Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Objective:To study the specific mechanism of LINC01018 involved in the pathogenesis of colon cancer.Methods:The expression of LINC01018 in colon cancer tissues and cells and normal colon tissues and cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cell line which overexpresses LINC01018 stably was established. RNA binding protein immunoprecipitation (RIP) assay was used to detect the interaction between LINC01018 and E2F1 protein. Dual luciferase assay was used to detect the regulatory effect of E2F1 on CDK6 promoter. The expression of E2F1 or CDK6 was up-regulated in HT-29 cell line which overexpresses LINC01018, then the proliferation, invasion and migration of HT-29 cells and the expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells were detected by cell counting method (CCK-8) assay, Transwell assay and Western blot.Results:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. The result of RIP assay showed that LINC01018 interacted with E2F1 protein. The result of dual luciferase assay showed that E2F1 protein could enhance the efficiency of CDK6 promoter, and E2F1 had a positive regulatory effect on CDK6. Overexpression of LINC01018 could attenuate the positive regulatory effect of E2F1 on CDK6. Up-regulation of E2F1 or CDK6 expression could attenuate the effects of LINC01018 overexpression on the proliferation, invasion, migration and expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. LINC01018 may regulate the proliferation, invasion and migration of HT-29 cells through E2F1/CDK6/MMP-2 axis, and participate in the pathogenesis of colon cancer.

Objective:To investigate the effect of decreasing DKC1 gene expression on radiosensitivity of HeLa cells.Methods:A cell model with low expression of DKC1 gene was established by shRNA technology with lentivirus as vector, and the interference efficiency was verified by RT-PCR and Western blot assay. Cells were divided into two groups of interference (Lv-shDKC1) and its negative control. Telomerase activity was detected by TRAP-ELISA, and telomere length was measured by Real-time PCR. Cell survival was obtained through clone formation assay and fitted by multi-target single-hit model, and radiobiological parameters ( D0, Dq, N, SF2) and radiosensitization ratio (SER) were calculated. Results:After DKC1 interfering, the expression levels of mRNA and protein of DKC1 in HeLa cells were significantly decreased by (71.330±4.112)% ( t=25.53, P<0.05) and (35.520±3.804)% ( t=4.833, P<0.05), respectively. Compared with the blank control group and negative control group, the telomerase activity of Lv-shDKC1 group decreased significantly from 0.900±0.044 and 0.897±0.031 to 0.713±0.021 ( F=31.44, P<0.05), the relative telomere length was significantly decreased from 4.233±0.306 and 4.633±0.379 to 2.667±0.404 ( F=39.15, P<0.05). The telomerase activity and relative telomere length of blank control group and Lv-shDKC1 negative control group had no significant difference( P>0.05). SF2 in the interference group (0.571±0.006) was significantly lower than that of the blank control group (0.861±0.009) and the Lv-shDKC1 negative control group (0.807±0.002) ( F=1812, P<0.05), and the radiosensitization ratio (SER) of shDKC1 interference was 1.508. Conclusions:Downregulation of DKC1 in human cervical cancer HeLa cells enhances the radiosensitivity through inhibiting the activity of telomerase and shortening the length of telomere. DKC1 gene may become a new target of radiosensitization.

Objective To analyze the current status and clinical characteristics of urinary incontinence in 138 elderly female inpatients so as to provide thoughts and directions for management and intervention implemented by medical institutions for urinary incontinence people. Methods Cross-sectional investigation was used in this study. From August 2018 to November 2018, this study selected elderly female inpatients at a Class Ⅲ Grade A hospital in Beijing by cluster sampling. The primary screening was carried out with the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICI-Q-SF) and urinary incontinence knowledge scale. This study analyzed the clinical characteristics and urinary incontinence knowledge in elderly female inpatients with urinary incontinence. Results Among 1105 elderly female inpatients ≥ 60 years old, there were 138 of them with urinary incontinence accounting for 12.5％. Among 138 elderly female inpatients with urinary incontinence, the ages were (74.37±8.49) ranged from 60 to 99; the score of urinary incontinence assessment was (7.09±4.59) from 1 to 21; patients with the mild or moderate level of urinary incontinence occupied 90.6％ (125/138);87.0％ (120/138) of patients were with basic diseases interacted with urinary incontinence. There was a statistical difference in the self-perception influence of the urinary incontinence on life among patients with different conditions (P < 0.05). There were statistical differences in the urinary incontinence knowledge among patients with different education levels (P< 0.01). Conclusions In China, it still faces severe problem of urinary incontinence in elderly female inpatients. Basis diseases of some patients interact with urinary incontinence. Urinary incontinence medical problems should be explored with the scientific, standardized and effective methods because of the bottleneck that public lack knowledge.

