In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.

In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

Objective To explore the effects of bronchoalveolar lavage combined with microbiological rapid on-site evaluation in potential donor lung maintenance.Methods Brain death patients who met the inclusion criteria and were admitted to the Intensive Care Unit(ICU)of Calmette Hospital Affiliated to Kunming Medical University from September 2020 to December 2022 were selected for bronchoalveolar lavage(BAL)and(BAL)and the lavage fluid were collected for M-ROSE to compare the pathogen detection rate and initial diagnosis time.According to the positive results of the microbiological rapid on-site evaluation,patients with the brain death were treated with empirical anti-infective therapy,and the oxygenation index,chest X-ray score,and the infection index(WBC,CRP,PCT)of anti-infective treatment 48 hours were evaluated.Results 1.Comparison of the detection rate of pathogenic microorganisms:The results of M-ROSE were highly consistent with a routine microbiological smear(Kappa = 0.921,P<0.001).2.Comparison of diagnostic time:The initial diagnosis time of M-ROSE was significantly lower than routine microbiological smear time and microbial culture time(P<0.001).3.Comparison of therapeutic effects of anti-infective therapy for 48 hours:There was no significant difference in oxygenation index,white blood cells and hypersensitive C-reactive protein before and after the anti-infective treatment(P>0.05).There were significant differences in procalcitonin and chest X-ray before and after the anti-infective treatment(P<0.05).Conclusion Bronchoalveolar lavage combined with microbiological rapid on-site evaluation has the high timeliness in the diagnosis of potential donor pulmonary infection,which can provide a preliminary basis for the early anti-infective therapy of donor lung maintenance.

Objective To investigate the effects of transcranial direct current stimulation(tDCS)on the topologic attributes of brain functional network in the patients with mild cognitive impairment(MCI).Meth-ods Thirty-three included patients with MCI were randomly divided into the real stimulation group(18 ca-ses)and pseudo-stimulation group(15 cases).All patients received the tDCS treatment for consecutive 10 d.The left dorsolateral prefrontal cortex(DLPFC)was stimulated by the anode,while the right orbital socket DLPFC was stimulated by the cathode.The neuropsychological scale assessment and resting state functional magnetic resonance imaging(rs-fMRI)image collection were performed before and after treatment.The GRETNA software was used to preprocess the rs-fMRI images and analyze the graph theory.The Pearson correlation analysis was used to calculate the correlation between behavioral indicators and network attribute indicators of significant difference between the two groups.Results There were statistically significant differ-ences in the node attributes(intermediate number centrality,degree centrality and local efficiency of nodes)before and after treatment,and between the two groups after treatment(P＜0.05).Compared with before treatment,the scores of MMSE,MoCA,AVLT-N7 and BNT after treatment in the real stimulation group were significantly increased[(25.89±2.16)points,(21.16±2.77)points,(4.95±1.81)points,(19.47±3.13)points].Conclusion tDCS could effectively regulate the local topological attributes of nodes in the cognitive-related brain region of MCI and improve the cognitive function.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objectives:To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics.Methods:This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA).Results:Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions:The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer, which has shown an increasing trend in incidence and mortality in recent years, with a poor prognosis. The clinical diagnosis and treatment of ICC currently face the challenges of low detection rate, high mortality rate, poor treatment outcome, and urgently need more in-depth research to promote the improvement of clinical diagnosis and treatment level. In recent years, ICC diagnosis and treatment related research has made new progress in many aspects, and the knowledge about these new clinical diagnosis and treatment advances should be updated in a timely manner. This article reviewed the latest research results in recent years, summarized some new views on ICC typing, prevention and diagnosis staging that have been proposed recently, as well as the new progress made in surgical treatment and systemic treatment, and briefly discussed the potential of ICC individualized precision treatment and the occurrence of rare complications caused by combined treatment.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objectives:To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics.Methods:This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA).Results:Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions:The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer, which has shown an increasing trend in incidence and mortality in recent years, with a poor prognosis. The clinical diagnosis and treatment of ICC currently face the challenges of low detection rate, high mortality rate, poor treatment outcome, and urgently need more in-depth research to promote the improvement of clinical diagnosis and treatment level. In recent years, ICC diagnosis and treatment related research has made new progress in many aspects, and the knowledge about these new clinical diagnosis and treatment advances should be updated in a timely manner. This article reviewed the latest research results in recent years, summarized some new views on ICC typing, prevention and diagnosis staging that have been proposed recently, as well as the new progress made in surgical treatment and systemic treatment, and briefly discussed the potential of ICC individualized precision treatment and the occurrence of rare complications caused by combined treatment.