1.Study on Cardiac Aging Phenotypes of SHJHhr Mice
Rongle LIU ; Hao CHENG ; Fusheng SHANG ; Shufu CHANG ; Ping XU
Laboratory Animal and Comparative Medicine 2025;45(1):13-20
ObjectiveTo investigate the spontaneous premature cardiac aging in SHJHhr mice. MethodsA comparative study was conducted between SHJHhr mice (SHJHhr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJHhr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJHhr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJHhr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJHhr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJHhr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.
2.Diagnostic value of plasma SPINK4 expression in colorectal adenocarcinoma and progressive adenoma
Longmei ZHOU ; Ping LI ; Yuhuan SHANG ; Yanling WANG ; Chunying YIN ; Dan LI ; Peiyuan HE
Chongqing Medicine 2024;53(1):50-54
Objective To investigate the clinical diagnostic value of plasma serine protease inhibitor Ka-zal-type 4(SPINK4)expression in colorectal adenocarcinoma(CRC)and progressive adenoma(AA).Methods A total of 62 patients with CRC(CRC group)and 15 patients with AA(AA group)diagnosed by colonoscopy and pathological examination in this hospital from June 2020 to December 2021 were selected,and 22 healthy people undergoing physical examination during the same period were selected as the HC group.The expression of SPINK4 in plasma was detected by ELISA,and the expression of CEA in plasma was detected by electrochemiluminescence,and the correlation was analyzed.The diagnostic efficiency was analyzed by re-ceiver operating characteristic(ROC)curve,and the expression of p53 in CRC tissues was detected by immu-nohistochemistry.Results The expression of plasma SPINK4 in the CRC group and AA group was lower than that in the HC group(Z=3.72,-0.41,P<0.05),and the expression of CEA in the CRC group was higher than that in the HC group(Z=-3.63,P<0.05).The area under the curve(AUC),accuracy,sensi-tivity and specificity of SPINK4 combined with CEA in the diagnosis of CRC and AA were higher than those of SPINK4 and CEA alone.The positive rate of mutant type p53 in SPINK4 low expression group and CEA high ex-pression group was significantly increased in CRC patients(72.55%,75.00%,P<0.05).Conclusion The expression of plasma SPINK4 is decreased in CRC and AA,and the combined detection of SPINK4 and CEA has a good di-agnostic efficiency in CRC and AA.
3.Somatostatin mediates Nrf2/HO-1 pathway to improve acute pancreatitis-associated acute lung injury
Hou-Ping ZHOU ; Yuan YUAN ; Bei-Bei LI ; Ting-Zheng OU ; Ming-Ming SHANG
The Chinese Journal of Clinical Pharmacology 2024;40(18):2729-2733
Objective To explore the mechanism of somatostatin in improving acute lung injury associated with acute pancreatitis.Methods Wistar rats were randomly divided into sham operation group(injection of normal saline),model group(puncture of common bile duct and injection of 5%sodium taurocholate with wire ligation),somatostatin group(injection of somatostatin into tail vein of model group),somatostatin+miR-146a-5p inhibitor group(on the basis of somatostatin group,tail vein injection of miR-146a-5p inhibitor and somatostatin+oe-angiogenin-like protein 4(ANGPTL4)group(on the basis of somatostatin group,tail vein injection of oe-ANGPTL4 plasmid).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic and lung tissues;pathological score and tissue wet-dry weight ratio were determined,real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-146a-5p and ANGPTL4 mRNA expression and Western blot was used to detect the expression of related proteins in lung tissues of rats.Tumor necrosis factor-α(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA).Results In sham operation group,model group and somatostatin group,the damage degree of pancreas tissue(based on modified computed tomography severity index)were 1.25±0.28,3.20±0.34,2.15±0.31,respectively;the damage degree of lung tissue(based on the Smith lung injury score system)were 1.40±0.13,5.10±0.58,3.10±0.38,respectively.The relative expression levels of ANGPTL4 mRNA in sham operation group,model group,somatostatin group and somatostatin+miR-146a-5p inhibitor group were 1.00±0.17,1.63±0.20,1.21±0.18 and 1.73±0.28.The levels of TNF-α in sham operation group,model group,somatostatin group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group were(76.33±7.25),(125.05±13.56),(80.11±10.68),(118.62±14.32)and(105.32±13.52)pg·mL-1,respectively;the relative expression levels of nuclear factor E2-related factor 2(Nrf2)protein were 1.00±0.27,0.51±0.07,0.88±0.14,0.68±0.12,0.51±0.09,respectively;the relative expression levels of heme oxygenase-1(HO-1)protein were 1.00±0.25,0.58±0.11,0.79±0.18,0.48±0.07 and 0.50±0.08,respectively.The above indexes of the model group were compared with those of the sham operation group,and the above indexes of the somatostatin group were compared with those of the model group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group,and the differences were statistically significant(all P<0.05).Conclusion Somatostatin has antioxidant and anti-inflammatory effects and can ameliorate acute lung injury associated with acute pancreatitis.The mechanism may be related to Nrf2/HO-1 pathway mediated by miR-146a-5p/ANGPTL4.