Objective To explore the value of the cavum vergae vanishing sign for prenatal ultrasound diagnosis of fetal agenesis of the corpus callosum ( ACC ) . Methods Fifty-one cases of ACC of 20 - 32 gestational weeks were confirmed by MRI or induced fetal autopsy . A random selection of 80 normal fetuses of 20 - 32 gestational weeks were chosed as control group . The displays of the cavum septum pellucidum ( CSP) and the cavum vergae( CV ) in the two groups were observed . Results There were 36 cases of complete agenesis of the corpus callosum ( CACC) and 15 cases of partial agenesis of the corpus callusom ( PACC) in ACC group . In 51 ACC cases ,43 cases were confirmed by prenatal MRI ,while 8 cases were confirmed by postnatal MRI . The comparison of display of CSP and CV between the ACC group and the health group was as follows : ① CSP vanishing rate in ACC group was 70 .6％ ( 36/51 ) ,meanwhile the disappearance rate of CSP in the health group was 0 ( 0/80 ) ,the difference between the two groups was statistically significant( χ2 = 77 .870 , P = 0 .000) . ② CV vanishing rate in ACC group was 96 .1％ (49/51) , meanwhile the disappearance rate of CV in the health group was 1 .2％ ( 1/80) ,the difference between the two groups was statistically significant ( χ2 = 118 .673 , P = 0 .000) . The correlation coefficient between the CV vanishing sign and the occurrence of ACC was 0 .952 ( P = 0 .000) ,while the correlation coefficient between the CSP vanishing sign and the occurrence of ACC was 0 .771 ( P = 0 .000) . There were significant differences in CSP disappearance rate and CV disappearance rate between ACC group and control group at different gestational weeks ( 20 - 24 weeks ,25 - 28 weeks and 29 - 32 weeks) ( all P < 0 .001) . Conclusions The cavum vergae vanishing sign ,as an important indirect sign of fetal agenesis of the corpus callosum ,can be obtained quickly from horizontal transverse section of the cavum septum pellucidum . During the middle pregnancy ,it could be an important prenatal ultrasound screening clue for fetal agenesis of the corpus callosum .

Objective To observe the correlation between CD4+ CD29+ T cells and metastasis and radiotherapy for patients with pulmonary adenocarcinoma. Method Seventy-one patients with lung adenocarcinoma, 93 patients with lung adenocarcinoma ,76 cases of chronic obstructive pulmonary disease (COPD),63 cases of healthy volunteers were enrolled. Frequencies of blood CD4+ CD29+ T cells and their intracellular necrosis factor alpha(TNF-α)and interleukin 1(IL-1)were compared. Compare TNF-α,IL-1,integrin beta 1 and vascular endothelial growth factor(VEGF)levels in the patients with transferred pulmonary adenocarcinoma or with non-transferred pulmonary adenocarcinoma and their changes with the treatment of radiotherapy. Results the patients with lung adenocarcinoma and non lung adenocarcinoma were significantly higher than that of COPD and health group,and patients with lung adenocarcinoma is significantly higher than patients with non lung adenocarcinoma (P<0.05);Integrin beta 1,VEGF and CD4+CD29+T cells,TNF-αand IL-1 level in patients with lung adeno-carcinoma metastasis were significantly higher than non-transferred group(P < 0.05);After radiotherapy,CD4+CD29+T cells,TNF-αand IL-1 in patients with lung adenocarcinoma were significantly lower than before(P<0.05);CD4+ CD29+ T cells,TNF alpha and IL-1 with integrin beta 1 and VEGF had significantly positive correlations. Conclusion CD4+CD29+T cells and cytokines increase significantly in the blood of patients with lung adenocarci-noma,and are related to the prognosis of metastasis and radiation therapy,which has important clinical significance.

Objective To explore the direct economic loss caused by healthcare-associated infection(HAI)in general hospitals in China.Methods 68 hospitals were selected,a retrospective 1:1 matched survey was conducted to compare the direct medical cost in patients with and without HAI between January 1,2015 and December 31,2015. Results A total of 2 123 pairs of patients with and without HAI were included in the survey.The average cost of hospitalization in HAI and non-HAI groups were ￥25 845.30 and ￥12 006.14 respectively,￥13 839.16 on average was increased due to HAI.The average economic loss in provincial and ministerial levels of hospitals were￥21 409.83.The average economic loss in different regional hospitals were ￥9 725.42-￥18 909.59,and north China ranked the first.Economic loss caused by bloodstream infection and lower respiratory tract infection were more than other sites,which were ￥23 190.09 and ￥18 194.50 respectively.Conclusion HAI resulted in considerable direct economic loss.Prevention and control of HAI,especially bloodstream infection and lower respiratory tract infection should be paid more attention.

