Relationship between nursing student's learning engagement and teacher's support in a medical school in Shaanxi Province: mediating role of professional identity / 中华医学教育探索杂志

Objective:To analyze the mediating effect of professional identity between teacher's support and student's learning engagement in nursing students.Methods:A total of 409 nursing students were enrolled in this cross-sectional study. Their professional identity, teacher's support, learning engagement were evaluated by Professional Identification Scale (PIS), Nursing Students' Perceptions of Instructor Caring (NSPIC), and Utrecht Work Engagement Scale-Student (UWES-S). A mediating model was proposed and the impacts of professional identity on teacher's support and learning engagement were observed.Results:The average score of NSPIC was (4.60±0.67) points, that of PIS was (3.58±0.63) points, and that of UWES-S was (4.79±0.97) points. The scores of NSPIC and PIS were a highly positive correlation ( r=0.504, P<0.001). The scores of NSPIC was positively correlated with the scores of UWES-S ( r=0.362, P<0.001). The scores of PIS was positively correlated with the scores of UWES-S ( r=0.315, P<0.001). Multiple linear regression analysis showed that learning engagement of nursing students was associated with the total score of PIS and supportive learning atmosphere, which accounted for 16.6% of the total variability. Professional identity had a mediating effect between teacher's support and learning engagement, with statistic significance among all coefficients of each path ( P<0.05), and all the fitting indexes were good. Teachers support had direct effect (0.31) on learning engagement and indirect effect (0.11) on learning engagement through professional identity. Conclusion:Teacher's support can directly predict student's learning engagement and professional identity plays an mediating role between them.

Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model / 中华消化外科杂志

Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.

Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases / 中华消化外科杂志

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy / 中国结合医学杂志

OBJECTIVE@#To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.@*METHODS@#In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.@*RESULTS@#Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.@*CONCLUSION@#Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Design, synthesis and evaluation of phenoxyacetic acid-based PTP1B inhibitors / 药学学报

Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.

Modulation of gut microbiota during alleviation of antibiotic-associated diarrhea with Zingiberis Rhizoma / 中国中药杂志

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.

