1.Medicinal properties and mechanisms of p-cymene with mild and warm nature based on deficiency-cold and deficiency-heat syndrome models.
Xiao-Fang WU ; Yi LI ; Xing-Yu ZHAO ; Lin-Ze LI ; Qi ZHANG ; Yin-Ming ZHAO ; Ying-Li ZHU ; Chun WANG ; Jian-Jun ZHANG ; Lin-Yuan WANG
China Journal of Chinese Materia Medica 2025;50(8):2032-2040
This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals
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Cymenes
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Disease Models, Animal
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Humans
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Cyclic AMP/metabolism*
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Monoterpenes/administration & dosage*
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Liver/metabolism*
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Cyclic GMP/metabolism*
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TRPV Cation Channels/genetics*
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Uncoupling Protein 1/genetics*
2.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
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Rats
3.Modulation of cardiac inflammation by Qifu Yixin Granules in rats with heart failure via TLR4/MyD88/NF-κB signaling pathway
Qian-rong LI ; Xiao-dong ZHI ; Bing JIANG ; Chun-ling WANG ; Chun-zhen REN ; Xin-ke ZHAO ; Kai LIU ; Ying-dong LI
Chinese Traditional Patent Medicine 2025;47(8):2535-2541
AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P<0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P<0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P<0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P<0.05,P<0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P<0.05,P<0.01);mitigated inflammation and collagen deposition(P<0.05,P<0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.05,P<0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.
4.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
5.Changing distribution and antimicrobial resistance profiles of clinical isolates in children:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Qing MENG ; Lintao ZHOU ; Yunsheng CHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Chuanqing WANG ; Aimin WANG ; Lei ZHU ; Jinhua MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Zhiyong LÜ ; Shuping ZHOU ; Yan ZHOU ; Shifu WANG ; Fangfang HU ; Yingchun XU ; Xiaojiang ZHANG ; Zhaoxia ZHANG ; Ping JI ; Wei JIA ; Gang LI ; Kaizhen WEN ; Yirong ZHANG ; Yan JIN ; Chunhong SHAO ; Yong ZHAO ; Ping GONG ; Chao ZHUO ; Danhong SU ; Bin SHAN ; Yan DU ; Sufang GUO ; Jiao FENG ; Ziyong SUN ; Zhongju CHEN ; Wen'en LIU ; Yanming LI ; Xiaobo MA ; Yanping ZHENG ; Dawen GUO ; Jinying ZHAO ; Ruizhong WANG ; Hua FANG ; Lixia ZHANG ; Juan MA ; Jihong LI ; Zhidong HU ; Jin LI ; Yuxing NI ; Jingyong SUN ; Ruyi GUO ; Yan ZHU ; Yi XIE ; Mei KANG ; Yuanhong XU ; Ying HUANG ; Shanmei WANG ; Yafei CHU ; Hua YU ; Xiangning HUANG ; Lianhua WEI ; Fengmei ZOU ; Han SHEN ; Wanqing ZHOU ; Yunzhuo CHU ; Sufei TIAN ; Shunhong XUE ; Hongqin GU ; Xuesong XU ; Chao YAN ; Bixia YU ; Jinju DUAN ; Jianbang KANG ; Jiangshan LIU ; Xuefei HU ; Yunsong YU ; Jie LIN ; Yunjian HU ; Xiaoman AI ; Chunlei YUE ; Jinsong WU ; Yuemei LU
Chinese Journal of Infection and Chemotherapy 2025;25(1):48-58
Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1%of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9%)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5%)was lower than that in inpatient children(31.5%).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1%)than in inpatient children(59.4%).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14%,11.7%,47.8%in outpatients,but 24.2%,20.6%,and 52.8%in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.
6.Surveillance of antimicrobial resistance in clinical isolates of Escherichia coli:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Shanmei WANG ; Bing MA ; Yi LI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Zhaoxia ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Aimin WANG ; 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 ; 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 2025;25(1):39-47
Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)%.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0%vs 29.5%).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7%vs 7.8%,0.8%vs 0.1%,both P<0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)%with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9%and 1.8%,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1%).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10%.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P<0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.
