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Optimizing prediction models for pancreatic fistula after pancreatectomy:Current status and future perspectives

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World Journal of Gastroenterology 2024年第10期30卷 1329-1345页

作者： Feng Yang John A Windsor De-Liang Fu department of Pancreatic Surgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Surgical and translational Research Centre Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1142New Zealand

Postoperative pancreatic fistula(POPF)is a frequent complication after pancre-atectomy,leading to increased morbidity and mortality.Optimizing prediction models for POPF has emerged as a critical focus in surgical research.Although over sixty models following pancreaticoduodenectomy,predominantly reliant on a variety of clinical,surgical,and radiological parameters,have been documented,their predictive accuracy remains suboptimal in external validation and across diverse populations.As models after distal pancreatectomy continue to be pro-gressively reported,their external validation is eagerly anticipated.Conversely,POPF prediction after central pancreatectomy is in its nascent stage,warranting urgent need for further development and validation.The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance.Moreover,there is potential for the development of personalized prediction models based on patient-or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF.In the future,prospective multicenter studies and the integration of novel imaging technologies,such as artificial intelligence-based radiomics,may further refine predictive models.Addressing these issues is anticipated to revolutionize risk stratification,clinical decision-making,and postoperative management in patients undergoing pancre-atectomy.

关键词： Pancreatic fistula Pancreaticoduodenectomy Distal pancreatectomy Central pancreatectomy Prediction model Machine learning Artificial intelligence

Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading:A multicenter retrospective study

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Chinese medical Journal 2024年第6期137卷 720-728页

作者： Ju Huang Huimin Liu Dekun Yang Tianming Xu Jing Wang Jingnan Li department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China Key Laboratory of Gut Microbiota translational Medicine Research Chinese Academy of Medical SciencesBeijing 100730China department of Gastroenterology Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical CollegeYantaiShandong 264000China department of Gastroenterology Beijing Zhong-Neng-Jian HospitalBeijing 102401China

Background:The incidence of well-differentiated gastric neuroendocrine tumors(G-NET)is increasing annually,and while they have a good prognosis and low mortality rate,their high recurrence rate makes treatment options controversial.This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods:We performed a multicenter,retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union medical College Hospital,Yantai Yuhuangding Hospital,and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023.Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results:After a median follow-up of 49 months,the overall recurrence rate among the 94 G-NET patients was 14%(13/94).The recurrence rates of endoscopic mucosal resection(EMR),endoscopic submucosal dissection(ESD),somatostatin analog(SSA)therapy,and surgery were 43%(6/14),10%(5/49),5%(1/22),and 11%(1/9),respectively.Post-treatment recurrence rates were significantly different(P=0.014)among four treatments(EMR,ESD,SSA,and surgery),and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group.From the second month onward,SSA therapy considerably reduced the gastrin levels from 1081.0(571.5,2472.8)pg/mL to 461.5(255.3,795.0)pg/mL(Z=-3.521,P<0.001).Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied,only the pre-treatment gastrin level(P=0.018 and 0.005)and the type of treatment(P=0.014 and 0.017)were significantly associated with G-NET recurrence.Conclusions:Individualized treatment strategies may reduce the risk of relapse after G-NET treatment.Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions,and it substantially decreases the incidence of post-treatment recurrence.

关键词： Well-differentiated G-NET Serum gastrin Personalized treatment Endoscopic submucosal dissection Endoscopic mucosal resection Somatostatin analog therapy Surgical resection Recurrence

Prevalence of retinal pathologies in people over 60 years:the Tehran Geriatrics Eye Study

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 721-728页

作者： Abolghasem Mortazavi Alireza Hashemi Alirerza Jamali Hassan Hashemi Mohammadreza Aghamirsalim Mehdi Khabazkhoob department of Neurosurgery Sina HospitalTehran University of Medical SciencesTehran ***Iran Noor Ophthalmology Research Center Noor Eye HospitalTehran ***Iran Rehabilitation Research Center Department of OptometrySchool of Rehabilitation SciencesIran University of Medical SciencesTehran ***Iran Noor Research Center for Ophthalmic Epidemiology Noor Eye HospitalTehran ***Iran translational Ophthalmology Research Center Tehran University of Medical SciencesTehran ***Iran department of Basic sciences School of Nursing and MidwiferyShahid Beheshti University of Medical SciencesTehran ***Iran

