1.Exploration of mechanism of polydatin in learning and cognitive impairment in aging mice based on Keap1/Nrf2/HO-1 pathway
Xiao-Xuan MA ; Yi LIU ; Yu CAI ; Chun-Chao YAN ; Yun-Zhong CHEN
Chinese Pharmacological Bulletin 2024;40(7):1287-1295
Aim To study the regulatory effect of poly-datin on D-galactose-induced aging model mice.Methods Fifty-six ICR mice(half male and half fe-male)were divided into normal group,model group,positive group,low,medium and high polydatin treat-ment groups.Aging model was established by subcuta-neous injection of D-galactose(500 mg·kg-1)into the back of neck every day.During the modeling peri-od,the positive group was given donepezil hydrochlo-ride tablets(0.75 mg·kg-1)by gavage,the treat-ment group was given polydatin(40,70,100 mg·kg1)by gavage,and the normal group was given the same amount of normal saline.The learning and cogni-tive ability of mice was evaluated by nesting experi-ment,new object recognition experiment and Morris water maze experiment.The heart,liver,spleen,kid-ney and thymus of mice were taken to calculate the or-gan index.The pathological changes of whole brain tis-sue in mice were observed by hematoxylin-eosin(HE)staining.The levels of T-SOD,MDA,GSH-Px and AchE in serum and whole brain tissue of mice were de-tected by ELISA.The protein expression levels of Keap1,Nrf2 and HO-1 in hippocampus of mice were detected by Western blot.Results Compared with the model group,the nesting ability,the ability to recog-nize new objects and the ability to find platforms under-water of the mice in the positive group and the low,medium and high dose groups of polydatin were im-proved.The organ index increased.The neuronal dam-age in the cerebral cortex and hippocampus was signifi-cantly ameliorated.The activities of T-SOD and GSH-Px in serum and brain tissue increased and the activi-ties of MDA and AchE decreased.The expression lev-els of Nrf2 and HO-1 protein in hippocampus in-creased,and the expression level of Keap1 protein de-creased.Conclusions Polydatin can ameliorate the learning and cognitive impairment in D-galactose-in-duced aging model mice,and its mechanism may be related to the Keap1/Nrf2/HO-1 pathway.
2.Mechanism of Kechuanting granules in suppressing IL-33/ILC2s and pathogenic T cells to intervene in allergic airway inflammation
Nan-Ting ZOU ; Zhao WU ; Xiao-Dong YAN ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ming-Qian JU ; Jin-Zhu XU ; Chun-Ping WAN
Chinese Pharmacological Bulletin 2024;40(7):1350-1357
Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.
3.CBX4 regulates proliferation and apoptosis of esophageal squamous cell carcinoma through p38 MAPK signaling pathway
Yan-Chun MA ; Yu-Yan HUA ; Rui LIU ; A-Jing WU ; Xiao-Jie YIN ; Jie YANG
Chinese Pharmacological Bulletin 2024;40(9):1673-1679
Aim To investigate the expression level of CBX4 in esophageal squamous cell carcinoma(ESCC)and the effect of CBX4 on ESCC proliferation and un-derlying molecular mechanisms.Methods The ex-pression of CBX4 in different cancers was analyzed in Pan-cancers.The expression level of CBX4 in ESCC was analyzed by t-test based on Gene Expression Omni-bus(GEO)data.The viability of CBX4-overex-pressed/knockdown ESCC cells was detected by MTT assay,colony formation assay and flow cytometry assay.Furthermore,the tumor volumn,tumor weight and Ki67 expression were measured by mouse xenograft assay and immunohistochemistry.The mRNA and protein ex-pression levels of apoptosis-related genes PARP、Bcl-2、Bax were determined by qRT-PCR and Western blot,respectively.In addition,the underlying molecular mechanism of CBX4 in ESCC was revealed by qRT-PCR and Western blot.Results CBX4 was upregulat-ed in various cancers.The expression level of CBX4 in ESCC was higher than that in normal tissues(P<0.05)based on Gene Expression Omnibus(GEO)da-ta.Compared with the normal group,the proliferation of CBX4 knockdown ESCC cells was significantly in-hibited and the apoptosis was promoted(P<0.05).Meanwhile,the mRNA and protein expression levels of cleaved PARP and Bax were upregulated while that of Bcl-2 was downregulated.In CBX4 overexpression group,tumor volume in vivo increased(P<0.05).Immunohistochemical results also showed an increase in Ki67 expression.Furthermore,the results of RNA-seq,bioinformatics analysis and qRT-PCR experiments indicated that CBX4 probably regulated the prolifera-tion and apoptosis of ESCC through p38 MAPK signa-ling pathway.Conclusion CBX4 is highly expressed in ESCC and plays as an oncogene role,which might regulate cell proliferation through the p38 MAPK signa-ling pathway.
