CI: 4.5-36.0, P < 0.001], 41-65 years [OR = 14.8, 95% CI: 5.2-42.1, P <  0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1-186.5, P < 0.001]). CONCLUSIONS: Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.

Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China.

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS: From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Correlation between pre-procedural plaque morphology and patterns of in-stent neointimal hyperplasia at 1-year follow-up in patients treated with new-generation drug-eluting stents: An optical coherence tomography based analysis.

INSTRUCTION: Several factors affect the in-stent intimal healing process after drug-eluting stents (DESs) implantation. We hope to investigate the influence of plaque characteristics on subsequent heterogeneous neointimal hyperplasia (NIH) using optical coherence tomography (OCT). METHODS: The study population consisted 217 patients with single-vessel de novo lesions who underwent both pre-procedural OCT scan and 12-month follow-up OCT examination. NIH is defined as at least five consecutive cross-sectional images with no less than 100µm neointimal thickness. According to OCT follow-up, patients were divided into three groups: neointima-covered group, homogeneous, and heterogeneous NIH group. RESULTS: 102 patients were categorized in neointima-covered group, 91 and 24 patients in homogeneous and heterogeneous group, respectively. Time interval between OCT scans was similar (P = 0.55). No significant differences in the patients' age, gender, comorbidities, laboratory findings, procedural, and lesion-related findings were found among these three groups. Heterogeneous group tended to have more subjects presented as acute coronary syndrome (ACS) (P = 0.04) and mean macrophage grade was higher in this group (P = 0.01). While no statistically significant difference concerning mean intimal thickness (P = 0.21) or neointimal burden (P = 0.73) was found between homogeneous and heterogeneous group. Multivariate logistic regression analysis showed that mean macrophage grade (OR: 2.26, 95%CI: 1.12 to 4.53, P = 0.02) and initial clinical presentation of ACS (OR: 2.81, 95%CI: 1.03 to 7.72, P = 0.04) were significant independent risk factors for heterogeneous NIH. CONCLUSION: Mean macrophage grade measured by OCT as a semi-quantitative morphological risk factor, as well as clinical presentation of ACS, was associated with in-stent neointimal heterogeneity after DES implantation.

Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway.

The study aimed to investigate the effect of niacin on vascular inflammatory lesions in vivo and in vitro as well as its lipid-regulating mechanism. In vivo study revealed that niacin downregulated the levels of inflammatory factors (IL-6 and TNF-α) in plasma, suppressed protein expression of CD68 and NF-κB p65 in arterial wall, and attenuated oxidative stress in guinea pigs that have been fed high fat diet. In vitro study further confirmed that niacin decreased the secretion of IL-6 and TNF-α and inhibited NF-κB p65 and notch1 protein expression in oxLDL-stimulated HUVECs and THP-1 macrophages. Moreover, niacin attenuated oxLDL-induced apoptosis of HUVECs as well. In addition, niacin significantly lessened lipid deposition in arterial wall, increased HDL-C and apoA levels and decreased TG and non-HDL-C levels in plasma, and upregulated the mRNA amount of cholesterol 7 α-hydroxylase A1 in liver of guinea pigs. These data suggest for the first time that niacin inhibits vascular inflammation in vivo and in vitro via downregulating NF-κB signaling pathway. Furthermore, niacin also modulates plasma lipid by upregulating the expression of factors involved in the process of reverse cholesterol transport.