As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

BackgroundSuicidal behavior in adolescence and early adulthood is a major public health concern， and suicide attempts are found to be associated with reasons for living and self-control， whereas there remains a striking lack of empirical research exploring the association among the three in college students. ObjectiveTo explore the relationship among suicide attempts， reasons for living and self-control， and to inform targeted efforts to prevent the development of suicidal behavior. MethodsFrom April to May 2023， a sample of 775 college students from 10 colleges and universities in Shaanxi province， Sichuan province and Chongqing municipality were selected using random sampling method. All students were subjected to complete Self-Control Scale （SCS）， the Reasons for Living Inventory for Adolescents （RFL-A）， and the self-administered Suicide Attempt Questionnaire. Spearman correlation analysis was utilized to examine the correlation among the above scales in students， and mediation analysis was performed using Mplus 8.3. ResultsA total of 738 college students （95.32%） completed the effective questionnaire survey.Suicide attempts were detected in 99 college students （13.41%）. SCS score was positively correlated with RFL-A score （r=0.329， P<0.01）， and SCS score and RFL-A score were both negatively correlated with the risk of suicide attempts （r=-0.194， -0.285， P<0.01）. The indirect mediation effect value of self-control on the relationship between reasons for living and suicide attempts was -0.059 （95% CI： -0.105~-0.018）， accounting for 11.07% of the total effect. There was a gender difference in the mediating effect of self-control， among which the effect was significant in male group， with an indirect effect value of -0.089 （95% CI： -0.163~-0.030） and accounting for 15.72% of the total effect， whereas the mediating effect was not significant in female group （95% CI： -0.407~0.115）. ConclusionReasons for living can negatively predict suicide attempts among college students， and self-control may play a mediating role in the relationship between reasons for living and suicide attempts among college students， and the mediating effect of self-control appears to be statistically significant only in male but not in female students.

Objective: To investigate the correlation between takeaway food consumption and poor sleep status of college students in Jiangxi Province, to provide a theoretical basis for poor sleep prevention and intervention among college students. Methods: A total of 2 610 college students were selected from a university in Shangrao City, Jiangxi Province by cluster stratified random sampling in May of 2018. The frequency and type of takeaway food consumption, sleep quality and drowsiness were investigated. Results: The detection rate of takeaway food consumption behavior(≥4 times in a week) for college students was 74.8%. The detection rates of poor sleep quality and drowsiness were 17.0% and 18.3%, respectively. The difference of sleep quality was statistically significant with sex, college, different self rated family conditions, study burden, physical activity level, depression and daily smoking ( χ 2=4.33，8.67，23.14，39.03，12.89，313.37，15.23， P <0.05). There were statistically significant differences between drowsiness and college, grade, learning burden, physical activity and depression ( χ 2=12.81，6.57，20.61，8.42，228.06， P <0.05). Logistic regression analysis showed that takeaway consumption (≥4 times in a week) had statistical significance with poor sleep quality and drowsiness ( P <0.05). Conclusion College students takeaway consumption (≥4 times in a week) of rice noodles, malatang, fragrant pot hot pot increase the risk of poor sleep. It is suggested that schools should strengthen nutrition and health education for college students.

Objective: To explore the turnover intention of nurses in Quzhou and its influential factors. Methods: From July to August in 2017 cross-sectional study and self-filled questionnaire are used to investigate 980 nurses from 7 hospitals in Quzhou, including two third-level hospitals and five second-level ones. T-test, F-test, Pearson and linear regression are used in data with the method of statistical analysis. Results: The total score of turnover intention of nurses was (14.95±3.17) points, and the index value was 62.27%, of which the turnover intention was above 78%. The analysis of Single factor showed that age (F=4.895) , Department (F=2.971) , title, nursing age (F=5.863) , self-assessment of physical conditions (F=4.092) were closely related to nurses’ turnover intention(P<0.05). According to Person’s correlation analysis, there are positive correlations between turnover intention and source of stressor, and moral distress (P<0.05) . Multiple linear regression showed that the nurses’ turnover intention was age, Department, health selfevaluation, stressor and moral distress. Conclusion The turnover intention of nurses is high, which is related to age, Department, self-evaluation of health, stressor and moral distress.

