Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.
Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Down-Regulation ; Epithelial Cells/metabolism* ; Extracellular Vesicles/pathology* ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/pathology* ; PTEN Phosphohydrolase/metabolism* ; Tumor Suppressor Protein p53/metabolism*

Objective:To investigate the effects of ulinastatin combined with meropenem on immune function, interleukin 2(IL-2), interleukin 4(IL-4), interleukin-6(IL-6), interleukin 10(IL-10) and tumor necrosis factor (TNF-) levels in elderly patients with severe infection.Methods:From January 2016 to June 2018, 60 elderly patients with severe infections admitted to the Second People's Hospital of Lishui were randomly divided into control group(30 cases) and observation group(30 cases). The patients in the control group were treated with meropenem, while the patients in the observation group were treated with ulinastatin on the basis of the control group.Both two groups were treated for 14 days.The therapeutic effects, changes of T lymphocyte subsets, IL-2, IL-4, IL-6, IL-10 and TNF-levels, recovery time of gastrointestinal function and occurrence of systemic inflammatory response syndrome(SIRS) before and after treatment were compared between the two groups.Results:The total effective rate of the observation group(93.33%) was higher than that of the control group(66.67%)(χ 2=6.667, P<0.05). After treatment, CD 3+ [(64.38±3.19)%], CD 4+ [(40.39±2.35)%]and CD 4+/CD 8+ (1.65±0.19) in the observation group were higher than those in the control group[(58.94±3.56)%, (35.47±2.87)% and (1.34±0.14)]( t=6.233, 7.265, 3.834, all P<0.05). The serum levels of IL-2[(126.87±17.49)ng/L], IL-4[(8.98±2.14)g/L], IL-6[(176.89±23.1)ng/L], IL-10[(37.94±12.56)ng/L] and TNF-α[(163.45±17.96)ng/L]in the observation group were lower than those in the control group[(343.27±28.56)ng/L, (19.65±4.56) g/L, (346.37±38.98)ng/L, (83.21±18.56)ng/L and (254.37±23.45)ng/L]( t=35.392, 10.602, 20.476, 11.064, 16.860, all P<0.05). The recovery time of gastrointestinal function in the observation group[(5.31±1.29)d] was shorter than that in the control group[(6.97±1.43)d]( t=4.721, P<0.05), while the incidence of SIRS(13.33%) was lower than that in the control group(43.33%)(χ 2=6.648, P<0.05). Conclusion:Ulinastatin combined with meropenem is effective in the treatment of elderly patients with severe infection.It can improve the immune function of the patients, reduce the levels of IL-2, IL-4, IL-6, IL-10 and TNF-, and alleviate the inflammatory reaction.It is worthy of clinical reference.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Portal vein tumor thrombus (PVTT) is a common finding in patients with advanced hepatocellular carcinoma (HCC),and the presence of PVTT usually indicates a poor prognosis.At present,two PVTT classifications are adopted in clinical practice;they are VP classification of Japan and eastern hepatobiliary classification (Cheng's classification).There are some differences in PVTT classification between the above two typing criterion.Certain correlation exists between patient's prognosis and PVTT typing;for example,PVTT of type Ⅰ0 carries the best prognosis,while PVTT of type Ⅳ indicates the worst prognosis.The choice of treatment plan is limited by the type of PVTT for a given patient.Therefore,the optimal therapeutic regimen should be formulated based on the type of PVTT in order to control HCC and to benefit the patient.

OBJECTIVE To explore the feasibility of detection for mutated BRAF V600E gene based on amplification refractory mutation system(ARMS),and to evaluate its clinical significance of BRAF V600E gene mutation in thyroid nodules.METHODS The method of ARMS was used to detect BRAF V600E mutation status in 179 patients with PTC and 115 patients with benign lesions.The diagnosis index of BRAF V600E mutation status for identifying the nature of the thyroid nodule was calculated.The potential correlation between BRAF V600E mutation and PTC clinicpathological characteristics was also analyzed.RESULTS Detection of BRAF V600E mutation status in thyroid lesions based on ARMS was feasible and believable.The positive rate of mutated BRAF V600E gene in PTC was 82.68％,whereas the rate in benign lesions was only 1.74％,indicating statistical differences between the two groups(x2=183.568,P＜0.01).The diagnostic sensitivity of BRAF V600E mutation was 82.68％,specificity was 98.26％,accuracy was 88.76％,and Youden index was 0.8094.There was no associations between the BRAF V600E mutation status and PTC clinicpathological characteristics(eg.gender,age,tumor size,numbers of lesions,bilateral lesions,extrathyroidal extension and lymph node metastasis).CONCLUSION Detection of BRAF V600E mutation based on ARMS has higher sensitivity and specificity in distinguishing PTC from benign lesions,indicating BRAF V600E gene is an ideal marker of PTC for clinical early diagnosis.

Cholangiocarcinoma is a malignant tumor that occurs in the bile duct epithelium,it is the second most common malignant tumor of the liver and bile duct after hepatocellular carcinoma.Imaging examination is an important method to detect bile duct cancer;the purpose of imaging is to determine the location of the tumor,and the extent of invasion and distant metastasis.Different imaging methods have their advantages and disadvantages,so they should be chosen based on the condition of patients,or be optimized as the combined detection.