AIM:To determine the prevalence of some retinal pathologies in people over 60y and their association with demographic and ocular factors.METHODS:A cross-sectional study was conducted in Tehran using multistage cluster sampling.After selecting subjects aged 60 and over,optometric,and ophthalmic examinations were done.For retinal examination,a 90 D lens was used and indirect ophthalmoscopy was performed after instilling tropicamide drops.Biometry was done using the IOL Master for all participants.RESULTS:Of 3791 people that were invited through cluster sampling,3310 participated in the study(response rate=82%).The prevalence of retinal pigmented epithelium(RPE)change,drusen,geographic atrophy(GA),hypertensive retinopathy(HTR),nonproliferative diabetic retinopathy(NPDR),proliferative diabetic retinopathy(PDR),choroidal neovascularization(CNV),central retinal artery occlusion(CRAO),myopic retinopathy(MR),branch retinal vein occlusion(BRVO),and central retinal vein occlusion(CRVO)was 27.42%,11.08%,4.52%,3.03%,4.05%,0.54%,0.82%,0.39%,0.20%,0.49%,and 0.19%,respectively.After removing the effect of age,the odds of NPDR were 1.68 times higher in women compared to men(P=0.014).After removing the effect of sex,the odds of drusen,RPE change,GA,CNV,BRVO,and CRVO increased with age.CONCLUSION:There is a higher prevalence of RPE change,drusen,GA,CNV and a lower prevalence of MR and CRAO in the elderly population of Tehran aged over 60y compared to global average values.Considering the correlation of most of the diseases with age and their effects on vision,attention should be paid to these diseases and the related screening programs to prevent vision impairment.

关键词： retinal pathologies cross-sectional study vision impairment

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

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World Journal of Gastroenterology 2024年第17期30卷 2294-2297页

作者： Fabiola Di Dato Raffaele Iorio department of translational medical Science Section of PediatricsUniversity of Naples Federico IINaples 80131Italy

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.

关键词： Hepatitis B virus Interferon Nucleos(t)ide analogues Functional cure Children

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National translational Science Center for Molecular Medicine & department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

PINK1 is involved in determining the cellular autophagic hierarchy

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Science China(Life sciences) 2024年第5期67卷 1087-1088页

作者： Zhuchen Zhou Zhong Chen Yanrong Zheng Key Laboratory of Neuropharmacology and translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 311402China

The protein PINK1 plays a crucial role in the regulation of the cellular autophagic hierarchy.Autophagy,a highly conserved biological process,serves as a mechanism for the degradation of intracellular components by lysosomes.Autophagosomes play a pivotal role in this process by selectively sequestering specific targets,including damaged organelles,protein aggregates,and pathogens.

关键词： PINK1 determining hierarchy

Association of Congenital Heart Defects (CHD) with Factors Related to Maternal Health and Pregnancy in Newborns in Puerto Rico

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Congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado Caliani Gaytan Naydi Perez Eric Miranda Bryan Colón Morales Mónica Santos Biochemistry&Pharmacology department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for Clinical and translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico department of Internal Medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BMI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal development.Methods:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BMI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with CHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BMI,whereas 126 displayed a normal BMI.Conclusion:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of CHD.However,our analysis did not show a statistically signiﬁcant association between maternal BMI and the likelihood of CHD.These results may aid in developing effective strategies to prevent and manage CHD in neonates.

关键词： Congenital heart defects(CHD) obesisty maternal health diabetes body mass index(BMI)

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

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Chinese medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life sciences Westlake UniversityHangzhouZhejiang 310024China Key Laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus