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.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

Objective To explore the clinical significance of miR-423-5p in ischemic stroke and its effects on SH-SY5Y cell apoptosis along with the underlying mechanisms.Methods Plasma samples were collected from three stroke-prone patients who subsequently developed acute ischemic stroke(AIS)within 24 hours.High-throughput sequencing was used to identify miR-423-5p as a key target.Venous blood samples were collected from 46 AIS pa-tients within 24 hours of onset and from 46 matched control cases.RT-qPCR was performed to measure the plasma expression of miR-423-5p in both groups.The diagnostic value of miR-423-5p for AIS was evaluated using receiver operating characteristic(ROC)curve.After overexpression and knockdown of miR-423-5p in SH-SY5Y cells,flow cytometry was performed to detect apoptosis in each group to analyze the potential relationship between miR-423-5p and SH-SY5Y cell apoptosis.Western blot was used to measure changes in the expression level of the ap-optotic protein cleaved caspase-3 and the anti-apoptotic proteins Bcl-2 and Bcl-xL.Results The expression of miR-423-5p in 3 AIS patients showed significant difference before and after onset.Plasma miR-423-5p expression was significantly elevated in AIS patients versus controls(P＜0.001).ROC analysis indicated its strong diagnostic potential for AIS.Overexpression of miR-423-5p increased the apoptosis rate and cleaved caspase-3 ex-pression of SH-SY5Y cells after OGD/R,and decreased the expression of Bcl-2 and Bcl-xL,while knocking down miR-423-5p had the opposite effect.Conclusions The expression of miR-423-5p is upregulated in the plasma of patients with ischemic stroke compared to healthy controls.Furthermore,miR-423-5p promotes OGD/R-induced apoptosis in SH-SY5Y cells by increasing the level of cleaved caspase-3 and suppressing the expression of Bcl-2 and Bcl-xL.

Objective To explore the effects of nail-tail transverse connection in the treatment of atlantoaxial dislocation(AAD)and its impacts on bone metabolism,serum vascular endothelial growth factor(VEGF),and fibroblast growth factor-2(FGF-2)levels.Methods A total of 150 pa-tients with AAD were selected as the research subjects and divided into two groups using the random number table method,with 75 cases in each group.The observation group was treated with nail-tail transverse connection combined with posterior atlantoaxial pedicle screw internal fixation(C1-C2 PSR),while the control group was treated with C1-C2 PSR alone.Serum bone metabolism indicators[osteocalcin(BGP),type Ⅰ collagen N-terminal peptide(NTX),bone alkaline phosphatase(BALP),tartrate-resistant acid phosphatase(TRAP),type Ⅰ collagen carboxy-terminal peptide(CTX)],VEGF and FGF-2 levels were compared between the two groups at different time points.The Japanese Orthopaedic Association(JOA)score was used to evaluate the patients' neurological function before surgery and 3 years after surgery.Bone graft fusion was evaluated at 6 months,1 year,2 years,and 3 years after surgery.Results At 1,3 and 6 months after surgery,the serum VEGF and FGF-2 levels in the observation group were higher than those in the control group,and the differences were statistically significant(P＜0.05).After treatment,the BALP,BGP,NTX,TRAP and CTX levels in both groups were lower than those before treatment,and their levels in the observation group were lower than those in the control group,with statistically significant differences(P＜0.05).Before surgery,there was no statistically significant difference in the JOA scores be-tween the two groups(P＞0.05).At 3 years after surgery,the JOA scores in both groups were higher than those before surgery,and the JOA score and the score improvement rate in the observa-tion group were higher than those in the control group,with statistically significant differences(P＜0.05).At 6 months,1 year,2 years and 3 years after surgery,the success rate of bone graft fusion in the observation group was higher than that in the control group,with statistically significant differ-ences(P＜0.05).Conclusion Nail-tail transverse connection has significant effects in the treat-ment of AAD,which can effectively improve patients' bone metabolism and increase the serum VEGF and FGF-2 levels.

Proteolysis-targeting chimeras(PROTACs)represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can,potentially revolu-tionizing drug discovery and treatment strategies.However,the links between in vitro and in vivo data are poorly understood,hindering a comprehensive understanding of the absorption,distribution,metabolism,and excretion(ADME)of PROTACs.In this work,14C-labeled vepdegestrant(ARV-471),which is currently in phase Ⅲ clinical trials for breast cancer,was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics(PK)by estab-lishing a physiologically based pharmacokinetics(PBPK)model.For in vitro-in vivo extrapolation(IVIVE),hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did.PBPK models,which were initially developed and validated in rats,accurately simulate ARV-471's PK across fed and fasted states,with parameters within 1.75-fold of the observed values.Human models,informed by in vitro ADME data,closely mirrored postoral dose plasma profiles at 30 mg.Furthermore,no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans.This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Objective:To design a wireless regulation system based on STM 32 single chip microcomputer for three-dimension(3D)water tank,so as to improve the efficiency of physical verification for radiation.Methods:The wireless regulation system of 3D water tank was designed on the basis of STM32F103 single chip microcomputer and ZigBee technique through combined with regulation and control system for conventional 3D water tank,and the indicators of testing performance was also evaluated.Results:The wireless regulation system for 3D water tank can realize remote control to drive the operation of motor.The accuracy error of the detector was less than 0.2 mm along the x axis,y axis and z axis of the water tank.The repetitive error of the designated position was less than 0.1 mm after the detector repetitively reached the specified location along each axis.The vertical error of motion was less than 0.5 mm when the itinerary was less and equal to 200 mm,and this error was less than 1.0 mm when it was greater than 200 mm.Conclusion:The wireless regulation system of 3D water tank based on STM 32 can improve the information and intelligence levels that are measured and verified by ray beam,which is more in line with the requirement of radiation physics for measurement,and it can provide better technical support for the metrological verification of the equipment of nuclear medicine.

Recent studies indicate that paternal exposures significantly affect offspring health.Adverse factors such as poor diet,toxin exposure,and stress can reduce semen quality and disrupt epigenetic marks in sperm,leading to changes in off-spring traits.Paternal transgenerational inheritance mainly occurs through epigenetic factors like DNA methylation,histone modi-fication,and non-coding RNAs.While researches have begun to reveal how sperm transmits epigenetic information,paternal epi-genetics largely remains correlational.Increasing concerns about environmental pollution and lifestyle changes have shifted focus to paternal sperm quality and its impact on offspring health before conception.Future studies should explore how different envi-ronmental and male infertility factors influence paternal epigenetics and how specific marks affect embryonic development,ulti-mately enhancing diagnostics,treatments,and preconception care.

ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.