During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Objective: : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods: : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results: : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

OBJECTIVE: To observe the effect of acupuncture-moxibustion on negative emotions and plasma tryptophan (Trip)-kynurenine (Kyn) metabolism in the patients with Crohn's disease (CD) at the mild and moderate active stage. METHODS: A total of 66 CD patients were randomized into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, acupuncture was applied in combination with moxibustion. In the control group, the sham-acupuncture was used in combination with sham-moxibustion. In both of the observation group and the control group, acupuncture was applied to Zhongwan (CV 12), Shangjuxu (ST 37), Sanyinjiao (SP 6), Gongsun (SP 4), Hegu (LI 4), Quchi (LI 11), Taixi (KI 3) and Taichong (LR 3), and moxibustion was applied to Tianshu (ST 25) and Zusanli (ST 36). The treatment was given once every two days, 3 times a week, totally for 12 weeks. Separately, before and after treatment, the score of the hospital anxiety-depression scale (HADS) and the score of intestinal core symptoms (degree of abdominal pain and frequency of diarrhea) were observed in the patients of the two groups. The concentration of plasma indoleamine 2,3-dioxygenase 1 (IDO1) and the ratios of Kyn/Trp, QuinA/Kyn, KynA/Kyn and KynA/QuinA were compared between the two groups. RESULTS: Compared with before treatment, the scores of HADS-A and HADS-D in the observation group and the score of HADS-A in the control group were all reduced after treatment ( CONCLUSION Acupuncture and moxibustion relieve the negative emotions of anxiety and depression in CD patients at mild and moderate active stage, which is probably related to the regulation of plasma Trp-Kyn metabolic pathway.
Acupuncture Points ; Acupuncture Therapy ; Crohn Disease/therapy* ; Emotions ; Humans ; Moxibustion ; Plasma ; Treatment Outcome ; Tryptophan

China ; Constipation/therapy* ; Humans ; Massage ; Medicine, Chinese Traditional

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.

In this paper, a novel and simple RP-HPLC method for the determination of related substances of tiopronin for injection was described. The RP-HPLC analysis was performed on a C18 column, with acetonitrile-0. 1% phosphoric acid(8 ∶92), mobile phase in isocratic mode at a rate of 1. 0 mL/min. The photodiode array detector was set at 210 nm. Seven related substances were detected and the structures were characterized by mass spectrometry. The method showed great suitability, specificity and excellent linearity over the concentration range of 0. 3 to 50 μg/mL(r≥0. 999), and the limits of detection and quantitation were found to be 0. 10 and 0. 31 μg/mL, respectively. The accuracy of the method determined by the entire mean recovery ranged from 98. 7% to 103. 7%. The intra-and inter-day precision was satisfactory(RSD≤4. 4%)and robust(RSD≤6. 4%). And this method was successfully applied for the determination of related substances of tiopronin for injection, which revealed the retention of sulfhydryl compounds and glycine analogues on the RP-HPLC and the effect of the pH value of the mobile phase on the chromatographic behavior of the analytes.

Saliva is being attached great importance for its application in illness diagnosis and have more advantage on the diagnose in oral cavity cancer (OCC). Studies have showed that interleukin (IL) in the saliva could be used as a potential biomarker for OCC diagnosis. Moreover, they have a close connection with tumor genesis, invasion, and metastasis in OCC. Therefore, we reviewed research progress on the relationship between salivary interleukins and OCC.

Objective To investigate the alterations and phenotypes of dendritic cells, inflamma-tory monocytes and macrophages in immunocompetent mice during Pneumocystis murina ( P.murina) infec-tion for further analysis of the function of these cells during P.murina infection.Methods Wild type male C57BL/6 mice at age 6-8 weeks were randomly divided into two groups including the group with P.murina infection and the group receiving sham surgery.The mice without any intervention were used to set up the blank control group.The loads of P.murina strains in lung tissues of each mouse were quantified by TaqMan real-time fluorescence polymerase chain reaction after the infection.Histopathological examination was per-formed to evaluate the degree of inflammation in lung tissues.The numbers of dendritic cells, inflammatory monocytes and macrophages in lung tissues, peripheral blood and bone marrow samples, and the changes of inflammatory monocytes in spleen tissues were measured by flow cytometry analysis.The expression of major histocompatability complexⅡ(MHCⅡ), CX3C chemokine receptor 1 (CX3CR1) and CC chemokine re-ceptor 2 ( CCR2 ) by dendritic cells, inflammatory monocytes and macrophages in lung tissues during P.murina infection were analyzed by flow cytometry analysis.All of the data were collected one, two, three and four weeks after the corresponding treatments.Results The loads of P.murina strains in P.murina in-fected mice were elevated after two and three weeks infection, but decline at week 4 (P>0.05).Significant pathological changes including the alveolar destruction, inflammatory cell infiltration and thickened alveolar septum in mice with P.murina infection were observed under a microscope at week 3 and week 4.Compared to the sham surgery treatment group, the number of CD11c+CD11b+dendritic cells were increased in lung tissues, but decreased in blood samples during P.murina infection ( P<0.05) .The levels of inflammatory monocytes in blood samples fell at week 3 and then rose at week 4 during P.murina infection (P<0.05). No significant difference with the change of macrophages in mice was observed during P.murina infection ( P>0.05).The CD11c+CD11b+dendritic cells in lung tissues of mice with P.murina infection expressed high levels of MHCⅡand CX3CR1, and low levels of CCR2.The inflammatory monocytes in lung tissues of mice expressed high levels of CCR2, moderate levels of MHCⅡand low levels of CX3CR1 during P.murina in-fection.High levels of CX3CR1 and low levels of MHCⅡ and CCR2 were observed in macrophages from lung tissues of mice with P.murina infection.Conclusion Highly expressed CD11c+CD11b+dendritic cells and MHCⅡwere detected in lung tissues of mice during P.murina infection, indicating that CD11c+CD11b+dendritic cells were involved in the host defense against P.murina infection.

BACKGROUNDExtranodal natural killer/T-cell (NK/T cell) lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to investigate the clinicopathologic features, immunophenotype, T cell receptor (TCR) gene rearrangement, the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.

METHODSThe clinicopathologic analysis, immunohistochemistry, in situ hybridization for EBER1/2, TCR gene rearrangement by polymerase chain reaction (PCR), mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.

RESULTSIn the 19 cases, the tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical staining showed that most of the cases expressed CD45RO, CD56, CD3ε, TIA-1 and GrB. Three cases were positive for CD3 and two cases were positive for CD30. Monoclonal TCRγ gene rearrangement was found in 7 of 18 cases. The positive rate of EBER1/2 was 100%. No p53 gene mutation was detected on the exon 4 - 9 in the 18 cases. Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72. The expression of p53 protein was 72% (13/18) immunohistochemically.

CONCLUSIONSCutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was detected on the exon 4 - 9, and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the result of p53 gene mutation.

Adolescent ; Adult ; Aged ; Child ; Epstein-Barr Virus Infections ; diagnosis ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Lymphoma, T-Cell ; diagnosis ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Receptors, Antigen, T-Cell ; genetics ; metabolism ; Skin Neoplasms ; diagnosis ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; Young Adult