In vivo study of the effect of anlotinib on the stemness of the lenvatinib-resistant hepatocellular carcinoma cells and the underlying mechanisms

Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the underlying molecular mechanisms.Methods:A subcutaneous xenograft model of Hep3B-derived HCC was established in nude mice,which were randomly divided into 2 groups(n=5 males per group):(1)intragastric administration of anlotinib(0.4 mg/kg)and(2)intragastric administration of normal saline.We constructed lenvatinib-resistant cell lines and randomly divided the mice into 3 groups(n=5 males per group):(1)intragastric administration of anlotinib,(2)intragastric administration of lenvatinib,and(3)intragastric administration of normal saline.After 2 weeks of treatment,tumor tissues were harvested,and mRNA and proteins were isolated from the tissues.Changes in the expression of cancer stemness markers(epithelial cell adhesion molecule[EpCAM],CD13,CD90,aldehyde dehydrogenase 1[ALDH1],CD44,and CD45),totipotency factors(sex-determining region Y-box 2[Sox2],Nanog,octamer-binding transcription factor 4[Oct4]),and genes related to the Notch signaling pathway were examined.Results:Compared with that in the control group,tumor size and weight were reduced in nude mice treated with anlotinib.These differences were statistically significant in both the types of nude mice.Anlotinib affected stemness markers and totipotency factors by downregulating the expression of CD133,CD90,and G-protein–coupled receptor 5(LGR5)and upregulating the expression of intercellular adhesion molecule 1(ICAM-1)and Sox2.In addition,lenvatinib-resistant cell lines increased Notch signaling pathway,whereas anlotinib inhibited Notch signaling pathway.Conclusions:The antitumor effect of anlotinib on HCC and lenvatinib-resistant HCC cellsmay occur through inhibition of the Notch signaling pathway.Anlotinib may be the drug of choice for sequential therapy in lenvatinib-resistant liver cancer.

Research Progress of HOXA13/HOTTIP Gene and Digestive Tract Cancer

The occurrence and development of digestive tract tumors are mainly caused by the interaction of genetic and environmental factors, multiple incentives, multiple genes involved, and multi-step regulation. With the development of gene sequencing technology, precise treatment of tumor era has arrived. Studies have shown that the HOXA13 gene in the homeobox gene is abnormally expressed in digestive system tumors. Studies have shown that HOXA13 may have a certain relationship with the occurrence, development and prognosis of the tumor, pending the diagnosis and treatment of digestive tract tumors with a new gene target.

Analysis of 87 Cases of laparoscopic Choledochotomy with Primary Suture

To investigate the feasibility and clinical effect of laparoscopic choledochotomy for primary suture of bile duct.Methods:There were 190 cases of cholecystolithiasis with choledocholithiasis.They were randomly divided into endoscopic group and open group.In the endoscopic group,87 patients underwent laparoscopic choledocholithotomy and primary bile duct suture.A total of 103 patients in open group were treated with open bile duct incision and T tube drainage.The operative time,intraoperative blood loss,postoperative ventilation time,hospital stay and postoperative complications were compared between the two groups.Results:The length of hospital stay,the amount of bleeding during operation and the time of postoperative ventilation were less than those in open group.The operation time was longer than that in open group,P<0.01.There were 0 cases of postoperative incision infection,2 cases of bile leakage and 1 case of residual stone in endoscopic group.The incidence of complications was 5.7%.The open group was 5,3,3 and 10.7% respectively.Comparison of complications between the two groups,P<0.01.Conclusion:Select the right case strictly,Laparoscopic and choledochoscopy combined with cholecystolithiasis with choledocholithiasis is effective,safe and minimally invasive,short hospitalization time and less complications.

Exploring the psychological impact of the 2022 SARS-CoV-2 Omicron variant outbreak in China

To the editor:The impact of the coronavirus disease 2019(COVID-19)pandemic in 2020 on mental health was substantialin Chinai2and various other countries.34 Beyond the direct consequences of COVID-19,the pandemic created an environment in which many determinants of mental health were affected.Issues associated with the pandemic,such as loss of livelihood,limited access to medical services,reduced social interactions,and economic downturn,could potentially have adverse effects on the population's mental well-being.5 In November 2021,the World Health Organization(WHO)designated the new variant of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),variant B.1.1.529,as a variant of concern and named it Omicron;its rapid mutation and spread raised a new global health concern.

Crowned Dens Syndrome: Recent Progress on Diagnosis and Treatment

Defined as an association of acute cervical pain and calcifications in the peri-odontoid space, crowned dens syndrome (CDS) is a major imaging manifestation of “coronary”. CDS is a rare but under-recognized cause of severe neck pain in older adults. As such, it is often misdiagnosed. So, we review the literature with particular attention to the clinical and radiological aspects of this syndrome.

Progress in Endoscopic Treatment of Upper Gastrointestinal Bleeding

Due to the increase in the incidence of upper gastrointestinal bleeding, the treatment methods are more and more diversified. With the popularization of endoscopic techniques and the wide range of endoscopic hemostasis methods, endoscopy has become an important method for the treatment of upper gastrointestinal bleeding, and greatly updated the treatment concept of upper gastrointestinal bleeding. In this paper, we reviewed the literature reports of endoscopic treatment of upper gastrointestinal bleeding in recent years.

Venous thromboembolism in patients with liver cancer:a retrospective study

Background:Little is known about the association between venous thromboembolism(VTE)and tumors.In this study,we identified the clinical features of patients with liver cancer who presented with at least 1 VTE episode.Methods:This was a retrospective case-control study of a single-institution database with univariate and multivariate analyses usingχ^(2)and Fisher exact tests.Statistical significance was set at P<0.05.Results:The overall incidence of VTE in the patients with liver cancer was 1.2%.More than half(53.8%)of the 13 patients with liver cancer and venous thrombosis died within 2 months.The thrombus in 12 patients(92.3%)was located within the deep veins,whereas the other patient(7.7%)was diagnosed with a pulmonary embolism.Of the 11 patients,9(69.2%)had swelling and/or pain symptoms.All 6 patients with peripherally inserted central catheters(PICCs)had thrombosis,accounting for 46.2%of all patients with liver cancer and venous thrombosis.Compared with the controls,liver cancer patients with PICC tubes,thrombosis-related symptoms such as swelling and pain,traumatic stimulation such as fracture,acute respiratory distress syndrome,and interventional therapy or hemostasis drugs were prone to be diagnosed with VTE(P<0.05).Conclusions:Liver cancer and thrombosis are rare and have poor prognoses.Liver cancer with thrombosis may be associated with PICC catheterization,traumatic stimulation,or hemostatic drugs.Patients with liver cancer and thrombosis often present with swelling and pain.

Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer

Liver cancer presents divergent clinical behaviors.There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been studied.In this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer prognosis.Model performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,respectively.The seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic factors.Moreover,the model successfully categorizes patients into high-low risk groups.Diagnostic and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.