Objective To compare the efficacy of mediastinoscope-assisted transhiatal esophagectomy (MATHE) and functional minimally invasive esophagectomy (FMIE) for esophageal cancer. Methods Patients who underwent minimally invasive esophagectomy at Jining No.1 Hospital from March 2018 to September 2022 were retrospectively included. The patients were divided into a MATHE group and a FMIE group according to the procedures. The patients were matched via propensity score matching (PSM) with a ratio of 1 : 1 and a caliper value of 0.2. The clinical data of the patients were compared after the matching. Results A total of 73 patients were include in the study, including 54 males and 19 females, with an average age of (65.12±7.87) years. There were 37 patients in the MATHE group and 36 patients in the FMIE group. Thirty pairs were successfully matched. Compared with the FMIE group, MATHE group had shorter operation time (P=0.022), lower postoperative 24 h pain score (P=0.031), and less drainage on postoperative 1-3 days (P<0.001). FMIE group had more lymph node dissection (P<0.001), lower incidence of postoperative hoarseness (P=0.038), lower white blood cell and neutrophil counts on postoperative 1 day (P<0.001). There was no statistically significant difference in the bleeding volume, R0 resection, hospital mortality, postoperative hospital stay, anastomotic leak, chylothorax, or pulmonary infection between the two groups (P>0.05). Conclusion Compared with the FMIE, MATHE has shorter operation time, less postoperative pain and drainage, but removes less lymph nodes, which is deficient in oncology. For some special patients such as those with early cancer or extensive pleural adhesions, MATHE may be a suitable surgical method.

Objective:In this study,we explored the application prospects and mechanisms of action of co-inhibiting fibroblast growth factor receptor 2(FGFR2)and Src homology region 2-containing protein tyrosine phosphatase 2(SHP2)in gastric cancer with the TACC2-FGFR2 fu-sion gene.Methods:We established human gastric cancer cell lines overexpressing the TACC2-FGFR2 fusion gene(MKN45TACC2-FGFR2 and NUGC4TACC2-FGFR2 cells)or a control lentiviral virus(MKN45NC and NUGC4NC cells).The cells were treated with the FGFR2 inhibitor AZD4547,the SHP2 inhibitor SHP099,or a combination of both.The proliferation and migration of tumor cells were detected using cell counting Kit-8(CCK-8)and scratch assays.After treating MKN45TACC2-FGFR2 and NUGC4TACC2-FGFR2 cells with different formulations for 1 or 48 h,Western blot was used to detect variations in the levels of FGFR2,SHP2,and proteins downstream of the RAS/ERK and PI3K/AKT signaling pathways.Results:Com-pared to monotherapy,the combination of AZD4547 and SHP099 significantly inhibited the proliferation and migration of MKN45TACC2-FGFFR2 and NUGC4TACC2-FGFFR2 cells.After 1 h of treatment,the combination therapy inhibited the RAS/ERK and PI3K/AKT pathways in MKN45TACC2-FGFFR2 cells to a greater extent than the AZD4547 monotherapy.Forty-eight hours of AZD4547 monotherapy resulted in feedback activation of p-FGFR and p-SHP2,but failed to inhibit the RAS/ERK pathway.However,combination therapy continuously suppressed upstream FGFR2 and SHP2 signaling,as well as downstream RAS/ERK and PI3K/AKT pathways.Conclusions:Co-inhibiting FGFR2 and SHP2 further inhibit gastric cancer with the TACC2-FGFR2 fusion gene by suppressing the RAS/ERK and PI3K/AKT pathways.These findings provide a new treatment mode for patients with gastric cancer with the TACC2-FGFR2 fusion gene.

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.

Objective:To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff.Methods:From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout.Results:Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) ( rs=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (Δ R2=0.073, 0.06, 0.006, P<0.001) . Conclusion:Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.

Objective:To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff.Methods:From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout.Results:Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) ( rs=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (Δ R2=0.073, 0.06, 0.006, P<0.001) . Conclusion:Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Objective : To explore the epicardial adipose tissue ( EAT) of patients with coronary heart disease , KLF7 stimulates macrophages to secrete inflammatory factors and promotes the differentiation and maturation of adipocytes through the NF⁃κB signaling pathway , and to clarify the mechanism of KLF7 in the occurrence and development of CAD. Methods : 30 patients with coronary heart disease ( CAD group) and 30 patients without coronary heart disease (non⁃CAD group) were collected , and general data and biochemical indicators were collected. qRT⁃PCR was used to detect the expression levels of KLF7 , APN , IL⁃6 , and TNF⁃α mRNA in EAT. Human THP⁃1 cells were cultured in vitro and induced into M1 type macrophages and 3T3 ⁃L1 preadipocytes. The cells were divied into 3 groups : KLF7 up⁃regulated group ( transfected with KLF7 mimic) , KLF7 down⁃regulated group ( transfected with siRNA knockdown KLF7 ) , NC group ( transfected oligopeptide sequence) , transfected two kinds of cells. qRT⁃PCR was used to detect the expression of APN , MCP⁃1 , IL⁃6 and TNF⁃α mRNA in M1 type macrophages , and the protein expression levels of key factors in the NF⁃κB signaling pathway were detected by Westren blot. The qRT⁃PCR method was used to detect APN , KLF4 , IL⁃6 , MCP⁃1 mRNA and adipocyte differentiation marker peroxisome proliferator⁃activated receptor⁃γ (PPARγ) in 3T3 ⁃L1 preadipocytes 24 h after transfection. CCAAT/enhancer binding protein α (C/EBPα ) , fatty acid binding protein 4 (FABP4) mRNA relative expression levels , and Westren blot was used to detect protein expression levels. Results : Compared with the non⁃CAD group , the expression of CAD group decreased , APN decreased , IL⁃6 and TNF⁃α increased significantly , and the difference was statistically significant (P < 0. 01) . KLF7 was highly expressed in human THP⁃1 derived M1 macrophages induced by inflammatory stimuli (LPS) . In M1 macrophages derived from human THP⁃1 , knocking down KLF7 could inhibit the release of inflammatory factors. Transfection with KLF7 ⁃siRNA could significantly inhibit LPS⁃induced phosphorylation of JNK⁃MAPKs , the level of p⁃p65 and the activation of p ⁃IκBa (P < 0. 05) . In 3T3 ⁃L1 preadipocytes , upregulation of KLF7 increased the expression of adipocyte differentiation markers PPARγ , C/EBPa , FABP4 mRNA , and promoted the differentiation of 3T3 ⁃L1 preadipocytes into adipocytes (P < 0. 05) . Conclusion The expression of KLF7 in EAT in CAD patients increases. KLF7 activates the activation of macrophages mediated by the JNK⁃NF⁃KB signaling pathway in EAT , promotes inflammation in EAT in CAD patients , and promotes the differentiation and maturation of adipocytes , thereby promoting the development of CAD. It indicates that KLF7 may be a potential therapeutic target for cardiovascular diseases (such as CAD) .

