Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Development of a novel combined nomogram integrating deep-learning-assisted CT texture and clinical-radiological features to predict the invasiveness of clinical stage IA part-solid lung adenocarcinoma: a multicentre study.

AIM: To develop a novel combined nomogram based on deep-learning-assisted computed tomography (CT) texture (DL-TA) and clinical-radiological features for the preoperative prediction of invasiveness in patients with clinical stage IA lung adenocarcinoma manifesting as part-solid nodules (PSNs). MATERIALS AND METHODS: This study was conducted from January 2015 to October 2021 at three centres: 355 patients with 355 PSN lung adenocarcinomas who underwent surgical resection were included and classified into the training (n=222) and validation (n=133) cohorts. PSN segmentation on CT images was performed automatically with a commercial deep-learning algorithm, and CT texture features were extracted. The least absolute shrinkage and selection operator was used for feature selection and transformed into a DL-TA score. The combined nomogram that incorporated the DL-TA score and identified clinical-radiological features was developed for the prediction of pathological invasiveness of the PSNs and validated in terms of discrimination and calibration. RESULTS: The present study generated a combined nomogram for predicting the invasiveness of PSNs that included age, consolidation-to-tumour ratio, smoking status, and DL-TA score, with a C-index of 0.851 (95% confidence interval: 0.826-0.877) for the training cohort and 0.854 (95% confidence interval: 0.817-0.891) for the validation cohort, indicating good discrimination. Furthermore, the model had a Brier score of 0.153 for the training cohort and 0.135 for the validation cohort, indicating good calibration. CONCLUSION: The developed combined nomogram consisting of the DL-TA score and clinical-radiological features and has the potential to predict the individual risk for the invasiveness of stage IA PSN lung adenocarcinomas.

CT texture analysis-based nomogram for the preoperative prediction of visceral pleural invasion in cT1N0M0 lung adenocarcinoma: an external validation cohort study.

AIM: To develop a nomogram based on computed tomography (CT) texture analysis for the preoperative prediction of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma. MATERIALS AND METHODS: A dataset of chest CT containing lung nodules was collected from two institutions, and all surgically resected nodules were classified pathologically based on the presence of visceral pleural invasion. Each nodule on the CT image was segmented automatically by artificial-intelligence software and its CT texture features were extracted. The dataset was divided into training and external validation cohorts according to the institution, and a nomogram for predicting visceral pleural invasion was developed and validated. RESULTS: Of a total of 313 patients enrolled from two independent institutions, 63 were diagnosed with visceral pleural invasion. Three-dimensional (3D) CT long diameter, skewness, and sphericity, and chronic obstructive pulmonary disease were identified as independent predictors for visceral pleural invasion by multivariable logistic regression. The nomogram based on multivariable logistic regression showed great discriminative ability, as indicated by a C-index of 0.890 (95% confidence interval [CI]: 0.867-0.914) and 0.864 (95% CI: 0.817-0.911) for the training and external validation cohorts, respectively. Additionally, calibration of the nomogram revealed good predictive ability, as indicated by the Brier score (0.108 and 0.100 for the training and external validation cohorts, respectively). CONCLUSIONS: A nomogram was developed that could compute the probability of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma with good calibration and discrimination. The nomogram has potential as a reliable tool for clinical evaluation and decision-making.

[Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals].

OBJECTIVE: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. METHODS: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1ß、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. RESULTS: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1ß, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1ß: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) µg/L, P < 0.001]. CONCLUSION: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

[Association between serum uric acid to creatinine ratio and metabolic syndrome based on community residents in Chashan town, Dongguan city].

