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Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke:Insights from Network Pharmacology and in vivo Experiments

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Chinese Journal of Integrative Medicine 2024年第8期30卷 713-720页

作者： LI Zhong-hao PU Xiao-qi LI Sha-sha DONG Xiao-ke ZHANG Guo-qiang WANG Yu LIU Jin-min department of Emergency China-Japan Friendship HospitalBeijing100029China department of Neurology Beijing University of Chinese Medicine Dongfang HospitalBeijing100078China department of Radiology China-Japan Friendship HospitalBeijing100029China Graduate School Beijing University of Chinese MedicineBeijing100029China

Objective To explore the neuroprotective effects and mechanism of Tanreqing Injection(TRQ)on treating ischemic stroke based on network pharmacology and in vivo experimental *** The chemical compounds of TRQ were retrieved based on published data,with targets retrieved from PubChem,Therapeutic Target Database and *** visualization and analysis were performed using Cytoscape,with protein-protein interaction networks derived from the STRING *** analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology *** in vivo experiments,the middle cerebral artery occlusion(MCAO)model was *** volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western *** docking was performed to predict ligand-receptor *** We screened 81 chemical compounds in TRQ and retrieved their therapeutic *** the targets,116 were therapeutic targets for *** enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic ***,in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats(P<0.05).In addition,protein levels of the apelin receptor(APJ)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway were increased by TRQ(P<0.05).In addition,41 chemical compounds in TRQ could bind to *** The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling ***,further studies are needed to confirm the findings.

关键词： Tanreqing Injection Chinese medicine ischemic stroke middle cerebral artery occlusion quantitative estimate of drug-likeness

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Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

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Neural Regeneration Research 2024年第11期19卷 2522-2531页

作者： Shaojun Wang Siti Tong Xin Jin Na Li Pingxiu Dang Yang Sui Ying Liu Dajiang Wang Division of ophthalmology The Third Medical Center of PLA General HospitalBeijingChina department of ophthalmology Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain *** models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular *** results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and *** single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular *** extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct *** found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of *** study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular *** data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

关键词： apoptosis axon degeneration high intraocular pressure microglia ocular hypertension photoreceptor cells retina retinal degeneration retinal ganglion cells single-cell RNA sequencing

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Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2673-2682页

作者： Huang Chen Rui-Ying Jiang Zhan Hua Xiao-Wei Wang Xiao-Li Shi Ye Wang Qian-Qian Feng Jie Luo Wu Ning Yan-Fen Shi Da-Kui Zhang Bei Wang Jian-Zheng Jie Ding-Rong Zhong department of Pathology China-Japan Friendship HospitalBeijing 100029China department of Gastrointestinal Surgery China-Japan Friendship HospitalBeijing 100029China department of Scientific Research GeneisBeijing 100012China

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly *** To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in *** We enrolled 2271 Chinese CRC patients at the China-Japan friendship *** proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain *** status was determined using an MSI detection *** analyses were conducted using SPSS software and logistic *** The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,*** mutations were more likely to occur in patients with moderate-to-high *** mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural *** MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous ***,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,*** dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II *** This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

关键词： Colorectal cancer Deficient mismatch repair Microsatellite instability Gene mutation Comprehensive analysis

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Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 227-235页

作者： Ning Zhang Pengyao Yang Yanmeng Li Qin Ouyang Fei Hou Guixin Zhu Bei Zhang Jian Huang Jidong Jia Anjian Xu Experimental and Translational Research Center Beijing Friendship HospitalCapital Medical UniversityBeijingChina department of Gastroenterology Beijing Shunyi HospitalBeijingChina department of Critical Liver Diseases Beijing Friendship HospitalCapital Medical UniversityBeijingChina MOE Key Laboratory of Protein Science School of Life SciencesTsinghua UniversityBeijingChina Liver Research Center Beijing Friendship HospitalCapital Medical UniversityBeijingChina

Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD ***,serum iron overload can also activate SMAD but does not induce BMP6 ***,the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain *** study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD ***:A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin(Holo-Tf).A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 *** blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of ***:Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to *** E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression;specifically,SMURF1 expression dramatically decreased when the serum iron concentration was ***,the expression of SMURF1 substrates,which are important molecules involved in the transduction of BMP/SMAD signaling,was significantly ***,in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron ***:SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.

关键词： BMP/SMAD pathway Hepcidin Holo-transferrin Ubiquitin-proteasome degradation Hemochromatosis

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Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

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World Journal of Emergency Medicine 2024年第3期15卷 206-213页

作者： A-ling Tang Yan Li Li-chao Sun Xiao-yu Liu Nan Gao Sheng-tao Yan Guo-qiang Zhang department of Emergency China-Japan Friendship HospitalBeijing 100029China Graduate School Beijing University of Chinese MedicineBeijing 100105China

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its ***:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ *** was intraperitoneally injected 2 h before *** data(blood pressure and heart rate) were *** intestinal microcirculation data of the rats were analyzed via microcirculation ***-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the *** analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in *** expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western ***:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory ***,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small ***:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

