ObjectiveTo investigate the expression of scaffold protein PDLIM5 in multiple sclerosis （MS） patients and the mouse microglial cell line BV2， and to explore its effects on the phagocytosis of microglial cells. MethodsPeripheral blood samples were collected from 24 MS patients and 6 healthy volunteers as controls. The expression levels of PDLIM5 were detected by real-time quantitative PCR. A neuroinflammation cell model was established by treating the mouse microglial cell line BV2 with lipopolysaccharide （LPS， 1 µg/mL）. The expression levels of PDLIM5 were measured by Western Blot. The effect of PDLIM5 expression on phagocytosis was analyzed by transfecting BV2 cells with PDLIM5 shRNA plasmids or PDLIM5 overexpression plasmids. ResultsReal-time quantitative PCR results showed that compared with the healthy control group， the expression level of PDLIM5 from the MS patients was significantly increased in monocytes ［2.78 （0.70-6.86） vs. 0.54 （0.39-1.51）， P=0.036］ and lymphocytes ［1.62 （0.90-2.26） vs. 0.11 （0.05-0.21）， P<0.001］. Western Blot results indicated that PDLIM5 expression was significantly upregulated in BV2 cells following LPS stimulation （P<0.05）. Plasmid transfection experiments demonstrated that knockdown of PDLIM5 inhibited the phagocytic capacity of BV2 cells as measured by trypan blue uptake （P<0.05）， while overexpression of PDLIM5 enhanced the phagocytic ability of BV2 cells （P<0.001）. ConclusionUnder neuroinflammatory conditions， PDLIM5 expression is elevated， and this upregulation promotes the phagocytosis of microglial cell.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) genotype of Yersinia pestis and its regional distribution characteristics in natural plague focus of Tibet Autonomous Region. Methods:A total of 125 representative Yersinia pestis strains isolated from natural plague focus in Tibet Autonomous Region at different times, regions, hosts and vectors were selected as experimental strains, and the phenol chloroform mixed extraction method was used to extract Yersinia pestis DNA. Three pairs of CRISPR primers (for YPa, YPb, YPc locus) were used to amplify the DNA of the experimental strains, and the CRISPR genotype of Yersinia pestis was determined by sequencing. Results:All 125 strains of Yersinia pestis had three CRISPR locus: YPa, YPb, and YPc. A total of 18 spacer were found, including 8 in YPa loci, 6 in YPb loci, and 4 in YPc loci. Two new types of spacers had been discovered, namely b52 and c14. CRISPR typing revealed 10 genotypes, including G1, G7, G7-b4''', G7-b52, G7-c2 -, G8, G22, G22-a4 -, G22-b4''', and G22-c14, of which 6 were newly discovered genotypes. Among the 125 experimental strains, G7 was the main genotype, accounting for 65.6% (82/125), which was distributed in 6 prefecture level citys and 1 region of Tibet Autonomous Region. Next were G22 and G7-c2 - genetypes, accounting for 14.4% (18/125) and 11.2% (14/125), respectively. G22 gene type was distributed in Nagqu, Changdu, Lhasa citys, and Ngari Prefecture, while G7-c2 - genetype was distributed in Shigatse and Shannan cities. Conclusion:The CRISPR locus of Yersinia pestis in natural plague focus of Tibet Autonomous Region is highly polymorphic, and the Yersinia pestis strains with different genotypes have obvious regional distribution characteristics.

ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.

Objective To investigate the best evidence application of exercise prescription in patients with chronic heart failure in clinical practice and evaluate its effectiveness.Methods The best evidence of exercise prescription for patients with chronic heart failure was summarized,and the evidence-based practice plan was developed,and it was implemented in the cardiology department of a tertiary hospital in Zhejiang Province from August to October,2022.Nurses'exercise prescription knowledge-attitude-practice level,implementation rate of review indicators,the length of hospital stay,exercise endurance,daily living ability and grip strength of both groups before and after the intervention were compared.Results After the application of the best evidence,the score of knowledge dimension was(9.34±0.98)points;the score of attitude dimension was(63.29±1.37)points;the score of practice dimension was(25.49±1.51)points,which were statistically significant compared with the scores before the application of evidence(P<0.05).After the application of the best evidence,the implementation rate of 16 review indicators was higher than that before the application of evidence(P<0.001).The length of hospital stay in the evidence application group was shorter than that in the baseline examination group(Z=-2.610,P<0.001).After intervention,the exercise endurance,daily living ability and grip strength of patients in the evidence application group were improved compared with the baseline review group,and the difference was statistically significant(P<0.05).Conclusion After the application of the best evidence of exercise prescription in patients with chronic heart failure,it can improve the level of knowledge,attitude and practice of nurses on exercise prescription,standardize the compliance of nurses'exercise prescription,reduce the number of days in the hospital,and improve patients'exercise endurance,daily living ability and grip strength.