7.Promotive effect of M2 macrophages on epithelial-mesenchymal transition and cisplatin resistance in non-small cell lung cancer A549 cells by regulating NF-κB signaling pathway
Xingxiang WANG ; Ying ZHAO ; Qiaotong REN ; Hefei WANG ; Gang PU ; Chun LI
Journal of Jilin University(Medicine Edition) 2025;51(3):642-652
Objective:To discuss the role of M2 macrophages in epithelial-mesenchymal transition(EMT)and cisplatin(DDP)resistance in the non-small cell lung cancer(NSCLC),and to clarify the regulatory mechanism of nuclear factor κB(NF-κB)signaling pathway.Methods:The human monocytic leukemia THP-1 cells were selected and differentiated into M0 macrophages by phorbol myristate acetate(PMA)induction,followed by M2 macrophage polarization through interleukin(IL)-4 and IL-13 stimulation.Western blotting and immunofluorescence methods were used to detect the protein expression levels of CD163,CD86,and arginase-1(Arg-1)in M0 and M2 macrophages.The human NSCLC A549 cells were co-cultured non-contactly with M0 or M2 macrophages in Transwell chambers,and the cells were divided into A549+M0 group(A549 cells co-cultured with M0 macrophages),A549+M2 group(A549 cells co-cultured with M2 macrophages),and A549+M2+BAY11-7082 group(A549 cells co-cultured with M2 macrophages and treated with 10 mmol·L-1 NF-κB inhibitor BAY11-7082).Wound healing assay was used to detect the wound healing rate of the A549 cells in various groups;Transwell assay was used to detect the number of invasion A549 cells in various groups;cell counting kit-8(CCK-8)assay was used to detect the inhibitory rate of proliferation and half maximal inhibitory concentration(IC50)value of the A549 cells after treated with DDP in the co-culture system;Western blotting method was used to detect the expression levels of vimentin,E-cadherin,N-cadherin,transcription factor Snail,phosphorylated P65(p-P65),P-glycoprotein(P-gp),and programmed death-ligand 1(PD-L1)proteins in the A549 cells in various groups.Results:The Western blotting results showed that compared with M0 group,the expression levels of CD163 and Arg-1 proteins in the macrophages in M2 group were significantly increased(P<0.05),while the expression level of CD86 protein was significantly decreased(P<0.05).The immunofluorescence results showed that compared with M0 group,the expression of CD163 protein in the macrophages in M2 group was enhanced and the expression of CD86 protein was weakened.The wound healing assay results showed that at 24 and 48 h of culture,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the wound healing rate of the A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05).The Transwell assay results showed that compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the number of invasion A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05);in the co-culture system,compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05).The CCK-8 assay results showed that after treated with 2.50,5.00,10.00,20.00,and 40.00 mg·L-1 DDP,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);in the co-culture system,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);compared with A549+M2 group,the inhibitory rate of proliferation of the A549 cells in A549+M2+BAY11-7082 group was significantly increased(P<0.05),and the IC50 value was significantly decreased(P<0.05).The Western blotting results showed that compared with A549+M0 group,the expression level of E-cadherin proteins in the A549 cells in A549+M2 group was significantly decreased(P<0.05),while the expression levels of N-cadherin,vimentin,and Snail proteins were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of vimentin,Snail,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05),while the expression level of E-cadherin proteins was significantly decreased(P<0.05);compared with A549+M2 group,the expression levels of vimentin,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05),while the expression level of E-cadherin proteins was significantly increased(P<0.05);compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);compared with A549+M2 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05).Conclusion:The M2 macrophages can regulate EMT in the NSCLC cells to promote the invasion and metastasis of tumor,and modulate the expressions of P-gp and PD-L1 to enhance DDP resistance,which is associated with the NF-κB signaling pathway.
8.Research and Application of Scalp Surface Laplacian Technique
Rui-Xin LUO ; Si-Ying GUO ; Xin-Yi LI ; Yu-He ZHAO ; Chun-Hou ZHENG ; Min-Peng XU ; Dong MING
Progress in Biochemistry and Biophysics 2025;52(2):425-438
Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.
9.Preliminary investigation into the role of Sneathia Sanguinegens in unexplained recurrent spontaneous abortion
Fu-ju ZHAO ; Xian-yang HU ; Lu LIU ; Xi-xi HUANG ; Fei-fei WANG ; Jing GAO ; Mei-rong DU ; Chun-mei YING
Fudan University Journal of Medical Sciences 2025;52(1):99-106,138
Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.
10.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; 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 ; 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 ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

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