Objective To investigate the role of exhaled nitric oxide (FeNO) detection in patients with bron-chial asthma,and to observe the correlation between FeNO level and pulmonary function .Methods The clinical data of 61 patients with acute exacerbation of bronchial asthma were retrospectively analyzed .The patients were included in the case group .According to the disease condition ,the patients were divided into mild asthma group ( 30 cases ) and moderate asthma group (31 cases).A total of 60 healthy people were selected as the control group .All the patients were given corresponding symptomatic treatment ,before and after treatment ,the FeNO and lung function were deter-mined in two groups.Results After treatment,the level of FeNO in the mild asthma group was (22.22 ±8.39)ppb, which was significantly lower than (35.21 ±10.84)ppb in the moderate asthma group (t=5.22,P=0.00).The levels of FEV1 and PEF in the mild asthma group were (2.49 ±0.38)%,(3.82 ±0.24)L/min,respectively,which in the moderate asthma group were (2.52 ±0.41)%,(3.74 ±0.35)L/min,respectively,the differences between the two groups were not statistically significant (t=0.29,1.03,P=0.76,0.30).The FeNO levels of the two groups after treatment were significantly lower than those before treatment ,and the FEV1 ,PEF levels were significantly higher than those before treatment (all P<0.05).Before treatment,the levels of FeNO,FEV1 and PEF in the case group were(50.41 ±30.09) ppb,(1.98 ±0.37)%,(3.24 ±0.36) L/min,respectively,which in the control group were (12.59 ±6.39)ppb,(2.79 ±0.34)%,(4.02 ±0.18)L/min,respectively,the differences were statistically signifi-cant between the two groups (t=9.52,12.53,15.03,P=0.00,0.00,0.00).After treatment,the levels of FeNO, FEV1 and PEF in the case group were (23.52 ±10.54)ppb,(2.81 ±0.35)%,(3.91 ±0.40)L/min,respectively, which in the control group were (12.59 ±6.39)ppb,(2.79 ±0.34)%,(4.02 ±0.18)L/min,respectively,the difference of FeNO between the two groups was statistically significant (t=6.88,P=0.00),the differences of FEV1 and PEF were not statistically significant between the two groups (t=0.31,1.94,P=0.75,0.05).The difference of FeNO between males and females was not statistically significant (P >0.05).There was a negative correlation between FeNO and FEV1 before treatment(r=-0.172,P=0.02),and FeNO negatively correlated with FEV (r=-0.163,P=0.01).There was no correlation between FeNO and FEV 1 after treatment(r=-0.031,P=0.754), independent of FEV(r=-0.141,P=0.09).Conclusion The level of FeNO is helpful to evaluate the severity of airway inflammation and lung function in bronchial asthma patients , and it is not related to sex .FeNO level is negatively correlated with pulmonary function ,and is helpful to evaluate the clinical efficacy .

OBJECTIVE: To investigate the therapeutic effect of nasal continuous positive airways pressure (nCPAP) combined with antireflux medicine on obstructive sleep apnea hypopnea syndrome (OSAHS) with gastroesophageal reflux (GER). METHOD: Sixty patients with moderate to severe OSAHS with GER were simultaneously received PSG and esophageal pH monitoring and randomly divided into control group and treatment group with each group 30 patients. The control group were simply received nCPAP for every night. The treatment group were received the same treatment and combined antireflux medicine, with esomeprazole 40 mg/d and mosapride citrate 5 mg, 3 times a day,oral. Both the groups symptomatic status of OSAHS and GER were observed on the third day and the 14th day during therapy, and then the same tests above were repeated on the 14th day. RESULT: Compared with the control group, the symptomatic improvement rate of OSAHS on the third day and 14th day during therapy,the symptomatic improvement rate of GER on the third day during therapy were increased with statistical significance in the treatment group (P<0.05), however, the difference of symptomatic improvement rate of GER between the two groups on the 14th day during therapy did not have statistical significance (P>0.05). Compared with those of the control group on the 14th therapeutic night, AHI, LSaO2, the percentage of time with pH<4, the longest reflux duration,reflux episodes and DeMeester scoring did not have statistical significance in the treatment group (P>0.05). CONCLUSION nCPAP is the most effective method for patients suffering OSAHS associated with GER, but nCPAP used in conjunction with anti-reflux drugs do not improve efficacy.
Adult ; Continuous Positive Airway Pressure ; Female ; Gastroesophageal Reflux ; complications ; therapy ; Gastrointestinal Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; complications ; therapy

It has been demonstrated that the activated protein C (APC) plays an important role in the inhibition of inflammation. The activation of protein C can be significantly enhanced by the endothelial cell protein C receptor (EPCR). Previous studies proposed that the APC regulates the inflammatory response in endothelial cells by suppressing the expression of adhesion molecules and the secretion of chemokines and cytokines. However, the precise mechanism of the inhibitory effect of APC on inflammation is still poorly understood. In the present study, we evaluated the anti-inflammatory effect of recombinant human APC (rhAPC) and whether its inhibitory effect is conducted through the EPCR-dependent mechanism on human umbilical vein endothelial cells (HUVECs). By exposing HUVECs to: (1) TNF-alpha; (2) rhAPC plus TNF-alpha; (3) anti EPCR antibody that prevents rhAPC interaction with EPCR; (4) TNF-alpha plus anti EPCR antibody; (5) rhAPC plus TNF-alpha in the presence of anti EPCR antibody, we found that APC was able to significantly inhibit the TNF-alpha-induced secretion of cytokines such as IL-1beta and IL-8, as well as the expression of adhesion molecules such as ICAM-1, VCAM-1 and E-selction in HUVECs. These results reveal a novel pathway by which APC protects endothelial cells from inflammatory mediators through an EPCR-dependent mechanism.
Antigens, CD ; metabolism ; Cells, Cultured ; Cytokines ; metabolism ; Endothelial Protein C Receptor ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Inflammation ; metabolism ; Protein C ; pharmacology ; Receptors, Cell Surface ; metabolism ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

