Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.

Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.

Objective:To explore the mechanism of modified Xiaoyao Powder on inflammatory response of rats with syndrome of stagnation of liver qi and spleen deficiency of experimental autoimmune thyroiditis (EAT) from the perspective of differentiation of microrna 326 (miR326) regulating Th17 cell.Methods:48 rats were randomly divided into normal group (12 rats) and model group (36 rats) respectively and they were immunized twice a week with high iodine water combined with subcutaneous injection of thyroglobulin. From the fifth to eighth weeks, 36 rats were immunized once a week. From the fifth week, the model group with liver depression and spleen deficiency syndrome of Traditional Chinese Medicine was reproduced with chronic restraint stress, excessive fatigue and eating incoherence methods. The modelrats were randomly divided into model group, Xiaoyao Powder group and Jinshuibao group. Rats in Xiaoyao Powder group were gavaged with 13.63 g/(kg·d) Xiaoyao Powder modified granule suspension, and rats in Jinshuibao group were gavaged with 477 mg/(kg·d) Jinshuibao suspension, twice a day, for 8 weeks.The levels of serum FT3, FT4, TSH, TGAb and TPOAb were detected by ELISA; the expression of miR326, IL-17 mRNA, IL-4 mRNA and IFN-γ mRNA were detected by PCR. The expression of Ets-1 protein in thyroid tissue was detected by Wes method, and the proportion of CD4 + IFNγ + T cells, CD4 + IL-4 + T cells and CD4 + IL-17 + T cells were detected by flow cytometry, HE staining was used to detect the pathological manifestations of thyroid tissue in each group. Results:Compared with the model group, the serum TSH [(3 328.88±724.45) pg/ml vs. (1 900.25±203.91) pg/ml] in Xiaoyao Powder group increased ( P<0.01), TGAb [(63.60±9.01) IU/ml vs. (96.19±10.74) IU/ml] and TPOAb [(6.84±1.45) IU/ml vs. (11.62±2.06) IU/ml] decreased ( P<0.01), and the expression of miR326 (3.57±0.57 vs. 7.63±0.90),IL-17 mRNA (6.71±0.97 vs. 13.02±1.18) significantly decreased ( P<0.01), the expression of Ets-1 (0.71±0.40 vs. 0.39±0.02) significantly increased ( P<0.01), the ratio of CD4 +IFN-γ + T cell [(13.10±2.23)% vs. (20.7±2.07)%], CD4 +IL-17 + T cell ratio [(18.90±1.31)% vs. (25.1±1.03)%] significantly decreased ( P<0.01), and thyroid histopathology changed significantly. Conclusion:Modified Xiaoyao Powder could regulate the expression of target protein Ets-1 upward, inhibit the differentiation of Th17 cells and further reduce the expression of IL-17 mRNA by regulating the expression of mir-326 downward in the thyroid tissue of EAT rats, so as to improve the inflammatory response of rats with liver depression and spleen deficiency.

Objective:To compare the clinical characteristics and prognosis of children with necrotizing pneumonia (NP) infected by bacteria and Mycoplasma pneumoniae (MP). Methods:The clinical data of 69 children with NP from January 2012 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. Among them, there were 27 cases of bacterial infection NP (bacterial infection group) and 42 cases of MP infection NP (MP group). The clinical symptoms and signs, extrapulmonary complications, laboratory examination, imaging examination, treatment, outcome and follow-up were compared between 2 groups.Results:There were no significant differences in the rale rate, respiratory tone reduction rate and total fever time between 2 groups ( P>0.05); the incidence of shortness of breath in bacterial infection group was significantly higher than that in MP group: 77.8% (21/27) vs. 14.3% (6/42), and there was statistical difference ( P<0.01). There were no significant differences in the incidence of extrapulmonary complications between 2 groups ( P>0.05). The white blood cell, C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL) -10 in bacterial infection group were significantly higher than those in MP group, the tumor necrosis factor (TNF)-α and interferon (IFN) -γ in bacterial infection group were significantly lower than those in the MP group, and there were statistical differences ( P<0.05). There were no significant differences in neutrophils, lactate dehydrogenase (LDH) and IL-6 between 2 groups ( P>0.05). The time of necrosis in bacterial infection group was significantly earlier than that in MP group: (14.5 ± 4.2) d vs. (21.7 ± 6.4) d, and there was statistical difference ( P<0.05); there was no significant difference in the incidence of pleural effusion between 2 groups ( P>0.05), but the incidence of pleural effusion separation in bacterial infection group was significantly higher than that in MP group: 70.4% (19/27) vs. 2.4% (1/42), and there was statistical difference ( P<0.01). There were no significant differences in antibiotic application time, CRP recovery time and hospital stay between 2 groups ( P>0.05); the oxygen uptake rate and closed thoracic drainage rate in bacterial infection group were significantly higher than those in MP group: 88.9% (24/27) vs. 35.7% (15/42) and 25.9% (7/27) vs. 11.9% (5/42), the recovery times of WBC and PCT in bacterial infection group were significantly longer than that in MP group: (12.8 ± 4.1) d vs. (9.2 ± 2.0) d and (10.5 ± 2.5) d vs. (7.6 ± 1.9) d, the bronchoalveolar lavage rate was significantly higher than that in MP group: 25.9% (7/27) vs. 76.2% (32/42), and there were statistical differences ( P<0.01 or <0.05). There was no significant difference in the absorption time of necrotic lesions between 2 groups ( P>0.05). Conclusions:Compared with MP infection, the clinical process of bacterial infection NP is serious, the necrosis time appears earlier, and the course of disease is longer. However, most of the children with NP can obtain a good prognosis after active symptomatic and antiinfective treatment.

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Objective:To systematically evaluate the clinical efficacy of programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors versus traditional first-line regimens for the treatment of solid tumors.Methods:Databases including PubMed, Embase and Cochrane Library were searched for literatures from the date of their establishment to October 2018 with the key words including "PD-1/PD-L1, solid tumors, melanoma, non-small cell lung cancer, renal cell carcinoma, immunotherapy" . The randomized controlled trial or non randomized controlled trial of high quality about PD-1/PD-L1 inhibitors and traditional fist-line regimens for the treatment of solid tumors were received and enrolled. Patients underwent PD-1/PD-L1 inhibitors immunotherapy were allocated into treatment group, patients underwent traditional first-line regimens treatment were allocated into control group. Two reviewers independently screened literatures, extracted data and assessed the risk of bias. Count data were described as odds ratio ( OR) and 95% confidence interval (95% CI). The heterogeneity of the studies included was analyzed using the I2 test. Funnel plot was used to test potential publication bias if the studies included≥5, and no test was needed if the studies included<5. Results:(1) Document retrieval: a total of 11 available randomized clinical trials were included. There were 5 161 patients, including 2 677 in the treatment group and 2 484 in the control group. (2) Results of Meta analysis. ① There was a significant difference in the objective response rate between the treatment group and the control group ( OR=4.49, 95% CI: 3.01-6.68, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ② There was no significant difference in the disease control rate between the treatment group and the control group ( OR=1.53, 95% CI: 1.01-2.32, P=0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ③ There was a significant difference in disease stability rate between the treatment group and the control group ( OR=0.49, 95% CI: 0.33-0.73, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ④ There was no significant difference in disease progression rate between the treatment group and the control group ( OR=0.71, 95% CI: 0.45-1.15, P>0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ⑤ There were significant differences in overall incidence of adverse events and incidence of adverse events not less than three levels between the treatment group and the control group ( OR=0.53, 0.54, 95% CI: 0.38-0.74, 0.31-0.93, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 11 studies, suggesting that publication bias had little influence on results of Meta analysis. Conclusion:Compared with traditional first-line regimens treatment, PD-1/PD-L1 inhibitors immunotherapy can improve the objective response rate and decrease the incidence of adverse events.

