【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

Objective:To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer, and to investigate its anti-tumor molecular mechanism.Methods:In this study, we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups: the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period, we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment, we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore, we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results:The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs), white blood cells(WBCs), alanine aminotransferase(ALT), aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs, WBCs, ALT, AST and Scr in the placebo group were(6.97 ± 0.41)× 10 12/L, (13.26 ± 0.29)× 10 9/L, (33.33 ± 2.51)U/L, (235.33 ± 57.62)U/L and(20.67 ± 2.08)μmol/L, respectively.The corresponding values in the beat chemotherapy group were(6.87 ± 0.66)× 10 12/L, (12.59 ± 2.27)× 10 9/L, (38.67 ± 3.79)U/L, (225.33 ± 6.81)U/L and(20.33 ± 3.79)μmol/L.Statistical analysis showed no significant differences between the two groups( t=0.509, 0.209, 2.032, 0.299, 0.134, P=0.638, 0.845, 0.112, 0.780, 0.900).Furthermore, there were no signs of inflammatory infiltration or pathological changes in the liver, kidney, spleen, and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes, which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways, including the transforming growth factor β(TGF-β)signaling pathway, the interleukin-17(IL-17)signaling pathway, and the tumor necrosis factor(TNF)signaling pathway. Conclusions:The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways, including the TGF-β signaling pathway, IL-17 signaling pathway, and TNF.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Cisplatin/metabolism* ; Esophageal Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Growth Differentiation Factor 15/therapeutic use* ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

【Objective】 To study the role and mechanism of sinomenine in the macrophage polarization induced by gastric cancer cells. 【Methods】 Sinomenine was added to gastric cancer cells BGC-823 and MKN-45， cell viability was measured by CCK-8， cell proliferation was measured by colony formation experiment， Co-culture and Transwell cell migration experiments were used to evaluate the recruitment and polarization of macrophages by sinomenine， flow cytometry was used to evaluate the polarization of macrophages， and qRT-PCR and Western blot were used to detect the expression of gene RNA and protein levels. 【Results】 Sinomenine could inhibit the proliferation of gastric cancer cells and the recruitment of gastric cancer cells to macrophages， thus promoting macrophage M2 polarization. It simultaneously inhibited the expression of STAT6 as well as the expression and phosphorylation of C/EBPβ. When STAT6 is overexpressed， it could reduce these inhibitory effects of sinomenine on gastric cancer cells. Further research found that STAT6 mediated the secretion of IL-6 by gastric cancer cells， which was the cause of sinomenine-mediated macrophage recruitment and M2 polarization. 【Conclusion】 The natural drug sinomenine has a good tumor-suppressing ability against gastric cancer， directly inhibits the survival and migration of gastric cancer cells， and inhibits the expression of IL-6 and the M2 phenotype in the tumor microenvironment， reshapes the tumor environment， and reduces the risk of M2 type macrophages for gastric cancer tumors.

Objective:To construct an evaluation index system of teaching quality in medical schools.Methods:The text entry analysis was used to construct the index entry pool. The thematic group discussions were used to determine the preliminary index system. The Delphi method was used to further select the index. Finally, the analytic hierarchy process was used to determine the index weight and perform consistency test. EpiData 3.2 was used to build database, and MATLAB was used for statistical analysis and solving judgment matrix.Results:The index framework was established by attitude, content, method and effect, which was refined into 10 secondary indicators and 20 tertiary indicators such as passing on knowledge, knowledge mastering, and so on. The consistency test coefficients of each layer was less than 0.1.Conclusion:The method of constructing the indicator system is scientific, and the selection of indicators is in line with the current medical education reform, which has certain feasibility and guiding significance.

Objective:To study LIM kinase 1 (LIMK1) expressional condition, and its regulatory effects on the proliferation and metastasis of hepatocellular carcinoma cells and tissues.Methods:The online database starBase v3.0 and GEPIA were used to analyze the LIMK1 expression in hepatocellular carcinoma cells and normal liver tissues, and then the relevant survival analysis was performed. LIMK1 expression in hepatocellular carcinoma cell line was analyzed by Western blot. Hep3B and Huh7 cells were transiently transfected after LIMK1 protein expression was down-regulated by small interfering RNA (siRNA). LIMK1 effects on the proliferation of Hep3B and Huh7 cells were observed by MTT assay and colony formation assay. Transwell assay was used to detect the change in metastatic ability of hepatocellular carcinoma cell after the down-regulation of LIMK1 expression. Western blot was used to detect the changes of related indexes in the process of epithelial mesenchymal transition after the down-regulation of LIMK1 expression. Data were analyzed by one-way ANOVA.Results:The expression level of LIMK1 in liver cancer tissues was significantly higher than that of normal liver tissues, and was related with prognosis ( P ?< 0.01). Furthermore, LIMK1 expression in HCC cell lines was significantly higher than that of immortalized liver L02 cells ( P < 0.05). Functional correlated experiment showed that the proliferation and metastatic ability of liver cancer cells were significantly inhibited after LIMK1 expression down-regulation ( P < 0.05). Simultaneously, LIMK1 was also involved in the process of epithelial-mesenchymal transition. Conclusion:LIMK1 was overexpressed in HCC tissues and cells, and may regulate the proliferation and metastasis of HCC cells and participate in epithelial-mesenchymal transition process.

Objective:To investigate the current Kangaroo Mother Care(KMC) knowledge among registered nurses working in neonatal intensive care unit (NICU) in China.Methods:A convenience sample of 607 registered nurses participated in this descriptive, cross sectional exploratory study. An online self-designed questionnaire was used to collect the data, including 12 items, 3 sections (Basic knowledge, Emergency handling, Breast feeding).Results:The total score was 6.52±2.29 (the total score was 12). The 5 items, accuracy below 50%, were ①In your opinion, the optimal duration of KMC was (10.2%,62/607); ②What to do if the baby had respiratory arrest or became blue during KMC (18.8%,114/607); ③Who should implement KMC (42.5%, 258/607); ④what could we do if the baby was not gaining weight (47.3%, 287/607); ⑤How to feed the baby during KMC (47.8%, 290/607). Registered nurses with more than 10 years of working experience in NICU scored higher; junior registered nurses scored lower; registered nurses learned by individuals scored lower ( F values were 9.413, 9.862, 5.368, all P<0.01). Conclusions:The insufficiency of KMC knowledge is common among NICU registered nurses. The understanding of basic concepts of KMC should be strengthened. Stratified training should be conducted for nurses′ ability to deal with emergencies, assess the changes in infants' conditions, and knowledge of breast feeding. All registered nurses′ KMC operation should be standardized to improve the level of implementation of KMC by NICU registered nurses.

Objective: To investigate the prognostic value of prognostic nutritional index (PNI) in patients with diffuse large B-cell lym-phoma (DLBCL). Methods: We retrospectively reviewed the medical records of 82 patients with DLBCL treated at Tianjin Union Medi-cal Center between June 2010 and June 2016. The optimal cutoff value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients, therapeutic ef-ficacy, and prognosis were analyzed. Results: Overall, mean PNI of the patients was 46.17±8.8. When the PNI was 44.15, the Youden in-dex was found to be maximal, with a sensitivity of 74.6% and specificity of 67.2%. There were 38 patients (46.3%) in the low PNI group (<44.15) and 44 patients (53.7%) in the high PNI group (≥44.15). Data analysis showed that PNI was correlated with Eastern Coopera-tive Oncology Group performance status (ECOG PS), Ann Arbor stage, international prognostic index (IPI) score, and lactic acid dehydro-genase (LDH) level (P<0.05). The total effective rate of the low PNI group was significantly lower than that of the high PNI group (65.8% vs. 86.4%; χ2=4.848; P=0.028). The 3-year overall survival (OS) rate of the entire group of patients was 69.1%. The 1-, 2-, and 3-year OS rates of the low PNI group (86.8%, 67.8%, and 56.9%, respectively) were significantly lower than that of the high PNI group (96.7%, 89.5%, and 80.2%, respectively; χ2=9.421, P=0.002). Univariate analysis showed that PNI<44.15, ECOG PS≥2, IPI>2, stageⅢ/Ⅳ, and lymphocyte count<1.0×109/L had a significant impact on predicting OS (P<0.05). Multivariate analysis showed that PNI<44.15 (P=0.006) and stageⅢ/Ⅳ(P=0.011) were independent factors for predicting OS. Conclusions: PNI might be used as a simple and feasible clinical prognostic indicator in patients with DLBCL.