The role of PACAP (pituitary adenylate cyclase activating polypeptide), a peptidergic transmitter, in the pathogenesis of acute pancreatitis is not yet clear. This experiment was conducted to examine the action of exogenous PACAP on rat pancreas and on the course of experimental acute pancreatitis. The results showed that 5-30 microg/kg of PACAP slightly raised the serum amylase level, induced pancreatic edema (23.88% +/- 2.532%-25.86% +/- 1.974% of experiment groups versus 29.21% +/- 5.657% of control group), inflammatory cell infiltration, vacuolization of acinar cells, and occasionally fatty and parenchymal necroses. 15-30 microg/kg of PACAP aggravated cerulein-induced acute pancreatitis; the pancreatic edema became more marked (13.45% +/- 2.045%-17.66% +/- 4.652% of expreiment groups versus 21.83% +/- 3.013% of cerulein group, P<0.05), the serum amylase level became higher; and ascites, pancreatic bleeding, fatty and parenchymal necroses, and extensive vacuolization of acinar cells appeared. For sodium taurocholate-induced pancreatitis, 5-10 microg/kg of PACAP mildly attenuated the pancreatic edema, reduced the serum amylase level (1986.91 +/- 710.97-2944.33 +/- 1182.47 IU/L vs 3690.87 +/- 2277.99 IU/L, P<0.05), whereas it caused multifocal hemorrhage and prominent necrosis in pancreas. Except the cerulein-induced pancreatitis groups, other groups were found to have reduced pancreatic functional capillary density (FCD); when pancreatic edema was taken into consideration and calibrated FCD was introduced (FCD weighted against pancreatic wet/dry ratio), all groups revealed increases in pancreatic functional capillaries when compared with normal control. In conclusion, PACAP is proinflammatory in the pathogenesis of acute pancreatitis, PACAP plus cerulein can induce acute hemorrhagic/necrotizing pancreatitis, and the action of PACAP on cerulein-induced panceatitis may differ from that on sodium taurocholate-induced one. In this experiment, pancreatic FCD was underestimated due to pancreatic edema.
Amylases ; blood ; Animals ; Capillaries ; pathology ; Ceruletide ; Disease Models, Animal ; Male ; Pancreas ; blood supply ; Pancreatitis, Acute Necrotizing ; chemically induced ; enzymology ; pathology ; Rats ; Rats, Wistar

The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-kappaB and mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-kappaB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1 (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-kappaB activation and reduction of adhesion molecules expression.
Adult ; Anti-Inflammatory Agents ; therapeutic use ; Colitis, Ulcerative ; drug therapy ; metabolism ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; biosynthesis ; genetics ; Intestinal Mucosa ; metabolism ; Male ; NF-kappa B ; metabolism ; Prednisone ; therapeutic use ; RNA, Messenger ; biosynthesis ; genetics ; Sulfasalazine ; therapeutic use ; Vascular Cell Adhesion Molecule-1 ; biosynthesis ; genetics

To investigate the antitumor effect of herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system on human bladder cancer cells (T24), a retroviral vector with the gene (pLXSN-TK) was transduced into the packaging cell line PA317. A nude mouse model with human T24 was established to examine the in vivo efficacy. The animals were randomly assigned to two treatment groups and two control groups. Treatment I and Treatment II were given in situ injection of virus suspension and PA317/TK respectively, followed by treatment with GCV for 14 days. Control I and Control II were given in situ injection of same volume of normal saline and PA317/TK respectively, followed by treatment with GCV and with normaly physiologic saline respectively for 14 days. The weight and the volume of tumor were measured. HSV-TK mRNA expression was determined by hybridization in situ. Cell apoptosis was evaluated by flow cytometry (FCM) and termininal deoxynucleofidyl transferase-mediated dUTP nick end labelling (TUNEL) technique. The results showed: (1) In vivo, the retrovirus transferred HSV-TK gene can be transduced into human bladder cancer cell T24. The tumors in T24 mice with TK gene transduced were much smaller than those in other groups. (2) After treatment with HSV-TK/GCV, the phenomenon of bladder ceancer cell apoptosis was more conspicuous as compared with that of other groups. Therefore, HSV-TK/GCV system can suppress the growth of T24 in vivo and may relate to "bystander effect". It could be a valuable therapy for human bladder cancer.
Animals ; Antiviral Agents ; therapeutic use ; Ganciclovir ; therapeutic use ; Gene Transfer Techniques ; Genetic Therapy ; Herpesvirus 1, Human ; enzymology ; genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Thymidine Kinase ; genetics ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms ; genetics ; pathology ; therapy