Pancreatic cancer is called as "the king of carcinoma" owing to its poor prognosis. The current treatment methods range from the world-famous Whipple surgery to combination chemotherapy, neoadjuvant radiotherapy and chemotherapy, and emerging immunological checkpoint inhibitors. However, they all have certain limitations and the overall survival rate of pancreatic cancer has not been improved significantly in recent decades. With the further study of tumor immunology, tumor immunotherapy has gradually become the focus of cancer therapy. As a novel immunotherapy idea, oncolytic virus therapy is gradually accepted by scholars for its safety and effectiveness. Oncolytic virus can specifically infect and lyse tumor cells. It can not only directly lyse tumor cells by self-replication but also release immune molecules and tumor antigens by lysing tumor cells, which further enhance immune anti-tumor effect without damaging normal tissues. In addition, the oncolytic virus can carry the abundant exogenous target gene through gene editing technology to further enhance the anti-tumor effect of the oncolytic virus. Due to the complexity of the microenvironment of pancreatic cancer, the oncolytic virus monotherapy has limited effects, and combination therapy has shown promising prospects. Compared with other tumor immunotherapy, oncolytic virus therapy displays high killing efficiency, targeting ability and small adverse reaction, multiple anti-tumor pathways to avoid drug resistance and low cost, and is expected to become an ideal new way for oncotherapy. Based on domestic and overseas literatures, the authors have reviewed the development of ancolytic virus therapy, treatment mechanism of oncolytic virus and its advances in pancreatic cancer in this article.

Exocrine pancreatic insufficiency is a commom complication after pancreatic operation with high morbidity.At present,surgeons have insufficient understanding of it,and there is no internationally normalized standard for the diagnosis and treatment of exocrine pancreatic insufficiency.Through systematic reviewing of the relevant literature,this review summarizes the research progress of exocrine pancreatic insufficiency after pancreatic operation,including the definition of exocrine pancreatic insufficiency,aetiological agent,diagnosis,treatment,prevention,and morbidity of pancreatic exocrine insufficiency in different surgical procedures,in order to provide a reference for the improvement of diagnosis and treatment of exocrine pancreatic insufficiency in the future.

Objective To explore the value of the 7th and 8th edition AJCC TNM staging systems for hepatocellular cancer about disease free survival (DFS) after surgery.Methods Clinical data of hepatocellular cancinoma patients were analyzed retrospectively.The difference of the two staging systems in predicting DFS were compared by Kaplan-Meier analytical method and ROC test.Results Based on AJCC 7th edition,there were 114 phase Ⅰ patients,64 phase Ⅱ patients,18 phase Ⅲ patients,4 phase Ⅳ patients,while based on 8th edition,there were 33 phase ⅠA patients,85 Ⅰ B patients,60 phase Ⅱ patients,18 phase Ⅲ patients and 4 phase Ⅳ patients.There was a significant difference in the survival curve between the two stages (x2 =31.177,40.073,P ＜ 0.01).At the same time,the area under the ROC curve in the 8th edition was better than that in the 7th edition.In addition,in the 8th edition the DFS curve of phase ⅠA was superior to that of phase Ⅰ in 7th edition,and to that of phase ⅠB in the 8th edition (x2 =5.701,P =0.017;x2 =7.865,P =0.005).There was no significant difference between that of phase Ⅰ in the 7th edition and that of phase ⅠB in the 8th edition (~ =0.753,P =0.385).Conclusion The value of the 8th AJCC TNM staging in evaluating postoperative DFS is better than the 7th stage,especially for stage I patients.

Objective:Previous studies have shown an association between programmed death-ligand 1 expression(PD-L1)in non-small cell lung cancer(NSCLC)and clinical factors and that PD-L1 is positively correlated with TNM staging.This study aimed to explore the prognostic significance of PD-L1 and its correlation with the maximum standardized uptake value(SUVmax).Methods:Clinicopath-ological data and the follow-up information of the 122 de novo primary NSCLC patients were analyzed.PD-L1 expression was detected by immunohistochemistry in this 122 surgically resected non-small cell lung carcinoma tissues.Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model.Correlation between SUVmax and PD-L1 expression was analyzed using Spearman's rank correlation analysis.Results:Multivariate analysis revealed that PD-L1 expression(HR=4.518,95% CI:1.176-17.352,P=0.028)and tumor size(HR=1.404,95%CI:1.020-1.933,P=0.037)were independent risk factors for overall survival(OS) in early NSCLC patients.Sex,age,pathological type,CEA level,and SUVmax group had no obvious effect on OS(P 0.05)in early NSCLC patients.In univariate analyses,sex,pathological type,tumor size,and SUVmax group affected OS in stageⅢ-ⅣNSCLC patients.How-ever,age,CEA level,and PD-L1 expression had no effect on OS.PD-L1 expression was not an independent risk factor for OS in stageⅢ-ⅣNSCLC patients.The SUVmax group had no association with PD-L1 in all patients.Conclusions:PD-L1 expression is an independent risk factor for OS in early NSCLC patients but not in stageⅢ-Ⅳpatients.