Eosinophils predict short-term outcomes in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between eosinophil count and short-term outcomes of patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke treated in Fuyang People's Hospital from June 2017 to June 2019 were enrolled retrospectively. The demographic and baseline clinical data were collected. The modified Rankin Scale was used to evaluate the short-term clinical outcome at the time of discharge or 14 d after onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor short-term outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of eosinophil count for poor short-term outcome. Results:A total of 300 patients with acute ischemic stroke were enrolled, including 187 males (62.3%) and 113 females (37.7%); their age was 63.62±12.14 years; baseline National Institutes of Health Stroke Scale (NIHSS) score was 5.48±4.85. Two hundred and twenty-eight patients (76.0%) had a good outcome and 72 (24.0%) had a poor outcome. Univariate analysis showed that age, hypertension, baseline NIHSS score, C-reactive protein, atrial fibrillation, and neutrophil count of the poor outcome group were significantly higher than those of the good outcome group, while male, smoking, eosinophil count and percentage of eosinophils were significantly lower than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [ OR] 1.726, 95% confidence interval [ CI] 1.400-2.128; P<0.001), hypertension ( OR 3.744, 95% CI 1.227-11.426; P=0.020) and eosinophil count ( OR 0.287, 95% CI 0.102-0.616; P=0.043) were the independent influencing factors for the poor short-term outcome. ROC curve analysis showed that the area under the curve of eosinophil count for predicting the poor short-term outcome was 0.717 (95% CI 0.642-0.792), the best cutoff value was 0.075×10 9/L, and its sensitivity and specificity for predicting the poor short-term outcome were 88.6% and 51.4% respectively. Conclusion:The decreased eosinophil count had a certain predictive value for the poor short-term clinical outcome of patients with acute ischemic stroke.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Correlation between serum alkaline phosphatase level and early functional outcomes in young patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the correlation between serum alkaline phosphatase (ALP) level and early functional outcomes in young patients with acute ischemic stroke. Methods From January 2017 to December 2018, consecutive young patients (18-45 years old) with acute ischemic stroke admitted to the Department of Neurology, Fuyang People's Hospital were enrolled. According to the modified Rankin Scale score at discharge or on the 14th day of hospitalization (whichever occurs first), the patients were divided into poor outcome group ( > 2) and good outcome group (0-2). Multivariate logistic regression analysis was used to determine the independent correlation between the serum ALP level and outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline serum ALP level for poor outcomes. Results A total of 200 young patients with acute ischemic stroke were enrolled, and 138 (69. 0％) in the good outcome group and 62 (31. 0％) in the poor outcome group. Univariate analysis showed that the serum ALP level (87. 72 ±25. 60 U/L vs. 81. 70 ±22. 95 U/L; t = -4. 464, P < 0. 001) and baseline National Institutes of Health Stroke Scale (NIHSS) score (median and interquartile range: 9 [8- 12] vs. 2 [1-4]; Z = -10. 540, P < 0. 001) in the poor outcome group were significantly higher than those in the good outcome group. Multivariate logistic regression analysis showed that high serum ALP levels (odds ratio 1. 030, 95％ confidence interval 1. 001-1. 060; P = 0. 040) and high baseline NIHSS score (odds ratio 2. 387, 95％ confidence interval 1. 799-3. 142; P < 0. 001) were the independent risk factors for early poor outcomes. ROC curve analysis showed that the optimal cut-off value of the baseline serum ALP level predicting poor outcome was 86. 25 U/L, and its sensitivity and specificity were 53. 2％ and 79. 7％, respectively. Conclusions High serum ALP level is independently associated with poor early outcomes in young patients with acute ischemic stroke. Baseline serum ALP level has certain predictive value for poor outcomes.

Anti-inflammatory and immunomodulatory effects of Tripterygium wilfordii processed with licorice on mice model of ulcerative colitis / 中国中药杂志

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.

Therapeutic window analysis of Tripterygium wilfordii processed by liquorice: an instantiation using allergic contact dermatitis / 中国中药杂志

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.

Construction of engineered exosomes with high loading efficiency of cellular endogenous proteins / 生物工程学报

Exosomes have many advantages as natural drug delivery carriers, but their application is limited by the inefficient loading of intracellular drugs (such as proteins and nucleic acids). In this study, mCherry, a red fluorescent protein, was used as the endogenous cargo target. Through gene modification of donor cells and fusion expression of membrane localization elements (PB, CAAX, Palm and CD63), mCherry was specifically sorted into exosomes through biogenesis. Results show that CD63 had the highest sorting efficiency, followed by Palm. PB and CAAX led enrichment of mCherry on the plasma membrane, but not in exosomes. The approach provides an alternative to facilitate packaging of cargo by exosomes and thus to increase the efficient delivery of endogenous protein drugs.

Prevalence of severe fever with thrombocytopenia syndrome virus infection in Zhoushan island and duration of serum positive IgG antibody in infected patients / 中华临床感染病杂志

Objective@#To analyze the prevalence of severe fever with thrombocytopenia syndrome virus(SFTSV)infection in Zhoushan island of Zhejiang province and the duration of serum positive IgG antibody in patients infected with SFTSV.@*Methods@#One thousand one hundred and twenty-two healthy people from Zhoushan island of Zhejiang province were recruited for cross-sectional study in August 2019, including 641 from non-epidemic areas and 481 from epidemic areas. The serum SFTSV-IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA), and the positive rates of SFTSV-IgG antibody were compared between people from the epidemic areas and non epidemic areas. Meanwhile, the antibody titer of SFTSV-IgG in 19 patients confirmed between July 2011 and June 2018 was detected by indirect ELISA. SPSS 17.0 software was used to analyze data.@*Results@#The positive rate of SFTSV-IgG antibody was 1.5% (7/481) in the epidemic area, which was higher than that in the non-epidemic area (0/641) (χ2=7.187, P<0.01). The positive rates of SFTSV-IgG antibody in 2019 were lower than those in the epidemic area (11.7%) and non-epidemic area (2.5%) in 2013 (χ2=22.556 and 10.352, both P<0.01). The serum SFTSV-IgG antibody of 18 patients with previous infection was still positive, and the longest one lasted for 8 years.@*Conclusions@#There is a SFTSV latent infection in population from epidemic area of Zhoushan island. The SFTSV-IgG antibody can last for a long time in patients with SFTS and it may have certain protective effect.