Objective To evaluate the efficacy and safety of neurokinin1 (NK1) receptor antagonist aprepitant combined with prednisone and tropisetron in prevention of nausea and vomiting (CINV) induced by R-CHOP or CHOP regimen. Methods A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) who accepted R-CHOP or CHOP regimen in the People''s Hospital of Tianjin from October 2015 to January 2016 were divided into aprepitant group (45 cases) and the control group (45 cases) according to the random number table. In aprepitant group, day 1: aprepitant 125 mg 1 h before chemotherapy, prednison 100 mg, tropisetron 10 mg, and tropisetron 5 mg 2 hours after chemotherapy;day 2-3:aprepitant 80 mg and prednison 100 mg, tropisetron 10 mg; day 4-5: prednison 100 mg. In the control group, day 1: prednison 100 mg 1 h before chemotherapy, tropisetron 10 mg, and tropisetron 5 mg 2 h after chemotherapy; days 2-3: prednison 100 mg, tropisetron 10 mg; day 4-5: prednison 100 mg. Data on nausea, vomiting and remission treatment were collected every day. The complete remission (CR) rates of CINV without vomiting and remission drugs in the whole cycle were recorded. Functional living index-emesis questionnaire (FILE) was used to assess the effect of CINV on the life quality of the patients. Results CR in aprepitant group was higher than that in the control group (77.8 ％ vs. 55.6 ％, χ2= 5.000, P= 0.025). The rate of no vomiting in aprepitant regimen was higher than that in the control regimen (82.2 ％ vs. 62.2 ％, χ2 = 4.486, P= 0.034). The average scores of FILE between the two groups were (113 ±10) and (100 ±11) scores respectively, and there was a significant difference (t=12.437, P<0.001). The related adverse reactions of vomiting-stopping drugs in both groups had no statistical difference. Conclusion The aprepitant combined with tropisetron and prednisone can improve effectively nausea and vomiting induced by R-CHOP or CHOP chemotherapy regimen for DLBCL patients.

OBJECTIVE:To observe therapeutic efficacy and safety of modified Longdan xiegan tang in the treatment of psoria-sis vulgaris(blood heat type). METHODS:A total of 80 patients with psoriasis vulgaris(blood heat type)were randomly divided into control group(38 cases)and observation group(42 cases),other 30 healthy volunteers were included in healthy control group. Control group was given Xiaoyin tablet 1.6 g orally,3 times a day for 4 weeks. Observation group was given modified Longdan xiegan tang,400 mL after detected with water,1 h after breakfast and supper,7 d as a treatment course,for 4 courses. Clinical ef-ficacies and PASI score were observed before and after treatment. The levels of inflammatory factors(IL-1,IL-6,IL-8,TNF-α), the expression of NF-κB protein and NF-κB gene were observed in observation group before and after treatment,and then were compared with healthy control group. The relationship of inflammatory factor levels with NF-κB protein expression in observation group before treatment,the relationship of PASI score with inflammatory factor and NF-κB expression were observed in observa-tion group before and after treatment,and the occurrence of ADR was recorded. RESULTS:Total response rate of observation group(85.7%)was significantly higher than that of control group(52.6%),with statistical significance(P<0.05). Before treat-ment,there was no statistical significance in PASI score between 2 groups (P>0.05). After treatment,PASI score of 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group,with statis-tical significance (P<0.05). After treatment,The levels of IL-1,IL-6,IL-8 and TNF-α in observation group were significantly lower than before treatment,but there was no statistical significance with healthy control group(P>0.05);the expression of NF-κB protein and NF-κB gene in observation group were significantly higher than healthy control group,with statistical significance(P<0.01 or P<0.05). The levels of IL-1, IL-6, IL-8 and TNF-α were positively associated with the expression of NF-κB protein in observation group before treatment. The levels of IL-1,IL-6,IL-8 and TNF-α and the expression of NF-κB pro-tein were both positively associated with PASI score in observa-tion group before and after treatment. CONCLUSIONS:Modified Longdan xiegan tang show significant therapeutic efficacy for psoriasis vulgaris(blood heat type),can reduce PASI score,the levels of NF-κB protein expression and inflammatory factors.