关键词： Sepsis Xuebijing Vascular endothelial growth factor A Microcirculation Rat Phosphoinositide 3-kinase Protein kinase B

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Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3493-3512页

作者： Longhao Cheng Xiaoxue Wang Aijun Liu Ying Zhu Hu Cheng Jiangling Yu Lili Gong Honglin Liu Guolin Shen Lihong Liu Institute of Clinical Medical Sciences ChinaeJapan Friendship HospitalCapital Medical UniversityBeijing 100029China department of Pharmacy ChinaeJapan Friendship HospitalBeijing 100029China beijing Chao-Yang hospital Capital Medical UniversityBeijing 100020China Institute of Chemicals Safety Chinese Academy of Inspection and QuarantineBeijing 100020China

Amino acid metabolic remodeling is a hallmark of cancer,driving an increased nutritional demand for amino *** acids are pivotal for energetic regulation,biosynthetic support,and homeostatic maintenance to stimulate cancer ***,the role of phenylalanine in multiple myeloma(MM)remains ***,we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow(BM)*** the treatment,phenylalanine levels increase in plasma and decrease in *** suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM *** requirement for phenylalanine by MM cells exhibits a similar *** phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib(BTZ)treatment in vitro and murine ***,phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3eCHOPeDR5 *** with ATF3 significantly affects phenylalanine deprivation *** conclusion,we have identified phenylalanine metabolism as a characteristic feature of MM metabolic *** is necessary for MM proliferation,and its aberrant demand highlights the importance of lowphenylalanine diets as an adjuvant treatment for MM.

关键词： Multiple myeloma Phenylalanine Amino acid metabolism Nutrient deprivation Cancer therapy Endoplasmic reticulum stress ATF3 Apoptosis

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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina department of General Surgery Tianjin Medical University General HospitalTianjinChina department of Anorectal Tianjin People's HospitalTianjinChina department of Radiology beijing friendship hospital Capital Medical UniversityBeijingChina department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina department of Thoracic Surgery/Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

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Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

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Biomedical and Environmental Sciences 2024年第8期37卷 887-896页

作者： Hao Zhang Jie Feng Shiyu Zhang Wenjia Liu Lin Ma Chinese PLA Medical School Beijing 100853China department of Radiology First Medical CenterChinese PLA General HospitalBeijing 100853China department of Radiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea *** CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS *** analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)*** The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those *** CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of *** Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

关键词： Acute mountain sickness High-altitude headache Cerebral blood flow Arterial spin labeling Magnetic resonance imaging

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Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

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World Journal of Gastroenterology 2024年第31期30卷 3668-3679页

作者： Hong-Wei Zhao Jin-Long Zhang Fu-Quan Liu Zhen-Dong Yue Lei Wang Yu Zhang Cheng-Bin Dong Zhen-Chang Wang department of Radiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China department of Radiology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China department of Interventional Radiology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver *** GM composition is diverse and associated with different etiologies of liver ***,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in ***,understanding the role of GM alterations in patients with HBV infection-related PH is *** To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)*** This was a prospective,observational clinical *** were 30 patients(with a 100%technical success rate)recruited in the present *** with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were *** samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon *** One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE *** was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE *** Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated *** microbiome therapies may be useful for preventing and trea

关键词： Transjugular intrahepatic portosystemic shunt Hepatic encephalopathy Gut microbiota Hepatitis B virus Portal hypertension

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Surgical approaches to correct corneal astigmatism at time of cataract surgery: a mini-review

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International Journal of ophthalmology(English edition) 2024年第7期17卷 1370-1374页

作者： Xiao-Lei Yin Zhi-Yang Ji Xiu-Xin Li Xue-Mei Liang Shu-Xing Ji department of ophthalmology the 305 Hospital of PLABeijing 100017China department of ophthalmology Daping HospitalArmy Medical UniversityChongqing 400042China department of Medical Administration the 305 Hospital of PLABeijing 100017China

Among refractive errors,astigmatism is the most common optical aberration,where refraction changes in different meridians of the *** causes blurred vision at any distance and includes corneal,lenticular,and retinal *** surgery used to cause a progressive increase in the pre-exisiting corneal astigmatism because of creating a surgically induced astigmatism,for example,a large size surgery *** development of surgical techniques during last decades has made cataract surgery interchange to treat preoperative corneal astigmatism at time of ***,three surgical approaches can be *** placing a sutureless clear corneal incision on the steep meridian of the cornea,a preoperative corneal astigmatism less than 1.0 D can be *** or paired peripheral corneal relaxing incisions(PCRIs)provide 1.0-3.0 D corneal astigmatism *** are typically used for treating 1.0-1.5 D of regular corneal astigmatism,if more than 2.0 D,the risk of overcorrection and irregular astigmatism is *** toric intraocular lenses(IOLs)are unavailable in markets,PCRIs are still a reasonable option for patients with up to 3.0 D of pre-existing corneal *** IOLs implantation can correct 1.0-4.5 D of corneal *** IOLs are approved to correct a high degree of corneal astigmatism with cylinder power up to 12.0 *** approaches can be used alone or in combination.

关键词： cornea astigmatism cataract surgery peripheral corneal relaxing incisions toric intraocular lens

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