Early and mid-term outcomes of aortic root enlargement with supraannular prostheses replacement for adult patients with aortic stenosis and small aortic root / 中华胸心血管外科杂志

Objective To summarize the short and mid-term outcome of adult patient suffered with aortic stenosis and small aortic root treated by aortic root enlargement with supraannular prostheses replacement or supraannular prostheses replace-ment.Methods From January 2005 to January 2017, 223 patients with aortic stenosis and small aortic root who underwent i-solated aortic valve replacement(AVR) were included in this retrospective study cohort.Patients with aortic insufficiency who underwent isolated AVR or those who underwent combined valve replacement were excluded from the study cohort .Aortic root enlargement with supraannular prostheses replacement was performed in 98 patients(ARE), and supraannular prostheses re-placement was performed in the remaining 125 patients as a control group(SP).The mean age and other baseline characteristics were compared between the two group, except that body surface area(BSA) in ARE were higher than that in SP[(1.62 ± 0.04)m2 vs(1.61 ±0.04)m2, P=0.015].Results Operative mortality occurred in 6 patients(2.7%), the cause of death including low cardiac output syndrome(LCOS, 3 patients), multiple organ failure(MOF, 2 patients) and stroke(1 patient). Reoperation for bleeding occurred in 5 patients and acute renal failure in 9 patients, pneumonia in 5 patients.The other nonfa-tal operative complications included wound complication(8 patients), temporary pacing therapy(24 patients), and new onset of acute mitral regurgitation(1 patient).The operative mortality and nonfatal complication were not statistically different be-tween the two groups.Patients in ARE received more bioprotheses and iEOA was higher than those in SP .Transvalvular pres-sure gradients and incidence of patient-prostheses mismatch were lower in ARE.At the 2 years of follow-up, transvalvular pres-sure gradients and left ventricular mass index were statistically lower in ARE compared with SP .The iEOA of ARE was higher than that in SP(1.22 ±0.13 vs 0.87 ±0.13, P<0.01).However, during the mid-term follow up(mean duration of follow-up was 6.31years), the overall survival rate was not statistically different between the two groups.Conclusion The strategy of aortic root enlargement with supraannular prostheses to treat adult patients with aortic stenosis and small aortic root can provide more optimal hemodynamic effect , effectively avoid PPM and was not associated with increased risk of mortality or adverse event when compared with strategy of supraannular prostheses replacement.However, the mid-term survival rate was not statistically different between the two strategies.

Study on the Effects of HMGB1-mediated Inflammatory Pathway on Liver Injury Induced by Tripterygium wilfordii / 中国药房

