BACKGROUND: Small cell lung cancer (SCLC) with high c-Myc expression is prone to relapse and metastasis, leading to extremely low survival rate. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib plays a key role in the treatment of tumors, but the effects and mechanisms on SCLC remain unclear. This study was to analyze the effect and molecular mechanism of Abemaciclib in inhibiting proliferation, migration and invasion of SCLC with high c-Myc expression, with a view to expanding a new direction for reducing the recurrence and metastasis. METHODS: Proteins interacting with CDK4/6 were predicted using the STRING database. The expressions of CDK4/6 and c-Myc in 31 cases of SCLC cancer tissues and paired adjacent normal tissues were analyzed by immunohistochemistry. The effects of Abemaciclib on the proliferation, invasion and migration of SCLC were detected by CCK-8, colony formation assay, Transwell and migration assay. Western blot was used to detect the expressions of CDK4/6 and related transcription factors. Flow cytometry was used to analyze the effects of Abemaciclib on the cell cycle and checkpoint of SCLC. RESULTS: The expression of CDK4/6 was associated with c-Myc by STRING protein interaction network. c-Myc can directly modalize achaete-scute complex homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1) and Yes-associated protein 1 (YAP1). Moreover, CDK4 and c-Myc regulate the expression of programmed cell death ligand 1 (PD-L1). Immunohistochemistry showed that the expressions of CDK4/6 and c-Myc in cancer tissues were higher than those in adjacent tissues(P<0.0001). CCK-8, colony formation assay, Transwell and migration assay verified that Abemaciclib could effectively inhibit the proliferation, invasion and migration of SBC-2 and H446OE(P<0.0001). Western blot analysis further showed that Abemaciclib not only inhibited CDK4 (P<0.05) and CDK6 (P<0.05), but also affected c-Myc (P<0.05), ASCL1 (P<0.05), NEUROD1 (P<0.05) and YAP1 (P<0.05), which are related to SCLC invasion and metastasis. Flow cytometry showed that Abemaciclib not only inhibited the cell cycle progression of SCLC cells (P<0.0001), but also significantly increased PD-L1 expression on SBC-2 (P<0.01) and H446OE (P<0.001). CONCLUSIONS Abemaciclib significantly inhibits the proliferation, invasion, migration and cell cycle progression of SCLC by inhibiting the expressions of CDK4/6, c-Myc, ASCL1, YAP1 and NEUROD1. Abemaciclib can also increase the expression of PD-L1 in SCLC.
Humans ; Small Cell Lung Carcinoma ; B7-H1 Antigen ; Sincalide ; Lung Neoplasms ; Neoplasm Recurrence, Local ; Transcription Factors ; Adaptor Proteins, Signal Transducing ; Cell Proliferation

Objective: To explore the effects of Kruppel⁃like factor 7 (KLF7) on the proliferation , migration and cycle of esophageal squamous cell carcinoma cell line Eca109. Methods: Bioinformatics analysis was used to study the expression pattern of KLF7 in esophageal squamous cell carcinoma and its relationship with prognosis and pathological grade. The expression pattern of KLF7 in esophageal squamous cell carcinoma cells was studied by real⁃time PCR , Western blot and cellular immunofluorescence in vitro. The KLF7 overexpression in Eca109 cells was carried out by transfection of the plasmid of pcDNA⁃3. 10⁃KLF7 , and the effects of KLF7 on the proliferation and migration of ESCC cells were detected by CCK⁃8 assay , plate clone formation assay and Transwell assay , and the cell cycle was studied by Flow cytometric analysis. Results: KLF7 was expressed in the tissues and cells of esophageal cancer, and its expression was significantly associated with the pathological grade of esophageal cancer patients ( P <0. 05) , however, there was no significant associaition of KLF7 expression with the survival rate of patients. The expression level of KLF7 in esophageal cancer cells ( Eca109 and EC9706) was significantly higher than that in normal esophageal epithelial cells (Het⁃1A , P < 0. 05) . In addition , the expression of KLF7 was higher in the cytoplasm and nucleus of Het⁃1A cells , while only in the nucleus of esophageal cancer cells (Eca109 and EC9706) Additionally , the overexpression of KLF7 in Eca109 cells changed the cell cycle , promoted cell proliferation and migration , and up⁃regulated the expression levels of CCND1 and P53 (P < 0. 05) . Conclusion Overexpression of KLF7 might promote the proliferation and migration of esophageal cancer cells.

