1.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
2.Effect of Bushen Tongfu decoction on neuroinflammation in AD mice based on intestinal flora and metabolomics
Jie ZHANG ; Xu WANG ; Xiao-Yu SONG ; Si-Min LI ; Jian-Ping DUAN ; Yun-Min XU ; Min ZHAO
Chinese Pharmacological Bulletin 2024;40(7):1258-1266
Aim To explore the mechanism of Bushen Tongfu decoction(BSTF)improving the learning and memory ability of APP/PS1 mice.Methods The APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of all mice were detected by Morris water maze.The changes in the intestinal microbiota and gut metabolites of mice were detected by 16S rDNA and LC-MS/MS technolo-gy.Results Compared with the model group,the es-cape latency and swimming path in BSTF-H,BSTF-M and BSTF-L groups were shortened and the times of target crossings after removing the platform increased significantly(P<0.01).The 16S rDNA results showed that BSTF could increase the abundance of beneficial bacteria of Firmicutes and reduce the abun-dance of harmful bacteria of Bacteroidota in APP/PS1 mice.A total of 25 differential metabolites were identi-fied by LC-MS/MS,including sphingolipid metabo-lism,lysine metabolism and tyrosine metabolism.KEGG enrichment analysis showed that the therapeutic effect of BSTF was mainly through inflammation-related signaling pathways such as NF-κB pathways and Apelin pathways.Conclusions The mechanism of BSTF im-proving the learning and memory ability of APP/PS1 mice may be related to the improvement of intestinal flora composition,the effect of sphingolipid metabo-lism,lysine metabolism and tyrosine metabolism and the regulation of inflammation-related signaling path-ways such as NF-κB and Apelin pathways.
3.Effects of Radix Angelica sinensis and Radix Hedysari ultrafiltration on oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation and its mechanism
Li-Rong WANG ; Ling-Yun WANG ; Xiao-Jing LI ; Hui-Lin ZHAO ; Yao-Hui HUO ; Hui CHAI ; Kai LIU
Chinese Pharmacological Bulletin 2024;40(8):1501-1509
Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.
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.mfat-1 gene therapy prevents and ameliorates multiple sclerosis in mice
Min-Yi TANG ; Xin-Yun BI ; Shuai WANG ; Chao-Feng XING ; Xiao-Li WU ; Zi-Jian ZHAO ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(10):1930-1936
Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P<0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P<0.05),and improve inflammation and de-myelination of spinal cords(P<0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P<0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.
6.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; 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 ; Wei LI ; 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 ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
7.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
8.Morphological classification and molecular identification of Hyalomma asiaticum in parts of Xindi Township,Xinjiang
Xiao-Qing ZAN ; Qiao-Yun REN ; Jin LUO ; Yan-Long WANG ; Pei-Wen DIAO ; Li-Yan CHE ; Jian-Xun LUO ; Hong YIN ; Gui-Quan GUAN ; Guang-Yuan LIU ; Hong-Xi ZHAO
Chinese Journal of Zoonoses 2024;40(4):289-294
The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.
9.Isolation and identification of genotype A Chlamydia psittaci strain from duck
Zhao-Cai LI ; Ping LIU ; Yun-Hui LI ; Huai-Yu ZHANG ; Qian XIAO ; Chun-Guo LIU ; Ji-Zhang ZHOU
Chinese Journal of Zoonoses 2024;40(9):823-828
Chlamydia psittaci is a worldwide distributed zoonotic pathogen that infects a variety of birds.In order to char-acterization of the duck originated C.psittaci strains,lung samples were collected from suspected infection ducks and was de-tected by real-time PCR.The positive samples were homogenized in phosphate buffered saline with kanamycin and streptomy-cin,and then inoculated onto L929 cells monolayer.After several sets of passages,chlamydial inclusions of the isolate in cul-tured cells were observed after Giemsa staining or by electron microscope.For species identification,16S rRNA,16-23S IGS gene fragments were sequenced and analyzed.Genotyping of the isolate was performed by comparative analysis of the obtained ompA gene sequence with that of different genotype of C.psittaci strains.A C.psittaci strain was successfully isolated from the lung sample of duck by cell culture and was identified as genotype A.This study expanded our understanding of the host range of genotype A C.psittaci strain,and provided basis for further research on the pathogenicity,transmission,and public health risk of this pathogen.
10.The Molecular Mechanism and Potential Clinical Value of Lysophosphatidic Acid in Macrophages
Jia-Yi ZHAO ; Xiao YANG ; Xiao-Yun YANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(11):1522-1530
Macrophages are an important class of immune cells that are mainly derived from myeloid pro-genitor cells in the bone marrow.They function in phagocytosis and antigen presentation,and participate in innate immune and inflammatory responses.Lysophosphatidic acid (LPA) is an active phospholipid signaling molecule that induces macrophage differentiation and polarization,regulates macrophage migra-tion and infiltration,and modulates the inflammatory response in which macrophages participate.In this paper,we review the molecular mechanisms underlying the role of LPA in macrophages in recent years by taking the role of LPA in macrophages as an entry point:LPA plays an important role in macrophage dif-ferentiation and polarization by inducing related regulatory factors and cytokines;LPA receptors mediaterelated signaling pathways to regulate macrophage migration and infiltration;and the ATX/LPA signaling axis and related cytokines are involved in macrophage inflammatory regulation.In addition,the regulatory role and potential clinical value of LPA in tumor-associated macrophages and macrophage inflammatory response diseases are reviewed.At present,the molecular mechanism of action of LPA in macrophages has not been fully elucidated.And an in-depth study of the receptor expression,biological roles,and regulatory mechanisms of LPA in macrophages will provide new strategies for the treatment of macro-phage-associated diseases and cancers.

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