Objective To evaluate the combination use of thyroid fine needle aspiration biopsy (FNAB)and V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation testing in differentiating benign from malignant thyroid nodules.Methods A total of 64 patients with pathologically-proved thyroid nodules were included in this study.The clinical data,including preoperative ultrasound-guided thyroid FNAB and BRAF V600E gene mutation detection,were retrospectively analyzed.Taking postoperative histopathological results as diagnostic gold standard for the thyroid nodule,the diagnostic values of simple FNAB,simple BRAF V600E gene mutation testing,and combination use of FNAB and BRAF V600E gene mutation detection were separately assessed.Results In the 62 patients a total of 64 nodules were detected (2 patients having bilateral nodules) and treated with surgery.Of the 64 nodules,BRAF V600E mutation was detected in 44 nodules,and 43 nodules were proved to be thyroid papillary carcinoma by postoperative pathological examination.Among the 44 nodules showing BRAF V600E mutation,FNAB made malignant diagnosis in 28,benign diagnosis in 6,and uncertain diagnosis in 10.Of the 20 nodules showing no BRAF V600E mutation,FNAB made malignant diagnosis in 5,benign diagnosis in 3,and uncertain diagnosis in 12.The postoperative pathological examination confirmed that 14 lesions were thyroid papillary carcinoma,4lesions were nodular goiter,one lesion was subacute thyroiditis,and one lesion was thyroid adenoma.Among the 57 thyroid papillary carcinomas,BRAF V600E mutation was detected in 43,with the mutation rate being 75.4％.Compared with the gold standard based on pathological diagnosis,the sensitivity,specificity,positive predictive value,negative predictive value,correct diagnosis rate of FNAB for judging benign or malignant thyroid nodules were 78.9％,85.7％,97.8％,33.3％ and 79.7％ respectively,which of BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 75.4％,85.7％,97.7％,30.0％ and 76.6％ respectively,and which of FNAB plus BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 94.7％,71.4％,96.4％,62.5％ and 92.2％ respectively.By using McNemar paired data x2 test to compare FNAB with combination use of FNAB plus BRAF V600E gene mutation detection in diagnosing thyroid nodules,the results indicated that statistically significant deference in differentiating benign from malignant thyroid nodules existed between the two methods (P＜0.001).Conclusion For the qualitative diagnosis of thyroid nodules which nature cannot be determined by simple FNAB,FNAB combined with BRAF V600E gene mutation detection can improve the diagnostic accuracy for benign and malignant thyroid nodules.

Abstract: Objective To summarize the clinical characteristics of 35 patients with human monkeypox in Chengdu City, in order to provide theoretical basis for prevention and control of monkeypox epidemic in China. Methods A total of 35 patients diagnosed with monkeypox infection by Chengdu CDC from July 1 to July 23, 2023 were included in our study. The results of general clinical data, blood laboratory tests, lymph node ultrasound and chest CT results were collected in order to analyze the clinical features of human monkeypox patients in Chengdu City. Results All 35 monkeypox patients were young adult males, and there were no serious or fatal cases. Among them, 32 cases (91.4%) were men who have sex with men (MSM), and 30 cases had engaged in male-to-male sexual behavior within 21 days prior to the onset of the disease, of which 13 cases had taken protective measures. Fever symptoms were observed in 26 cases (74.3%) of the patients, with 19 cases experiencing fever within 1-6 days after the appearance of rash. The initial rash commonly occurred in the male external genitalia. Color ultrasound examinations indicated that all patients had swollen inguinal lymph nodes. C-reactive protein was elevated in 26 cases (74.3%) of patients, and 19 cases showed CD3+CD4+T/CD3+CD8+T< 1.0. 15 cases (42.8%) of the patients were infected with both monkeypox virus and HIV, 28.5% (10/35) of patients had concomitant skin infections and anorectal proctitis,respectively. The mean time from rash onset to the shedding of rash scabs was 14.8 days. Conclusions The MSM population in sexually active age group is the main infection object of human monkeypox virus. In monkeypox patients in Chengdu City, the rash starting at genital areas and rash occurring before systemic symptoms were common. Swollen inguinal lymph nodes are especially common in monkeypox patients. Skin infection and anorectal proctitis are the most common complications in monkeypox patients in Chengdu City. The abnormal cellular immune function in monkeypox patients is mainly reflected in the inverted ratio of CD3+CD4+T/CD3+CD8+T. Currently, there is no evidence to suggest that protective measures during male-to-male sexual behavior can reduce the risk of human monkeypox infection.