Objective To investigate the adjustment of miRNA-155 on CD4+ CD25+ Treg regulative T cell in peripheral blood in patients with acute cerebral infarction (ACI) and its pathogenesis. Methods Sixty patients with ACI were divided into three groups according to clinical neurological deficit score. Twenty healthy volunteers were enrolled into the control group. The expression levels of plasma miR-155 mRNA and Foxp3 mRNA were detected by real-time quantitative PCR(qRT-PCR). IL-10 levels in plasma were detected by ELISA. Results Expression of miR-155, Treg, Foxp3 mRNA and levels of IL-10 were significantly increased in patients with ACI compared with normal control group, with statistical differences; Expression of miR-155, Treg, Foxp3 mRNA and levels of IL-10 were gradually increased. The values showed significant statistical difference among the mild, moderate and severe ACI groups (P < 0.01). Among the patients,the levels of miR-155, Treg, Foxp3 mRNA and levels of IL-10 in the survival group were obviously lower than those in the non (P<0.05 or P<0.01). There was a positive correlation between miR-155 and Treg, Foxp3 mRNA (P < 0.01). Conclusion This study suggests that miR-155 is involved in the cell proliferation regulation of CD4+ CD25+ Treg cells,and plays some role in the immunological dissonance with ACI.

BACKGROUND:A few studies have reported that autologous chondrocyte implantation is better than microfracture for treating cartilage defects of the knee. But there are few meta-analyses on the clinical outcomes of autologous chondrocyte implantation versus microfracture. OBJECTIVE:To evaluate the effects of autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee based on existing clinical data. METHODS:A systematic search for control ed clinical trials or control ed prospective observational studies published from 1979 to January 2015 was done in electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Central Register, Wanfang, CNKI and VIP. The literatures about the effects of autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee were retrieved. We screened the retrieved literature according to the inclusion and exclusion criteria and performed a Meta-analysis with the software RevMan 5.2 after identification of the relevant data. RESULTS AND CONCLUSION:Eight studies were enrol ed according to the selection criteria, which revealed a statistical y significant difference, representing a clinical y relevant superiority of autologous chondrocyte implantation over microfracture, in IKDC scores at final fol ow-up [weighted mean difference (WMD),-9.93;95%confidence interval (CI):-13.16 to-5.43;P<0.000 01] and available scores at 5-year fol ow-up [standard mean difference (SMD),-0.30;95%CI: -0.55 to-0.05;P=0.02). In contrast, there were no significant differences, thus representing no clinical relevant superiority of microfracture versus autologous chondrocyte implantation, in Tegner scores at final fol ow-up (WMD=0.44;95%CI:0.04 to 0.84;P=0.03), Lysholm scores at final fol ow-up (WMD=-10.21;95%CI:-33.68 to 13.26;P=0.39), and available scores at 2-year fol ow-up (SMD=-0.25;95%CI:-0.92 to 0.43;P=0.47). These findings demonstrate that autologous chondrocyte implantation can result in a better long-term outcome than microfracgure. However, whether autologous chondrocyte implantation has a better treatment effect than microfracture in general needs more research.

Objective To explore whether Forkhead O transcription factor-3a (FoxO3a) activity affects the capability of sphere-formation of ovarian cancer SKOV3 cell line.Methods Sphere-forming cells (SFCs) were obtained and amplified through suspended culture with conditioned medium of the stem cells in SKOV3 cell line.After SKOV3 cells were transfected with FoxO3a specific siRNA,the protein expressions of FoxO3a and Bmi1 and the ratio of sphere-formation were compared with Western blot and sphere-forming assay,respectively.Results Compared to parental cells,SFCs from SKOV3 cell line had higher ratio of sphere-formation and over-expressed Bmi1 and pFoxO3a.Transfection of FoxO3a specific siRNA down-regulated the protein expression of FoxO3a and upregulated expression of Bmi1 in SKOV3 cells,and enhanced the capability of sphere-formation.Conclusions Silence of FoxO3a leads to enhanced capability of sphere-formation in SKOV3 cell line.

Objective To study the efficacy of combining Entecavir with TACE to treat patients with primary hepatocellular carcinoma with undetectable levels of HBV-DNA.Methods From Aug 2011 to Sep 2013, patients with HBV-related hepatocellular carcinoma but with undetectable levels of HBV DNA who underwent TACE were divided into the treatment group (treated with Entecavir antiviral therapy) and the control group.The endpoints of the study were HBV reactivation rates, liver function, and survival rates.Results Using our predefined inclusion and exclusion criteria, 64 patients with primary liver cancer were divided into the treatment group (n =32) and the control group (n =32).The transaminase and bilirubin levels were raised and the albumin level was reduced at 5 days after TACE.However, there were no significant differences between the 2 groups (P ＞0.05).At 12-month follow-up after TACE, 8 (25.0％) patients developed HBV reactivation in the control group and 2 (6.3％) in the treatment group, the difference was significant (P ＜ 0.05).The level of transaminase was significantly higher in the HBV reactivation group when compared with the no HBV reactivation group (P ＜ 0.05).The overall 6-and 12-month survival rates in the treatment group and the control group were 93.8％ and 84.4％ vs 90.6％ and 59.4％ respectively.There were significant differences in the 12-month survival rates (P ＜ 0.05).Conclusion Entecavir combined with TACE to treat patients with HBV-related primary liver cancer with undetectable HBV-DNA effectively reduced HBV reactivation and improved survival at 12 months.