Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.

Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To observe the clinical efficacy of acupuncture in treating chronic insomnia disorder based on Huang Yuanyu's theory of"central qi ascending and descending,harmony of the four dimensions"regarding visceral qi movement.Methods Sixty patients diagnosed with chronic insomnia disorder at the Preventive Treatment Department of Yangjiang Hospital of Traditional Chinese Medicine from March 2022 to February 2023.The patients were randomly divided into an observation group and a control group according to a random number table,with 30 cases in each group.The observation group received acupuncture therapy,while the control group received oral administration of Alprazolam Tablets.The treatment duration spanned 4 weeks with 1 course per week.Clinical efficacy was evaluated after 1 month,and the changes in the Pittsburgh Sleep Quality Index(PSQI)scores and Hamilton Anxiety Rating Scale(HAMA)scores were observed.The Hamilton Depression Rating Scale(HAMD)scores were compared between groups before and after treatment.Results(1)After treatment,the PSQI scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the PSQI scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the HAMA scores and HAMD scores in the two groups of patients were significantly improved(P＜0.05),an the observation group in improvement of HAMA and HAMD was significantly superior to the control group,with statistically statistical significance(P＜0.05).(3)The total effective rate was 83.33%(25/30)in the observation group and 70.00%(21/30)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture based on the ascending and descending of visceral qi movement theory significantly alleviates anxiety and depressive states while improving sleep quality in patients with chronic insomnia disorder,demonstrating notable clinical efficacy.

Objective To investigate the incidence of intraoperative hypothermia(IH)and rewarming efficacy in elderly patients with different traditional Chinese medicine(TCM)constitutions undergoing general anesthesia.Methods A total of 500 elderly patients undergoing general anesthesia at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2022 to November 2022 were enrolled.The patients were divided into IH group and non-IH group depending on the occurrence of IH.Baseline data of the patients were collected,and univariate and multivariate logistic regression analyses were performed to identify risk factors for IH.A risk prediction model was constructed after value-assignment of influencing factors and its diagnostic efficiency was assessed by receiver operating characteristic(ROC)curve.External validation of the model was conducted in 50 elderly patients undergoing general anesthesia at the same period.From December 2022 to February 2023,80 elderly patients undergoing general anesthesia and complicated with IH were randomized into a control group(routine measures for keeping warm)and an observation group(keeping warm with forced-air-warming blanket)to compare the rewarming efficacy.Results(1)Among 500 elderly patients undergoing general anesthesia,180 cases developed IH,with an incidence of 36.0%.(2)Except for age,sex,type of surgery,American Society of Anesthesiologists(ASA)classification,type of anesthesia,and total fluid output volume,statistically significant differences were presented in body mass index(BMI),TCM constitution type,surgical complexity grading,preoperative core body temperature,operating room temperature,rewarming strategy,surgical duration,anesthesia duration,total fluid intake volume,intraoperative irrigation volume,and intraoperative blood transfusion between the two groups(P＜0.05 or P＜0.01).(3)Multivariate logistic regression analysis identified BMI,TCM constitution type,surgical complexity grading,preoperative core body temperature,operating room temperature,rewarming strategy,anesthesia duration,total fluid intake volume,and intraoperative irrigation volume as independent influencing factors for the occurrence of IH in elderly patients undergoing general anesthesia.ROC curve analysis demonstrated that the area under the curve(AUC)of the constructed risk prediction model was 0.816,with a sensitivity of 74.40%and a specificity of 77.50%.(4)In an external validation cohort of 50 elderly patients undergoing general anesthesia(19 IH cases versus 31 non-IH cases),the constructed risk prediction model exhibited a sensitivity of 73.68%and a specificity of 77.42%.