Objective To study the effects of Batroxobin( BX) on the intimal proliferation of graft veins. Methods In this study 25 dogs were selected and evenly divided into experimental group, control group and sham operation group. In experiment and control group, a segment of auto- femoral vein were grafted into femoral artery by clean microsurgery technique. In experimental group, BX was given at the dosage of 0. 1 BU/kg, dayly?2 preoperatively, and once a day for consecutive 6 days postoperatively. Plasma NO, ET was determined in the three groups. Computer image analysis system was applied to calculate the thickness of neointima and media in the vein grafts, immunohistochemistry was used to identify PCNA and C-myc. Result The experimental group had a higher level of NO and lower level of ET compared with control group and sham operation group(P 0. 05 ). The PCNA expression in experimental group was statistically different from that of the control group(P

Objective:To investigate the correlation between serum 25-hydroxyvitamin D (serum 25(OH)D) and Meige syndrome.Methods:A retrospective analysis was performed on 47 patients with Meige syndrome (Meige syndrome group) treated in Yuquan Hospital of Tsinghua University admitted from August 2012 to July 2018 in our hospital.In the same period, 69 healthy people of the same age group were selected as the healthy control group.The difference of serum 25(OH)D concentration among different subtypes of Meige syndrome (type I, II, III) was compared.Logistic regression analysis was used to analyze the correlation between serum 25(OH)D level and Meige syndrome.Results:The serum 25(OH)D concentration in patients with Meige syndrome was (12.68±6.77) μg/L, which was significantly lower than that in the healthy control group ((17.93±6.93) μg/L). The difference was statistically significant ( t=4.044, P<0.001). The serum 25(OH)D concentrations of subtypes I, II and III in patients with Meige syndrome were (14.7±8.14), (11.4±5.02), (8.38±4.99) μg/L, respectively. There was no significant difference among the three types ( F=1.892, P=0.231). Logistic regression results showed that serum 25(OH)D levels were correlated with Meige syndrome ( OR=0.938, 95% CI: 0.885-0.995, P=0.034). Conclusion:The serum 25(OH)D expression level in patients with Meige syndrome is low, suggesting that vitamin D deficiency may be involved in the pathogenesis of Meige syndrome.

Objective To evaluate the prognostic value of human antibacterial peptide LL-37 in elderly patients with sepsis. Methods Elderly sepsis patients over 65-year-old satisfied the diagnostic criteria for sepsis and septic shock admitted to intensive care unit of East Hospital of Tongji University from January 2016 to December 2017 were enrolled (elderly sepsis group). Aged community-acquired pneumonia (CAP) patients hospitalized during the same period were enrolled as a control group for pneumonia, and the aged health check-ups served as a healthy control group during the same period. The peripheral blood LL-37 levels of all patients on the 1st, 3rd, 7th day of admission and the results on the day of physical examination in the healthy control group and on the day of admission in aged CAP group were recorded. C-reactive protein (CRP), arterial blood lactate (Lac), procalcitonin (PCT) were monitored, and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were calculated based on the worst values within 24 hours. The correlation between LL-37 and various indicators was analyzed by Spearman method. According to the 28-day clinical outcome, the elderly patients with sepsis were divided into survival group and non-survival group. The differences in all parameters between the two groups were compared. The statistically significant indicators were analyzed by receiver operating characteristic (ROC) curve, and the predictive value of each indicator for prognosis was evaluated. Results ① A total of 113 elderly patients with sepsis were enrolled in the final analysis, including 67 patients in sepsis group and 46 patients in septic shock group. Thirty-two patients were enrolled as healthy controls and 31 elderly patients with CAP as elderly pneumonia group. The PCT, CRP, Lac, APACHEⅡ and SOFA scores of the patients in the three groups were higher than those of the healthy control group, and they were gradually increased with the severity of infection. There was no significant difference in gender or age among the groups. Compared with the healthy control group, the other three groups had higher LL-37 level after admission, the LL-37 levels in the sepsis group and the septic shock group were decreased with the prolongation of the hospitalization time, and they were lower than the pneumonia group at 7 days after admission [LL-37 (μg/L): 1 403.9±501.9, 1 517.1±676.4 vs. 1 608.4±816.2, both P > 0.05]. It was shown by correlation analysis that the LL-37 level in peripheral blood of elderly patients with sepsis was significantly negatively correlated with APACHEⅡ score (r = -0.329, P = 0.007) and SOFA score (r = -0.344, P = 0.005), but no significant correlation with Lac was found (r = -0.128, P = 0.311). ② The 28-day survival analysis revealed that of the 113 elderly patients with sepsis, 54 (47.8%) survived at 28 days and 59 (52.2%) died. There was no significant difference in gender, age, PCT or CRP levels at 1 day after admission between the two groups. The 1-day Lac, APACHEⅡ and SOFA scores of the patients in the non-survival group were significantly higher than those in the survival group, they were gradually increased with the prolongation of the hospitalization time, and they were significantly higher than those in the survival group at 7 days after admission [Lac (mmol/L): 2.4 (1.4, 4.4) vs. 1.0 (0.8, 1.7), APACHEⅡ score: 21.77±5.85 vs. 13.74±4.99, SOFA score: 9.62±4.78 vs. 3.18±2.71, all P < 0.01]. With the prolongation of admission, there was no significant change in LL-37 level of peripheral blood in the survival group. The LL-37 level in the non-survival group showed a downward tendency, and it was significantly lower than that in the survival group at 7 days after admission (μg/L: 1 277.8±642.6 vs. 1 620.6±461.6, P < 0.05). It was shown by ROC curve analysis that the LL-37 in peripheral blood, Lac, APACHEⅡ score and SOFA score at 7-day of admission of elderly patients with sepsis had predictive value for prognosis, and LL-37 had the best predicted effect for 28-day death, the area under the ROC curve (AUC) of LL-37 was 0.670, 95% confidence interval (95%CI) = 0.513-0.757, when the optimal cut-off value was 1 283.0 μg/L, the sensitivity was 75.7%, and the specificity was 61.5%. Conclusions The expression of LL-37 increased in the early course of the disease in elderly patients with sepsis. However, as the disease progressed and worsened, the level of LL-37 had a decline tendency and was associated with death. The dynamic monitoring of LL-37 combined with APACHEⅡ and SOFA scores had clinical guidance value in predicting the prognosis of sepsis in the elderly.

