Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

OBJECTIVE To analyze the correlation between styloid process related parameters and symptoms in patients with styloid process syndrome.METHODS A retrospective study was conducted on the 3D reconstruction CT results of the styloid process in 68 patients diagnosed with styloid process syndrome who visited the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2024.The relationship between parameters such as styloid process length,angle,distance from styloid process tip to pharynx,and specific symptoms in patients with styloid process syndrome was analyzed.RESULTS Among 68 patients with styloid process syndrome,44 had unilateral symptoms and 24 had bilateral symptoms.The length of the styloid process on the symptomatic side of patients with unilateral symptoms(3.86±0.16)cm was significantly longer than that on the asymptomatic side(2.98±0.17)cm(Z=-2.191,P=0.028);The length of the styloid process on the side with severe symptoms in patients with bilateral symptoms(3.98±0.37)cm was also significantly longer than that in patients with mild symptoms(3.37±0.15)cm(t=2.448,P=0.024).Patients with styloid process syndrome mainly present with pharyngalgia(64.71%,44/68).There were no significant differences in the length,inclination angle,anteversion angle,and distance between the styloid process tip and the pharynx among those with unilateral pharyngalgia(n=29),bilateral pharyngalgia(n=15),and non pharyngalgia(n=24)(P>0.05).However,among the 68 patients with styloid syndrome,12 had calcification of the styloid hyoid ligament,while 56 did not.The incidence of unilateral pharyngalgia was significantly higher in patients with calcification of the styloid hyoid ligament than in patients without calcification(66.7%vs.35.7%,χ2=3.909,P=0.048).CONCLUSION The severity of symptoms in patients with styloid process syndrome is related to the length of the styloid process,and those with calcification of the styloid hyoid ligament are more likely to experience pharyngalgia.

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Immune checkpoint inhibitors(ICI),an immunotherapy,have an important role in the treatment of various cancers.However,ICIs induce several immune-related adverse events(irAEs).Interleukin(IL)-6 is an important inflammatory factor that promotes cancer progres-sion and modulates the clinical application of ICIs through various mechanisms.Herein,we postulate possible mechanisms that are involved in the ICI-regulatory effects mediated by the expression of the cytokine interleukin-6(IL-6),elucidate the effect of IL-6 on checkpoint-block-ade therapy and irAEs,and summarize the role of IL-6 signaling-targeted interventions in ICIs efficacy and irAEs management.

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer and the third leading cause of cancer-related deaths,and it is a serious threat to human health and has become a clinical problem that needs to be solved urgently.Extracellular vesicles(EV)are membrane vesicles containing multiple components and play an important role in the development and progression of HCC.This article summarizes the effect of EVs of different origins on HCC and analyzes the mechanism of action of EV on HCC,so as to provide new perspectives for the diagnosis and treatment of HCC.

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.

Digestive system tumors are malignant tumors with high malignancy,easy metastasis,and poor prognosis,which are difficult to diagnose due to the insidious onset.Most of the patients have reached the middle and advanced stages at the time of diagnosis,so the effect of treatment is usually not good.Studies have shown that the long non-coding RNA(lncRNA)small nucleolar RNA host gene 6(SNHG6)is highly expressed in a variety of solid tumors,and can participate in malignant biological processes such as tumor proliferation,invasion and migration.SNHG6 is closely related to the emergence of chemotherapy drug resistance.This article reviews the biological function and clinical significance of SNHG6 in 6 different tumors of the digestive system,and discusses its mechanism of action in tumorigenesis and development,in the hope to search for effective early diagnosis and treatment targets and thereby improve the survival rate of cancer patients.

Digestive system tumors are malignant tumors with high malignancy,easy metastasis,and poor prognosis,which are difficult to diagnose due to the insidious onset.Most of the patients have reached the middle and advanced stages at the time of diagnosis,so the effect of treatment is usually not good.Studies have shown that the long non-coding RNA(lncRNA)small nucleolar RNA host gene 6(SNHG6)is highly expressed in a variety of solid tumors,and can participate in malignant biological processes such as tumor proliferation,invasion and migration.SNHG6 is closely related to the emergence of chemotherapy drug resistance.This article reviews the biological function and clinical significance of SNHG6 in 6 different tumors of the digestive system,and discusses its mechanism of action in tumorigenesis and development,in the hope to search for effective early diagnosis and treatment targets and thereby improve the survival rate of cancer patients.