OBJECTIVE:To study the effects of high-mobility group box 1 protein(HMGB1) -mediated inflammatory pathway HMGB1-Toll like receptor 4 (TLR4) /nuclear transcription factor κ B(NF-κ B)on liver injury of rats induced by Tripterygium wilfordii,and to provide reference for clarify the mechanism of liver injury induced by T.wilfordii. METHODS:Totally 24 SD rats were randomly divided into blank group(normal saline,i. g. ),T. wilfordii group(16 g/kg by crude drug,i. g. )and neutralizer group(16 g/kg T. wilfordii crude drug i. g. after i. p injection of 100 mg/kg Ammonium glycyrrhizinate solution 3 h),with 8 rats in each group. All rats were treated for consecutive 3 weeks. The serum levels of AST and ALT in rats were detected every week. After the end of medication,the serum levels of HMGB1,IL-1β,IL-2 and TNF-α were detected by ELISA method;the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats were detected by Western blot assay. The pathological changes of liver tissue in rats were measured with HE staining method. RESULTS:After 3 weeks of treatment,the serum levels of AST, ALT,HMGB1,IL-1β,IL-2 and TNF-α in rats,the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats in T. wilfordii group were significantly higher than blank group and neutralizer group(P<0. 05 or P<0. 01). Hepatocyte edema was found around the central vein of the liver,and circular vacuoles were seen in some hepatic cytoplasm in T. wilfordii group;only varying size of vacuoles were found in a small number of cells in neutralizer group. CONCLUSIONS:T. wilfordii induced liver injury may be associated with the activation of HMGB1-TLR4/NF-κB inflammation pathway.

Benign ovarian cystic lesions: CT and MRI findings / 实用放射学杂志

Objective To study the CT and MRI features of benign ovarian cystic lesions (BOCL) and to improve the understanding of imaging features.Methods CT and MRI findings were retrospectively reviewed and analyzed in 48 patients with BOCL proved by surgical pathology.CT scan was performed in 35 cases, among which 20 cases were performed with CT enhancement scan;MRI scan was performed in 8 cases, among which 3 cases were performed with MRI enhancement scan and diffusion weighted imaging(DWI).Five cases were performed with both CT and MRI.Results There were 11 cysts (3 simple cysts, 3 corpus luteum cyst, and 5 endometriotic cyst), 10 serous cystadenomas with 13 lesions, 8 mucinous cystadenomas, 9 teratomas with 10 lesions, and 10 struma ovarii.The CT and MRI characteristics of the lesions in size, shape,thickness of cyst wall,wall nodule,density or signal intensity,and enhancement features were helpful in differential diagnosis of BOCL.Conclusion CT and MRI findings of BOCL have certain characteristics, which is significant in the diagnosis, preoperative evaluation and prognosis.

Study of metabolic pathway of Radix glycyrrhiza in decreasing liver toxicity of Tripterygium wilfordii / 药学学报

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

Idiosyncratic hepatotoxicity evaluation of Zhuangguguanjie wan mediated by immune stress / 药学学报

On basis of the idiosyncratic lipopolysaccharide(LPS)-mediated hepatotoxicity model, liver injury induced by Zhuangguguanjie wan(ZGW)was evaluated, and the mechanism was explored. Idiosyncratic hepatotoxicity model was established in rats by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into the normal control group, LPS group, ZGW group and LPS+ZGW group. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were analyzed in serum; pathological changes(HE staining)and the content of cytokines of liver were tested; and immune cell subpopulation ration were determined in blood and liver. Compared with the control group, the ZGW group and LPS group had no significant changes in ALT, AST and liver pathology(P> 0.05); while the ZGW+LPS group exhibited an elevation in ALT and AST(P< 0.05). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in the group. Several cytokines in the liver were increased in LPS group and ZGW+LPS group(P< 0.05 or P< 0.01), and the level in ZGW+LPS group was higher than that of LPS group. Compared with the control group, the ratio of CD3+ T cell/lymphocyte of blood in LPS group was significantly decreased(P< 0.01); while the percentage of CD3+ T cells in the liver were significantly increased(P< 0.05). The contents of immune cells of blood had no significant changes between LPS group and ZGW+LPS group(P> 0.05). CD3+ T cell in the liver of ZGW+LPS group was significantly increased over the LPS group(P< 0.05). Aggregation or activity of CD3+ T cell was increased by ZGW combined with LPS. These results suggest that ZGW could promote T lymphocyte recruitment to liver under the immune activation state leading to inflammatory response, which may contribute to idiosyncratic liver injury.