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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki chan.Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching chan.Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng Leung Chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma:A systematic review and meta-analysis

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World Journal of Virology 2024年第1期13卷 107-119页

作者： Feng Yi Cheo Kai Siang chan.Vishal G Shelat Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore

BACKGROUND Cholangiocarcinoma is the second most common primary liver *** incidence and mortality rates have been increasing in recent *** C virus(HCV)infection is a risk factor for development of cirrhosis and ***,surgical resection remains the only curative treatment option for *** aim to study the impact of HCV infection on outcomes of liver resection(LR)in intrahepatic cholangiocarcinoma(ICC).AIM To study the outcomes of curative resection of ICC in patients with HCV(i.e.,HCV+)compared to patients without HCV(i.e.,HCV-).METHODS We conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)and observational studies to assess the outcomes of LR in ICC in HCV+patients compared to HCV-patients in tertiary care ***,EMBASE,The Cochrane Library and Scopus were systematically searched from inception till August *** studies were RCTs and non-RCTs on patients≥18 years old with a diagnosis of ICC who underwent LR,and compared outcomes between patients with HCV+vs HCV-.The primary outcomes were overall survival(OS)and recurrence-free *** outcomes include perioperative mortality,operation duration,blood loss,intrahepatic and extrahepatic *** Seven articles,published between 2004 and 2021,fulfilled the selection *** of the studies were retrospective ***,incidence of male patients,albumin,bilirubin,platelets,tumor size,incidence of multiple tumors,vascular invasion,bile duct invasion,lymph node metastases,and stage 4 disease were comparable between HCV+and *** transaminase[MD 22.20,95%confidence interval(CI):13.75,30.65,P<0.00001]and aspartate transaminase levels(MD 27.27,95%CI:20.20,34.34,P<0.00001)were significantly higher in HCV+group compared to *** of cirrhosis was significantly higher in HCV+group[odds ratio(OR)5.78,95%CI:1.38,24.14,P=0.02]compared to *** of poorly

关键词： Cholangiocarcinoma Bile duct cancer Hepatitis C Surgical resection Hepatectomy

Omental fibroma combined with right indirect inguinal hernia masquerades as a scrotal tumor: A case report

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World Journal of Clinical Cases 2024年第5期12卷 988-994页

作者： Ping Zhou chan.Hui Jin Ying Shi Guo-Qing Ma Wen-Hao Wu Yu Wang Kun Cai Wu-Feng Fan Tian-Bao Wang Department of Gastrointestinal Surgery South China Hospital of Shenzhen UniversityShenzhen 518000Guangdong ProvinceChina

BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is *** patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even ***,omental tumors are mostly metastatic,and primary omental fibroma is *** SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 *** examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the ***,tumor resection and tension-free inguinal hernia repair were *** final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal *** This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.

关键词： Hernia Indirect inguinal hernia Fibroma Omental tumor Scrotal tumor Greater omentum Case report

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

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Traditional Medicine Research 2024年第2期9卷 52-65页

作者： Yu-Ming Wang Hong-Wei Tao Feng-chan.Wang Ping Han Na Liu Guo-Jing Zhao Hai-Bo Hu Xue-Chao Lu College of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Respiratory and Critical Care Medicine Qingdao Hospital of Traditional Chinese Medicine(Qingdao Hiser hospital)Qingdao 266000China.

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and *** clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechan.sm of action of MFJT on PAH remains ***:In this study,a monocrotaline-induced PAH rat model was established and treated with *** therapeutic effects of MFJT on PAH rat model were *** pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried *** key targets identified from network pharmacology were ***:Results showed significant therapeutic effects of MFJT on PAH rat *** of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular *** docking showed that the key components were well docked with the core *** experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

关键词： Mufangji tang pulmonary arterial hypertension apoptosis inflammatory response oxidative stress vascular remodeling

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

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World Journal of Gastroenterology 2024年第12期30卷 1751-1763页

作者： Ting Yang Kang Chao Xia Zhu Xue-Ding Wang Sumyuet chan.Yan-Ping Guan Jing Mao Pan Li Shao-Xing Guan Wen Xie Xiang Gao Min Huang School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Institute of Clinical Pharmacology Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261United States

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of *** optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia *** To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite *** leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two *** Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate *** patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

关键词： Thiopurine-induced late leucopenia DNA-thioguanine 6-thioguanine nucleotide Proactive therapeutic drug monitoring Crohn’s disease

“Keyboard sign”and“coffee bean sign”in the prenatal diagnosis of ileal atresia:A case report

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World Journal of Clinical Cases 2024年第24期12卷 5622-5627页

作者： Zhi-Hui Fei Qi-Yi Zhou Ling Fan chan.Yin Department of Ultrasound Changde Maternal and Child Health Care HospitalChangde 415000Hunan ProvinceChina

BACKGROUND Ileal atresia is a congenital abnormality where there is significant stenosis or complete absence of a portion of the *** overall diagnostic accuracy of prenatal ultrasound in detecting jejunal and ileal atresia is *** report a case of ileal atresia diagnosed prenatally by ultrasound examination with the“keyboard sign”and“coffee bean sign”.CASE SUMMARY We report a case of ileal atresia diagnosed in utero at 31 weeks'of *** ultrasound examination revealed two rows of intestines arranged in an‘S’shape in the middle *** inner diameters were 1.7 cm and 1.6 cm,respectively.A typical“keyboard sign”was *** intestine canal behind the“keyboard sign”showed an irregular strong *** was no normal intestinal wall structure,showing a typical“coffee bean sign”.Termination of the pregnancy and autopsy findings confirmed the *** The prenatal diagnosis of ileal atresia is *** sonographic features of the“keyboard sign”and“coffee bean sign”are helpful in diagnosing the location of congenital jejunal and ileal atresia.

关键词： Ileal atresia The prenatal diagnosis Keyboard sign Coffee bean sign

First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang chan.Zhu Dongsheng Chen Baorui Liu Juan Du The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The Comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key Laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

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Nano Research 2024年第10期17卷 9141-9151页

作者： Jeong Yu Lee Shonit Nair Sharma Sung-Yu Hong Young-Guk Ko Yangsoo Jang Minjae Do Michael Christopher Stark Qiwen Peng Benjamin Allen Mossburg Bo chan.Seo Yuhan Lee Department of Materials Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeon 305-701Republic of Korea Department of Anesthesiology Perioperativeand Pain MedicineCenter for Accelerated Medical Innovation&Center for NanomedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Department of Biological Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Cardiovascular Product Evaluation Center Yonsei University College of MedicineSeoul 120-752Republic of Korea Division of Cardiology Department of Internal MedicineSeverance Cardiovascular HospitalYonsei University College of MedicineSeoul 120-752Republic of Korea

Cardiovascular diseases remain the leading cause of mortality worldwide,with percutaneous coronary interventions(PCI)using drug-eluting stents(DES)as the standard treatment for coronary artery *** advancements in DES technology,challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks,highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention *** balloons(DEBs)coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion ***,efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a ***,we developed a pressure-responsive and pH-triggered,paclitaxel(PTX)coated DEB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites,overcoming the limitations of drug dispersion and inefficiencies associated with conventional *** the charge reversion of albumin around its isoelectric point,paclitaxel-loaded human serum albumin nanoparticles(PTX-HSA-NPs)and heparin were coated using a layer-by-layer deposition method at pH *** exposure to physiological pH(i.e.,7.4),the coating is rapidly released from the balloon *** with a protective shellac coating,the DEB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo(up to 400μg per gram tissue),exceeding current DEBs in the *** results suggest the pH-responsive,multi-layer coated DEB’s potential for superior procedural outcomes,addressing a critical unmet need in PCI.

关键词： drug-eluting balloon layer-by-layer coating coronary artery disease paclitaxel

Accuracy and safety of a novel aqueous humor collector versus 29 G insulin syringe for anterior chamber paracentesis and aqueous humor collection:A multicenter randomized clinical trial

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Chinese Medical Journal 2024年第12期137卷 1507-1509页

作者： Feiyue Xiao Pengcheng Li Hang Song Mingchan. Zhang Youxin Chen chan.Zhao Department of Ophthalmology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100005China Key Laboratory of Ocular Fundus Diseases Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Ophthalmology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

To the Editor:Anterior chamber(AC)paracentesis is a commonly performed procedure to lower intraocular pressure(IOP),and to sample aqueous humor(AH)for clinical and research *** suggested by an international collaboration team,an immediately performed AC paracentesis before an intravitreal injection can also prevent post-injection IOP spike.[1]While IOP could immediately be reduced by AC paracentesis,the procedure of obtaining an AH sample(liquid biopsy)is more *** methods have been developed to facilitate AH collection and transfer,[2-7]among which a vacuum-based AH collector(SnovoDAHC I-50,Sightnovo Medical Technology Co.,Beijing,China)has better performance than the commonly used insulin syringe in accurate sampling of about 50μL AH in rabbits by one hand.[7]The current clinical trial aimed to evaluate the performance and safety of this product in human subjects.

关键词： vacuum injection clinical

Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer

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Cancer Innovation 2024年第4期3卷 67-86页

作者： Yuan‐yuan Sun Hai‐cheng Gao Peng Guo Na Sun chan.Peng Zhi‐hua Cheng Jing Gu Jin‐yi Liu Fei Han Department of Clinical Pharmacy Jilin University School of Pharmaceutical SciencesChangchunChina Institute of Toxicology College of Preventive MedicineArmy Medical UniversityChongqingChina Department of Hepatobiliary Surgery Third Affiliated Hospital of Chongqing Medical UniversityChongqingChina Breast and Thyroid Surgery Southwest HospitalArmy Medical UniversityChongqingChina College of Pharmaceutical Sciences Southwest UniversityChongqingChina Vascular Surgery Department General Surgery CenterFirst Hospital of Jilin UniversityChangchunChina Department of Toxicology School of Public HealthChongqing Medical UniversityChongqingChina Laboratory of Reproductive Biology Chongqing Medical UniversityChongqingChina

Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival *** identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently ***:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in *** UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic ***‐of‐function assays were performed to examine the *** ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular ***:NR3C2 was identified as a potentially important molecule in ***3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these *** operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC *** NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC *** results have been confirmed both with database analysis and real‐world clinical samples on a tissue *** number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in *** NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application ***3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell ***3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially si

关键词： diagnosis and prognosis expression regulation function immune cell infiltration non‐small cell lung cancer NR3C2 therapeutic target tumor microenvironment