Myosteatosis is one of the common complications in patients with end-stage liver disease, which is significantly associated with poor outcomes after liver transplantation. Currently, diagnostic criteria of myosteatosis have not been established, and CT is the most commonly used for diagnosis. The pathogenesis of myosteatosis is multifactorial, and the pathophysiological mechanisms linking it to end-stage liver disease are not fully understood. An increasing number of scholars have recognized that the severity of myosteatosis is closely related to its clinical consequences, but there are no effective treatment options available. This article reviews the pathophysiological mechanisms and diagnostic methods of myosteatosis, and its impact on the prognosis of liver transplant recipients, and discusses current treatment strategies to provide references for the perioperative management of liver transplant recipients.

In recent years, intratumoral immune injection, as an emerging drug delivery modality in the treatment of advanced malignant tumors, has not only improved drug bioavailability, but also reduced systemic toxicity by injecting bacteria and toxins, oncolytic viruses, cytokines, monoclonal antibodies, immune cells, pattern recognition receptor agonists, chemotherapeutic agents, mRNA, and antibody-drug conjugates into solid tumors. In addition, the development of drug delivery carriers such as iodized oil, hydrogel, nanoparticles and drug-carrying microspheres has solved the problem that drugs injected intratumorally are prone to diffuse through the vascular system and are difficult to remain locally for a long period of time. An in-depth exploration of the research progress of intratumoral immune injection of drugs and drug delivery carriers can provide a reference for further research on intratumoral immune injection, and improve the clinical benefits for patients with solid tumors.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

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.

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.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Small cell lung cancer (SCLC) is a rapidly developing malignant tumor, which is highly heterogeneous and prone to drug resistance, and the prognosis is usually poor. Poly ADP-ribose polymerase (PARP) inhibitors target the DNA damage response pathway, preventing DNA repair, thereby exerting anti-tumor effects. Currently, PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited, it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC.

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

Objective:To determine the evaluation indexes of national standard strains of genotypes 1, 3 and 5 of Japanese encephalitis virus (JEV) and evaluate the national standard JEV strains.Methods:According to the national standard strain evaluation technical standards of pathogenic microbial bacteria (virus) species, based on the application of Japanese encephalitis virus research, and according to the morphological characteristics, biological characteristics, molecular biological characteristics and other research data to identify the characteristics of G1, G3 and G5 genotypes of JEV.Results:Spherical virus particles with a diameter of about 60 nm were visible under electron microscope of the three Japanese encephalitis virus strains. The cytopathic effect was mainly characterized by cell shrinkage and exfoliation in BHK-21 and Vero cell lines, cell fusion and exfoliation were shown after infection with C6/36 cell line; the virus titer was 10 5-10 7 PFU/ml, and the plaque size was different by genotype. The median lethal dose of intrabitoneal challenge in G1, G3 and G5 JEV in three weeks-old mice was 50.51 PFU, 6.98 PFU, and 8.13 PFU, and the median lethal dose of intracranial challenge in five weeks mice was 3 PFU, 0.3 PFU, 1.35 PFU. The whole genome length of G1, G3 and G5 JEV was 10 967 bp, 10 976 bp and 10 983 bp, respectively. Conclusions:Three genotypic national standard strains of JE V were identified and evaluated by electron microscopy, cell, animal and genome laboratory indexes, which provided reference for the identification and evaluation of other national standard strains of JEV.