4.Clinical trial of daglizin in the treatment of patients with acute myocardial infarction complicated with type 2 diabetes
Wei LIN ; Shang-Quan XIONG ; Ping ZHAN ; Li ZHAO ; Cui-Yun LI ; Chao LIN ; Fei-Ning LIN ; Ting WANG
The Chinese Journal of Clinical Pharmacology 2024;40(20):2924-2928
Objective To observe the influence of dapagliflozin tablets on myocardial enzymes,mitral valve blood flow and major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI)complicated with type 2 diabetes mellitus(T2DM)after interventional therapy.Methods AMI patients with T2DM were divided into control group and treatment group by cohort method.The control group was given aspirin tablets 300 mg and ticagrelor 180 mg orally,qd,until the day of interventional treatment.After interventional therapy,aspirin tablets 100 mg,qd,oral ticagrelor tablets 90 mg each time,once in the morning and once in the evening.On the basis of the treatment in the control group,the patients in the treatment group were given dapagliflozin tablets 5-10 mg,qd,every morning after admission.After 3 months of continuous treatment,the clinical efficacy,blood glucose control effect[fasting plasma glucose(FPG),2 hour postprandial blood glucose(2 h PG)],myocardial enzymes indicators[creatine kinase(CK),creatine kinase isoenzyme-MB(CK-MB)],ventricular remodeling indicators[left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVESD)],adverse drug reactions and MACE were compared between the two groups.Results There were 55 cases in the control group and 59 cases in the treatment group.After treatment,the total effective rates of the treatment group and the control group were 88.14%(52 cases/59 cases)and 72.73%(40 cases/55 cases),respectively,the difference was statistically significant(P<0.05).After treatment,the FPG of the treatment group and the control group were(7.29±0.71)and(7.81±0.75)mmol·L-1,respectively;the 2 h PG were(8.66±1.33)and(9.59±1.38)mmol·L-1,respectively;the CK were(145.68±29.82)and(163.68±42.16)U·L-1,respectively;the CK-MB were(8.21±2.37)and(10.33±3.08)U·L-1,respectively;the LVEF were(57.63±8.74)%and(51.41±6.49)%,respectively;LVESD were(33.26±5.33)and(39.51±5.38)mm,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P<0.05).During the treatment,the adverse drug reactions in the treatment group mainly included nausea and vomiting,diarrhea,constipation.The adverse drug reactions in the control group mainly included hypoglycemia,diarrhea,headache.The total incidence of adverse drug reactions in the treatment group and the control group was 6.68%(4 cases/59 cases)and 9.09%(5 cases/55 cases),respectively,and the difference was not statistically significant(P>0.05).After 3 months of follow-up,the total incidence of MACE in the treatment group and the control group was 5.08%and 18.18%,respectively,the difference was statistically significant(P<0.05).Conclusion Dapagliflozin has a significant efficacy in the treatment of AMI patients with T2DM,and it can enhance the effect of blood glucose control,reduce the myocardial injury,inhibit the ventricular remodeling,and reduce the risk of MACE,with high safety.
5.Artificial intelligence for brain disease diagnosis using electroencephalogram signals
SHANG SHUNUO ; SHI YINGQIAN ; ZHANG YAJIE ; LIU MENGXUE ; ZHANG HONG ; WANG PING ; ZHUANG LIUJING
Journal of Zhejiang University. Science. B 2024;25(10):914-940
Brain signals refer to electrical signals or metabolic changes that occur as a consequence of brain cell activity.Among the various non-invasive measurement methods,electroencephalogram(EEG)stands out as a widely employed technique,providing valuable insights into brain patterns.The deviations observed in EEG reading serve as indicators of abnormal brain activity,which is associated with neurological diseases.Brain?computer interface(BCI)systems enable the direct extraction and transmission of information from the human brain,facilitating interaction with external devices.Notably,the emergence of artificial intelligence(AI)has had a profound impact on the enhancement of precision and accuracy in BCI technology,thereby broadening the scope of research in this field.AI techniques,encompassing machine learning(ML)and deep learning(DL)models,have demonstrated remarkable success in classifying and predicting various brain diseases.This comprehensive review investigates the application of AI in EEG-based brain disease diagnosis,highlighting advancements in AI algorithms.
6.Design and implementation of medical alliance nursing collaborative management system based on block chain
Mei-Gui CHEN ; Xu XU ; Xiao-Ping ZHU ; Xiong CHEN ; Qiao-Mei SHANG
Chinese Medical Equipment Journal 2024;45(3):47-55
Objective To design a medical alliance nursing collaborative management system based on block chain to provide technical support for nursing collaborative management.Methods A medical alliance system was designed based on the five-layer technical architecture of consortium blockchain,which used Linux system for establishing a Fabric development environment and network configuration,smart contract and Java language software development kit for realizing user interface operation,Bootstrap and Jquery technologies for constructing the front-end Web interface,Spring Boot for constructing the back-end interface.There were five functional modules for consortium blockchain member management,business management,data storage and sharing,patient medical record management and platform supervision involved in the system,which were developed with the technologies of encryption algorithm,hash operation,smart contract,consensus mechanism and etc.Results The system developed contributed to improving the mechanism for quality nursing resource sinking and continuous nursing care,reconfiguring the point incentive mechanism,promoting the collaborative development of nursing symbiotic network and enabling multi-node interactions to form a synergistic synergy.Conclusion The system developed conforms to the development trend of integrated care service of medical alliance,enhances the core competitiveness of nursing care and provides references for formulating blockchain solutions applicable to medical alliance scenarios.[Chinese Medical Equipment Journal,2024,45(3):47-55]
7.Economic burden increment of CRE infection based on propensity score matching
Pei SUN ; Lin-Ping SHANG ; Wen-Ting ZHAO ; Wei GUO
Chinese Journal of Infection Control 2024;23(5):621-627
Objective To investigate the length of hospital stay,hospitalization expense and mortality attributable to the occurrence of carbapenem-resistant Enterobacterales(CRE)infection in patients in intensive care unit(ICU).Methods Patients admitted to the ICU in a tertiary first-class hospital from 2017 to 2022 were selected for the study.According to whether CRE infection occurred,patients were divided into infected group and non-infected group.Propensity score matching method was used to conduct a 1∶1 match between the infected group and non-infected group.Length of hospital stay,hospitalization expense and mortality of patients after matching were analyzed sta-tistically.A generalized linear model was established to recalculate the odds ratio(OR)of length of hospital stay,hospitalization expense and mortality of patients after matching.Results After propensity score matching,length of hospital stay of patients in the infected group extended by 10.56 days(P<0.001),hospitalization expense in-creased by 36 021.02 Yuan(P<0.001),and mortality increased by 6.70%(P=0.035).The results of the gene-ralized linear model indicated that OR for length of hospital stay,hospitalization expense,and mortality were 1.187(95%CI:1.013-1.393),1.134(95%CI:0.975-1.318),and 1.130(95%CI:1.049-1.218)respectively for CRE infected patients,compared with non-infected patients,except for hospitalization expense,length of hospital stay and mortality between two groups were statistically significant(both P<0.05).Conclusion CRE infection in ICU patients will increase the length of hospital stay,economic burden,and mortality of patients.Measures should be taken to prevent and control CRE infection.
8.Genetic correlations among Brucella melitensis isolates from sheep in four provinces of northwest China
Xiao-An CAO ; Zhi-Jie LIU ; Ping LIU ; Jin-Yan WU ; You-Jun SHANG ; Ji-Jun HE ; Zhi-Guo LIU ; Zhen-Jun LI
Chinese Journal of Zoonoses 2024;40(10):922-927
Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90%(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87%of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.
9.CP-25 inhibits GRK2 activity to treat osteoarthritis in mice
Hui-Min WANG ; Xu-Lei WANG ; Zhu-Ping CHU ; Ting-Ting GUO ; Nuo XU ; Kang WANG ; Ying LI ; Wei WEI ; Shang-Xue YAN
Chinese Pharmacological Bulletin 2024;40(5):936-944
Aim To investigate the protective poten-tial of paeoniflorin 6-oxy-benzenesulfonate(CP-25)in preserving knee cartilage integrity in osteoarthritis mice through inhibition of GRK2 activity.Methods The posttraumatic osteoarthritis model was established fol-lowing DMM surgery.The experiment consisted of a sham operation group,a model group,a CP-25 admin-istration group,and a paroxetine positive control group.Intragastric administration commenced after the surgery.After 12 weeks of administration,the animals were euthanized.Micro-CT imaging was used to ob-serve the knee cartilage degeneration and abnormal bone remodeling,and the joint histopathology of mice was observed by staining with ferrubens solid green.Immunohistochemistry and immunofluorescence were used to detect the expression level of related molecules in cartilage tissue.Furthermore,Western blot was em-ployed to determine GRK2 and EP4 membrane protein expression levels as well as total protein levels of GRK2 and MMP13 following CP-25 treatment.Results Compared with the sham operation group,the articular cartilage in the model group was significantly degrad-ed,with the cartilage surface calcifying and osteo-phytes forming.CP-25 could significantly reduce the number of osteophytes and the thickness of the sub-chondral plate of articular cartilage,promote the regen-eration of the cartilage matrix,reduce the expression of cartilage matrix degradation protein,and have a signifi-cant protective effect on knee cartilage.Immunohisto-chemical and immunofluorescence results showed that compared with the model group,CP-25 treatment sig-nificantly decreased the expressions of GRK2,AD-AMTS5 and MMP13 in knee tissue and increased the expressions of Col Ⅱ and Aggrecan in knee tissue.The results of in vitro experiments showed that CP-25 ad-ministration could significantly reduce the expression levels of GRK2 membrane protein and total protein,in-crease the level of EP4 membrane protein,and de-crease the level of MMP13.Conclusions The ad-ministration of CP-25 can significantly promote the re-generation of articular cartilage matrix in OA mice,re-duce the degradation of cartilage matrix,and exhibit therapeutic effects on OA.The mechanism behind this is related to the inhibition of GRK2-mediated cartilage matrix metabolism.
10.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.

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