Objective: To analyze the association between serum uric acid to creatinine ratio (SUA/Cr) and metabolic syndrome among community residents in Chashan town, Dongguan city. Methods: Participants were from the prospective cohort study of chronic diseases in natural populations in South China conducted in Chashan town, Dongguan city from 2018 to 2019. A total of 11 334 participants with complete data were included by using convenient sampling method. Demographic characteristics, lifestyle and health status were collected through questionnaire and physical examination. The venous blood of the subjects was collected to detect the levels of serum uric acid, creatinine and blood lipid. All participants were divided into four groups (Q1-Q4) according to the quartile of SUA/Cr level. The relationship between SUA/Cr and metabolic syndrome and its components (abdominal obesity, high triglyceride, low level of high density lipoprotein cholesterol, hypertension and abnormal glucose metabolism) were analyzed by using logistic regression model. Results: The mean age of 11 334 participants was (49.52±10.02) years. Male participants accounted for 44.2% (5 015/11 334). The prevalence of metabolic syndrome was 31.2% (3 532/11 334), and the level of SUA/Cr was 5.17±1.53. The prevalence of metabolic syndrome in group Q1-Q4 was 22.3% (631/2 834), 26.5% (752/2 833), 34.9% (988/2 833) and 41.0% (1 161/2 834), respectively. After adjusting for relevant confounding factors, the result of logistic regression model showed that compared with group Q1, the risk of metabolic syndrome in group Q2-Q4 was significantly higher, with OR (95%CI) values about 1.41 (1.23-1.60), 2.19 (1.93-2.49) and 3.01 (2.65-3.42) respectively. The risk of each component of metabolic syndrome in group Q2-Q4 was higher (Ptrend<0.001). The SUA/Cr level of participants with normal uric acid level was significantly positively correlated with metabolic syndrome. The risk of metabolic syndrome increased with the increase of SUA/Cr level, but there was the same trend without significant differences in patients with hyperuricemia (Pinteraction=0.008). Conclusion: There is a positive correlation between SUA/Cr level and the risk of metabolic syndrome among community residents in Chashan town, Dongguan city.

[Clinical study of FibroTouch and six serological models for assessing the degree of liver fibrosis in patients with chronic hepatitis B].

Objective: To evaluate the using value of FibroTouch and six serological models in detecting the degree of liver fibrosis in patients with chronic hepatitis B, in an attempt to provide reference for accurate diagnosis. Methods: Two hundred and fifty-eight cases with chronic hepatitis B admitted to Xixi Hospital of Hangzhou from September 1, 2015 to September 1, 2017 were selected. All patients underwent liver histopathological examination and FibroTouch measurement to determine liver stiffness (LSM). Serum biochemical parameters were detected and the scoring values of six serological models were calculated. SAS 9.4 statistical software was used for statistical analysis, and the correlation between FibroTouch and the six serological models was analyzed by Spearman correlation. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC) based on liver histopathological findings. Results: The median LSM of 258 cases with chronic hepatitis B was 9.4 (6.5-13.8) kPa. In the six serological models, the median value of aspartate transaminase to platelet ratio index (APRI), FIB-4 index, S-index, Forn's index, PRPindex, and FIB-5 were 0.42 (0.28-0.62), 1.27 (0.78-2.03), 0.11 (0.07-0.20), 6.95 (5.89-8.51), 0.000 8 (0.000 6-0.000 9),and 38.59 (36.28-40.97). FibroTouch had positive correlation with APRI, FIB-4, S-index, Forn's index, PRP, fibrosis stage (r= 0.73,P< 0.001) and inflammation grade, and had negative correlation with FIB-5, and both had statistical significance. The area under curve (AUC) of FT-LSM at S≥2, S≥3, S = 4 were 0.89, 0.90 and 0.85, respectively, which was significantly higher than serological models (P< 0.001). The AUC of S-index model at S≥2, S≥3, S = 4 were higher than other five serological models. Conclusion: The diagnostic performance of FibroTouch is significantly better than serological model. S-index model has the best diagnostic performance in the six serological models, and the combination of S-index and FT-LSM may better diagnose the grading of liver fibrosis, and thus can be applied and promoted in clinic.

[Effect of non-diabetic postoperative hyperglycemia on complications after pancreaticoduodenectomy].

