Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Objective To investigate the effect of long-chain non-coding RNA(lncRNA)AP000892.6 on the migration,inva-sion and epithelial-mesenchymal transition of bladder cancer cells and the related molecular mechanism.Methods The expression of AP000892.6 in bladder cancer and adjacent tissues was analyzed using GEPIA dataset.The expression levels of AP000892.6 in bladder cancer cell lines 647V,T24,UMUC3,5637,RT4 and normal bladder epithelial cells SV-HUC-1 were detected by real-time quanti-tative polymerase chain reaction(RT-qPCR).The AP000892.6 overexpression plasmid or negative control plasmid was transfected into T24 cells,and the experiment was divided into AP000892.6 group and NC group.The plasmid transfection efficiency was verified by RT-qPCR.The migration and invasion abilities of transfected T24 cells were detected by cell scratch method and Transwell assay,re-spectively.The downstream target gene of AP000892.6 was predicted and validated using bioinformatics method and dual-luciferase re-porter gene experiment.The expression of AP000892.6downstream target gene was detected by RT-qPCR.Western blot was used to de-tect the expression of epithelial phenotype proteins E-cadherin,ZO-1 and mesenchymal phenotype proteins Vimentin,N-cadherin and Twist.Results Compared with adjacent tissues,the expression of AP000892.6 was decreased in bladder cancer tissues(P＜0.01).Compared with SV-HUC-1 cells,the expression of AP000892.6 was decreased in bladder cancer cell lines(P＜0.05),and the rela-tive expression level of AP000892.6 in T24 cells was the lowest(P＜0.01).Compared with the NC group,overexpression of AP000892.6 inhibited the migration(P＜0.01)and invasive ability(P＜0.01)of bladder cancer T24 cells.Dual-luciferase reporter gene analysis proved that miR-616-5p was the target gene of AP000892.6(P＜0.01).Compared with the NC group,AP000892.6 negatively regu-lated the expression of miR-616-5p(P＜0.01).Compared with the NC group,the expression of epithelial phenotype proteins E-cad-herin and ZO-1 were up-regulated in T24 cells of AP000892.6group,and the expression of mesenchymal phenotype proteins Vimentin,N-cadherin and Twist were down-regulated.Conclusion AP000892.6 inhibits the migration,invasion and epithelial-mesenchymal transition process of bladder cancer T24 cells by targeting miR-616-5p.

Objective:To investigate the expression of long non-coding RNA (lncRNA) CALCOCO1 in bladder cancer tissue and its effect on the proliferation and migration of bladder cancer cells by regulating miR-200a-3p.Methods:The relative expression levels of CALCOCO1 in bladder cancer tissues and adjacent tissues were analyzed by TCGA database. Human bladder cancer cells UM-UC-3 were selected, and the cells were divided into negative control group and CALCOCO1 group, and NC plasmid and CALCOCO1 plasmid were transfected into UM-UC-3 cells respectively. The expression level of CALCOCO1 in each group was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation and migration ability of UM-UC-3 cells were detected by MTT assay and Transwell migration assay. Bioinformatics technology was used to predict and dual-luciferase reporter gene experiments to verify the targeting relationship between CALCOCO1 and miR-200a-3p. The expression levels of miR-200a-3p in UM-UC-3 cells in each group were detected by qRT-PCR. Western blotting was used to detect the expression of UM-UC-3 cells proliferation and migration phenotype in each group. Measurement data were expressed as mean ± standard deviation ( ± s), t-test was used for comparison between two groups, and repeated measurement analysis of variance was used for comparison at different time. Results:Compared with adjacent tissues, the relative expression level of CALCOCO1 in bladder cancer tissues was significantly lower, the difference was statistically significant( P<0.01). The relative expression of CALCOCO1 in UM-UC-3 cells in CALCOCO1 group and negative control group was 9.66±2.51 and 1.07±0.59, respectively. The relative expression level of CALCOCO1 in CALCOCO1 group was significantly higher than that in negative control group, the difference was statistically significant ( P<0.01). Compared with the negative control group, the proliferation activity of UM-UC-3 cells in the CALCOCO1 group was decreased ( P<0.05), and the migration number of UM-UC-3 cells was significantly decreased ( P<0.01). CALCOCO1 had a binding site with miR-200a-3p ( P<0.01). The relative expression of miR-200a-3p in UM-UC-3 cells in CALCOCO1 group and negative control group was 1.02 ± 0.31 and 5.79 ± 1.68, respectively, the difference was statistically significant ( P<0.01). Compared with the negative control group, the expression levels of proliferation phenotype proteins CCNB1, CCNE1 and CCND2 in UM-UC-3 cells in CALCOCO1 group decreased, and the expression levels of migration phenotype proteins FOXC2 and Fibronectin decreased. Conclusion:The expression of CALCOCO1 is down-regulated in bladder cancer tissue, promoting the expression of CALCOCO1 can inhibit the proliferation and migration of bladder cancer UM-UC-3 cells through targeted down-regulation of miR-200a-3p expression.

