Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To explore the effect of quality management circulation (plan-do-check-act, PDCA) mode combined with clinical pathway nursing on leakage rate and nursing satisfaction in patients with ascites due to cirrhosis.Methods:A total of 418 patients with cirrhotic ascites in hospital infectious department were selected and divided into control group and 209 patients in study group according to random digital table method. The leakage rate, quality of life score and total nursing satisfaction were compared between the two groups.Results:The local leakage rates were 17.22% (36/209), 14.83% (31/209), 12.92% (27/209), 8.61% (18/209), respectively, at 24 hours, 48 hours, 72 hours and 1 week after abdominal tube placement. The control group was 22.01% (46/209), 20.10% (42/209), 23.92% (50/209), 25.84% (54/209). The difference between 72 hours and 1 week was statistically significant ( χ2 values were 8.421, 1.746, P<0.01). Quality of life scores were (3.15±1.15), (1.25±1.10), (1.15±1.08), (2.40±1.45), (2.35±1.50) in the study group and (3.75±1.05), (3.25±1.05), (3.60±1.25), (4.35±1.25), (3.15±1.25) in the control group, and the difference was statistically significant ( t values were 5.570-21.441, P<0.05). The total satisfaction of the study group was 96.65% (202/209), which was significantly higher than that of the control group 85.65% (179/209), and the difference was statistically significant ( χ2 value was 15.686, P<0.01). Conclusion:PDCA mode combined with clinical pathway nursing can reduce the leakage rate of abdominal administration, improve the quality of life score and nursing satisfaction, and improve the quality of nursing, which is a safe and effective nursing mode.

In recent years, more and more people have recognized the importance of patients' family in the intensive care unit (ICU) in medical care, and advocated the use of patient- and family-centered care (PFCC) in the ICU. This article explains the content (family presence, family support, communication with family members, consultations and ICU team members, environmental issues) and significance of PFCC in the ICU, and provides guidance for the practice of PFCC in China.

Objective To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation. Methods The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve. Results A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiO2) was 0.50 (0.40, 0.60). Eighteen patients experienced HFNC failure (18.2%). Compared with the HFNC success group, the sequential organ failure assessment (SOFA) score in the HFNC failure group was higher [4 (3, 5) vs. 2 (1, 3), P < 0.01], B type natriuretic peptide (BNP) before HFNC therapy were significant higher [ng/L: 647.2 (399.2, 1 331.3) vs. 127.2 (55.2, 369.5), P < 0.01], and respiratory frequency (RR) and heart rate (HR) were significant faster, mean arterial pressure (MAP) was significant higher, oxygen index (PaO2/FiO2) was significant lower after 30 minutes HFNC treatment [RR (times/min): 26 (22, 28) vs. 19 (17, 21), HR (bpm): 105 (97, 107) vs. 85 (77, 90), MAP (mmHg, 1 mmHg = 0.133 kPa): 104.3 (101.7, 110.7) vs. 92.3 (88.3, 97.7), PaO2/FiO2 (mmHg): 207.3 (185.8, 402.8) vs. 320.2 (226.2, 361.5), all P < 0.05]. It was shown by multiple Logistic regression analysis that the SOFA score [odds ratio (OR) = 2.818, P = 0.022, β = 1.036], BNP before HFNC treatment (OR = 1.002, P = 0.033, β = 0.002) and HR after HFNC treatment 30 minutes (OR = 1.140, P = 0.032, β = 0.131) were independent risk factors for HFNC treatment failure. It was shown by ROC curve that the area under the ROC curve (AUC) for the prediction of HFNC failure was 0.840, 0.859, 0.860 and 0.962 for SOFA, BNP before HFNC treatment, HR after HFNC treatment 30 minutes, and regression model, all had good forecast values (all P < 0.01). Conclusions HFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.

Objective: To investigate the Effects of entinostat on the expression of NKG2D ligands in the non-small cell lung cancer (NSCLC) cell lines, A549 and HCC-827, and to detect the effect of entinostat-mediated NK cell killing of A549 and HCC-827 cells. Meth-ods: The effect of entinostat on A549 and HCC-827 cell proliferation was measured by MTT assay. Flow cytometry was used to detect the expression of NKG2D ligands. mRNA levels of the ligands were detected by RT-PCR . The level of soluble MICA in cell culture super-natant was evaluated by ELISA. The cytotoxicity of NK cells against A549 and HCC-827 cell lines (treated with entinostat) was assessed using lactate dehydrogenase release assay. Results: Entinostat showed a time-and dose-dependent inhibition effect on the prolifera-tion of A549 and HCC-827 cell lines. The expression of NKG2D ligands and mRNA transcription levels of MICA and MICB were en-hanced after treatment with 0.5, 1μmol/L entinostat for 48 h. The soluble MICA level in A549 cell culture supernatant was increased by 1μmol/L entinostat. The sensitivity of HCC-827 cells to NK cells was enhanced upon treatment with 0.5, 1μmol/L entinostat. Con-clusions: entinostat enhanced the killing effect of NK cells on non-small cell lung cancer cells by up-regulating the expression of NKG2D ligands. This provides a new method and theory for the treatment of NSCLC.