Objective:To evaluate the efficacy of compatibility of different opioids for postoperative patient-controlled intravenous analgesia (PCIA) in the patients undergoing gastrointestinal surgery.Methods:A total of 6 556 patients undergoing PCIA after gastrointestinal surgery in the first affiliated Hospital of Air Force military Medical University from May 2018 to March 2022 were retrospectively collected and divided into sufentanil plus nalbuphine group (SN group), hydromorphine plus nalbuphine group (HN group) and sufentanil group (S group). In SN, HN and S groups, the PCIA solutions contained sufentanil 100 &mu;g+ nalbuphine 40 mg, hydromorphone 10 mg+ nalbuphine 40 mg, sufentanil 200 &mu;g, respectively, in 100 ml of normal saline, and the PCA pump was set up with a background infusion at a rate of 1 ml/h, bolus dose 0.5 ml, and lockout interval 10 min.The demographic data, the number of patients with insufficient analgesia at rest and during activity (visual analog scale score≥4) at 24 and 48 h after operation, adverse reactions, time to first flatus and first postoperative off-bed time were collected.Results:Compared with S group, the incidence of insufficient analgesia at rest and during activity, dizziness, nausea and vomiting, effective pressing times of PCA and consumption of drugs in the analgesic pump were significantly decreased at 24 and 48 h after operation in HN group and SN group, the incidence of drowsiness was decreased at 24 h after operation, and the time to first flatus and first postoperative off-bed time were shortened in HN group, and the incidence of somnolence was increased at 48 h after operation in SN group ( P<0.05). Compared with SN group, the incidence of insufficient analgesia at rest at 24 and 48 h after operation was significantly increased, the incidence of insufficient analgesia during activity, dizziness, nausea and vomiting, effective pressing times of PCA and consumption of drugs in the analgesic pump were decreased, the incidence of drowsiness was increased at 24 h after operation, the incidence of somnolence was decreased at 48 h after operation, and the time to first flatus and first postoperative off-bed time were shortened in HN group ( P<0.05). Conclusions:Hydromorphine mixed with nalbuphine provides better efficacy than sufentanil mixed with nalbuphine and sufentanil and is helpful in shortening the recovery time of gastrointestinal function when used for postoperative PCIA in the patients undergoing gastrointestinal surgery.

Objective    To analyze the incidence and drainage pattern of the specific collateral vein (VL) located between several adjacent segments of the bilateral upper lung, and its clinical significance in the surgical treatment of early lung cancer. Methods    The preoperative three-dimensional computed tomography bronchography and angiography (3D CTBA) data of 1 515 patients in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020 were analyzed retrospectively, including 524 males and 991 females, with an average age of 54.27±11.43 years. There were 712 patients of right upper lung and 803 patients of left upper lung. The incidence and drainage pattern of VL in bilateral upper lungs were analyzed. Furthermore, the imaging data and medical records of 113 patients in the left upper lung were reviewed to investigate the influence of the relative position relationship between nodules and VL on the selection of operation. Results    The overall incidence of VL was 72.7% (1 102/1 515) in the bilateral upper lungs, including 68.0%(484/712) in the right upper lung, and 77.0% (618/803) in the left upper lung. The incidence of VL in the left side was significantly higher than that in the right side (P<0. 05). VL mainly drained into V2a+b (327/484, 67.6%) in the right upper lung and into V1+2b+c (389/618, 62.9%) in the left upper lung. When the spherical simulative cutting margin of 2 cm of the nodule did not involve VL, it was more feasible to undergo sublobectomy than those whose simulative cutting margin of 2 cm involved VL, and the difference was statistically significant (91.9% vs. 61.5%, P<0.05). When the spherical simulative cutting margin of 2 cm of nodule involved VL, the lesion located in the middle or inner zone was more feasible to undergo lobectomy than that in the outer zone, but the difference was not statistically significant (43.8% vs. 34.8%, P>0.05). Multivariate logistic regression analysis showed that diameter of the lesion, whether the spherical simulative margin of 2 cm involving VL and the depth ratio of the lesion were independent risk factors affecting the surgical options (P<0.05). Conclusion    The incidence of the specific collateral vein in bilateral upper lungs is high, and the drainage pattern is diverse, which has important guiding significance for preoperative planning and intraoperative manipulation. For deep nodules adjacent to VL, lobectomy or resection of left upper division is often performed to ensure a safe margin.

