The Chinese guideline for management of snakebites

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Development of a model based on the age-adjusted Charlson comorbidity index to predict survival for resected perihilar cholangiocarcinoma

BACKGROUND Perihilar cholangiocarcinoma(pCCA)has a poor prognosis and urgently needs a better predictive method.The predictive value of the age-adjusted Charlson comorbidity index(ACCI)for the long-term prognosis of patients with multiple malignancies was recently reported.However,pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis,and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear.AIM To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients.METHODS Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database.The patients were randomly assigned 3:1 to training and validation cohorts.In the training and validation cohorts,all patients were divided into low-,moderate-,and high-ACCI groups.Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival(OS)for pCCA patients,and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS.An online clinical model based on the ACCI was developed and validated.The concordance index(C-index),calibration curve,and receiver operating characteristic(ROC)curve were used to evaluate the predictive performance and fit of this model.RESULTS A total of 325 patients were included.There were 244 patients in the training cohort and 81 patients in the validation cohort.In the training cohort,116,91 and 37 patients were classified into the low-,moderate-and high-ACCI groups.The Kaplan-Meier curves showed that patients in the moderate-and high-ACCI groups had worse survival rates than those in the low-ACCI group.Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection.In addition,an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts.The calibration curve and ROC curve indicated that the model had a good fit and prediction performance.CONCLUSION A high ACCI score may predict poor long-term survival in pCCA patients after curative resection.High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.

Percutaneous biliary stent combined with brachytherapy using 125I seeds for treatment of unresectable malignant obstructive jaundice:A meta-analysis

BACKGROUND Malignant obstructive jaundice(MOJ)is a common pathologic manifestation of malignant biliary obstruction.Recently,several clinical trials have explored the clinical effectiveness of intraluminal^(125)I seed-based brachytherapy for MOJ patients,and various outcomes have been reported.AIM To assess the efficacy and safety of percutaneous biliary stents with^(125)I seeds compared to conventional metal stents in patients with unresectable MOJ.METHODS A systematic search of English-language databases(PubMed,Embase,Cochrane Library,and Web of Science)was performed to identify studies published prior to June 2020 that compared stents with or without^(125)I seeds in the treatment of unresectable MOJ.The outcomes analyzed included primary outcomes(stent patency and overall survival)and secondary outcomes(complications and liver function parameters).RESULTS Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis.Of the 875 included patients,404 were treated with^(125)I seed stents,while 471 were treated with conventional stents.Unadjusted pooled analysis demonstrated that compared to conventional stents,^(125)I seed stents extended the stent patency time[hazard ratio(HR)=0.36,95%confidence interval(CI)=0.28-0.45,P<0.0001]and overall survival period(HR=0.52,95%CI=0.42–0.64,P<0.00001).Subgroup analyses based on the type of^(125)I seed stent and type of study design showed consistent results.However,there were no significant differences in the occurrence of total complications[odds ratio(OR)=1.12,95%CI=0.75-1.67,P=0.57],hemobilia(OR=1.02,95%CI=0.45-2.3,P=0.96),pancreatitis(OR=1.79,95%CI=0.42-7.53,P=0.43),cholangitis(OR=1.13,95%CI=0.60-2.13,P=0.71),or pain(OR=0.67,95%CI=0.22-2,P=0.47).In addition,there were no reductions in the levels of serum indices,including total bilirubin[mean difference(MD)=10.96,95%CI=-3.56-25.49,P=0.14],direct bilirubin(MD=7.37,95%CI=-9.76-24.5,P=0.4),alanine aminotransferase(MD=7.52,95%CI=-0.71-15.74,P=0.07),and aspartate aminotransferase(MD=-4.77,95%CI=-19.98-10.44,P=0.54),after treatment.Publication bias was detected regarding the outcome overall survival;however,the conclusions were not changed after the adjustment.CONCLUSION Placement of stents combined with brachytherapy using^(125)I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage.Thus,it can be considered an effective and safe treatment for unresectable MOJ.

Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

Application of artificial neural networks in detection and diagnosis of gastrointestinal and liver tumors

As a form of artificial intelligence,artificial neural networks(ANNs)have the advantages of adaptability,parallel processing capabilities,and non-linear processing.They have been widely used in the early detection and diagnosis of tumors.In this article,we introduce the development,working principle,and characteristics of ANNs and review the research progress on the application of ANNs in the detection and diagnosis of gastrointestinal and liver tumors.