4.Effect of total flavonoids of Dracocephalum moldavica on TMAO-mediated JAK/STAT axis against atherosclerosis in rats and inflammation in RAW264.7 cells
Wen-Jiang CAO ; Chun-Yan DU ; Chuan-Sheng HUANG ; Yun-Li ZHAO ; Xiao-Li MA ; Yong YUAN ; Xin-Chun WANG
Chinese Pharmacological Bulletin 2024;40(9):1766-1772
Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.
5.Changing resistance profiles of Staphylococcus isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Yuling XIAO ; Mei KANG ; Yi XIE ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Ping JI ; Fengbo ZHANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WEN ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2024;24(5):570-580
Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8%)strains of Staphylococcus aureus and 68,040(33.2%)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)%,wound,pus and secretions(33.6±4.2)%,and blood(11.9±1.5)%.The CNS strains were predominantly isolated from blood(73.6±4.2)%,cerebrospinal fluid(12.1±2.5)%,and pleural effusion and ascites(8.4±2.1)%.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)%,outpatient and emergency(11.6±1.7)%,and department of surgery(11.2±0.9)%,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)%,outpatient and emergency(12.8±4.7)%,and department of internal medicine(11.2±1.9)%.The prevalence of methicillin-resistant strains was 32.9%in S.aureus(MRSA)and 74.1%in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1%to 29.2%,and the prevalence of MRCNS decreased from 82.1%to 68.2%.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2%to 2.3%over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.
6.Effects of climate change on scrub typhus in Xiamen
Xue-Mei KE ; Jiao-Na CHEN ; Shan-Shan MA ; Si-Han WU ; Chun-Xiang CAI ; Xiao-Yan WANG ; Shi-Jie HUANG
Chinese Journal of Zoonoses 2024;40(10):965-970
This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P<0.001,daily average temperature(r=0.627,P<0.001),daily maxi-mum temperature(r=0.612,P<0.001),sunshine duration(r=0.405,P<0.001),average relative humidity(r=0.346,P<0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P<0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.
7.NDRG2 Activates Endoplasmic Reticulum Stress via IRE1α-XBP1 to Reverse Tamoxifen Resistance in ER+Breast Cancer
Shou-Ying WANG ; Yan-Yan DU ; Peng CAO ; Wen-Yu LIU ; Jun-Yu QI ; Wei-Ye SHI ; Chun-Xiao ZHANG ; Xiao-Lei ZHOU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(10):1409-1416
Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P<0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P<0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P<0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P<0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P<0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.
8.Design of nurse-driven intelligent individualized medication management system
Xiao-Yan DENG ; Xiao-Fang HU ; Yan GUO ; Chun-Li WANG ; Yi-Fan HUANG ; Tian REN
Chinese Medical Equipment Journal 2024;45(11):44-48
Objective To design a nurse-driven intelligent individualized medication management system to enhance the whole-course patient management efficiency.Methods The system consisted of an in-hospital PC terminal,a mobile patient terminal and a mobile medical terminal.The in-hospital PC terminal was developed with B/S architecture and.NET;the patient and medical terminals both were realized with Java.The patient terminal was made up of a personal information module,a data reporting module and a message center module,and the in-hospital PC and medical terminals were composed of several modules for patient management,data management,statistical analysis and system management.Results The system developed provided whole-course intelligent management for out-of-hospital patients comprehensively,continuously and actively,lowering acute morbidity and nurses'workload for follow-up.Conclusion The system developed enhances patients'awareness of self-health management and improves nurses'efficiency for individualized medication management.[Chinese Medical Equipment Journal,2024,45(11):44-48]
9.Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas:a multicenter clinical research protocol
Bi ZE ; Jin GAO ; Xiao-Fen ZHAO ; Yang-Fang LI ; Tie-Song ZHANG ; Xiao-Mei LIU ; Hui MAO ; Ming-Cai QIN ; Yi ZHANG ; Yong-Li YANG ; Chun-Ye HE ; Yan ZHAO ; Kun DU ; Lin LIU ; Wen-Hao ZHOU ; Chinese High Altitude Neonatal Medicine Alliance
Chinese Journal of Contemporary Pediatrics 2024;26(4):403-409
Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]
10.Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold
He-Ying CHENG ; Yun-Ge ZHANG ; Yan CHEN ; Sun YIN ; Ming LÜ ; Chun-Xiao LI
Journal of Forensic Medicine 2024;40(1):15-19
Objective To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response(ABR)in adults using CE-Chirp to ana-lyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold.Methods Subjects(aged 20-77 with a total of 100 ears)who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold,and pure tone air conduction hearing threshold tests were conducted at 0.5,1.0,2.0 and 4.0 kHz,respectively,to obtain pure tone listening threshold.The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups.The correlation,differences and statistical differences between the two tests at each frequency were analyzed for all subjects.The lin-ear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established,and the feasibility of the equation was tested.Results There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold dif-ference between different hearing level groups and different age groups(P>0.05).There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance(P<0.05),and linear regression analysis showed a significant linear correla-tion between the two(P<0.05).Conclusion The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects'pure tone hearing threshold under certain conditions,and can be used as an audiological test method for forensic hearing impairment assessment.

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