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Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

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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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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Value of procalcitonin and presepsin in the diagnosis and severity stratification of sepsis and septic shock

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World Journal of Emergency Medicine 2024年第2期15卷 135-138页

作者： Enfeng Ren Hongli Xiao Guoxing Wang Yongzhen Zhao Han Yu Chunsheng Li Department of Emergency Medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Emergency Medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100050China

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnormalities,and can increase mortality to>40%.[1-3]Early recognition and risk stratification of septic shock are crucial but challenging because of the heterogeneity of its presentation and progression.

关键词： diagnosis sepsis mortality

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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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Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

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Journal of Geriatric Cardiology 2024年第1期21卷 90-103页

作者： Cheng-Yan HU Yan-Ling WANG Zhen-Xing FAN Xi-Peng SUN Shuai WANG Zhi LIU Department of Geriatrics Fu Xing HospitalCapital Medical UniversityBeijingChina Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Emergency Department of Xuanwu hospital Capital Medical UniversityBeijingChina

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were *** on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up *** were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 *** aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel *** cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were *** CLR was observed in 44.4%of the overall *** differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene ***2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

关键词： CYP2C19 drugs PCI

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Narrative review of latest research progress about robotic percutaneous coronary intervention

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Journal of Geriatric Cardiology 2024年第8期21卷 816-825页

作者： Zhen-Yu LIU Guang-Yao ZHAI Department of Clinical Medicine Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Cardiology Beijing Luhe HospitalCapital Medical UniversityBeijingChina

Robotic percutaneous coronary intervention(R-PCI)is a novel technology in which operators can manipulate guidewires and catheter devices in interventional *** approach provides great benefits to interventional cardiologists in terms of reducing both radiation exposure and orthopedic *** large,high-quality cohort studies have confirmed the short-term safety and high technical success rate of ***,randomized long-term data are still needed before adopting them as part of standard coronary ***,tele-stenting for complex coronary lesions has significant potential for *** need to overcome the present relevant challenges for its application such as inherent delays,bedside care for unstable patients from R-PCIs to manual PCIs(M-PCIs),incompatibility for a thrombus aspiration catheter and heavily calcified *** is a great future in laboratory workflow teams,3D-printed anatomical models and multiple joint collaborative control *** narrative review summarizes the latest developments in R-PCI,with a focus on developments in robotic technology,and discusses the current and future potential use of R-PCI in clinical practice globally.

关键词： coronary injuries unstable

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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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Full title: Function， mechanism of action， metabolism， and commercial application of Lonicera japonica: a review

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Food Science and Human Wellness 2024年

作者： Xinli Yang Dan Yan beijing Institute of Clinical Pharmacy beijing friendship hospital， capital medical university

Lonicera japonica (honeysuckle) is a traditional Chinese medicinal food， in which the main active ingredients are phenolic acids， polysaccharides， flavonoids， and volatile oils. They have various biological activities， including antiviral， antibacterial， antioxidant， hypoglycemic and lipid-lowering， and anti-inflammatory effects. This review summarizes the health effects and pharmacodynamic mechanisms of Lonicera japonica extracts and the major active ingredients in these extracts， and the structures， metabolic process in vivo， and biotransformation processes of these compounds. In addition， the current status of the development of Lonicera japonica-related functional foods is summarized. The aim is to provide a theoretical basis and reference for the further development and use of the active ingredients in Lonicera japonica as functional foods for disease prevention and treatment.

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Association between stress hyperglycemia ratio and in-hospital outcomes:findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)Project

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Journal of Geriatric Cardiology 2024年第6期21卷 658-668页

作者： Wen-Jie WANG Ke-Xin WANG Jia-Long NIU Yi-Xuan LIU Hai-Long GE Hua SHEN On behalf of CCC-ACS investigators Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijingChina

BACKGROUND Stress hyperglycemia ratio(SHR)could provide accurate information on the acute status of *** relationship between SHR and acute coronary syndrome(ACS)prognosis remains *** study was conducted to identity the association between SHR and in-hospital outcomes in patients with *** A total of 12,010 patients were eventually enrolled in the *** relationship between SHR and in-hospital major adverse cardiovascular events(MACEs)was then modeled by restricted cubic spline(RCS)curves,and all patients were divided into three groups according to the *** multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes,described as odds ratios(ORs)and 95%confidence intervals(CIs).Subgroup analyses were also performed on different *** The median age of this cohort was 63(54,71)years old,and 8942(74.5%)were *** 1 was defined as SHR1(n=5763).Compared with Group 2,Group 1(OR=1.891,95%CI:1.028-3.479,Phospital *** was associated with higher risks of in-hospital MACEs in the subgroups of DM[OR=2.282,95%CI:1.477-3.524).CONCLUSIONS Both low and high SHR levels were independently associated with in-hospital *** males with DM,hypertension,and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

关键词： acute cardiovascular finding

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Pharmacological Effects of Botanical Drugs on Myocardial Metabolism in Chronic Heart Failure

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Chinese Journal of Integrative Medicine 2024年第5期30卷 458-467页

作者： HU Yu-xuan QIU Sheng-lei SHANG Ju-ju WANG Zi LAI Xiao-lei beijing hospital of Traditional Chinese Medicine Capital Medical UniversityBeijing 100010China

Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related *** studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart ***,most of the drugs that increase cardiac energy are still in the theoretical or testing *** research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate *** this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related *** the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.

关键词： botanical drugs chronic heart failure myocardial metabolism pharmacological effects review

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