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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan Lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina clinical research Center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and clinical Translational research of Neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral *** E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and ***,the effect of Spi1 on intracerebral hemorrhage remains *** this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage *** showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained ***,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and *** conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral *** new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes:An analysis of 15,124 normal ovarian responders in China

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Chinese Medical Journal 2024年第7期137卷 837-845页

作者： Danlei Zheng Yuanyuan Wang Lixue Chen Lin Zeng Rong Li department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China research Center of clinical Epidemiology Peking University Third HospitalBeijing 100191China

Background:High body mass index(BMI)results in decreased fecundity,and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection(IVF/ICSI).Meanwhile,ovarian responses show great heterogeneity in patients with a high *** study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian ***:We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital,with 3530(23.3%)in the overweight group and 1380(9.1%)in the obese group,who had a normal ovarian response(5-15 oocytes retrieved)and underwent fresh embryo transfer(ET)cycles from January 2017 to December 2018,followed by linked frozen-thawed embryo transfer(FET)cycles from January 2017 to December *** live birth rate(CLBR)was used as the primary ***,a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the *** used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI ***:High BMI was associated with poor IVF/ICSI outcomes,both in cumulative cycles and in separate fresh ET or FET *** cumulative cycles,compared with the normal weight group,obesity was correlated with a lower positive pregnancy test rate(adjusted odds ratio[aOR]:0.809,95%confidence interval[CI]:0.682-0.960),lower clinical pregnancy rate(aOR:0.766,95%CI:0.646-0.907),lower live birth rate(aOR:0.706,95%CI:0.595-0.838),higher cesarean section rate(aOR:2.066,95%CI:1.533-2.785),and higher rate of large for gestational age(aOR:2.273,95%CI:1.547-3.341).In the generalized additive model,we found that CLBR declined with increasing BMI,with 24 kg/m^(2)as an inflection *** the decision tree,BMI only made a difference in the population aged≤34.5 years,with anti-Muller

关键词： Obesity Body mass index fertilization Live birth Decision trees Normal ovarian response

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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： Kevin Tak-Pan Ng Li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau Lo Kwan Man Tan To Cheung department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not *** study was to find out whether systemic inflammation plays an important ***:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex *** relationships of the cytokines and the postoperative outcomes were compared between LLR and ***:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative *** to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly *** POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during *** levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital ***,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver ***:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental Sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

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Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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Chinese Journal of Natural medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The research Center of Integrative Cancer medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First clinical College of Guangzhou University of Chinese medicine Guangzhou 510000China Guangdong Provincial Key Laboratory of clinical research on Traditional Chinese medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China Guangdong-Hong Kong-Macao Joint Lab on Chinese medicine and Immune Disease research Guangzhou University of Chinese MedicineGuangzhou 510000China The research Center for Integrative medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Dampness Syndrome of Chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men *** Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of *** study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 *** conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their *** showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM ***,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by *** FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity *** studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture ***,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 ***,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional Chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment

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Hyperpolarized ^(13)C MRI in hepatocellular carcinoma:Unmet questions during clinical translation

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Chinese Medical Journal 2024年第13期137卷 1516-1518页

作者： Zheng Ye Bin Song Christoffer Laustsen department of Radiology West China HospitalSichuan UniversityChengduSichuan 610041China The MR research Center Department of Clinical MedicineAarhus UniversityAarhus N 8200Denmark

Hyperpolarized(HP)^(13)C magnetic resonance imaging(MRI)is a powerful molecular imaging *** dissolution dynamic nuclear polarization(d-DNP),it can achieve dramatic signal increase and allows for dynamic and quantitative investigation of real-time metabolism in vivo.[1]The typical HP^(13)C MRI workflow begins with formulating the^(13)C probe,and then placing it in the hyperpolarization equipment to achieve the desired signal amplification level,which typically amounts to an increase in the MRI signal by more than 10,000 *** subsequent data acquisition is supported by a specialized^(13)C coil and^(13)C acquisition sequence,and finally quantitative and visualized metabolic information is obtained through a post-processing *** date,research of HP^(13)C MRI has focused on diabetes,cardiovascular diseases,and cancers,[2]showing great promises in tumor detection and the evaluation of therapeutic efficacy.

关键词： metabolism polarized specialized

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Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 300-309页

作者： Qing Huang Jia-Wen Liu Hai-Bin Dong Zheng-Jie Wei Jin-Zhe Liu Yu-Tang Ren Xuan Jiang Bo Jiang department of Gastroenterology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains *** has been reported that pyroptosis worsens *** present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic ***:Thirty-six male Sprague Dawley(SD)rats were divided into six different *** rats were randomly divided into the SAP and control *** monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP *** SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or *** collected blood and tissue samples from pancreas,gut and MAT for ***:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological *** cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and *** SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological *** expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP *** injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in *** upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological *** administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of ***:In SAP,MAT B lymphocytes aggravated local

关键词： Acute pancreatitis Mesenteric adipose tissue B lymphocyte Intestinal barrier Pyroptosis

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Biochemical consequences of glucocerebrosidase 1 mutations in Parkinson’s disease

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Neural Regeneration research 2024年第4期19卷 725-727页

作者： Jeong Hyun Yoon Chiao-Yin Lee Anthony HV Schapira department of clinical and Movement Neurosciences University College London Institute of Neurology Faculty of medicine Imperial College London Aligning Science Across Parkinson's(ASAP)Collaborative research Network

Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 *** is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural *** usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic *** gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.***.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).

关键词： cerebro consequences

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Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration

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Chinese Journal of Integrative medicine 2024年第1期30卷 52-61页

作者： ZHOU Qi-chun XIAO Shi-lin LIN Ru-kun LI Chan CHEN Zhi-jie CHEN Yi-fei LUO Chao-hua MO Zhi-xian LIN Ying-bo School of Traditional Chinese medicine Southern Medical UniversityGuangzhou(510515)China clinical and Basic research Team of TCM Prevention and Treatment of Non-Small Cell Lung Cancer the Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou(510120)China department of Chinese medicine Zhujiang Hospital Affiliated to Southern Medical UniversityGuangzhou(510282)China department of Pharmacy Jiangmen Central HospitalJiangmen(529000)China

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata(PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 μg/m L, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction(qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with normal saline, positive control group(LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The cell apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein(P <0.05), up-regulation of Caspase-3 protein(P<0.05) and ERK1 mRNA(P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

关键词： polysaccharide of Alocasia cucullata tumor cells Bcl-2 Caspase-3 ERK1/2 Chinese medicine

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Benefit-Risk Assessment of Chinese medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The First clinical Medical College of Henan University of Traditional Chinese medicine Zhengzhou450046China Personal department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific research department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical *** controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation *** total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, *** on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

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