Objective: To examine the association of hyperglycemia and postoperative complications in non-diabetic patients underwent pancreaticoduodenectomy(PD). Methods: The clinical data of 209 non-diabetic patients who underwent PD from January 2012 to June 2018 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University and met the inclusion criteria were retrospectively analyzed. According to the diagnostic criteria of postoperative hyperglycemia, the patients were divided into postoperative hyperglycemia group (167 cases, 79.9%) and control group(42 cases, 20.1%). The propensity score matching(PSM) method was used to eliminate the difference between groups(caliper value=0.02; 38 cases in control group including 30 males and 8 females with age of 59.0 years;38 cases in postoperative hyperglycemia group including 32 males and 6 females with age of 61.0 years;37 cases of pancreatic head carcinoma,30 cases of periampullary carcinoma and 9 cases of benign diseases). A comparative analysis was applied for preoperative data, surgical related indicators and postoperative complication rates.The receiver operating characteristic(ROC) curve was used to calculate the area under the curve(AUC) of blood glucose values on postoperative day 1,3 and 5(POD1, POD3, POD5), to determine the high-risk blood glucose cutoff value of complications and to evaluate its sensitivity and specificity for the prediction of postoperative complications. Results: Univariate analysis showed that the differences in gender, body mass index, preoperative blood glucose, and serum urea nitrogen levels were statistically significant before PSM.There was no significant difference in the preoperative data between the two groups after PSM. Compared with the control group, the incidence of postoperative pancreatic fistula (31.6% vs. 5.3%), abdominal infection(29.0% vs. 7.9%) and Clavien-Dindo Ⅲ-Ⅴ complications(31.6% vs.7.9%) were statistically different(χ(2)=7.092,P=0.008; χ(2)=4.290,P=0.038; χ(2)=5.316,P=0.021), respectively. According to the AUC on POD3,the blood glucose value ≥8.860 mmol/L was an independent risk factor for pancreatic fistula with sensitivity of 58.3% and specificity of 76.9%,the blood glucose value ≥9.130 mmol/L was an independent risk factor for abdominal infection with sensitivity of 54.5% and specificity of 81.5% and the blood glucose value ≥7.685 mmol/L was independent risk factor of Clavien-Dindo Ⅲ-Ⅴ complications with sensitivity of 75.0% and specificity of 57.7%. Conclusions: Postoperative hyperglycemia in non-diabetic patients is associated with postoperative pancreatic fistula, abdominal infection, and Clavien-Dindo Ⅲ-Ⅴ complications.According to the early postoperative blood glucose value,the occurrence of postoperative pancreatic fistula, abdominal infection and Clavien-Dindo Ⅲ- Ⅴ complications can be effectively predicted.

[Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load].

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4(+)T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4(+)T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4(+)T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4(+)T cell counts <200 cells/µl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/µl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion: Decreased CD4(+)T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.

[Establishment of multiple predictor models of severe acute pancreatitis in elderly patients].

Objective: To investigate the prognostic factors related to the severity of acute pancreatitis and to establish the multiple predictor models of severe acute pancreatitis(SAP) in elderly patients. Methods: Clinical data of 146 consecutive elderly patients who met the inclusion criteria between January 2014 and May 2017 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University were retrospectively collected and analyzed, wherein 88 cases were mild acute pancreatitis, 29 cases were moderately severe acute pancreatitis and 29 cases were SAP. The patients data were subjected to univariate analysis and multiple classified Logistic regression analysis for independent prognostic factors of the severity of acute pancreatitis in elderly patients. Unweighted predictive score(unwScore) and weighted predictive score(wScore)for SAP in elderly patients were established according which the receiver-operating characteristic(ROC) curves of independent prognostic factors and predictor models were produced. The cutoff values of independeut prognostic factors and predictor models were determined. The area under the curve, the sensitivity, the specificity, the positive predictive value and the negative predictive value to verify the predictive efficiency of the independent prognostic factors and predictor models were calculated. Results: Procalcitonin(PCT)(Z=10.564, P=0.000), blood urea nitrogen(BUN)(Z=22.231, P=0.003), serum creatinine(Scr)(Z=14.151, P=0.030), serum calcium(Z=34.979, P=0.032) and pleural effusion(χ(2)=28.463, P=0.015) were independent prognostic factors of the severity of acute pancreatitis by univariate analysis and multiple classified Logistic regression analysis in elderly patients. Respectively, the area under the curve of PCT, BUN, Scr, serum calcium and pleural effusion were 0.908, 0.737, 0.701, 0.753, 0.712, the sensitivity were 0.828, 0.621, 0.552, 0.690, 0.517, the specificity were 0.915, 0.786, 0.846, 0.966, 0.906, the positive predictive value were 70.6%, 41.9%, 47.1%, 83.3%, 57.7%, the negative predictive value were 95.5%, 89.3%, 88.4%, 92.6%, 88.3%. Respectively, the area under the curve of unwScore and wScore were 0.915 and 0.953, the sensitivity were 0.759 and 0.931, the specificity were 0.889 and 0.915, the positive predictive value were 62.9% and 73.0%, the negative predictive value were 93.7% and 98.2%. Conclusions: PCT, BUN, Scr, serum calcium and pleural effusion were independent prognostic factors of the severity of acute pancreatitis in elderly patients. The multiple predictor models of SAP in elderly patients have a good predictive efficiency, which may provide valuable clinical reference for prediction and treatment.