Objective To compare conventional MRI manifestations of brain epithelioid glioblastoma(eGBM)and pleomorphic xanthoastrocytoma(PXA),and to explore the value of radiomics model for differentiating eGBM and PXA.Methods Forty-three cases of brain eGBM(eGBM group)and 79 cases of PXA(PXA group)confirmed by surgical pathology were retrospectively analyzed,and conventional MRI maniofestations were compared between groups.The patients were divided into training set(n=85,including 30 cases of eGBM and 55 cases of PXA)and test set(n=37,including 13 cases of eGBM and 24 cases of PXA)at the ratio of 7∶3.A radiomics regression model was established based on T2WI and enhanced T1WI.Receiver operating characteristic curve was drawn to assess the value of the model for discriminating eGBM and PXA.Results Patients in eGBM group were older than in PXA group,and the proportion of minors in eGBM group was lower than that in PXA group(both P＜0.05).Compared with PXA group,eGBM group showed higher proportion of multiple lesions,with high T1WI signals and peritumoral edema,more unclear boundary and uneven signals(all P＜0.05).After administration of contrast agents,circular enhancement was more often observed in eGBM group,while lesions in PXA group tended to present wall nodule enhancement(both P＜0.05).The sensitivity,specificity,accuracy and area under the curve(AUC)of the radiomics model based on 19 selected features was 88.91％,79.94％,86.75％and 0.892 in training set,respectively,which was 84.58％,79.20％,81.12％and 0.824 in test set,respectively.Conclusion Conventional MRI manifestations of eGBM and PXA were different to a certain extent.Radiomics model was valuable for distinguishing eGBM and PXA.

Objective: To investigate the current situation of cyberbullying and health risk behaviors among secondary vocational school students, to explore the effects of cyberbullying on health risk behaviors, so as to provide a reference for formulating intervention strategies to promote adolescent health related behaviors. Methods: From March to April 2023, a field survey was conducted on 1 184 students from one secondary vocational school each in Jilin City and Yanji City by random cluster sampling method. The data was analyzed using Chi square tests and generalized linear models. Results: Among secondary vocational school students, 839 individuals (70.9%) experienced the cyberbullying, and 1 036 individuals (87.5%) had one and more health risk behavior group. There was a positive correlation between cyberbullying and health risk behaviors ( r=0.60, P <0.01). The generalized linear model analysis showed that female and no Internet addiction were negatively correlated with the health risk behaviors of secondary vocational students ( β =-2.75, -8.90), and the single parent families and peer pressure was positively correlated with the health behaviors of secondary vocational students ( β =2.56, 4.82)( P ＜0.05). Secondary vocational students experienced cyberbullying who from single parent families, peer pressure and social oriented internet usage were more likely to engage in health risk behaviors ( β= 3.41, 4.88, 2.20, P <0.05). Conclusions The incidence of cyberbullying and health risk behaviors among secondary vocational school students is relatively high, and cyberbullying can influence the occurrence of health risk behaviors. It is important to focus on and implement guidance for internet use and health behavior education for secondary vocational students from multiple perspectives, including the family, school, and society. Corresponding intervention strategies should be taken to promote the healthy development of adolescents.

Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective To investigate whether endoscopic ultrasonography (EUS) can be an alternative method for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) by comparing the ability of EUS versus CT and transabdominal ultrasonography (TUS) in the diagnosis of muddy stones of the common bile duct. Methods A prospective study was conducted for 53 patients suspected of muddy stones of the common bile duct who attended Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to December 2021, and all patients underwent EUS, TUS, and CT before ERCP. With ERCP and endoscopic sphincterotomy (EST) for removing muddy stones of the common bile duct as the gold standard for the diagnosis of muddy stones of the common bile duct, EUS, TUS, and CT were compared in terms of their ability to display the muddy stones of the common bile duct. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results In the 53 patients, EUS, TUS, and CT had a positive rate of 88.68%, 50.94%, and 62.26%, respectively, in detecting muddy stones of the common bile duct. As for the positive results confirmed by EST under ERCP, EUS had a sensitivity of 93.75%, a specificity of 60.00%, and an accuracy of 90.57% in detecting muddy stones of the common bile duct, while TUS had a sensitivity of 56.25%, a specificity of 100.00%, and an accuracy of 60.38% and CT had a sensitivity of 66.67%, a specificity of 80.00%, and an accuracy of 67.92%. There was a significant difference between EUS and CT in the accuracy in detecting muddy stones of the common bile duct ( χ 2 =8.26, P =0.004), and there was also a significant difference in diagnostic accuracy between EUS and TUS ( χ 2 =13.05, P < 0.001). Conclusion EUS is more accurate than TUS and CT in the diagnosis of muddy stones of the common bile duct, and instead of ERCP, EUS is thus recommended for suspected muddy stones of the common bile duct when TUS and CT fail to identify the lesions in clinical practice, so as to make a confirmed diagnosis and reduce related costs and complications.