Hepatitis E virus infection in buffaloes in South China / [Hepatite E infecção viral em búfalos no Sul da China]

Hepatitis E virus (HEV) infection is an important global public health issue. HEV infections are recognized as a zoonotic disease. Swine are believed to be the main reservoir of HEV. Recently, yaks, cows, and yellow cattle have been reported as new reservoirs of HEV. However, whether other species of cattle and buffaloes are sensitive to HEV infection is unknown. To investigate the prevalence of HEV infection in buffaloes, enzyme-linked immunosorbent assay (ELISA) and reverse transcription-nested polymerase chain reaction (RT-nPCR) were performed. Only one buffalo was positive to anti-HEV IgM antibody (1/106, 0.94%), and none were positive for anti-HEV IgG antibody. To our surprise, five serum (5/106, 4.72%) and three milk samples (3/40, 7.50%) from buffaloes were positive to HEV RNA. All strains of HEV isolated from buffaloes belong to genotype 4. Results indicate that buffaloes may be a new reservoir of HEV.(AU)

Infecção com o vírus Hepatite E (HEV) é uma importante questão de saúde pública global. Infecções HEV são reconhecidas como doença zoológica. Acredita-se que suínos são o principal reservatório de HEV. Recentemente iaques, vacas, e gado amarelo foram reportados como novos reservatórios do HEV. Porém, não se sabe se outras espécies de gado e búfalo são sensíveis a infecção HEV. Para investigar a prevalência de infecção HEV em búfalos, foram realizados prova de imunoabsorção enzimática e polimerização em cadeia inversa ancorada em transcrição. Apenas um búfalo foi positivo para o anticorpo anti-HEV IgM (1/106, 0,94%), e nenhum foi positivo para o anticorpo anti-HEV IgG. Para nossa surpresa cinco (5/106, 4,72%) e três amostras de leite (3/40, 7,50%) de búfalos foram positivos para HEV RNA. Todas as estirpes de HEV isoladas de búfalos pertencem ao genótipo 4. Resultados indicam que búfalos podem ser um reservatório de HEV.(AU)

Novel retrograde puncture method to establish preperitoneal space for laparoscopic direct inguinal hernia repair with internal ring suturing

The aim of this study was to explore the clinical efficacy of a novel retrograde puncture approach to establish a preperitoneal space for laparoscopic direct inguinal hernia repair with inguinal ring suturing. Forty-two patients who underwent laparoscopic inguinal hernia repair with retrograde puncture for preperitoneal space establishment as well as inguinal ring suturing between August 2013 and March 2014 at our hospital were enrolled. Preperitoneal space was successfully established in all patients, with a mean establishment time of 6 min. Laparoscopic repairs were successful in all patients, with a mean surgical time of 26±15.1 min. Mean postoperative hospitalization duration was 3.0±0.7 days. Two patients suffered from postoperative local hematomas, which were relieved after puncturing and drainage. Four patients had short-term local pain. There were no cases of chronic pain. Patients were followed up for 6 months to 1 year, and no recurrence was observed. Our results demonstrate that preperitoneal space established by the retrograde puncture technique can be successfully used in adult laparoscopic hernioplasty to avoid intraoperative mesh fixation, and thus reduce medical costs.

Targeting PPM1D by lentivirus-mediated RNA interference inhibits the tumorigenicity of bladder cancer cells

Protein phosphatase magnesium/manganese-dependent 1D (PPM1D) is a p53-induced phosphatase that functions as a negative regulator of stress response pathways and has oncogenic properties. However, the functional role of PPM1D in bladder cancer (BC) remains largely unknown. In the present study, lentivirus vectors carrying small hairpin RNA (shRNA) targeting PPM1D were used to explore the effects of PPM1D knockdown on BC cell proliferation and tumorigenesis. shRNA-mediated knockdown of PPM1D significantly inhibited cell growth and colony forming ability in the BC cell lines 5637 and T24. Flow cytometric analysis showed that PPM1D silencing increased the proportion of cells in the G0/G1 phase. Downregulation of PPM1D also inhibited 5637 cell tumorigenicity in nude mice. The results of the present study suggest that PPM1D plays a potentially important role in BC tumorigenicity, and lentivirus-mediated delivery of shRNA against PPM1D might be a promising therapeutic strategy for the treatment of BC.

Feasibility and safety of early chest tube removal after complete video-assisted thoracic lobectomy.