[Reproducibility and comparison study of two methods evaluating the optic nerve subarachnoid space sectional area using MRI].

Objective: To optimize the method of acquiring the ONSAS parameter and to access the repeatability of the new method comparing with the traditional one. Methods: This is a cross-sectional study. Standard operation procedure of an optimized method of acquiring the ONSAS sectional area was made against the defect of the traditional method. Ten healthy volunteers (20 eyes) in different ages were recruited from March 2016 to October. Two times of MRI scan were proceeded with the interval of one week. The optimized and traditional methods were both applied for each scanning. The images were analyzed by two ophthalmologists. The rate of high quality images between two groups was compared with matching chi-square test. The orbital subarachnoid space areas between groups at different locations were compared using analysis of variance of repeated measurement data. The ICC between different scans and different ophthalmologists was calculated. Results: The mean age of the volunteers was 43.8±13.1 years old. Male/Female was 1∶1. The rates of high quality images from the optimized method (100%, 83%, 78%) was higher than those of the traditional method(80%, 78%, 70%). The orbital subarachnoid space area at 3 mm, 9 mm and 15 mm behind the eye ball acquired from the new method(7.2±1.8, 6.1±1.8, 5.9±1.4 mm(2)) were bigger than those of the traditional method (9.0±2.9, 7.6±2.4, 7.1±1.6 mm(2)). Statistical significances were found at 9 mm(F=4.30, P=0.048) and 15 mm(F=5.67, P=0.026) behind the eye ball. The ICC between two different scans (0.879, 0.857, 0.857 vs 0.741, 0.762, 0.639) and two different ophthalmologists (0.864, 0.890, 0.894 vs 0.785, 0.609, 0.753) were higher in the new method group than in the traditional method group. Conclusions: The optimized method of acquiring the parameters of optic nerve subarachnoid space is easier to get the sectional cross area. The measuring reproducibility is better than the traditional one. (Chin J Ophthalmol, 2017, 53: 440-444).

[Effect of nicorandil on ventricular arrhythmia in patients with acute ST-segment elevation myocardial infarction underwent emergent percutaneous coronary intervention treatment].

Objective: To investigate the effect of nicorandil on ventricular arrhythmia in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with emergent percutaneous coronary intervention (PCI). Methods: A total of 120 acute STEMI patients treated with emergent PCI in our hospital from January 2015 to June 2016 were randomly divided into control group and experiment group (n=60 each). Patients in both groups received conventional therapy.Patients in experiment group took 10 mg nicorandil orally before PCI and received oral nicorandil treatment (15 mg/d, three times daily) for 3 days.QT disperse(QTd), correct QTd(QTcd) and the occurrence rate of ventricular arrhythmia were compared between two groups. Results: QTd at 6, 24, 48 and 72 hours((70.6±4.4), (67.2±5.3), (55.7±8.5), (48.2±8.2) ms, respectively) after PCI was significantly lower in the experiment group than those of control group ((77.1±7.1), (71.3±6.5), (65.1±8.1), (57.2±5.4) ms, all P<0.05). The level of QTd was also significantly lower in the experiment group at 6, 24, 48 and 72 hours((77.5±7.7), (67.7±8.6), (61.2±7.5), (52.9±8.4) ms, respectively) after PCI comared to those of control group ((88.6±8.1), (79.2±7.8), (74.4±7.4), (69.6±8.6) ms, all P<0.05). There was no significant difference in the incidence of reperfusion arrhythmia during PCI procedure between the two groups.The prevalence of the ventricular premature beat in the experiment group (25/60, 41.7%) was significantly lower than in the control group(45/60, 75.0%) within 3 days after PCI(P<0.01), the prevalence of the no sustained ventricular tachycardia and ventricular fibrillation in the experiment group(6/60, 10.0%) was also significantly lower than in the control group (18/60, 30.0%, P<0.01) within 3 days after PCI. Conclusions: Nicorandil use prior and post PCI could decrease the occurrence rate of ventricular arrhythmia in STEMI patients undergoing emergent PCI, and this effect might be related with reduced QTd and QTcd post medication.

Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage.

BACKGROUND: Dexmedetomidine, a sedative agent, provides neuroprotection when administered during or before brain ischaemia. This study was designed to determine whether dexmedetomidine post-treatment induces neuroprotection against subarachnoid haemorrhage (SAH) and the mechanisms for this effect. METHODS: Subarachnoid haemorrhage was induced by endovascular perforation to the junction of the right middle and anterior cerebral arteries in adult rats. Dexmedetomidine was applied immediately or 2 h after onset of SAH. Neurological outcome was evaluated 2 days after SAH. Right frontal cortex area 1 was harvested 24 h after SAH for western blotting. RESULTS: Subarachnoid haemorrhage reduced neurological scores and increased brain oedema and blood-brain barrier permeability. These effects were attenuated by dexmedetomidine post-treatment. Neuroprotection by dexmedetomidine was abolished by PD98095, an inhibitor of extracellular signal-regulated kinase (ERK) activation. Phospho-ERK, the activated form of ERK, was increased by dexmedetomidine; this activation was inhibited by PD98095. CONCLUSIONS: Dexmedetomidine post-treatment provides neuroprotection against SAH. This effect appears to be mediated by ERK.

Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

BACKGROUND: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND METHODS: DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. RESULTS: Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. CONCLUSION: The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

Increased interventricular septum wall thickness predicts all-cause death in patients with coronary artery disease.

BACKGROUND: There is debate regarding the predictive value of interventricular septum (IVS) wall thickness for adverse events. AIMS: The study investigated the association between the severity of thickened IVS and all-cause death in Chinese patients with coronary artery disease (CAD). METHODS: A total of 2297 CAD patients verified by angiography was consecutively included. Patients were grouped according to the severity of thickened IVS. Cox regression analysis was conducted to determine the independent prognostic value of thickened IVS for all-cause death. RESULTS: During a median follow up of 25 months, 149 patients died. A gradient increase in the risk of death was observed across thickened IVS groups. Compared to patients with normal IVS thickness, the adjusted hazard ratio (HR) was 1.49 (95% confidence interval (CI) 1.00-2.23, P = 0.05) and 2.13 (95% CI 1.29-3.54, P = 0.003) for all-cause death in those with mildly and moderately/severely thickened IVS respectively. For one unit increase in IVS thickness, the risk of all-cause death was elevated by 14% (adjusted HR 1.14, 95% CI 1.05-1.24, P = 0.003). In patients with normal indexed left ventricular mass, thickened IVS was also demonstrated as an independent risk factor for all-cause death. CONCLUSION: Thickened IVS can be served as a reliable marker for predicting all-cause death in Chinese patients with CAD, even in those with normal left ventricular mass.

[An artificial neural network diagnostic model for scleroderma and immune cell infiltration analysis based on mitochondria-associated genes].

