1.PDGFC secreted by CAFs promotes resistance of breast cancer cells to doxorubicin by PI3K-mTOR signalling pathway
Hao DONG ; Xue-Jie WANG ; Wan-Li DUAN ; Zhi-Mei SHENG ; Li-Hong SHI ; Bao-Gang ZHANG
Chinese Pharmacological Bulletin 2024;40(5):833-839
Aim To explore whether platelet-derived growth factor C(PDGFC)derived from cancer-associat-ed fibroblasts(CAFs)can promote resistance of breast cancer cells to doxorubicin(DOX)and the underlying mechanisms.Methods CAFs and normal fibroblasts(NFs)were extracted from freshly resected breast cancer tissue and adjacent normal breast tissue respec-tively.Conditioned medium(CM)from CAFs and NFs was collected and co-cultured with breast cancer cells.Cell proliferation and toxicity were assessed using a Cell Counting Kit-8(CCK-8).The expression of PDG-FC in CAFs,NFs and corresponding CM was detected by Western blot and ELISA respectively.The influence of CAFs-CM on intracellular doxorubicin content in breast cancer cells was observed by fluorescence mi-croscopy.The impact of CAFs-CM on apoptosis-related proteins BAX and BCL2 was predicted and valifated u-sing the Starbase database and Western blot.The changes in ROS levels,mitochondrial membrane po-tential,and mitochondrial membrane proteins TOM20 and COX Ⅳ in breast cancer cells were measured using DCFH-DA fluorescence staining,JC-1 assay,and Western blot.Results CAFs-CM decreased the intra-cellular doxorubicin content and inhibited the sensitivi-ty of breast cancer cells to doxorubicin.Additionally,the expression of apoptosis protein BAX decreased while the anti-apoptotic protein BCL2 increased in breast cancer cells cultured with CAFs-CM.Further-more,CAFs-CM led to decreased ROS levels and in-creased mitochondrial membrane potential in breast cancer cells accompanied with elevated expression of mitochondrial membrane proteins TOM20 and COX Ⅳ.Further study found that PDGEF was highly expressed in CAFs and CAFs-CM,recombinant human PDGFC produced resistance of breast cancer cells to DOX simi-lar to CAFs-CM,and the specific inhibitors of PDGFRα significantly inhibited CAFs-CM.Further mechanistic studies revealed that PDGFC in CAFs-CM induced chemoresistance by activating PI3K-mTOR signaling pathway.Conclusion PDGFC secreted by CAFs promotes doxorubicin resistance in breast cancer cells through PI3K-mTOR signaling pathway,which provides a new perspective for the development of anti-cancer drugs targeting CAFs.
2.Synthesis of phenylacetamide derivatives and their protective effects on islet cell damage induced by palmitic acid
Ai-Yun LI ; Li GUAN ; Wan-Zhen SU ; Yang-Yang LU ; Sheng-Jie ZHANG ; Wei-Ze LI ; Xiang-Ying JIAO
Chinese Pharmacological Bulletin 2024;40(6):1130-1136
Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4%,and LY-6 had the highest cell activi-ty,reaching to 104.9%.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.