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

LIN28A attenuates high glucose-induced retinal pigmented epithelium injury through activating SIRT1-dependent autophagy

AIM:To evaluate the effects of LIN28A(human)on high glucose-induced retinal pigmented epithelium(RPE)cell injury and its possible mechanism.METHODS:Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose(HG)in ARPE-19 cells.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot tested the expression of the corresponding genes and proteins.Cell viability as well as apoptosis was determined through cell counting kit-8(CCK-8)and flow cytometry assays.Immunofluorescence assay was adopted to evaluate autophagy activity.Caspase 3 activity,oxidative stress markers,and cytokines were appraised adopting their commercial kits,respectively.Finally,ARPE-19 cells were preincubated with EX527,a Sirtuin 1(SIRT1)inhibitor,prior to HG stimulation to validate the regulatory mechanism.RESULTS:LIN28A was downregulated in HG-challenged ARPE-19 cells.LIN28A overexpression greatly inhibited HGinduced ARPE-19 cell viability loss,apoptosis,oxidative damage as well as inflammatory response.Meanwhile,the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression.In addition,treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis,oxidative damage as well as inflammation in ARPE-19 cells.CONCLUSION:LIN28A exerts a protective role against HG-elicited RPE oxidative damage,inflammation,as well as apoptosis via regulating SIRT1/autophagy.

Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma

BACKGROUND Postoperative morbidity after curative resection for hilar cholangiocarcinoma(HCCA)is common;however,whether it has an impact on oncological prognosis is unknown.AIM To evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODS Patients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled.The independent risk factors for morbidity in the 30 d after surgery were investigated,and links between postoperative morbidity and patient characteristics and outcomes were assessed.Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification,and major morbidities were defined as Clavien-Dindo≥3.Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival(RFS)and overall survival(OS).RESULTS Postoperative morbidity occurred in 146 out of 239 patients(61.1%).Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus,and obesity were independent risk factors. Postoperative morbidity was associated with decreasedOS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003;RFS: 16.0 mo vs 26.0 mo, respectively,P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity wasindependently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval(CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, majormorbidity was independently associated with decreased OS (HR: 2.175;95%CI: 1.470-3.216, P <0.001) and RFS (HR: 2.054;95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA.CONCLUSIONPostoperative morbidity (especially major morbidity) may be an independent risk factor forunfavorable prognosis in HCCA patients following curative resection.

Multiple primary malignancies-hepatocellular carcinoma combined with splenic lymphoma:A case report

BACKGROUND Primary liver cancer is one of the most common malignant tumours,while primary splenic lymphoma is a rare malignancy.Thus,cases of hepatocellular carcinoma(HCC)combined with splenic lymphoma are extremely rare.CASE SUMMARY We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound.Contrast-enhanced computed of the abdomen revealed a circular,low-density,shallow mass(approximately 2.6 cm in diameter)in the left intrahepatic lobe and multiple round,low-density shadows in the spleen with clear boundaries(maximum diameter 7.6 cm).Based on the characteristic clinical symptoms and explicit radiological findings,the clinical diagnosis was HCC with metastasis to the liver portal,retroperitoneal lymph nodes,and spleen.After transcatheter arterial chemoembolization and sequential radiofrequency ablation,the-fetoprotein level returned to the normal range,and the hepatitis B cirrhosis improved.In addition,splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma,which went into remission after chemotherapy.CONCLUSION HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed.Better understanding would facilitate early diagnosis,treatment and prognosis.

Precision interventional radiology

The recent interest in precision medicine among interventionists has led to the establishment of the concept of precision interventional radiology(PIR).This concept focuses not only on the accuracy of interventional operations using traditional image-guided techniques,but also on the comprehensive evaluation of diseases.The invisible features extracted from CT,MRI,or US improve the accuracy and specificity of diagnosis.The integration of multi-omics and molecule imaging provides more information for interventional operations.The development and application of drugs,embolic materials,and devices broaden the concept of PIR.Integrating medicine and engineering brings new image-guided techniques that increase the efficacy of interventional operations while reducing the complications of interventional treatment.In all,PIR,an important part of precision medicine,emphasizing the whole disease management process,including precision diagnosis,comprehensive evaluation,and interventional therapy,maximizes the benefits of patients with limited damage.