Objective To evaluate the clinical application of liver shear wave velocity (SWV) in comparison with common serum score systems [AST to platelet ratio index (APRI),Forns,S index and FIB-4] in assessment of liver fibrosis in patients with chronic hepatitis.Methods A total of 237 chronic hepatitis patients with liver fibrosis confirmed by liver biopsy,who were admitted in Ningbo Second Hospital during October 2010 and April 2013,were enrolled in the study.Liver shear wave velocity were measured by acoustic radiation force impulse (ARFI),and the score of APRI,Forns,S index and FIB-4 were calculated based on the measurement of serum markers.Liver fibrosis stages were classified as S0-S4 according to the Scheuer scoring system,and stages ≥ S2 were identified as significant liver fibrosis.The diagnosis value of SWV,4 common score systems and their combination for significant liver fibrosis was evaluated by receiver operating characteristic curve (ROC).Results A significant linear correlation was found between SWV and the stage of fibrosis (r =0.46,P ＜ 0.01).The areas under the ROCs of SWV and 4 common score systems (APRI,Forns,S index and FIB-4) for the diagnosis of significant liver fibrosis were 0.758 (0.696-0.821),0.727 (0.662-0.793),0.777 (0.717-0.836),0.747 (0.684-0.810) and 0.737 (0.673-0.802),respectively.The area under the ROC of the combined prediction nodel established with Logistic regression was 0.810.Conclusion Liver shear wave velocity measured by ARFI is of clinical value in noninvasive assessment of liver fibrosis,and the prediction accuracy can be improved when it is combined with other noninvasive indices.

Objective Analysis of the effect and the mechanism of adenovirus with down regulation of matrix metalloproteinase inhibitor 1 (TIMP-1) achieved targeting by ultrasound microbubbles combined with ultrasound irradiation for liver fibrosis in rats. Methods Recombinant adenovirus-mediated with down regulation of TIMP-1 gene was constructed and a mixture of recombinant adenovirus and ultrasound contrast agent was prepared.The rat liver fibrosis model was established and divided into 5 groups : model group; adenovirus group (recombinant adenovirus); adenovirus microbubble group (mixture of recombinant adenovirus and ultrasound contrast agent); experimental group (ultrasound irradiation + mixture of recombinant adenovirus and ultrasound contrast agent); ultrasound adenovirus group (ultrasound irradiation + recombinant adenovirus). The rats were sacrificed after 24 hours and liver sections were prepared. The expression of EGFP in each group was observed and the transfection rate was analyzed. The liver slices were stained by Masson to judge the stage of liver fibrosis. ANOVA analysis was used to compare the levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , bydroxyproline (Hyp) , hyaluronic acid (HA) , type IV collagen (CIV) and laminin (LN) in each group. The relative expression levels of TIMP-1 and matrix metalloproteinase 13 (MMP-13) in each group were detected by Western blot. Results The transfection rate of the experimental group was higher than that of the adenovirus group (q = 3.418) , the adenovirus microbubble group (q = 3.756) and the ultrasonic adenovirus group (q = 5.502) , and the difference was statistically significant (P < 0.05); Pathological examination showed that the degree of fibrosis in the experimental group and the grade of liver fibrosis were lower than the other groups (P < 0.01). The activities of ALT, AST, HA, LN, CIV and Hyp in the experimental group were lower than those in the other 4 groups.Western blot showed that the level of TIMP-1 protein expression was highest while the level of MMP-13 protein expression was lowest in the experimental group than those in the other groups. Conclusion Adenovirus with down regulation of TIMP-1 achieved targeting by ultrasound microbubbles combined with ultrasound irradiation can inhibit the activity of TIMP-1 and improve the degree of liver fibrosis. Gene therapy is an potential therapeutic method in the application of treating liver fibrosis.