3.Quercetin alleviates podocyte injury by inhibiting inflammation and pyroptosis through SIRT1/STAT3/GSDME
Jie-Qiong WANG ; Ge LI ; Shao-Hua WANG ; Yu WAN ; Yun LIU ; Cong-Gai HUANG ; Qu-Lian GUO ; Fang-Fang ZHONG
Chinese Pharmacological Bulletin 2024;40(7):1279-1287
Aim To investigate the effect of quercetin(Que)on podocyte inflammatory injury and the under-lying mechanism.Methods MPC5 cells were divided into normal glucose group(NG),mannitol group(MA),high glucose group(HG)and high glucose+quercetin group(HG+Que).Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry.The expression of SIRT1,STAT3,apoptosis-related proteins(Bax,Bcl-2,caspase-3)and pyroptosis pro-tein GSDME was detected by Western blot.The ex-pression levels of inflammatory factors(IL-6,TNF-α,IL-18,IL-1β)in cell supernatants were detected by ELISA.Then small interfering RNA technology was used to knockdown SIRT1 expression.To further eval-uate the biological significance of SIRT1 in response to high glucose and Que treatment,negative control group(HG+si-NC+Que)and SIRT1 interference group(HG+si-SIRT1+Que)were added in the presence of high glucose and Que.Results Compared with the high glucose group,40 μmol·L-1 Que could alleviate the apoptosis of MPC5 cells induced by high glucose,decrease the expression of apoptosis related protein Bax and caspase-3,as well as increase the expression of anti-apoptotic protein Bcl-2;ELISA results showed that Que could decrease the expression of TNF-α,IL-6,IL-1 β and IL-18 induced by high glucose.Mechanical-ly,Que could alleviate the inhibitory effect of high glu-cose on the expression of SIRT1,and further decrease the activation of STAT3 and N-GSDME,and inhibit pyroptosis.Compared with the si-NC group,si-SIRT1 group could reverse the protective effect of Que on the high glucose induced inflammatory damage of podo-cytes,the expression of apoptotic proteins Bax and caspase-3 increased,while the expression of anti-apop-totic protein Bcl-2 decreased.At the same time,the levels of inflammatory cytokines TNF-α,IL-6,IL-1 βand IL-18 in supernatants increased,and the expres-sion of STAT3 and N-GSDME increased.Conclusion Que could inhibit pyroptosis and relieve the inflam-matory damage of podocytes through SIRT1/STAT3/GSDME pathway.
4.Advances in the application of machine learning for stroke risk prediction
Hongyan WAN ; Shuxin HAO ; Jie LIU ; Yue LIU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(8):1275-1280
Stroke has diverse clinical manifestations and complex causes, characterized by high incidence, high disability rate, high recurrence rate, high mortality rate, and high economic burden. Currently, conventional clinical diagnostic and treatment methods face challenges such as difficulty in predicting disease and prognosis, low diagnostic accuracy, and slow treatment due to limitations in manpower and time. With the in-depth research in artificial intelligence and its application in the medical field, machine learning models can not only predict and diagnose stroke more accurately but also identify risk factors and determine high-risk populations. This paper reviews the current research status of machine learning algorithms, the identification of stroke risk factors, common machine learning algorithms for stroke prediction, and the effectiveness of these algorithms in stroke risk prediction. Findings from this paper will help provide a scientific basis for the early identification of high-risk populations, the adoption of effective preventive measures, and the formulation of precise treatment plans.
5.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.
6.Epidemic characteristics and spatiotemporal clustering of leptospirosis in Wenzhou from 2014 to 2023
Ling LI ; Qiong-Jiao PAN ; Jie-Ru HUANG ; Wan-Cang LI ; Jun-Qi YANG
Chinese Journal of Zoonoses 2024;40(10):959-964
This study analyzed the epidemic characteristics and spatial and temporal clustering of leptospirosis in Wenzhou from 2014 to 2023,to provide a scientific basis for prevention and control.Data for leptospirosis cases reported in Wenzhou from 2014 to 2023 were collected.Descriptive epidemiological approaches were used to analyze the cases'prevalence character-istics.Spatial autocorrelation analysis was performed in ArcGIS 10.2 software,and spatiotemporal clusters were scanned with SaTScan 10.1 software.From 2014 to 2023,189 leptospirosis cases were reported in Wenzhou,and the average annual inci-dence rate was 0.23/100 000.Relatively fewer cases occurred in 2014-2018,whereas significantly more cases occurred after 2019,and the largest number of reported cases was reported in 2021(62 cases).The peak incidence was from August to Octo-ber,accounting for 88.36%of the total incidence.The cases were mainly in males,and the sex ratio was 5.30∶1 male:female.Moreover,the cases were mainly in people in their 60s,accounting for 59.26%of total cases,and in people who were farmers,accounting for 72.49%of total cases.Global spatial autocorrelation analysis indicated that cases were randomly distributed from 2014 to 2018,and the incidence showed spatial clustering from 2019 to 2023(Moran's I>0,P<0.05).Local spatial autocor-relation and spatiotemporal scanning analysis revealed that leptospirosis cases were concentrated primarily in northern hilly areas of Yongjia County and other inland areas rich in vegetation from 2019 to 2023.In the past 5 years,the number of lepto-spirosis cases in Wenzhou increased,and the incidence of leptospirosis showed clear seasonal and spatial clustering.Cases were mainly in middle-aged and older farmers.Recommendations in-clude expanding the monitoring scope of leptospirosis,and per-forming prevention and control measures such as health education for key groups in key areas before the high-incidence season.