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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Cancer-Associated Fibroblasts/metabolism* ; Carcinogenesis ; Cell Transformation, Neoplastic/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; Tumor Microenvironment

Objective : To explore the effects of the nerve growth factor neutralizing antibody ( anti⁃NGF) and γ⁃secretase inhibitor 3,5⁃difluorophenylacetyl⁃L⁃alanyl⁃S⁃ph ⁃enylglycine⁃t⁃butyl ester (DAPT) on the nuclear expression of p75 neurotrophin receptor (p75NTR ) in esophageal cancer Eca109 cells and on cell proliferation and invasion. Methods : Immunofluorescence cytochemistry was used to detect the expression changes of p75NTR and Ki6 in Eca109 cells before and after treatment with the anti⁃NGF and γ⁃secretase inhibitor DAPT; CCK⁃8 kit and Transwell cell invasion experiment were used to detect the changes of cell proliferation and invasion ability before and after treatment of Eca109 cells with the anti⁃NGF and γ⁃secretase inhibitor DAPT alone or in combination. Results: Immunofluorescence cytochemistry showed that after treatment of cells with the anti⁃NGF and γ⁃secretase inhibitor DAPT, the number of cells expressing p75NTR in the nucleus decreased, and after the combined treatment of cells with the anti⁃NGF and γ⁃secretase inhibitor DAPT, the number of cells expressing p75NTR in the nucleus was the least, and the difference was statistically significant (P < 0. 05); CCK⁃8 method and Transwell cell invasion experiment showed that after treatment of cells with the anti⁃NGF and γ⁃secretase inhibitor DAPT, cell proliferation and invasion ability were correspondingly weaker than those before treatment, and the difference was statistically significant (P < 0. 05) . Conclusion The anti⁃NGF and γ⁃secretase inhibitor DAPT not only inhibit the nuclear transfer of p75NTR , but also reduce the nuclear expression rate of p75NTR and weaken the cell proliferation and invasion ability accordingly.

Objective:To explore the relationship between frailty and nutritional status of the elderly in communities.Method:Using the convenience sampling method, 458 elderly people in the community were investigated with the general data questionnaire, frailty phenotype, Mini-Nutritional Assessment, Mini-Mental State Examination, Self-Rating Depression Scale and Instrumental Activity of Daily Living.Results:The prevalence of frailty, pre-frailty and non-frailty in the elderly of the community was 9.2%, 60.0%, and 30.8% respectively, and 10.5% were malnourished or at risk of malnutrition. Logistic analysis showed that malnutrition increased the risk of frailty in the elderly ( OR=9.534, P=0.001). Conclusion:Malnutrition is a risk factor of frailty in the elderly in communities. Improving the nutritional status of the elderly in communities can help delay the development of frailty.