With the emergence and globally spread of drug-resistant bacteria, the discovery and development of new antibacterial drugs is imminent. The symbiotic bacteria distributed in different parts of the body can produce a variety of antibacterial molecules to inhibit the colonization and infection of pathogenic bacteria. Human symbiotic bacteria provide a potential treasure house of resource for the research and development of new drugs with broad new molecular structures and action mechanism. With the further development of bioinformatics tools, synthetic biology and omics technology such as genomics, the mining of human symbiotic bacteria antibacterial molecules will be more in-depth and provide an effective way to solve the problem of drug resistance. Here, we review the antimicrobial molecules produced by human symbiotic bacteria and introduce several methods to explore the resources of natural antibacterial drugs. With the development of modern biotechnology, the antimicrobial molecules of human symbiotic bacteria will be more comprehensively and systematically explored and applied.

Objective: To analyze the causes of preoperative miscarriage of pancreatic serous cystadenoma (SCN) and find the ways to improve it. Methods: Clinical data of 425 pancreatic cystic neoplasm patients who underwent surgical resection from January 2006 to December 2016 in Department of Pancreatic Surgery in Huashan Hospital were retrospectively analyzed.Excel database was created which covered 128 fields of 7 fields: general information of patients, preoperative blood biochemical indexes, tumor markers, surgical related data, postoperative complications, imaging findings and pathology.One hundred and sixty-one cases of SCN were analyzed in depth, mainly in three aspects: surgical benefit, preoperative imaging diagnostic value and interference factors in preoperative judgement.The classification data were analyzed by χ² test and the quantitative data were analyzed by t test.The Logistic regression model was used for multiple factor analysis. Results: Of the 425 PCN cases surgically removed, 161 cases (37.9%) were SCN, the incidence of operative complications was 40.4%(65/161), the hospitalization days was (20.7±12.1)days and the medical cost was (75 267±37 866) yuan.Only 3 of 161 cases of SCN were accurately diagnosed by preoperative imaging methods, 61 cases were diagnosed as "cystic lesions of pancreas" (37.9%) and 52 cases were diagnosed as "pancreatic cystadenoma" (32.3%). SCN was misdiagnosed as MCN(32.3%) and IPMN(28%) before operation.25.5% of them were diagnosed as SCN before operation, but still underwent radical operation.The rate of preoperative imaging diagnosis for identifying SCN was 62.8%.The lack of preoperative endoscopy and the lack of understanding of the image characteristics and biological behavior of SCN were the most important factors affecting the accuracy of preoperative judgment.Statistics found that gender, age, CA125 and tumor location can be used as independent factors contribute to the clinical identification(χ²=8.995, P=0.003; χ²=10.019, P=0.007; t=3.157, P=0.002; χ²=6.790, P=0.009). Logistic analysis showed that women, older than 60 years old, the tumors located in the pancreatic body and tail were the independent factors of SCN classification and diagnosis (OR=0.481, 0.376, 0.577, 0.666, 95% CI: 0.305-0.759, 0.199-0.710, 0.361-0.924, 0.433-1.024, P=0.002, 0.003, 0.022, 0.064). Conclusions SCN has more benign biological behavior.Although surgical excision is acceptable for clinical safety, the corresponding benefit is very limited.It is possible to improve the rationality of SCN clinical operation decisions to some extent by performing endoscopic examination, imaging doctors to improve the SCN feature recognition and surgeons to enhance the awareness of SCN.

Objective: To explore the relationship between longitudinal trajectory of systolic blood pressure (SPB) and atrial fibrillation (AF) in Kailuan group population. Methods: Our study cohort consisted of 40727 participants with the specific criteria in Kailuan group, Tangshan. SAS Proc Traj procedure was used to identify longitudinal trajectories of SPB throughout 2006-2007, 2008-2009 and 2010-2011. There were 5 longitudinal trajectories generated: Low-stable group,n=10950, Moderate-stable group, n=19158, Moderate-high stable group,n=3713, High-moderate stable group,n=4702 and High stable group,n=2181. Log-rank test was performed to compare AF incidence throughout 2012-2013 and 2014-2015 by physical examination among different groups; Multi Cox regression analysis was conducted to study the relationship among different SBP longitudinal trajectories and AF occurrence. Results:①The mean age of participants was (51.81±11.54) years including 30693 (75.4%) male.②AF occurrence rates in Low-stable, Moderate-stable, Moderate-high stable, High-moderate stable and High stable groups were 0.1%, 0.2%, 0.5%, 0.5% and 0.6% respectively, allP<0.05.③Multi Cox regression analysis presented that with adjusted confounding factors, compared with the patients in Low-stable group, Moderate-high stable, High-moderate stable and High stable SBP longitudinal trajectories were the risk factors for new AF occurrence (HR=7.58, 95% CI 2.08-27.73), (HR=5.30, 95% CI 1.88-14.95) and (HR=8.52, 95% CI 1.96-37.09) respectively, allP<0.05. With excluded history of myocardial infarction/stroke, the sensitivity study showed the similar result with the major research trend. Conclusion: Elevated long trajectory of SPB was the risk factor for new AF occurrence in Kailuan group population.