Objective To evaluate the efficacy and toxicity of induction chemotherapy with nedaplatin and docetaxel plus concurrent intensity?modulated radiotherapy ( IMRT) with nedaplatin or cisplatin in the treatment of locally advanced nasopharyngeal carcinoma (NPC). Methods A total of 223 patients with pathologically diagnosed locally advanced NPC in five treatment centers from 2011 to 2012 were randomly divided into two groups. In the test group, one hundred and thirteen patients received two cycles of induction chemotherapy with docetaxel (65 mg/ m2 on day 1) and nedaplatin (80 mg/ m2 on day 1) plus concurrent IMRT with nedaplatin (40 mg/ m2 on day 1). In the control group, 110 patients received two cycles of induction chemotherapy with the same regimens plus concurrent IMRT with cisplatin (40 mg/ m2 on day 1). The survival rates were calculated with the Kaplan?Meier method and the differences in the survival rates between the two groups were analyzed using the log?rank test. Comparison of the incidence rates of adverse reactions between the two groups was made by the chi?square test. Results The follow?up rate was 99?? 1%.The response rates at 3 months after treatment in the two groups were both 100%. The 2?year local recurrence?free, regional recurrence?free, distant metastasis?free, and overall survival rates were 94?? 0%, 94?? 2%, 88?? 2%, and 90?? 3%, respectively, in the test group, versus 93?? 4%, 94?? 1%, 86?? 7%, and 87?? 3% in the control group ( P= 0?? 757、 0?? 478、 0?? 509、 0?? 413). The incidence rates and severity of leucopenia, neutropenia, and thrombocytopenia were significantly higher in the test group than in the control group ( P= 0?? 027 , 0?? 028 , 0?? 035 ) . The incidence rates and severity of hemoglobin reduction and nausea /vomiting were significantly lower in the test group than in the control group (P= 0?? 000,0?? 023). There were no significant differences in the incidence rates of mucositis and xerostomia between the two groups ( P=0?? 483,0?? 781). Conclusions The short?term efficacy of induction chemotherapy with nedaplatin and docetaxel plus concurrent IMRT with nedaplatin is similar to that with cisplatin in the treatment of locally advanced NPC. The mild gastrointestinal reactions can be tolerated by patients. However, the severe myelosuppression should be closely monitored during the treatment.

Background and objectiveLung cancer is the leading cause of cancer-related deaths worldwide, and metastasis is the major cause of death in lung cancer patients. MiR-373 is closely associated with invasion and metastasis in other tumor cells. hTis study explored the expression of miR-373-3p in non-small cell lung cancer (NSCLC) and its effect on the invasive and metastatic capabilities of lung adenocarcinoma cells, as well as their mechanisms of action.MethodshTe expression of miR-373-3p in NSCLC tissues and lung adenocarcinoma cell lines was detected by quantitative reverse transcrip-tion polymerase chain reaction. hTe roles of miR-373-3p in regulating lung adenocarcinoma cell invasion and metastatic prop-erties were analyzed with miR-373-3p mimic/inhibitor-transfected cells via Transwell chamber assay. Matrix metalloproteinase MMP-9 and MMP-14 protein levels were detected by Western blot in lung cancer cells atfer transfection.Results MiR-373-3p was upregulated in 51 NSCLC tissues and 5 NSCLC cell lines. Gain-of-function and loss-of-function studies showed that overexpression of miR-373-3p promoted H1299 cell migration and invasion, which resulted in upregulation of MMP-9 and MMP-14. By contrast, miR-373-3p knockdown inhibited these processes in A549 cells and downregulated the expression of MMP-9 and MMP-14.ConclusionOur results demonstrated that miR-373-3p participated in the invasion and metastasis of lung adenocarcinoma cells, partly by upregulation of MMP-9 and MMP-14.

Objective To explore the effect and underlying mechanism of Sarcandra glabra Nakai on radiation pneumonnopathy in miniature pigs irradiated with 60Co γ-rays.Methods Totally 60 miniature pigs were randomly divided into blank control group,irradiated group with 15 Gy of 60Co γ-rays,and intervention group administered with Sarcandra glabra Nakai at the dosage of 0.3 g/kg before 15 Gy irradiation.At 4,8,12 and 24 weeks post-irradiation,the respiratory rate and weight were observed,and a portion of the right lung tissue was taken out to conduct HE and Masson staining examination,while the expressions of TGF-β1 and TNF-α as well as the content of hydroxyproline (HP) were detected.Results The respiratory rate,the lung coefficient and the content of HP in the irradiated group showed an increasing trend at 4,8,12 and 24 weeks post-irradiation and significantly higher than those in other two groups (F =21.035,146.014,32.610,P ＜ 0.05).Those indicators were indistinguishable between the control group and intervention group at 4 and 8 weeks post-irradiation (F =0.055,2.456,5.581,P ＞ 0.05),while the indicators of the irradiation group were significantly higher than that of intervention group (F =91.897,93.149,83.487,P ＜0.05) at 12 and 24 weeks post-irradiation.The pulmonary histopathological results showed that no inflammatory response or fibrosis was found in the control group and intervention TGF-β1 and TNF-α in the intervention group were negatively expressed at 4 and 8 weeks post-irradiation and had low expressions at 12 and 24 weeks post-irradiation which was lower than that of the irradiated group.Conclusions Sarcandrae has protective effect against radiation-induced lung injury in miniature pigs probably by inhibiting the expressions of TNF-α and HP.