OBJECTIVES: To investigate the effects of PLK1 inhibitors on osimertinib-resistant non-small cell lung carcinoma (NSCLC) cells and the anti-tumor effect combined with osimertinib. METHODS: An osimertinib resistant NCI-H1975 cell line was induced by exposure to gradually increasing drug concentrations. Osimertinib-resistant cells were co-treated with compounds from classical tumor pathway inhibitor library and osimertinib to screen for compounds with synergistic effects with osimertinib. The Gene Set Enrichment Analysis (GSEA) was used to investigate the activated signaling pathways in osimertinib-resistant cells; sulforhodamine B (SRB) staining was used to investigate the effect of PLK1 inhibitors on osimertinib-resistant cells and the synergistic effect of PLK1 inhibitors combined with osimertinib. RESULTS: Osimertinib-resistance in NCI-H1975 cell (resistance index=43.45) was successfully established. The PLK1 inhibitors GSK 461364 and BI 2536 had synergistic effect with osimertinib. Compared with osimertinib-sensitive cells, PLK1 regulatory pathway and cell cycle pathway were significantly activated in osimertinib-resistant cells. In NSCLC patients with epidermal growth factor receptor mutations treated with osimertinib, PLK1 mRNA levels were negatively correlated with progression free survival of patients (R=－0.62, P<0.05), indicating that excessive activation of PLK1 in NSCLC cells may cause cell resistant to osimertinib. Further in vitro experiments showed that IC₅₀ of PLK1 inhibitors BI 6727 and GSK 461364 in osimertinib-resistant cells were lower than those in sensitive ones. Compared with the mono treatment of osimertinib, PLK1 inhibitors combined with osimertinib behaved significantly stronger effect on the proliferation of osimertinib-resistant cells. CONCLUSIONS PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; ErbB Receptors/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; Mutation ; Cell Line, Tumor

ObjectiveTo observe the effect of warming needle moxibustion based on rehabilitation on rotator cuff injury. MethodsFrom January, 2019 to January, 2020, 70 patients with rotator cuff injury from Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine were randomly divided into control group (n = 35) and experimental group (n = 35). Both groups received Mulligan mobilization and rotator cuff muscle group muscle energy technique (MET) training, while the experimental group received warming needle moxibustion at Jianyu (LI15), Jügu (LI16), Jianqian and Jianzhen (SI9) in addition, for two weeks. They were assessed with Shoulder Pain and Disability Index (SPADI), Visual Analogue Scale for pain (VAS), range of motion of shoulder (ROM), and shoulder isokinetic muscle strength before and after treatment, and the complications and recurrence were observed. ResultsThere were five cases in the control group and four cases in the experimental group dropped. The SPADI score, VAS score decreased (|t| > 5.039, P < 0.001), and the ROM and R value of isokinetic muscle strength testing increased (|t| > 2.751, P < 0.01) in both groups after treatment, while the SPADI score, VAS score were less (|t| > 3.616, P < 0.001); the ROM, and R values of isokinetic muscle strength testing of flexion, extension, adduction and abduction were more (|t| > 2.214, P < 0.05) in the experimental group than in the control group. ConclusionWarming needle moxibustion can further relieve shoulder pain in patients with rotator cuff injury, and improve shoulder ROM, muscle strength and functioning.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation