Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Brain Neoplasms/drug therapy* ; Protein Kinase Inhibitors/adverse effects* ; Crizotinib

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Objective: To detect the prevalence of sleep disorders among metro staff and to analyze influencing effects of effort reward imbalance (ERI) on it. Methods: In January 2015, subway driver, dispatcher and station operator from Guangzhou subway were selected as the research object in the whole group sampling method. A total of 1200 questionnaires were distributed and 1124 were valid questionnaires, and the effective questionnaire recovery rate was 93.7%. Based on the effort reward imbalance questionnaire and the self-administered sleep questionnaire, the data of the general demographic characteristics, life satisfaction, occupational stress and sleep status of the respondents were collected. Epi.data3.1 and spss19.0 were used for analyzing. Results: A total of 1124 subway employees were surveyed, with an average age of (28±5) years; the working age was (4.5±3.6) years. ERI occupied 24.7% (278/1124) of the study population and sleep disorders as 42.2% (474/1124) . Single factor analysis showed that marital status, educational level, work position, life satisfaction and ERI could significantly influence sleep disorders of metro staff (P<0.05) . Logistic regression showed that higher effort (adjusted OR=2.56, 95%CI: 1.79-3.68) , lower reward (adjusted OR=1.90, 95%CI: 1.34-2.68) and ERI (adjusted OR=2.33, 95%CI: 1.69-3.22) could increase the risk of sleep disorders after the confounding factors were controlled. ERI (adjusted OR=2.89, 95% CI: 1.80-4.64) , and over commitment (adjusted OR=4.64, 95%CI: 2.81-7.68) could influence the risk of sleep disorders independently when over commitment was evaluated as a moderating variable. Conclusion Occupational stress as ERI could influence the risk of sleep disorders among metro staff. The situation should not be neglected for occupational health of metro staff.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.

Objective: To prepare the monoclonal antibody against ankyrin repeat domain 22（ANKRD22）and to investigate its expression in colorectal cancer tissues. Methods : The recombinant human ANKRD22 was expressed through E. coli and pET-42a and then used to immunize Balb/c mice after purification. Anti-human ANKRD22 specific monoclonal antibodies were selected by Western blotting with 293T cell lysate highly expressing ANKRD22 as antigen. The expression of ANKRD22 in the tissue microarrays of 112 patients with colorectal cancer was detected by immunohistochemical staining. Results : Four specific monoclonal antibodies against human ANKRD22 were screened out of 93 hybridoma cells,which reacted well with natural human ANKRD22. ANKRD22 was mainly distributed in the cytoplasm of colorectal cancer cells. In 112 cases of colorectal cancer,94 cases were detected positive for ANKRD22 expression,with the positive rate of 83.93%. The expression of ANKRD22 was statistically correlated with the expression of p53 and β-catenin（P<0.05）,but not with age,sex,location of tumors,AJCC stage,Dukes stage,degree of differentiation,lymph node metastasis and mismatch repair gene expression（P>0.05）. Conclusion The expression level of ANKRD22 was high in colorectal cancer. ANKRD22 might be involved in the carcinogenesis of colorectal epithelium and be a potential diagnostic marker.

Objective Assembly whole mitochondrial genome sequence of Rongshui miniature pig ( RMP ) breed and analysis the structure of mitochondrion based on the next-generation sequecing method.Comparison of phylogenetic relationship and genetic diversity among different pig breeds.Methods We collected peripheral venous blood sample from RMP and constructed two paired-end sequencing libraries.A whole-genome shotgun sequencing strategy and Illumina Genome Analyser sequencing technology were used in our study.Results The mitochondrial genome of RMP consists of 13 protein coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and the length of pig is 16888 bp.The GC content of this pig mitochondrial genome is about 44 %.Based on phlogenetic analysis, population genetic analysis, our findings confirmed that the ancestral cluster in East Asia mainly occurred among Diannan 7#pig, Hainan wild boar, Lanyu and RMP.Conclusion RMP, a typical miniature pig breed in China, is an earlier ancestor than Lanyu pig breed.

The provenances of Rongshui miniature pigs ( RMPs) were purchased from Rongshui, Guangxi, in 2012.130 RMPs were transported to Sanshui, Guangdong,China, which were breed according to the laboratory animal standards.83 RMPs were selected randomly from the first filial generations ( F1 ).The basic data were collected including breed characteristics, reproductive performance, grow curve, hematology, biochemical markers of serum and urine, organ coefficient, Chromosome analysis.According to the national and local standards, the quality control standards of RMP were set up including microbiological, parasitic, environment and facilities, fodder, pathology, genetic.The results showed that RMPs adapt to the climate of Guangdong.The natural mating and conceive rate was 88.3% with the pregnancy of 112 days.The average number of firstborn and still-born was 6.1 and 7.9 respectively.RMP was small body size with the adult body weight of 17.21 ±5.20 kg and 16.35 ±5.23 kg in female and male respectively.RMP was very tame.The mitochondrial genome analysis suggested RMP belonged a typical miniature pig breed in China, which is ancient than Lanyu pig.RMP could be breed as a new kind of laboratory animal.

Objective To investigate the distribution and sequence conservation of genes encoding the outer membrane lipoprotein D(LPD)of nontypeable Haemophilus influenzae(NTHi)isolates and to ana-lyze the immunogenicity and the immunoprotective effects of the expressed recombinant LPD(rLPD). Meth-ods PCR analysis was used to detect the genes encoding LPD of NTHi isolates. The PCR products were se-quenced after T-A cloning. A prokaryotic expression system for genes encoding LPD was established to ex-press the rLPD. Ni-NTA affinity chromatography was used for purification. SDS-PAGE and Bio-Rad Gel Im-age Analyzer were used to detect the expression and the yield of rLPD. The antigenicity and immunoreactivity of rLPD were detected by ELISA and Western blot assay. The immunoprotective effects of rLPD against lethal dose of NTHi were evaluated in a mouse model. Results All of the tested NTHi isolates were positive for the genes encoding LPD. They shared 98. 0% -99. 4% homologies in nucleotide sequences and 98. 5% -100% homologies in amino acid sequences. The established prokaryotic expression system expressed rLPD with a high yield. High levels of antibody in rabbits were induced by the rLPD. The anti-NTHi antiserum samples from rabbits and children could recognize and react with the rLPD. The result of ELISA indicated that 93. 6%(58 / 62)and 53. 2%(32 / 62)of the serum samples from children with NTHi infection were positive for rLPD-IgM and rLPD-IgG,respectively. The rLPD at concentrations of 100 μg and 200 μg could respectively protect 60. 0% and 73. 3% of mice from lethal NTHi infection. Conclusion The genes enco-ding LPD were extensively distributed in NTHi isolates with high sequence conservation. The expressed rLPD could be used as a potential candidate antigen in the development of genetic engineering vaccine against NTHi infection considering its high immunogenicity and immunoprotective effects.

Objective To assess the clinical short-term to mid-term efficacy of transcatheter closure of coronary artery fistula by using patent ductus arteriosus occluder in pediatric patients. Methods During the period from Jan. 2008 to May 2013 at authors’ hospital, transcatheter closure of coronary artery fistula using patent ductus arteriosus occluder was performed in 8 pediatric patients. The clinical data, including follow-up information, were retrospectively analyzed. Results A total of 8 pediatric patients with a mean age of (4.1 ± 3.8) years were enrolled in this study. The fistula originated from the right coronary artery in five cases and from the left coronary artery in three cases. The blood flow shunted to the right atrium (n=4) or to the right ventricle (n = 4). Obstruction of the fistula was successfully accomplished in all patients. All patients were followed up for (2.2 ± 1.2) years. No procedure-related complications or cardiac ischemia occurred. Conclusion For the treatment of coronary artery fistula in pediatric patients, the use of domestic patent ductus arteriosus occluder is safe and effective with satisfactory short-term to mid-term clinical efficacy.

Objective To investigate the correlation between neonatal infectious disease and brain injury.MethodsClinical data of 1266 newborns with infectious diseases were collected from Peking University First Hospital from November 2005 to August 2010.The occurrence of brain injury was summarized.Related factors of brain injury caused by infection and the risk factors for severe brain injury were analyzed by Logistic regression model. Results Among the newborns with neonatal infectious diseases, the incidence of brain injury was 8.6％(108/1266), including 101 (8.0％)mild cases and seven (0.6％) severe cases. The incidence of brain injury for the newborns with severe infectious diseases was higher than those with mild infectious diseases [38.7％(29/75) vs 6.7％(79/1191),x2=92.787,P=0.000].The incidence of brain injury for the newborns withobviousinflammatoryreactionwassignificantlyhigherthanthosewithout [(13.0％(26/200) vs 7.5％ (77/1025),x2=6.544,P=0.011].Severe infection was independent risk factor for severe brain injury by Logistic regression model analysis (OR =15.750,95％ CI:1.756-141.281,P=0.014).ConclusionsIniectious diseases could cause injury on central nervous system,especially when there are severe infections or inflammatory reactions. The severer the infection,the severer the brain injury,especially when complicated by some factors such as asphyxia and hypoglycemia.