1.Design and application of a virtual simulation tutorial system for bone traction nursing of the lower limbs
Shan HE ; Qianzhu CHEN ; Yunmei ZHANG ; Yongli TANG ; Jian ZENG ; Feng XIAO ; Fang LIU ; Hengyu ZHOU ; Shaoyu MU
Chinese Journal of Medical Education Research 2024;23(10):1413-1419
Objective:To design a virtual simulation tutorial system for bone traction nursing of the lower limbs, and to investigate its application effect.Methods:Based on clinical cases, a 3D model was established for the fractured lower limb using the virtual simulation technique. The design of the model considered the position and mechanical relationship between bone traction and fracture ends, as well as the assessment and intervention of the condition after bone traction, and such factors were taken as the core elements of simulation design. Virtual experiments were conducted for the four scenarios of pre-hospital first aid, triage in the hospital, bone traction operation, and postoperative nursing. Such experiments were conducted among junior nursing undergraduates, and examination results and student satisfaction survey were used to evaluate the application effect of the experiments.Results:The teaching software consisted of four training modules, i.e., theoretical knowledge learning of fractures, preparation before bone traction operation, methods and principles of bone traction operation, and observation of conditions after bone traction. The final score of experiments was (90.99±0.58) points among the students, and the degree of satisfaction with the experimental system and the teaching model was 87.85% (441/502) and 63.35% (318/502), respectively.Conclusions:The virtual simulation experiments for bone traction nursing of the lower limbs are scientific, professional, and interesting and have a relatively high degree of satisfaction among students, and therefore, they can be applied in the education of nursing students and the continuing education of nurses.
2.Exploration of the Mechanism of Toddalia asiatica in the Treatment of Ischemic Stroke:Based on Network Pharmacology and Experimental Validation
Jian-Hong GAO ; Dan YANG ; Gang WANG ; Tian-Ying SONG ; Fang-Yu ZHAO ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(7):1375-1383
Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P<0.05,P<0.01),while the expression of LC3-Ⅱ increased(P<0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.
3.Total saponins from Trillium tschonoskii maxim alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis through Keap-1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways
Jian-Hong GAO ; Tian-Ying SONG ; Chao-Xi TIAN ; Fang-Yu ZHAO ; Yi-Duo HE ; Xin LIU ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(10):1850-1857
Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P<0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P<0.01)and increased MDA levels(P<0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P<0.05,P<0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.
4.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.
5.Analysis of viral infections in adult acute respiratory infection cases in Shanghai, 2023
Huanru WANG ; Jiabin MOU ; Qi QIU ; Jiajing LIU ; Fang YUAN ; Meihua LIU ; Xiaode TANG ; Jingyi ZHANG ; Jian CHEN ; Min CHEN ; Huanyu WU ; Zheng TENG
Chinese Journal of Experimental and Clinical Virology 2024;38(4):439-445
Objective:To elucidate the etiological and epidemiological characteristics and epidemiological patterns of viral acute respiratory infections (ARI) in Shanghai during 2023, with the aim of providing robust laboratory evidence for effective prevention and control strategies against related respiratory diseases and facilitating risk assessment.Methods:Respiratory pathogens were detected in the clinical surveillance specimens submitted by sentinel hospitals through multiplex PCR, as part of the multi-pathogen surveillance of acute respiratory infections in Shanghai during 2023. The obtained detection result were statistically analyzed in conjunction with sample information.Results:The positive detection rate of viral pathogens in 2023 was 21.17% (984/4 648), with rates of 33.53% (504/1 503) observed in ILI cases and 15.62% (480/3 145) in SARI cases. Influenza A virus (FluA) was the predominant virus detected, accounting for 13.7% (637/4 648). Other viruses identified in the surveillance samples included influenza B virus (Flu B), human rhinovirus/enterovirus (HRV/HEV), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (HBoV). Regarding temporal distribution, HRV/HEV and RSV exhibited the highest detection rates during the second quarter at 2.27% each (28/1 236). PIV had its peak during the third quarter at a rate of 2.49% (35/1 405), and HMPV showed prevalence mainly during the third and fourth quarters, with detection rates of 2.63% (37/1 405) and 2.35% (32/1 360), respectively.Conclusions:In acute respiratory infection surveillance cases in Shanghai in 2023, Flu A emerged as the predominant respiratory pathogen. The detection rate of HMPV ranked second only to Flu A, while other respiratory viruses such as HRV/HEV, RSV, and PIV were detected during different seasons and co-circulated. The prevalence of various respiratory viruses varied among different infected populations and over times.
6.Surveillance of antifungal resistance in clinical isolates of Candida spp.in East China Invasive Fungal Infection Group from 2018 to 2022
Dongjiang WANG ; Wenjuan WU ; Jian GUO ; Min ZHANG ; Huiping LIN ; Feifei WAN ; Xiaobo MA ; Yueting LI ; Jia LI ; Huiqiong JIA ; Lingbing ZENG ; Xiuhai LU ; Yan JIN ; Jinfeng CAI ; Wei LI ; Zhimin BAI ; Yongqin WU ; Hui DING ; Zhongxian LIAO ; Gen LI ; Hui ZHANG ; Hongwei MENG ; Changzi DENG ; Feng CHEN ; Na JIANG ; Jie QIN ; Guoping DONG ; Jinghua ZHANG ; Wei XI ; Haomin ZHANG ; Rong TANG ; Li LI ; Suzhen WANG ; Fen PAN ; Jing GAO ; Lu JIANG ; Hua FANG ; Zhilan LI ; Yiqun YUAN ; Guoqing WANG ; Yuanxia WANG ; Liping WANG
Chinese Journal of Infection and Chemotherapy 2024;24(4):402-409
Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33%of which were isolated from sterile body sites,mainly from blood(38.86%)and pleural effusion/ascites(10.21%).The predominant species of Candida were Candida albicans(44.51%),followed by Candida parapsilosis complex(19.46%),Candida tropicalis(13.98%),Candida glabrata(10.34%),and other Candida species(0.79%).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62%).Only 2.97%of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61%and a resistance rate of 9.42%to fluconazole,and susceptibility rates above 90%to other drugs.Candida glabrata had a SDD rate of 92.01%and a resistance rate of 7.99%to fluconazole,resistance rates of 32.27%and 48.24%to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90%to other drugs.Candida tropicalis had resistance rates of 29.55%and 26.24%to fluconazole and voriconazole,respectively,resistance rates of 76.60%and 21.99%to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36%to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.