Programmed cell death receptor 1 (PD-1) is a membrance-spanning protein mostly expressed in the T cell, and combines with programmed cell death ligand 1 (PD-L1) in the targeting cell. When binding to the ligand on tumor cells, PD-1 as an immunosuppressive molecule, can inhibit the immune function of T cells, thus tumor immune escape. For example, depletion of peripheral effector T cell and accelerate the transformation of effector T cells into regulator T cells. To solve this problem, PD-1 antibody is used to bind to PD-1 on T cells to inhibit the interaction between PD-1 on the T cells and PD-L1 on the tumor cells so that it can restore the function of T cells to kill tumor cell. PD-1 antibodies, such as Nivolumab and Pembrolizumb, are approved as a first-line treatment for advanced non-small cell lung cell cancer. However, due to the interaction of tumor cells, T cells and cytokines, some patients developed drug resistance which reduces the efficacy of immunotherapy. Hence, how to overcome resistance has become a urgent problem. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex and the only known molecular receptor of immunoregulatory drugs, has been found to reverse PD-1 antibody resistance by binding to CRBN regulatory agents (CMS), exert T cell immune function by regulating proliferation, activation and metabolism of T cell. In this paper, the mechanism of down-regulation of T cells leading to resistance of PD-1 antibody in lung cancer, the mechanism of CRBN regulating T cells, and research progress of CRBN regulator in the treatment of lung cancer were reviewed.
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Objective: To examine the associations between suicide and self-injury behavior with psychological adaptability of college students, so as to provide the basic information for prevention of suicide and self-injury behavior. Methods: A sample of 825 college students completed a self-report questionnaire that measured sociodemographic characteristics, anxiety, depressive symptoms, resilience, self-compassion, and forgiveness. Results: Among 825 college students, the prevalence rates of suicidal ideation, suicidal plan, suicidal preparation, and suicidal action were 9.9%, 3.5%, 2.5%, 1.8% respectively. The rate of self-injury was 11.8%. Compared with the group with low scores of forgiveness dimension, high score of forgiveness was the protective factor of suicidal psychological behavior (OR=0.26) and self-injury (OR=0.31) (P<0.05). Compared with the score of Connor-Davidson Resilience Scale in each scale of mental resilience, low score was the risk factor of self-injury (OR=2.11), while high score was the protective factor of suicidal mental behaviors (OR=0.51) (P<0.05). Compared with the middle scores of the self-compassion scale and hearland forgiveness scale, the low scores were the risk factors for suicidal psychological behavior (OR=1.66, 2.28), while the high scores were the protective factors for suicidal psychological behavior (OR=0.33, 0.44) and self-injury (OR=0.35, 0.39) (P<0.05). Conclusion Psychological resilience, self-compassion and forgiveness are significantly correlated with suicide and self-injury, suggesting that colleges and universities should pay close attention to the mental health status of college students and help them reduce the incidence by improving their self-psychological adjustment ability.

ObjectiveTo investigate the association between baseline blood ammonia (BLA) and 90-day prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA retrospective analysis was performed for the clinical data of 789 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2016, and the association between baseline BLA and 90-day prognosis was analyzed. The Cox regression risk model was used for multivariate analysis. The Kaplan-Meier survival curve was used to analyze the 90-day survival rate of patients with different levels of baseline BLA, and the log-rank test was used for comparison. ResultsThe Cox multivariate regression analysis showed that BLA was independently and positively correlated with the risk of 90-day death in HBV-ACLF patients (Model 2: hazard ratio = 1.007, 95% confidence interval: 1.005-1.010, P＜0.00001). The log-rank test indicated that in the patients without hepatic encephalopathy (HE), the BLAhigh group had the highest 90-day cumulative mortality rate, followed by the BLAmid group and the BLAlow group (P=0002 3); among the patients with HE, the BLAhigh group had a significantly higher 90-day cumulative mortality rate than the other two groups (P=0.012), while there was no significant difference in 90-day cumulative mortality rate between these two groups (P=0.18). ConclusionBaseline BLA is independently and positively correlated with the risk of 90-day death in HBV-ACLF patients, and it may have a certain clinical value in treatment and prognostic evaluation.