Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.

BackgroundDomestic researches on the professional identity of psychiatrists are still relatively rare up to now， and effective evaluation tools remain inadequate. ObjectiveTo construct a professional identity questionnaire for psychiatrists with high reliability and validity， so as to provide an effective tool for the evaluation of professional identity of psychiatrists. MethodsA self-designed questionnaire titled "Professional Identity Questionnaire" was compiled. After preliminary screening of items and expert consultation， an initial questionnaire was formed and administered to a sample of 400 psychiatrists， and the final questionnaire was assessed by item analysis， reliability analysis and validity analysis. ResultsThe Cronbach's α coefficient was 0.930 for the final questionnaire， and ranged from 0.817 to 0.920 for each dimension. The value of KMO was 0.904 （χ²=2 931.652， P<0.01）. The cumulative variance contribution rate of factors extracted from exploratory factor analysis was 68.306%. Confirmatory factor analysis showed that the integrity of fit indexes were χ²/df=1.234， GFI=0.905， NFI=0.916， RMSEA=0.036， CFI=0.983， IFI=0.983. The final version of the professional identity questionnaire for psychiatrists consisted of 23 items relating to 4 dimensions， namely， professional cognition， professional behavior， professional emotion and professional values. ConclusionThe professional identity questionnaire for psychiatrists has good reliability and validity， and can be used as an effective tool to evaluate the professional identity of psychiatrists. ［Funded by Foundation of Sichuan Research Center of Applied Psychology of Chengdu Medical College （number， CSXL-22304）； Science and Technology Guiding Plan Project of Guangyuan City （number， 22ZDYF0072）］

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To investigate the efficacy of endoscopic histoacryl injection in cirrhotic patients with newly-developed esophagogastric varices (EGV) who have previously undergone splenectomy combined with pericardial devascularization.Methods:From January 2015 to January 2020, 125 cirrhotic patients with EGV treated with endoscopic histoacryl injection at the Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, were included in the retrospective analysis. There were 45 patients in the group of splenectomy combined with pericardial devascularization (splenectomy group for short) and 80 patients in the non-splenectomy group. The efficacy of endoscopic treatment, postoperative variceal improvement, rebleeding rate, and complications were analyzed between the two groups.Results:Endoscopic histoacryl injection was successfully completed in all 125 patients, and the median volume of histoacryl was 4.5 mL. The overall effective rate in splenectomy and non-splenectomy group was 80.0% (36/45) and 57.5% (46/80), respectively. The difference in the number of significantly effective, effective, and ineffective cases between the two groups was statistically significant (16, 20, 9 cases, and 20, 26, 34 cases, respectively, χ 2=6.469, P=0.039). Two and 14 patients developed rebleeding in the splenectomy group and non-splenectomy group, respectively; and the difference in the rebleeding rate between the two groups was statistically significant (4.4% VS 17.5%, Log-rank P=0.039). No patient died within 1 year in either group, and no serious complications such as ectopic embolism occurred. Conclusion:After splenectomy combined with pericardial devascularization in cirrhotic patients with EGV and hypersplenism, the application of histoacryl has better short-term efficacy and can significantly reduce the rebleeding rate compared with the non-splenectomy group.

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.

AIM:Observation of neuroprotective effects of Toddalia asiatica(TA)on cerebral ischemia-reper-fusion injury(CIRI)in rats by investigating the effects and mechanisms of drugs on the polarization of microglia M1/M2 subtype and the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)path-way.METHODS:The modified thread occlusion method was used to establish a rat model of CIRI,and the rats were ran-domly divided into the model group,Toddalia asiatica(1.08 g/kg)group,donepezil hydrochloride(0.45 mg/kg)group,and sham group,with 16 rats in each group.Based on the assessment of neurofunctional changes in each group of rats,HE and Nissl staining were used to observe the pathological changes in brain tissue.TUNEL staining was performed to de-tect neuronal apoptosis,immunohistochemistry was used to detect the expression of M1 microglia marker ionized calcium-binding adapter molecule 1(Iba1),M2 microglia marker arginase 1(Arg1),and TLR4 localization.Western blot was used to detect the expression of microglia polarization proteins and proteins related to TLR4/MyD88/NF-κB pathway in the hippocampus region.RESULTS:Compared with sham group,the model group rats had higher neurological function scores(P＜0.01),and neuronal arrangement in the hippocampus and cortex was loose and disordered,Nissl bodies de-creased,and neuronal apoptosis increased.The numbers of M1 microglia marker Iba1-,M2 microglia marker Arg1-,and TLR4-positive cells were significantly increased.In addition,the protein levels of TLR4,MyD88,p-NF-κB p65,NF-κB p65,p-NF-κB inhibitory factor(p-IκB),Iba1,interleukin-6(IL-6),and Arg1 in the hippocampus were elevated(P＜0.05),while IL-4 and IL-10 expression were decreased(P＜0.01).Compared with model group,the Toddalia asiatica group and Donepezil hydrochloride group showed increased protein expression of Arg1,IL-4 and IL-10(P＜0.05),while the other indicators were decreased(P＜0.05,P＜0.01).CONCLUSION:Toddalia asiatica possesses neuroprotective effects on CIRI rats,which may be attributed to its ability to regulate M1/M2 polarization and inhibit the TLR4/MyD88/NF-κB-mediated inflammatory pathway.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