Objective    To analyze the clinical features and prognosis of coronavirus disease 2019 (COVID-19) patients. Methods    A total of 379 confirmed COVID-19 patients admitted to Public Health Clinical Center of Chengdu from January 16 to November 30, 2020 were divided into two groups including an elderly group (42 patients, ≥60 years) and a non-elderly group (337 patients, <60 years) by age. The epidemiology, clinical features, laboratory tests, treatment and prognosis of the two groups were compared. Results    Among the 379 patients, 286 (75.5%) were males and 93 (24.5%) were females, aged from 2 months to 87 years, with an average age of 41.2 years. The average age of the elderly group was 69.5 years, and 61.9% of them were females. They were imported from Wuhan or local secondary patients (73.8%), mainly common or critical type (88.1%). While, the average age of the non-elderly group was 37.8 years, and males were more common (80.1%). There were mostly from foreign input (75.7%), mainly mild or ordinary type (95.0%). A total of 179 patients (47.2%) had one or more underlying diseases. Hypertension (15 patients, 35.7%) and diabetes (11 patients, 26.2%) were more common in the elderly group, while non-alcoholic steatohepatitis (132 patients, 39.2%) was more frequent in the non-elderly group. The most common clinical manifestations were fever (138 patients, 36.4%) and cough (129 patients, 34.0%). Fever, cough, dyspnea, and fatigue were more common in the elderly group than those in the non-elderly group (P<0.05). Compared with the non-elderly group, the elderly group had lower total lymphocyte count, CD4+ and CD8+ T-cell count, higher level of myocardial injury or inflammation markers (P<0.05). Abnormal echocardiography in 139 patients (36.7%) was mainly caused by decreased left ventricular diastolic function (22.7%) and heart valve regurgitation (14.0%), and the rate in the elderly group was significantly higher than that in the non-elderly group (85.7% vs. 30.6%, P<0.05). After treatment, 3 patients in the elderly group died, and the others were cured and discharged. The hospitalization duration of the elderly group was longer than that of the non-elderly group (22.1 d vs. 18.8 d, P=0.033). Conclusions    Elderly COVID-19 patients are mainly imported from Wuhan or secondary to the local population, mainly common or critical type, often associated with basic diseases such as hypertension or diabetes. While, non-elderly COVID-19 patients are mainly imported from abroad, mainly mild or common type, often associated with non-alcoholic steatohepatitis. After treatment, most of the patients have a good prognosis.

OBJECTIVE: To explore the effect of ROCK inhibitor Y-27632 on the matrix metalloproteinase 2 and 9 (MMP2 and MMP9) gene expression and activity in tumor necrosis factor α (TNF-α)-treated human umbilical vein endothelial cell (HUVEC).
 METHODS: HHUVEC was divided into 3 groups, a control group, a TNF-α group, and a TNF-α plus Y-27632 group. The expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), MMP2 and MMP9 were examined by real-time PCR. The MMP2/9 activity was measured by gelatin zymography.
 RESULTS: Compared to the control group, the mRNA expressions of ICAM-1, VCAM-1, MMP2 and MMP9 were increased TNF-α-treated cells, which were suppressed by ROCK inhibitor (P<0.01). The MMP2/9 activity was elevated in TNF-α-treated cells, which was reversed by ROCK inhibitor (P<0.05).
 CONCLUSION ROCK inhibitor can suppress TNF-α-induced inflammation in endothelial cells through down-regulation of MMP2/9.
Amides ; Cells, Cultured ; Down-Regulation ; Endothelial Cells ; Humans ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Pyridines ; Signal Transduction ; Tumor Necrosis Factor-alpha ; Umbilical Veins ; Vascular Cell Adhesion Molecule-1 ; rho-Associated Kinases

BACKGROUND: Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC). METHODS: We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage. RESULTS: From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P  < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P  < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P  = 0.001) and 0.474 (0.314-0.717; P  < 0.001) after adjusting for potential confounders, respectively. CONCLUSION ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.
Humans ; Carcinoma, Hepatocellular/drug therapy* ; Retrospective Studies ; Liver Neoplasms/pathology* ; Oxaliplatin/therapeutic use* ; Fluorouracil/adverse effects* ; Disease Progression ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Leucovorin/adverse effects* ; Colorectal Neoplasms/drug therapy*