(5)The observation group exhibited lower tympanic temperature upon post-anesthesia care unit(PACU)admission,shorter rewarming time and PACU stay duration,faster rewarming rate,and lower incidence of shivering than the control group,the differences being statistically significant(P＜0.05 or P＜0.01).Conclusion IH is common in elderly patients undergoing general anesthesia,particularly in those under the conditions of low BMI,qi/yang/blood deficiency constitutions,major surgery,low preoperative core body temperature,low operating room temperature,passive rewarming,prolonged anesthesia,high fluid intake volume,and high and intraoperative irrigation volume.The constructed risk prediction model demonstrates favorable diagnostic performance.Proactive use of forced-air-warming blankets effectively improves rewarming outcomes in elderly patients undergoing general anesthesia and complicated with IH.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Objective:The Fuxing Program was established in Zhuhai as an action plan to micro-eliminate hepatitis C in response to the World Health Organization's goal of eliminating hepatitis C by 2030. Therefore, the effectiveness of this program in terms of hepatitis C screening, treatment, follow-up, and other aspects is evaluated here.Methods:The "Fuxing Project" was established in May 2021 under the supervision of the Zhuhai Medical Quality Control Center for Infectious Diseases. A bridge was formed among the governmental entities, hospitals at all levels, and the community to train hepatitis C prevention and control strategies. Hepatitis C screening, publicity, and educational awareness were conducted in-and out-of-hospital. The responsibility for the diagnosis, treatment, and follow-up of a patient with hepatitis C was assigned to the staff. The screening and treatment rates of hepatitis C in hospitals before and after the initiation of the project were compared and analyzed using the χ2 test or Fisher's exact test. The hepatitis C virus (HCV) infection and treatment status were investigated and analyzed among the general population, high-risk populations such as human immunodeficiency virus (HIV) infection, drug addicts, and the population residing in supervised sites within Zhuhai communities, rural areas, schools, or factories. Results:Anti-HCV positivity rate (0.82% vs. 0.43%, P<0.001), HCV RNA detection rate (98.1% vs. 59.5%, P<0.001), HCV RNA detection positivity rate (52.56% vs. 29.76%, P<0.001), HCV RNA positivity rate (0.4% vs. 0.13%, P<0.001), and hepatitis C treatment rate (76.76% vs. 31.97%, P<0.001) were significantly higher among the inpatient population after the Fuxing Program initiation than before. The HCV RNA detection rate (58.52% vs. 6.93%, P<0.001) and HCV RNA detection positivity rate (77.72% vs. 29.41%, P<0.001) in Zhuhai were significantly higher after the Fuxing Program initiation than before. Anti-HCV positivity rate (0.46% vs. 1.28%, P=0.009) and HCV RNA (0.32% vs. 0.99%, P=0.03) were significantly lower in the Zhuhai general population of urban communities than those of the general population in rural areas. The HCV infection rate was more than three times higher in rural populations than in urban populations. Anti-HCV positivity rate, HCV RNA positivity rate, HCV RNA detection positivity rate, and hepatitis C treatment rates were 2.64% (31/1 175), 3.40% (69/2 022) and 94.4% (34/36), 2.64% (31/1 175), 2.72% (55/2 022), 50.00% (18/36), and 100% (31/31), 79.71% (55/69) and 52.94% (18/34), and 100% (31/31), 0 (0/55) and 55.55% (10/18) among the HIV infection, supervised population under supervised sites, and methadone maintenance treatment clinic population, respectively. Anti-HCV positivity rate (4.15% vs. 0.72%, P<0.001) and HCV RNA (3.22% vs. 0.53%, P<0.001) were significantly higher in the high-risk group than those in the general population, while the treatment rate of hepatitis C in the high-risk group (39.42% vs. 82.35%, P<0.01) was significantly lower than that of the general population. Conclusion:The establishment of the hospital grid linkage mechanism and the management model of hepatitis C follow-up by specialists, with the infectious diseases medical quality control center as the supervisory body, have improved the screening rate, the HCV RNA detection rate, and the treatment rate in the hospital, thereby providing a reference for exploring a management model to eliminate the nationwide threat of hepatitis C.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.