Objective:To explore the effect of TOMATIS auditory training on anxiety, depression and quality of life in patients with breast cancer after chemotherapy, and to verify its effectiveness.Methods:From July 2019 to July 2020, 72 breast cancer patients with chemotherapy admitted to the Second People's Hospital of Lianyungang, Jiangsu Province were selected as the research object. According to random drawing, the patients were divided into the control group and the observation group, with 36 cases in each group. The patients in the control group received routine nursing, and the patients in the observation group were treated with TOMATIS auditory training on the basis of routine nursing. The coping style, anxiety, depression and quality of life scores of the two groups before and after nursing were observed.Results:After the intervention, the coping style of the observation group was better than that of the control group, and the difference was statistically significant ( P<0.05) . The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores of the observation group were lower than those of the control group, and the difference was statistically significant ( P<0.05) . The quality of life score of the observation group was higher than that of the control group with a statistical difference ( P<0.05) . Conclusions:TOMATIS auditory training can effectively improve the coping style, reduce anxiety and depression, and improve the quality of life in breast cancer patients, which is worthy of clinical promotion.

OBJECTIVE：To provide reference for the R&D of TCM patents for treating gastric cancer and layout. METHODS：TCM patents for treating gastric cancer collected by the State Intellectual Property Office and the European Patent Office Espacenet were retrieved from the inception to Dec. 31st， 2019. After the initial examination ，a second search was conducted based on the keywords such as “Stomachache”“Fuliang” “Accumulation”“Cancer of stomach ”“Gastric”and their synonyms. Each literature was read one by one and screened manually. Excel 2007 software was used to input general information of included patents. SPSS modeler 15.0 software and SPSS 22.0 software were used for association rule analysis and hierarchical cluster analysis of TCM used more than 30 times and top 30 frequently used. Based on patent analysis ，internal strength （S），weakness（W），external opportunity （O）and threat （T）of TCM for treating gastric cancer were analyzed ；based on this ，four different types of combination strategies were formulated. RESULTS & CONCLUSIONS ：Finally，385 patents were obtained ，including 379 domestic patents （98.44％） and 6 foreign patents （1.56％）. The number of patent applications and applicants of TCM for treating gastric cancer in China was on the rise during 1994-2016. The commonly used TCM for treating gastric cancer were mainly tonifying deficiency drugs and heat clearing drugs ， and the meridian tropism were mostly the stomach meridian and spleen meridian. According to the efficacy ，the commonly used drug combinations include the combination of tonifying spleen and Qi ，the combination of anti-cancer and detoxification ，and the combination of drying dampness and resolving phlegm. The results of hierarchical cluster analysis showed that Poria cocos ， Atractylodes macrocephala ，Astragalus membranaceus ，Scutellaria barbata ，Hedyotis diffusa and Glycyrrhiza uralensis were clustered into one category and the common combination for treating gastric cancer. The remaining cluster distributions are also in line with the characteristics of TCM syndrome differentiation and treatment. Strength of domestic TCM patents for treating gastric cancer were that the number of patents in China was taking a leading position in the world ，the patent system of key applicants was mature，the combination of compound patents embodied the characteristics of disease and dialectical theory. Weakness included low patent authorization rate ，to-be-improved effectiveness and safety studies of TCM patents ，weak development of TCM extract patents，low degree of patent internationalization and hanging same-family patents. Opportunities were that the demand for drugs for gastric cancer was increasing with each passing day ，and natione actively support the development of the TCM industry. Threats were that competitors in the international market had the potential to seize the market. The development of TCM for treating gastric cancer in China should take market demand and national policy support as an opportunity ，learn from TCM patent characteristic system of key applicants ，continue to give full play to the advantages of TCM in prevention and syndrome differentiation of disease，pay more efforts to the development of weak links such as TCM extracts ，safety and effectiveness ，improve the international competitiveness in the field of patents ，while establish a warning and navigation analysis system for patents to effectively reduce the intellectual property threats and risks of invention patents of China in the international environment.