OBJECTIVE: To establish a diagnostic model for scleroderma by combining machine learning and artificial neural network based on mitochondria-related genes. METHODS: The GSE95065 and GSE59785 datasets of scleroderma from GEO database were used for analyzing expressions of mitochondria-related genes, and the differential genes were identified by Random forest, LASSO regression and SVM algorithms. Based on these differential genes, an artificial neural network model was constructed, and its diagnostic accuracy was evaluated by 10-fold crossover verification and ROC curve analysis using the verification dataset GSE76807. The mRNA expressions of the key genes were verified by RT-qPCR in a mouse model of scleroderma. The CIBERSORT algorithm was used to estimate the bioinformatic association between scleroderma and the screened biomarkers. RESULTS: A total of 24 differential genes were obtained, including 11 up-regulated and 13 down-regulated genes. Seven most relevant mitochondria-related genes (POLB, GSR, KRAS, NT5DC2, NOX4, IGF1, and TGM2) were screened using 3 machine learning algorithms, and the artificial neural network diagnostic model was constructed. The model showed an area under the ROC curves of 0.984 for scleroderma diagnosis (0.740 for the verification dataset and 0.980 for cross-over validation). RT-qPCR detected significant up-regulation of POLB, GSR, KRAS, NOX4, IGF1 and TGM2 mRNAs and significant down-regulation of NT5DC2 in the mouse models of scleroderma. Immune cell infiltration analysis showed that the differential genes in scleroderma were associated with follicular helper T cells, immature B cells, resting dendritic cells, memory activated CD4+T cells, M0 macrophages, monocytes, resting memory CD4+T cells and mast cell activation. CONCLUSION: The artificial neural network diagnostic model for scleroderma established in this study provides a new perspective for exploring the pathogenesis of scleroderma.

Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles.

We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor ß1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (P<0.01). These data suggest that delivery of an artificial miRNA targeted against CTGF using ultrasound-targeted cationic liposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections.

BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.

Identification of a novel HLA-B*27 allele, B*27:79 and the B*27 subtype polymorphism in the Hunan ethnic Han population of China.

This article describes a novel HLA-B*27 allele, HLA-B*27:79, which was identified in a Hunan Han ethnic individual of China by a PCR sequence-based typing method. The new sequence has one nucleotide mutation at position 437(A→T) compared with the allele B*27:04:01. This nucleotide change causes an amino acid substitution from Aspartate (Asp) to Valine (Val) at codon 122. This is the first report of mutation at this position in the HLA-B locus. Then, we investigated the HLA-B*27 subtype polymorphism of the Hunan Han population, and the results showed that B*27:04, B*27:05 and B*27:06 are the predominant subtypes with the allele frequencies 0.97%, 0.26% and 0.10% respectively.

Famine Exposure during Early Life and Risk of Cancer in Adulthood: A Systematic Review and Meta-Analysis.

OBJECTIVES: Emerging evidences have explored the association between famine exposure during early life and cancer risk in adulthood, but the results remain controversial and inconsistent. This study aimed to provide a comprehensive evidence on the relation of famine exposure to later cancer risk. DESIGN: Systematic review and meta-analysis. METHODS: Relevant reports published up to March, 2022 were identified by searching PubMed, Embase, Web of sciences and Medline databases. Pooled relative ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the effect famine exposure on cancer risk. RESULTS: Totally, 18 published articles with 6,061,147 subjects were included in this study. Compared with unexposed group, early life famine exposure dramatically increased the risk of cancer in adulthood (RR=1.13, 95% CI: 1.04-1.22). The pooled RRs were different in terms of sex, exposure severity, exposure period, famine type, study design type and cancer location. A remarkably elevated risk for cancer was discerned in women exposed to famine (RR=1.09, 95% CI: 1.00-1.18), severe exposure (RR=1.12, 95% CI: 1.02-1.22) and adolescence exposure (RR=1.76, 95% CI: 1.02-2.50), Chinese famine exposure (RR=1.55, 95% CI: 1.29-1.82) and cohort studies (RR=1.28, 95% CI: 1.13-1.42). Moreover, a significant association of early-life famine exposure with increased risk of breast (RR=1.16, 95% CI: 1.05-1.27) and stomach cancers (RR=1.89, 95% CI: 1.24-2.54) was observed. CONCLUSION: This meta-analysis suggests that exposure to famine during early life may increase the risk of cancer in adulthood. The above-mentioned association is pronounced in women exposed to famine, severe exposure, adolescence exposure, Chinese famine, cohort studies, breast and stomach cancers. It is essential for decision-makers to take targeted measures for improving population awareness regarding the long-term effect of early life nutritional status.