7.Molecular epidemiology of spotted fever group rickettsiae infections in wild rodents from Fengshan County,Guangxi
Si-Si CHEN ; Fang-Ni WANG ; Ze-Yun XU ; Rui JIAN ; Jing XUE ; Wen-Ping GUO
Chinese Journal of Zoonoses 2024;40(10):989-993
The aim of this study was to investigate the prevalence of spotted fever group rickettsia(SFGR)in wild rodents collected from Fengshan County in the Guangxi Zhuang Autonomous Region,and to determine their species.Wild rodents were captured in cages in Fengshan County,Hechi City,Guangxi Zhuang Autonomous Region.The rodents were identified according to morphological characteristics,and the findings were confirmed through molecular biology methods.Subsequently,spleen samples were collected,and DNA was extracted.The outer membrane protein A(ompA)gene was amplified with semi-nested PCR to determine the species of SFGR in captured wild rodents.After sequencing of the PCR products,homology and phylogenetic analyses of ompA gene sequences were performed.A total of 105 wild rodents belonging to seven species were captured.FGR was detected in six rodent species(Bandicota indica,Leopoldamys edwardsi,Mus caroli,Mus Pahari,Rat-tus andamanensis,and Rattus losea,but not Berylmys bower si),and the total positivity rate was 23.8%.Three Rickettsia species,Candidatus Rickettsia jingxinensis,Rickettsia raoultii,and Rickettsia sibirica,were identified from analysis of the ompA gene sequence.This study revealed the presence of three species of SFGR infecting wild rodents from Fengshan County,Guangxi Zhuang Autonomous Region,thus suggesting that Fengshan County is a natural focus of tick-borne spotted fever.This study highlights the need to strengthen monitoring and prevention measures for rickettsiosis.
8.Correlation of miR-155 Expression with Drug Sensitivity of FLT3-ITD+Acute Myeloid Leukemia Cell Line and Its Mechanism
Ling-Yan WANG ; Pei-Fang JIANG ; Jia-Zheng LI ; Yan-Xin CHEN ; Jian-Da HU
Journal of Experimental Hematology 2024;32(2):395-401
Objective:To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+acute myeloid leukemia(AML)cell line and its potential regulatory mechanism.Methods:By knocking out miR-155 gene in FLT3-ITD+AML cell line MV411 through CRISPR/Cas9 gene-editing technology,monoclonal cells were screened.The genotype of these monoclonal cells was validated by PCR and Sanger sequencing.The expression of mature miRNA was measured by RT-qPCR.The treatment response of doxorubicin,quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity.Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout,gene set enrichment analysis to analyze change of signaling pathway,and Western blot to verify expressions of key molecules in signaling pathway.Results:Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing.RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones.MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+AML drugs increased significantly after miR-155 knockout compared with wild-type clones.RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout.Western blot showed that the expressions of key molecules p-mTOR,Wnt5α and β-catenin in signaling pathway were down-regulated.Conclusion:Drug sensitivity of MV411 cells to doxorubicin,quizartinib and midostaurin can be enhanced significantly after miR-155 knockout,which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.
9.Clinical Study of Venetoclax Combined with Azacitidine in the Treatment of Patients with Adult Acute Myeloid Leukemia
Yong-Liang ZHENG ; Ting DING ; Xiao-Fang XIAO ; Si DONG ; Jun-Quan ZENG ; Yi-Jian CHEN
Journal of Experimental Hematology 2024;32(4):1046-1050
Objective:To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML).Methods:A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology,Affiliated Hospital of Jinggangshan University from January 2020 to December 2022.Among them,26 patients received venetoclax combined with azacitidine chemotherapy(observation group),and 22 patients received daunorubicin plus cytarabine chemotherapy(control group).The differences in complete response(CR)rate,objective response rate(ORR),progression-free survival(PFS),overall survival(OS)and adverse reactions(AR)were compared between the two groups.Results:There was no significant difference in age,sex ratio,absolute value of tri-lineage cell and proportion of bone marrow primordial cells between the two groups before treatment(all P>0.05).The CR rate and the ORR rate of the observation group was significantly higher than that of the control group(P<0.05).After treatment,there were no significant difference in the adverse reactions such as myelosuppression,granulocytosis,secondary infection,mucosal damage,liver and kidney damage,cardiotoxicity and gastrointestinal toxicity between the two groups(P>0.05).The median PFS and the median OS of the observation group were significantly better than those of the control group(P<0.05).Conclusion:The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia.Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.
10.Protective Effect of Endogenous ω-3 Polyunsaturated Fatty Acid Against Cisplatin-Induced Myelosuppression
Qi-Hua XU ; Zong-Meng ZHANG ; Chao-Feng XING ; Han-Si CHEN ; Ke-Xin ZHENG ; Yun-Ping MU ; Zi-Jian ZHAO ; Fang-Hong LI
Journal of Experimental Hematology 2024;32(5):1601-1607
Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P<0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P<0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P<0.001,P<0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

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