This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.

Porcine circovirus type 2(PCV2)is the main pathogen causing porcine circovirus related diseases.PCV2 infection in pigs may lead to porcine dermatitis and nephrotic syndrome(PDNS)and weaned piglets multiple system failure syndrome(PMWS),etc.At present,the pathogenic mechanism is not fully understood.PCV2 is a single strand of negative link DNA,which can cause immune suppression in the body and lead to increased secondary susceptibility,which has a syner-gistic effect with various pig diseases and brings major economic losses to the pig industry.Al-though there are commercial vaccines,the prevention of vaccines has certain limitations and there is no effective drug treatment so far,an outbreak will threaten people's life and health and public safety,resulting in significant economic losses.In order to understand the latest progress of PCV2 escape mechanism and prevention and control,this paper summarizes the inhibition of interferon production,regulation of apoptosis,regulation of autophagy,regulation of pyroptosis and inflam-matory response,evasion of adaptive immune response,and prevention and control of PCV2,in or-der to provide new theoretical ideas for the research and prevention and control of PCV2.

With the continuous development of cancer treatment, the immune checkpoint inhibitors have been applied to the treatment of a variety of malignant tumors, which improved the patient′s survival time and quality of life. However, immune-related adverse reactions occur inevitably. Like chemotherapeutics and targeted drugs, immunosuppressants can also cause cardiovascular events that affect the mortality of cancer patients. With the extension of the survival time of cancer patients, it will increasingly become a key factor which affects the prognoses of these diseases. This review focuses on the cardiotoxic mechanism, clinical manifestation, and future direction of immune checkpoint inhibitors during cancer treatment.

With the continuous development of cancer treatment, the immune checkpoint inhibitors have been applied to the treatment of a variety of malignant tumors, which improved the patient′s survival time and quality of life. However, immune-related adverse reactions occur inevitably. Like chemotherapeutics and targeted drugs, immunosuppressants can also cause cardiovascular events that affect the mortality of cancer patients. With the extension of the survival time of cancer patients, it will increasingly become a key factor which affects the prognoses of these diseases. This review focuses on the cardiotoxic mechanism, clinical manifestation, and future direction of immune checkpoint inhibitors during cancer treatment.

Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.

OBJECTIVEThis study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.

METHODSTwenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.

RESULTSAmong the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.

CONCLUSIONSCrizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; pathology ; Nausea ; chemically induced ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrazoles ; adverse effects ; therapeutic use ; Pyridines ; adverse effects ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; Vomiting ; chemically induced

Objective This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK?positive non?small cell lung cancer ( NSCLC) patients. Methods Twenty?eight patients with advanced ALK?positive NSCLC were given orally crizotinib 250 mg b. i. d., and were followed up to evaluate the therapeutic efficacy and safety. Results Among the 28 patients, the objective response rate ( ORR) was 71.4%(20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug?related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade Ⅰ or Ⅱ. Only one patient had grade Ⅲ myelosuppression. Among the 28 patients, 16 cases were disease?free and 12 cases had progressive disease, with a progression?free survival of 8.2 months. Conclusions Crizotinib is effective and tolerable in the treatment of advanced ALK?positive NSLCC. However, its long?term treatment efficacy requires to be further studied.

Target treatment based on driver genes in advanced non-small cell lung cancer is very important cur-rently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. hTis report reviews the tis-sue specimen alternatives of driver gene testing in non-small cell lung cancer.

Objective This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK?positive non?small cell lung cancer ( NSCLC) patients. Methods Twenty?eight patients with advanced ALK?positive NSCLC were given orally crizotinib 250 mg b. i. d., and were followed up to evaluate the therapeutic efficacy and safety. Results Among the 28 patients, the objective response rate ( ORR) was 71.4%(20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug?related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade Ⅰ or Ⅱ. Only one patient had grade Ⅲ myelosuppression. Among the 28 patients, 16 cases were disease?free and 12 cases had progressive disease, with a progression?free survival of 8.2 months. Conclusions Crizotinib is effective and tolerable in the treatment of advanced ALK?positive NSLCC. However, its long?term treatment efficacy requires to be further studied.

BACKGROUNDThe preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.

METHODSThe clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.

RESULTSThe objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity.

CONCLUSIONSIcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Crown Ethers ; adverse effects ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Quinazolines ; adverse effects ; therapeutic use ; Retrospective Studies