7.A Real-World Single-Center Study of Adult Hodgkin's Lymphoma
Ling-Li WANG ; Lei TIAN ; Fei DONG ; Ping YANG ; Wei WAN ; Qi-Hui LI ; Lan MA ; Jin-Jie GAO ; Ji-Jun WANG ; Wei ZHAO ; Hong-Mei JING
Journal of Experimental Hematology 2024;32(2):428-433
Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6%,followed by mixed cellularity HL(36.5%),lymphocyte-rich classical HL(3.2%),and lymphocyte depletion HL(0.7%),while nodular lymphocyte predominant HL accounted for 4.8%.The 3-year overall survival(OS)rate of HL patients was 89.8%,and 5-year OS was 85.0%.The 3-year progression-free survival(PFS)rate was 73.4%,and 5-year PFS was 63.1%.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4%and 76.0%in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4%and 55.9%(both P<0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0%,while that was 89.6%in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.
8.Preventive effect of probiotics on intestinal obstruction after gastrointestinal cancer surgery and its impact on gut micro-biota diversity
Wan-Hong ZHANG ; Lin-Jie LI ; Yu-Chao MA
Chinese Journal of Current Advances in General Surgery 2024;27(9):704-708
Objective:To explore the preventive effect of probiotics on postoperative intesti-nal obstruction in patients after gastrointestinal cancer surgery and to analyze their impact on the diversity of the gut microbiota.Methods:A prospective study was conducted involving 133 pa-tients who underwent gastrointestinal cancer surgery at the Shanxi Cancer Hospital's Department of Hepatobiliary pancereatogastric surgery from January 2021 to January 2022.Patients were ran-domly divided into two groups,Group A and Group B,using a simple randomization method based on coin toss,with Group A consisting of 74 cases and Group B of 59 cases.Group A received rou-tine postoperative management along with oral probiotic formulations,while Group B received only routine management.The study compared gastrointestinal functional recovery indicators,observed the counts of major gut microbiota before and 7 days after surgery,the degree of microbiota dys-biosis,and intestinal barrier function indicators such as diamine oxidase(DAO),D-lactic acid,and histidine decarboxylase(HDC)between the two groups,and compared the incidence of complica-tions such as intestinal obstruction.Result:(1)The time to first flatus,first bowel movement,re-sumption of oral intake,and hospital stay in Group A were significantly shorter than in Group B(P<0.05);(2)Seven days postoperatively,the counts of Enterococcus and Escherichia coli in Group A were significantly lower than in Group B,while the counts of Bifidobacterium and Lactobacillus were higher in Group A(P<0.05);(3)The degree of microbiota dysbiosis 7 days postoperatively was statistically significantly different between the two groups(P<0.05);(4)Seven days postoperatively,the levels of DAO,D-lactic acid,and HDC increased in both groups,with Group A having lower lev-els than Group B(P<0.05);(5)The overall incidence of complications in Group A was significantly lower than in Group B(4.05%vs 15.25%,P<0.05).Conclusion:Oral administration of probiotics after gastrointestinal cancer surgery can significantly improve the intestinal microecological environ-ment,regulate the counts of gut microbiota,promote the protective function of the gastrointestinal mucosal barrier,effectively reduce the incidence of complications such as intestinal obstruction,and has significant clinical application value.