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Objective:To compare the clinical efficacy of drug coated balloon (DCB) vs. plain old balloon (POB) on in-stent restenosis (ISR) of femoropopliteal artery occlusive disease of the lower limb. Methods:The clinical data of 91 ISR patients admitted at Shanxi Bethune Hospital from Jul 2016 to Dec 2017 were retrospectively analyzed. The primary patency rates were compared.Results:There were 43 patients treated with drug coated balloons and 48 patients treated with plain old balloons. The surgical procedure was successful in all cases, and the symptoms of lower limb ischemia were significantly improved after surgical procedure. The primary patency rate of patients who were treated by drug coated balloons was significantly higher than by plain old balloons at 12 months after surgery (83.7% vs. 62.5%, P<0.05). Conclusion:The use of drug coated balloons could acquire more satisfactory short-term clinical efficacy for ISR patients of femoropopliteal artery occlusive disease.

Objective To identify the predictors of postoperative acute kidney injury in patients undergoing surgery for Stanford type A acute aortic dissection. Methods A total of 220 patients who underwent surgery for type A acute aortic dissection in Qingdao Municipal Hospital from September 2010 to September 2017 were divided into two groups including a group A and a group B based on whether acute kidney injury occurred or not after surgery. There were 40 patients with 29 males and 11 females with the mean age of 54.6±9.2 years in the group A, 180 patients with 133 males and 47 females with the mean age of 48.5±7.9 years in the group B. Univariate and multivariate analyses (logistic regression) were used to identify the predictive risk factors. Results Overall in-hospital mortality was 5.5%. In univariate analysis, there were statistically significant differences with respect to the age, preoperative creatinine, preoperative white blood cell, the European system for cardiac operative risk evaluation (EuroSCORE), total cardiopulmonary bypass (CPB) time, deep hypothermic circulatory arrest (DHCA) time, arch replacement, red blood cell transfusion intraoperative and in 24 hours postoperatively, postoperative mechanical ventilation time, ICU stay duration, hospital stay duration and in hospital mortality. Multivariate logistic analysis showed that preoperative creatinine, preoperative white blood cell, CPB time, and red blood cell transfusion intraoperative and in 24 hours postoperatively were the independent predictors for postoperative acute kidney injury. Conclusion The incidence of acute kidney injury is high after surgery for acute Stanford type A aortic dissection. It can be predicted based on above factors, for patients with these risk factors, more perioperative care strategies are needed in order to induce the incidence of acute kidney injury.

To identify the predictors of prolonged mechanical ventilation in patients undergoing surgery for stanford type A acute aortic dissection. Methods 202 patients who underwent surgery for acute aortic dissection type A from May 2009 to May 2016 were divided into two groups based on their mechanical ventilation time after surgery, including 70 patients with mechanical ventilation 48 hours or more(group A), 132 patients with mechanical ventilation less than 48 hours (group B). Univariate and multivariate analysis(logistic regression) were used to identify the predictive risk factors. Results The mechanical ventilation time was(146. 8 ±78. 5)h and(21. 7 ±9. 5)h in group A and group B respectively. Overall inhospital mortality was 8. 6％ and 2. 3％. Multivariate logistic analysis showed that BMI(OR = 5. 956, 95％ CI: 2. 585 - 13. 723, P =0. 000), CPB time(OR =1. 108, 95％CI: 1. 052 -1. 166, P =0. 000), DHCA(OR =4. 562, 95％ CI: 1. 250 - 16. 640, P =0. 022), red blood cell transfusion intraoperative and in 24 hours postoperatively(OR =2. 625, 95％ CI: 1. 515 -4. 549, P =0. 001) were the independent predictors for prolonged mechanical ventilation. Conclusion The incidence of prolonged mechanical ventilation is high after surgery for stanford type A acute aortic dissection. It can be predicted based on above factors, for patients with these risk factors, more perioperative care strategies are needed in order to shorten the mechanical ventilation time.

In order to construct a novel multifunctional targeting nano-carrier based on pH-redox characteristics of tumor microenvironment,ketone bonds and disulfide bonds were bonded to the oligomeric hyaluronic acid (oHA) being sensitive to pH and the reduction environment.The chemical structure of oligomeric hyaluronic acid-8-mercaptomenthone 1,2-glycerolketal (oHMST) was characterized by 1H NMR,IR and ESI-MS.Curcuminloaded micelles were prepared by dialysis.The single factor investigation was carried out on the dosage form.Some properties,including particle size zeta potential,the morphology of micelles,and pH-sensitivity were studied.The materials were synthesized successfully.The micelles were spheric with a diameter of about 100 nm.The Zeta potential of the micelles was-(21.97 ± 1.08) mV.The in vitro test showed that oHMST carriers have good pH-sensitivity and redox-sensitivity.