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.

Objective:To explore the nurses' knowledge hiding behavior and its correlation with organizational climate and innovative behavior.Methods:From August to November 2021, 208 registered nurses from Henan Provincial People's Hospital were selected as the research object by convenient sampling. The nurses were investigated with the General Information Questionnaire, Knowledge Hiding Behavior Questionnaire, Organizational Climate Scale for Nursing, and Nurse Innovative Behavior Scale.Results:The score of nurses' knowledge hiding behavior was 18 (13, 26) , the total score of nursing organizational atmosphere was (93.76±15.95) , and the score of nurses' innovative behavior was (34.45±8.39) . The total score of knowledge hiding behavior was negatively correlated with the score of the Organizational Climate Scale for Nursing ( P<0.05) , and was negatively correlated with the innovative behavior of nurses ( P<0.05) , and the differences were statistically significant. Multiple linear regression analysis showed that gender, intimacy and enterprising atmosphere behavior were the influencing factors of knowledge hiding behavior ( P<0.05) . Conclusions:Nurses have knowledge hiding behavior, which is influenced by gender, intimacy and enterprising atmosphere. The knowledge hiding behavior can be reduced by creating a harmonious organizational atmosphere, so as to enhance the innovative ability of nurses, and improve the team fee performance and group competitiveness.

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

Objective:To study the effect of Xuebijing on inflammatory response and prognosis in patients with septic shock.Methods:A prospective randomized controlled study was conducted. Eighty septic shock patients admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January to December in 2019 were enrolled. The enrolled patients were divided into Xuebijing group and control group by randomized number table method, with 40 cases in each group. Both groups were strictly followed the guidelines for the diagnosis and treatment of septic shock to take comprehensive treatment measures against sepsis. On this basis, Xuebijing group received intravenous 100 mL Xuebijing injection twice a day for 7 days. Baseline data of enrolled patients were recorded. The levels of interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and heparin binding protein (HBP) were measured before treatment and 3, 7 and 10 days after treatment. Mechanical ventilation time, the length of intensive care unit (ICU) stay, total hospitalization time and 28-day mortality were recorded. The differences of every indicator between the two groups were compared. Independent risk factors affecting patient prognosis were analyzed by binary Logistic regression.Results:① There was no significant difference in baseline data such as gender, age, infection site, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure score (SOFA) between the two groups. ② The levels of serum inflammatory factors in both groups showed a decreasing trend after treatment. Compared with the control group, IL-6 and HBP in the Xuebijing group significantly decreased on day 7 [IL-6 (ng/L): 66.20 (16.34, 163.71) vs. 79.81 (23.95, 178.64), HBP (ng/L): 95.59 (45.23, 157.37) vs. 132.98 (73.90, 162.05), both P < 0.05]; on day 10, PCT, CRP, IL-6 and HBP significantly decreased [PCT (μg/L): 1.14 (0.20, 3.39) vs. 1.31 (0.68, 4.21), CRP (mg/L): 66.32 (19.46, 115.81) vs. 89.16 (20.52, 143.76), IL-6 (ng/L): 31.90 (13.23, 138.74) vs. 166.30 (42.75, 288.10), HBP (ng/L): 62.45 (29.17, 96.51) vs. 112.33 (58.70, 143.96), all P < 0.05]. ③ Compared with the control group, mechanical ventilation time and the length of ICU stay were significantly shortened and the total hospitalization expenses were significantly reduced in Xuebijing group [mechanical ventilation time (hours): 57.0 (0, 163.5) vs. 168.0 (24.0, 282.0), the length of ICU stay (days): 8.80±4.15 vs. 17.13±7.05, the total hospitalization expenses (ten thousand yuan): 14.55±7.31 vs. 20.01±9.86, all P < 0.05]. There was no significant difference in 28-day mortality and the total hospitalization time [28-day mortality: 37.5% vs. 35.0%, the total hospitalization time (days): 13.05±8.44 vs. 18.30±9.59, both P > 0.05]. ④ Patients were divided into death and survival groups according to the prognosis, and univariate analysis showed that white blood cell (WBC), neutrophil percentage (NEU%), CRP, lactic acid (Lac), APACHEⅡ score, IL-6, HBP were the factors influencing the prognosis of patients. The above indicators were further analyzed by Logistic regression, which showed that CRP, IL-6, and APACHE Ⅱ score were independent risk factors for prognosis [odds ratio ( OR) was 1.007, 1.828, 1.229, all P < 0.05]. Conclusions:Combined with Xuebijing to treat septic shock can reduce the body's inflammatory response to a certain extent, thereby reducing the time of mechanical ventilation, shortening the stay of ICU and reducing the total cost of hospitalization. But it cannot reduce the 28-day mortality of patients with septic shock.