9.Biomechanical study of laterality and stability during double-leg landing of college competitive aerobics athletes
Lili WANG ; Wan Ahmad Munsif Bin Wan Pa ; Yuxuan WANG ; Fenglei LI ; Mengning JIE ; Denise Koh Choon Lian
Chinese Journal of Sports Medicine 2024;43(4):266-274
Objective To analyze the biomechanical characteristics of the landing movements of com-petitive aerobics athletes,compare the laterality between their dominant and non-dominant limbs,and to explore the primary factors influencing landing stability.Methods Taking 26 female aerobics athletes in universities as the research objects,their kinematics and kinetics data of double-leg vertical land-ing with the height of 40 cm were simultaneously recorded.A comparison was made between the two limbs in terms of joint angles at initial contact,range of motion(ROM)of joint,ground reaction force(GRF),load-rate,the displacement and envelope area of the center of pressure(COP).The symmetry index(SI),reflecting laterality,was computed,and a multiple stepwise regression analysis was conduct-ed to examine the correlation between parameter asymmetry and COP envelope area.Results Compared with the non-dominant limbs,the dominant limbs had significantly greater knee external rotation and hip abduction angle at initial contact(P<0.05),significantly greater ROM of the ankle and hip flexion-extension and hip adduction-abduction,and smaller ROM of ankle rotation during landing(P<0.05).Moreover,the peak knee extension moment of the dominant limbs was significantly higher than the non-dominant limbs(P<0.01).The SI of vertical load rate and peak knee extension moment were signif-icantly positively correlated with the COP envelope area(P<0.05).In addition,the SI of vertical load rate,peak knee extension moment and knee rotation angle could explain 83.6%of the difference in the COP envelope area.Conclusion There is laterality between the dominant and non-dominant limb of competitive aerobics athletes during landing:the greater laterality of the load rate and peak knee ex-tension moment,the worse the landing stability.Furthermore,the SI of vertical load rate,peak knee extension moment,and knee rotation angle can be used as predictors of the landing stability.
10.Design of embedded cervical spine health intelligent system
Qian-Cheng ZHANG ; Wan-Yue ZHOU ; Jie-Min HUANG ; Jun-Ying GONG ; Yong-Ling HE
Chinese Medical Equipment Journal 2024;45(8):26-31
Objective To design an embedded cervical spine health intelligent system for health monitoring and disease prevention of cervical spine.Methods The system was composed of a portable monitoring terminal,a cloud server and a WeChat App.The portable monitoring terminal consisted of a data acquisition module,a data processing module and an IoT communication module,in which the data acquisition module used JY 901-S as the main data sensor,the data processing had STM32F4 as the main control chip and China-made RT-Thread as the embedded operating system and realized classified head motion identification with an activity recognition model,and the IoT communication module selected an ESPRESSIF ESP32-C3 series Wi-Fi Bluetooth dual-mode module.The cloud server had a Web server architecture of Linux+Nginx+uWSGI,which stored user data with MySQL database and assessed cervical health status with an evaluation model.The WeChat App was developed with WXML+WXSS+WXS.Results The system developed basically realized the functions for health status monitoring and motion guidance of cervical spine,with an average accuracy for classified head motion identification higher than 90%and a measurement accuracy for neck joint mobility being±1°.Condusion The system developed effectively help users establish and maintain regular cervical spine health exercise behaviors,and provides hospitals and other institutions with reliable rehabilitation exercise treatment programs and rehabilitation care data support.[Chinese Medical Equipment Journal,2024,45(8):26-31]

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