Objective:To investigate the effects of mitochondrial arginyl-tRNA synthase (RARS2) on cell proliferation, invasion, migration and chemotherapy resistance of pancreatic cancer.Methods:Human pancreatic cancer cell lines AsPC-1 and PANC-1 were divided into negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group. Cell proliferation and sensitivity to gemcitabine were detected by CCK-8 assay, and cell invasion and migration were detected by Transwell assay. Western blot was used to detect the expression of RARS2 under different concentrations and different times of gemcitabine treatment. Western blot and PCR were used to detect the expression of RARS2 in gemcitabine-resistant AsPC cell.Results:Inhibition of RARS2 expression in AsPC-1 and PANC-1 cells significantly inhibited cell proliferation and enhanced sensitivity of gemcitabine to chemotherapy. Overexpression of RARS2 enhanced cell proliferation and decreased sensitivity to gemcitabine. In AsPC-1 cells, the number of migrated cells (100×) in negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group were (586.7±37.4) cells/field, (195.7±18.6) cells/field, (237.0±17.1) cells/field, (157.7±19.1) cells/field, (456.0±23.1) cells/field, the number of invasive cells were (87.7±13.2) cells/field, (24.7±6.5) cells/field, (31.7±6.1) cells/field, (29.3±4.5) cells/field, (94.3±9.3) cells/field, respectively. The migration and invasion ability of cells were decreased after the expression of RARS2 was decreased, and the migration and invasion ability of cells were enhanced after the expression of RARS2 was increased. PCR and Western blot assay showed that RARS2 expression in the gemcitabine-resistant AsPC-1 was higher than that in the common cell line. In AsPC-1 cells, the expression of RARS2 increased with increasing gemcitabine concentration and treatment time.Conclusion:RARS2 promotes cell proliferation, invasion, migration and chemoresistance of pancreatic cancer, and expression of RARS2 is positively correlated with gemcitabine concentration and treatment time.

The high performance liquid chromatography (HPLC) and enzyme-linked immunoassay (ELISA) were used to investigate the changes of collagen and matrix metalloproteinase-1 (MMP-1) in liver, lung and kidney during growth process of mice. The mice from 0 to 18 weeks were used as the research objects. The contents and proportions of hydroxyproline (Hyp), which were used to calculate the collagen contents, in liver, lung and kidney of different weeks were analyzed with HPLC. The contents and activity of MMP-1 in liver, lung and kidney of different weeks were analyzed with ELISA. The results showed that the collagen contents in liver, lung, and kidney were different (Lung(COL)>Kidney(COL)>Liver(COL)), and they all increased first and then decreased with weeks. The collagen contents in liver, lung, and kidney reached the highest level in the ninth (5.52 ng/mg), sixth (54.10 ng/mg) and ninth (19.20 ng/mg) week, respectively. Then it declined slowly from 9 to 18 weeks. The result of ELISA showed that the MMP-1 contents in liver, lung and kidney decreased first and then increased with weeks, and the trend of MMP-1 activity was opposite. It indicated that the increase of collagen contents in the tissues will inhibit the secretion of MMP-1.
Animals ; Collagen ; Kidney ; Liver ; Lung ; Matrix Metalloproteinase 1 ; Matrix Metalloproteinase 2 ; Mice