Objective:To investigate the effectiveness of an enhanced CT automatic recognition system based on Faster R-CNN for pancreatic cancer and its clinical value.Methods:In this study, 4 024 enhanced CT imaging sequences of 315 patients with pancreatic cancer from January 2013 to May 2016 at the Affiliated Hospital of Qingdao University were collected retrospectively, and 2 614 imaging sequences were input into the faster R-CNN system as training dataset to create an automatic image recognition model, which was then validated by reading 1 410 enhanced CT images of 135 cases of pancreatic cancer.In order to identify its effectiveness, 3 750 CT images of 150 patients with pancreatic lesions were read and a followed-up was carried out.The accuracy and recall rate in detecting nodules were recorded and regression curves were generated.In addition, the accuracy, sensitivity and specificity of Faster R-CNN diagnosis were analyzed, the ROC curves were generated and the area under the curves were calculated.Results:Based on the enhanced CT images of 135 cases, the area under the ROC curve was 0.927 calculated by Faster R-CNN. The accuracy, specificity and sensitivity were 0.902, 0.913 and 0.801 respectively.After the data of 150 patients with pancreatic cancer were verified, 893 CT images showed positive and 2 857 negative.Ninety-eight patients with pancreatic cancer were diagnosed by Faster R-CNN.After the follow-up, it was found that 53 cases were post-operatively proved to be pancreatic ductal carcinoma, 21 cases of pancreatic cystadenocarcinoma, 12 cases of pancreatic cystadenoma, 5 cases of pancreatic cyst, and 7 cases were untreated.During 5 to 17 months after operation, 6 patients died of abdominal tumor infiltration, liver and lung metastasis.Of the 52 patients who were diagnosed negative by Faster R-CNN, 9 were post-operatively proved to be pancreatic ductal carcinoma.Conclusion:Faster R-CNN system has clinical value in helping imaging physicians to diagnose pancreatic cancer.

Objective:To investigate the effectiveness of an enhanced CT automatic recognition system based on Faster R-CNN for pancreatic cancer and its clinical value.Methods:In this study, 4 024 enhanced CT imaging sequences of 315 patients with pancreatic cancer from January 2013 to May 2016 at the Affiliated Hospital of Qingdao University were collected retrospectively, and 2 614 imaging sequences were input into the faster R-CNN system as training dataset to create an automatic image recognition model, which was then validated by reading 1 410 enhanced CT images of 135 cases of pancreatic cancer.In order to identify its effectiveness, 3 750 CT images of 150 patients with pancreatic lesions were read and a followed-up was carried out.The accuracy and recall rate in detecting nodules were recorded and regression curves were generated.In addition, the accuracy, sensitivity and specificity of Faster R-CNN diagnosis were analyzed, the ROC curves were generated and the area under the curves were calculated.Results:Based on the enhanced CT images of 135 cases, the area under the ROC curve was 0.927 calculated by Faster R-CNN. The accuracy, specificity and sensitivity were 0.902, 0.913 and 0.801 respectively.After the data of 150 patients with pancreatic cancer were verified, 893 CT images showed positive and 2 857 negative.Ninety-eight patients with pancreatic cancer were diagnosed by Faster R-CNN.After the follow-up, it was found that 53 cases were post-operatively proved to be pancreatic ductal carcinoma, 21 cases of pancreatic cystadenocarcinoma, 12 cases of pancreatic cystadenoma, 5 cases of pancreatic cyst, and 7 cases were untreated.During 5 to 17 months after operation, 6 patients died of abdominal tumor infiltration, liver and lung metastasis.Of the 52 patients who were diagnosed negative by Faster R-CNN, 9 were post-operatively proved to be pancreatic ductal carcinoma.Conclusion:Faster R-CNN system has clinical value in helping imaging physicians to diagnose pancreatic cancer.

Objective:To investigate the effects of TGF-β1 on T lymphocytes of BALB/c mice infected with Echinococcus granulosus( E.granulosus ) in vitro.Methods: The inhibitor group:the spleen cells of BALB/c mouse were co-cultured with E.granulosus and SB525334.The control group:the spleen cells of BALB/c mouse were co-cultured with E.granulosus and PBS.The blank group:the spleen cells of BALB/c mouse were co-cultured with RPMI-1640 medium and SB525334.The lymphocytes were collected at 48 h post-infection.The T lymphocyte subsets, the number of CD4+CD25+T cells, the number of NK cells, and the expression of NKG2D receptor were detected by flow cytometry.The NK cell activity was determined with the lactate dehydrogenase leakage assay(LDH).Results:The inhibition the TGF-β1 receptors resulted in the increase of in the number of CD4+T cells,the decrease in the number of CD8+T cells,the increase of in the ratio CD4+/CD8+T cells,the decrease of in the number of CD4+CD25+T cells,the increase in the expression of the NKG2D receptors,the increase in the lysis rate of Yac-1 cells by NK cells,and a positive cor-relation between the expression of activity receptor NKG2D and killing activity of NK, which were mediated by E.granulosus.Conclusion: The inhibition of TGF-β1 receptors can enhance the immune response of T lymphocytes against E.granulosus infection in vitro.

Acupuncture mechanics in acupuncture manipulation of traditional Chinese medicine is important information for elucidating the essence of acupuncture manipulation and clinically observed acupuncture effects and has some morphological, histochemical and biochemical effects on fibroblasts and cytoskeletons in the tissue. This article generalizes from the present newest research advances, which is of important significance for revealing the mechanism of the therapeutic effect of acupuncture.

OBJECTIVE: To explore the function of outer hair cells and its influencing factors in the workers of occupational exposure to low frequency electric and magnetic fields. METHOD: 502 high-strength LF EMFs-exposed workers were taken as the study subjects. The field intensity indicator and noise analyzer were employed for the examination of the electromagnetic energy intensity and noise value at the working sites. Self-administered questionnaires were adopted. Universal hearing screening by distortion product otoacoustic emission (DPOAE) and pure tone audiometry (PTA) were done. 100 workers who had abnormal POAE were taken as the observation group and 100 workers who had normal DPOAE were taken as the control group. The workers need be confirmed with ABR testing when the pure tone threshold of two consecutive frequencies were above 20 dB HL or DPOAE detection in any frequency did not pass. Multiple factor analysis with logistic regression was performed for the risk factors. RESULT: The average electric power density in job locations was 21-38 KV/m, which was higher than national standard (< 5 kv/m). Average noise-level in job locations was 52-65 dBHL, which was within the standard (< 85 dB(A). Questionnaire presented that low frequency electric and magnetic fields might increase the incidence of headache, insomnia and tinnitus in the observed group. The incidence of abnormal DPOAE was higher in the subjects of the observed group (P < 0.01). At 676, 933, 3616, 5 130, 7253 Hz, the DPOAE amplitudes of the observed group workers were significantly lower than the control group. Multivariate analysis showed that the risk factors of abnormal DPOAE included exposure of EMF, length of service, daily exposure time, conservatory measures might be protective factors. CONCLUSION The changes of DPOAE indicated that the exposure to low frequency electric and magnetic fields had a subtle, discreet and localized impairing effects on outer hair cells. Exposure of low frequency electric and magnetic fields, length of service, daily exposure time might be risk factors, conservatory measures might be protective factors.
Auditory Threshold ; Case-Control Studies ; Electromagnetic Fields ; adverse effects ; Hair Cells, Vestibular ; pathology ; Humans ; Magnetic Fields ; adverse effects ; Male ; Noise ; adverse effects ; Occupational Exposure ; Surveys and Questionnaires