Gastroesophageal varices in a patient presenting with essential thrombocythemia:A case report

BACKGROUND Gastroesophageal varices are a rare complication of essential thrombocythemia(ET).ET is a chronic myeloproliferative neoplasm(MPN)characterized by an increased number of blood platelets.CASE SUMMARY A 46-year-old woman,who denied a history of liver disease,was admitted to our hospital on presentation of hematemesis.Laboratory examination revealed a hemoglobin level of 83 g/L,and a platelet count of 397×109/L.The appearance of gastric and esophageal varices with red colored signs as displayed by an urgent endoscopy was followed by endoscopic variceal ligation and endoscopic tissue adhesive.Abdominal computed tomography revealed cirrhosis,marked splenomegaly,portal vein thrombosis and portal hypertension.In addition,bone marrow biopsy and evidence of mutated Janus kinase 2,substantiated the onset of ET.The patient was asymptomatic with regular routine blood testing during the 6-mo follow-up period.Therefore,in this case,gastroesophageal varices were induced by ET.CONCLUSION MPN should be given considerable attention when performing differential diagnoses in patients with gastroesophageal varices.An integrated approach such as laboratory tests,radiological examination,and pathological biopsy,should be included to allow optimal decisions and management.

Imaging-based diagnosis for extraskeletal Ewing sarcoma in pediatrics: A case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a member of the Ewing sarcoma family of tumors which is pathologically known as a small,round,blue cell tumor involving bone and soft tissue.The prevalence of EES is only 15%-25%of all Ewing sarcoma and EES often occurs in patients aged from 20-mo-old to 30-yearsold resulting in an unfavorable prognosis.CASE SUMMARY The present case report described a 7-year-old patient with a palpable EES mass of 33 mm×27 mm×28 mm in the deep neck with symptoms of persistent dyspnea over the past 5 mo.After laboratory examinations,abnormal physiological and biochemical indicators were not found.Ultrasound images presented the mass to be complex,solid and fluid-filled with circumscribed margins and posterior acoustic enhancement.The mass also presented with partial internal vascularity.The contrast-enhanced magnetic resonance imaging scan illustrated the outstanding enhancement with fast perfusion mode in the early arterial phase. CONCLUSIONOur study suggested that a quick-growing mass in the pediatric patient is possibly a malignanttumor whether the mass has well-defined margins or not.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3b/MMPs

Golgi membrane protein 1(GOLM1/GP73)is a serum marker of hepatocellular carcinoma(HCC).We have previously shown that mTOR promoted tumorigenesis of HCC through stimulating GOLM1 expression.In this study,we demonstrated that the mammalian target of rapamycin(mTOR)was a negative regulator of microRNA-145(miR-145)expression.miR-145 inhibited GOLM1 expression by targeting a coding sequence of GOLM1 gene.GOLM1 and miR-145 were inversely correlated in human HCC tissues.GOLM1-enriched exosomes activated the glycogen synthase kinase-3β/matrix metalloproteinases(GSK-3β/MMPs)signaling axis of recipient cells and accelerated cell proliferation and migration.In contrast,miR-145 suppressed tumorigenesis and metastasis.We suggest that mTOR/miR-145/GOLM1 signaling pathway should be targeted for HCC treatment.

Multifunctional Gd-CuS loaded UCST polymeric micelles for MR/PA imaging-guided chemo-photothermal tumor treatment

Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.

Anatomical hepatectomy for achieving textbook outcome for perihilar cholangiocarcinoma treated with curative-intent resection: A multicenter study

Background and aim:The textbook outcome(TO)is a comprehensive measure that is superior to individual measures for analysis of surgical quality of care.Anatomical hepatectomy(AH)is beneficial in terms of short-term outcomes in patients undergoing resection.This study was performed to investigate the association between AH and achieving the TO for patients with perihilar cholangiocarcinoma(pCCA)treated with curative-intent resection.Methods:This study involved patients who underwent curative-intent resection for newly diagnosed pCCA from January 2013 to January 2018 at three hospitals in China.All patients were divided into two groups according to the type of hepatectomy:the AH group and non-AH group.The incidence and distribution of achieving the TO were compared between the two groups.Univariable and multivariable logistic regression analyses were used to identify independently predictive factors associated with achieving the TO in patients with pCCA.Results:In total,333 patients were enrolled[AH group,225(67.6%);non-AH group,108(32.4%)].The incidence of achieving the TO in all patients was 24.3%,and the incidence was significantly higher in the AH than non-AH group(30.7%vs.11.1%,respectively).Multivariable analysis revealed that AH,total bilirubin concentration of<34μmol/L,maximum tumor size of<3 cm,no macrovascular invasion,and no lymph node metastasis were independently associated with a higher incidence of achieving the TO.Conclusions:The TO was achieved in approximately one-fourth of patients with pCCA who underwent curative-intent resection.The use of AH was more conducive to achieving the TO in patients with pCCA.