OBJECTIVE: The aim was to evaluate the feasibility and safety of early chest tube removal after complete video‑assisted thoracic lobectomy (CVATL). METHODS: Retrospective analysis was performed on effects of chest tube removal on patients with lung cancer after pulmonary lobectomy between November 2013 and October 2014. 154 eligible patients included 97 cases for CVATL and 57 cases for open thoracic lobectomy. Patients with CVATL were divided randomly into experimental group (EG) and control group (CG), in which 51 patients in EG had chest tube removal on the 2nd day after operation; 46 patients in CG had the tube removal when the drainage volume <100 ml/day. Patients in open thoracic lobectomy group (OG) had the tubes removal as CG. The drainage volumes of the 1st and 2nd 24 h after operation, duration of chest tubes, cases of pain alleviation, and recurrent pleural effusions requiring reintervention were measured. RESULTS: The average drainage volume of the 1st 24 h after operation of CVATL group from EG and CG was significantly reduced than that in OG (260.41 ml vs. 353.16 ml, P < 0.001). The average drainage volume of the 2nd 24 h after operation of CG was significantly reduced than that in OG (163.91 ml vs. 222.98 ml, P < 0.001). The average duration of chest tube of CG for 2.98 days showed significant different compared with OG for 3.81 days (P < 0.001). Chest tube removal in CVATL group increased more chest pain alleviation than OG (80.4% vs. 56.1%, P = 0.001). The frequencies of recurrent pleural effusions requiring reintervention were 5.88% (3/51), 4.35% (2/46) and 5.26% (3/57), respectively, which had no significant differences between three groups (P = 1.000). CONCLUSIONS: Complete video‑assisted thoracic lobectomy brings less drainage volume after operation. Early removal of chest tube in CVATL shows feasible and safe and demonstrates that it may reduce postoperative pain and help fast recovery.

Incidence, risk factors, and prognosis of acute kidney injury following transarterial chemoembolization in patients with hepatocellular carcinoma: A prospective cohort study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is an effective first‑line therapy for intermediate stage hepatocellular carcinoma (HCC). Acute renal injury may be induced after transarterial chemoembolization because of iodinated radiocontrast medium, but its incidence, risk factors, and prognosis remain unclear. PATIENTS AND METHODS: This prospective study enrolled 166 HCC patients with a total of 316 TACE treatments. The incidence, risk factors, and prognosis of acute kidney injury (AKI) were examined. RESULTS: The incidence of post‑TACE AKI was 21.84% (69/316) according to Barrett and Parfrey criteria, whereas 7.59% (24/316) according to acute kidney injury network (AKIN) criteria. Multivariate logistic regression analysis showed that serum total bilirubin (TB) (>13.5 μmol/L; odds ratio [OR]: 1.871 95% confidence interval [CI]: 1.044–3.352; P = 0.035) and hemoglobin (HGB) level (<120 g/L; OR: 1.823, 95% CI: 1.019–3.264; P = 0.043) were associated with the development of AKI after TACE procedure in accordance to Barrett and Parfrey criteria. Meanwhile, age (>55 years; OR: 3.456, 95% CI: 1.107–10.790; P = 0.033), post‑TACE AKI history (OR: 7.108, 95% CI: 1.387–36.434, P = 0.019), and serum aminotransferase level (>55 U/L; OR: 4.420, 95% CI: 1.792–10.906; P = 0.001) were associated with the development of AKI after TACE procedure in accordance to AKIN criteria. Total hospitalization cost was significantly higher (P = 0.034) in the patients with AKI after TACE procedure according to Barrett and Parfrey criteria. A post‑TACE AKI diagnosis was associated with mortality in any definition used (P = 0.034 and P = 0.001 for Barrett and Parfrey and AKIN criteria, respectively). CONCLUSION: The present study showed that the incidence of post‑TACE AKI was high in HCC patients (i.e., 7.59–21.84%) depending on criteria used. HGB (<120 g/L), serum TB (>13.5), and aminotransferase level (>55 U/L), age (>55 years) and post‑TACE AKI history may be predictors of post‑TACE AKI in HCC patients. The development of post‑TACE AKI was associated with the risk of renal replacement treatment, prolonged renal insufficiency, or mortality according to AKIN criteria.

Autophagy facilitates the sorafenib resistance of hepatocellular carcinoma cells / La autofagia facilita la resistencia al sorafenib de las células del carcinoma hepatocelular

Liver cancer is the second most frequent cause of cancer death in men and the sixth leading cause of cancer death in women. Hepatocellular carcinoma (HCC) represents the major subtype in liver cancer and its five-year survival rate remains very poor. Sorafenib, a molecular targeted therapeutic agent, was the first drug approved for the treatment of patients with HCC. However, the clinical response of sorafenib was seriously limited by drug resistance. Autophagy is an evolutionarily conserved mechanism among all eukaryotes. Recently, many studies have indicated that autophagy can be activated as a cellular protective mechanism in many tumour cells. Thus, we hypothesized that autophagy may play an important role in resistance to sorafenib in hepatocellular carcinoma. Although the exact role of autophagy in the sorafenib resistance of HCC is still complex and further studies are needed to be proven, at least it suggests that autophagy may be a new therapeutic target for the sorafenib resistance of HCC.

El cáncer de hígado es la segunda causa de muerte más frecuente por cáncer en los hombres y la sexta causa de muerte por cáncer en las mujeres. El carcinoma hepatocelular (CHC) representa el subtipo principal en el cáncer de hígado, y su tasa de supervivencia de cinco años sigue siendo muy pobre. El sorafenib, un agente terapéutico dirigido selectivamente a moléculas especificas, fue el primer medicamento aprobado para el tratamiento de pacientes con CHC. Sin embargo, la respuesta clínica de sorafenib estaba seriamente limitada por la resistencia al medicamento. La autofagia es un mecanismo evolutivamente conservado entre todos las eucariotas. Recientemente, muchos estudios han indicado que la autofagia puede activarse como mecanismo de protección celular en muchas células tumorales. Por consiguiente, postulamos la hipótesis de que la autofagia puede desempeñar un papel importante en la resistencia del carcinoma hepatocelular al sorafenib. Aunque el papel exacto de la autofagia en la resistencia al sorafenib del CHC es aún complejo y se necesitan estudios adicionales para ser probado, al menos se sugiere que la autofagia puede ser una nueva meta terapéutica frente a la resistencia del sorafenib en el CHC.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

application of ultrasound B-flow imaging in detection of carotid atherosclerotic micro-vessel with ischemic cerebrovascular disease

To investigate the detection and characterization of micro-vessels within the carotid atherosclerotic plaque using B-flow imaging [BFI] ultrasound with contrast-enhanced ultrasound [CEU] as the reference standard. Between August 2008 and July 2011, 78 patients with carotid atherosclerosis that were admitted at the Department of Ultrasonography in ZhongNan Hospital of Wuhan University, Wuhan, China underwent standard and BFI examination. Fifty-one patients received both BFI and CEU. We evaluated the relationship between BFI findings, and clinical symptoms in ischemic stroke, or transient ischemic attack patients. The correlation of cerebrovascular symptoms, stenosis, and plaque type on the detection of neovessels by BFI were statistically evaluated using chi2 test [McNemar test]. The agreement of the 2 sonographic methods was assessed by kappa coefficient. The diagnostic efficacy of BFI for carotid atherosclerotic micro-vessel detection was also calculated. The BFI findings of micro-vessel were correlated to patient's symptom. The agreement between BFI and CEU for diagnosis of microvascularization was good [kappa=0.406]. The following was calculated: sensitivity [0.483]; specificity [0.955]; positive predictive value [0.933]; negative predictive value [0.583]; and accuracy of BFI [0.686]. Logistic regression demonstrated a significant association between cerebrovascular events and the presence of BFI signals within carotid plaques [B: 2.422; 95% confidence interval: 1.728-73.407]. Compared with CEU, the BFI is less sensitive, however, it is a valid and practical method for detection of carotid atherosclerotic micro-vessels

Current understanding of the molecular basis of chloroquine-resistance in Plasmodium falciparum.

Chloroquine (CQ) is the most successful antimalarial drug ever discovered. Unfortunately, parasites resistant to the drug eventually emerged after its large scale use and are now widespread. Although great progress in our understanding of the mechanisms of CQ action and CQ resistance (CQR) has been achieved over the past two decades, including the identification of the molecules responsible for CQR (e.g., Plasmodium falciparum chloroquine resistant transporter, PfCRT) many questions remain unanswered. Here we highlight recent advances in our understanding of the genetics and molecular mechanisms of CQR, with particular emphasis on the role of genes such as pfcrt and pfmdr1 in the resistance to CQ and other drugs. New drug development and applications will undoubtedly benefit from a better understanding of CQR, eventually leading to more effective malaria control measures.

Domain III function of Mu transposase analysed by directed placement of subunits within the transpososome.

Assembly of the functional tetrameric form of Mu transposase (MuA protein) at the two att ends of Mu depends on interaction of MuA with multiple att and enhancer sites on supercoiled DNA, and is stimulated by MuB protein. The N-terminal domain I of MuA harbours distinct regions for interaction with the att ends and enhancer; the C-terminal domain III contains separate regions essential for tetramer assembly and interaction with MuB protein (IIIalpha and IIIbeta, respectively). Although the central domain II (the 'DDE' domain) of MuA harbours the known catalytic DDE residues, a 26 amino acid peptide within IIIalpha also has a non-specific DNA binding and nuclease activity which has been implicated in catalysis. One model proposes that active sites for Mu transposition are assembled by sharing structural/catalytic residues between domains II and III present on separate MuA monomers within the MuA tetramer. We have used substrates with altered att sites and mixtures of MuA proteins with either wild-type or altered att DNA binding specificities, to create tetrameric arrangements wherein specific MuA subunits are nonfunctional in II, IIIalpha or IIIbeta domains. From the ability of these oriented tetramers to carry out DNA cleavage and strand transfer we conclude that domain IIIalpha or IIIbeta function is not unique to a specific subunit within the tetramer, indicative of a structural rather than a catalytic function for domain III in Mu transposition.