Intrahepatic cholangiocarcinoma （ICC） is a type of primary liver cancer that accounts for about 10%‍ — ‍15% of the total cases， and its incidence and mortality rates tend to increase significantly around the world， especially in Asian countries. At present， radical liver resection is the only possible cure for ICC， but with a fairly high postoperative recurrence rate and a poorer prognosis than hepatocellular carcinoma. Therefore， it is urgently needed to further investigate the mechanisms of the development and progression of ICC and search for more effective treatment methods. Some epidemiological data suggest that chronic hepatitis B virus infection is one of the most important predisposing factors for ICC， yet little is known about its oncogenic effects. This article summarizes the epidemiological evidence that links the two diseases and briefly elaborates on the mechanisms of the development and progression of HBV-associated ICC， so as to help to gain a better understanding of the role of HBV in the development and progression of ICC.

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

ObjectiveTo understand the mortality trends among residents of Fuling District， Chongqing， before and after theCOVID-19 outbreak， and to provide references for the government to formulate disease prevention and control policies and measures. MethodsData on mortality and population in Fuling District from 2017 to 2022 were collected to analyze population mortality and standardized mortality rates， and to compare the changes in the causes of death by year and before and after the pandemic. ResultsFrom 2017 to 2022， the crude mortality rate in Fuling District showed an upward trend （APC=3.04%， P<0.05）， while the standardized mortality rate showed a downward trend （APC=-6.47%， P<0.01）. The mortality rate of males was higher than that of females （P<0.05）， with different age groups having different causes of death composition. The highest proportion of deaths in 0-year-old group was from infectious diseases， maternal and neonatal diseases， and nutritional deficiencies， the highest proportion of deaths in the 1‒24 age group， with the exception of those aged 5‒9， was from injuries， and the main cause of death for residents aged 25 and above was chronic diseases. The mortality rate of mental and behavioral disorders rose from the 13th to the 9th place. According to the epidemic situation of COVID-19， there were no changes in the top five causes of death among the entire population. The motility rate of endocrine， nutritional and metabolic diseases rose from the sixth to the fifth place in male population， and the motility rate of malignant tumor rose from the 3rd to the 2nd place in female population. ConclusionThere are no changes in the top five causes of death among the entire population of Fuling District before and after the COVID-19 outbreak. Chronic diseases remain the main cause of death. It is necessary to control the risk factors for cardiovascular and cerebrovascular diseases such as hypertension， diabetes， and dyslipidemia， and to curb the rising trend of mortality rates from strokes and acute myocardial infarction. For deaths caused by accidental injuries， targeted health education should be conducted for different populations.

Objective:To analyze the clinical advantages of the modified Trocar approach in laparoscopic cholecystectomy (LC) compared to the conventional three-hole approach.Methods:Clinical data of 202 patients undergoing the modified Trocar approach LC (the modified group) at the First Affiliated Hospital of Wenzhou Medical University from January 2015 to September 2023 were retrospectively analyzed, including 84 males and 118 females patients, aged (49.58±13.03) years old. The conventional group enrolled 606 patients, including 245 males and 361 females, aged (50.99±12.55) years old. The operative time, conversion to four-hole approach, postoperative complications, hospital stay, pain score, and satisfaction score were compared between the groups.Results:No severe complications occurred in either group. In modified group, three cases (1.5%, 3/202) required conversion to four-hole approach, while in conventional group, seven (1.2%, 7/606) required conversion, with one case conversed to open surgery ( P>0.05). The operative time in modified and conventional groups were (40.28±13.51) min and (40.38±18.75) min, respectively ( P>0.05). The postoperative pain scores were 2.49±1.23 and 3.02±1.48, respectively ( t=5.05, P<0.001). The average postoperative hospital stays were (2.87±0.93) d and (3.80±1.31) d, respectively ( t=11.05, P<0.001). The postoperative Kiyak satisfaction scores were 4.31±0.66 and 4.15±0.63, respectively ( t=2.93, P=0.004). Conclusion:The safety of modified Trocar approach is comparable to that of conventional three-hole approach. The modified approach showed a shorter postoperative hospital stay, less pain, better scars, and higher patient satisfaction.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

Objective To explore the problems of health poverty faced by a special group of people with disabilities and the difficulties in the practice of health poverty alleviation, so as to provide a scientific basis for the health poverty alleviation of the disabled. Methods A self-made questionnaire was used for one-to-one survey, and a database was established by Excel. SPSS was used for descriptive analysis and horizontal comparison. Results The participation rate of basic medical insurance for the disabled was relatively high (93.40%), and the medical insurance payment was mainly paid by individuals (70.13%). The satisfaction of medical insurance was low (43.12%), and 84.64% of the disabled thought that their medical expenses were high. 45.22% of the families of disabled patients met the universal standard of catastrophic health expenditure. Compared with Shandong Province, the basic medical insurance coverage rate of the disabled in Hubei Province was slightly lower, the satisfaction rate of medical insurance was higher, and the proportion of catastrophic health expenditure of families was larger. The analysis of the results showed that the disabled people with a lower disability level, children and middle-aged with disabilities, the disabled people with less or more family members, and the disabled people without the minimum living subsistence allowances were not satisfied with the medical insurance. Conclusion The basic medical insurance in the two places has alleviated the difficulty of medical treatment for the disabled to a certain extent, but the family burden of diseases of the disabled was still heavy. The level of medical security for people with disabilities should be improved, and their economic burden of disease should be reduced, so as to improve the satisfaction of medical insurance.

JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (I) to label JS001 probes to target the human PD1 (hPD1) antigen. , the half maximal effective concentration (EC) value of I-JS001 did not significantly differ from that of JS001. The uptake of I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous Ihuman IgG (IhIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the I-JS001 group at different time points was significantly higher than that of the blocking group or the I-hIgG group in the humanized mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.

Objective To evaluate the efficacy and safety of XELOX regimen combined with hepatic artery chemoembolization in the treatment of gastric cancer with liver metastasis.Methods 50 cases of gastric cancer with liver metastasis were randomly divided into two groups,the experimental group (25 cases) received chemotherapy regimen of XELOX first:Xeloda tablets 1 000 mg/m2,orally,twice a day,days1-14;Oxaliplatin 130 mg/m2,intravenous drip,day 1.Hepatic artery chemoembolization was performed one a week later,and a cycle consists of 4 weeks.The control group (25 cases) received chemotherapy regimen of XELOX,3 weeks as a cycle.All patients were evaluated for efficacy and toxicity every 2 cycles.Results In the experimental group,the overall response rate was 56％,the tumor control rate was 80％,the increase rate of Karnofsky was 60％,and 10 patients got chance of tumor resection.In the control group,the overall response rate was 32％,the tumor control rate was 52％,the increase rate of Karnofsky was 48％,and 6 patients got chance of operation.The overall response rate,tumor control rate,surgical treatment rate and the increase rate of Karnofsky in the experimental group were significantly different from those in the control group (P ＜0.05).The median total survival time was 12.5 months in the experimental group and 10.5 months in the control group (P ＜0.05).There was no significant difference in toxicity and side effects between the two groups.Conclusion XELOX regimen combined with hepatic artery chemoembolization is effective and safe in the treatment of gastric cancer with liver metastasis.