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.

Recent research progress into the use of Chinese medicine has demonstrated good therapeutic effects for increasing numbers of Chinese medicines for immune system diseases.Atopic dermatitis(AD)is an inflammatory disease characterized by type 2 immunity,and research into its pathogenesis and therapeutic immunopharmaceuticals has result ed in various different types of animal models.This review summarizes the existing animal models of AD and their immune-related characteristics,with the aim of providing appropriate references for the selection of future research models related to AD.

Recent research progress into the use of Chinese medicine has demonstrated good therapeutic effects for increasing numbers of Chinese medicines for immune system diseases.Atopic dermatitis(AD)is an inflammatory disease characterized by type 2 immunity,and research into its pathogenesis and therapeutic immunopharmaceuticals has result ed in various different types of animal models.This review summarizes the existing animal models of AD and their immune-related characteristics,with the aim of providing appropriate references for the selection of future research models related to AD.

Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)％,(2.40±0.25)％,(3.65±0.25)％,(5.43±0.29)％,(6.97±0.36)％and(9.38±0.49)％;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P＜0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP＜0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

Myasthenia gravis(MG)is an autoimmune disease characterized primarily by skeletal muscle weakness and,in severe cases,respiratory involvement.Western medical treatment predominantly relies on immunosuppressants,but long-term administration often leads to notable side effects.In contrast,traditional Chinese medicine(TCM)offers the advantage of multi-target interventions.However,the pathogenesis of MG has not been fully elucidated,and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development.This paper systematically reviews the etiology and pathogenesis,diagnostic criteria,and progress of animal model research for MG from both Chinese and Western medicine perspectives.In Western medicine,the pathogenesis of MG is closely related to genetic susceptibility,environmental factors,and autoantibody-mediated postsynaptic membrane damage.In TCM,MG is classified under the category of"flaccidity syndrome",attributed to congenital deficiencies and acquired malnourishment.Western diagnostic criteria involve a combination of clinical symptoms,fatigue testing,serum antibody assays,and electrophysiological evaluation.In contrast,TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation.Currently available animal models mainly include experimental autoimmune myasthenia gravis(EAMG)and passive transfer myasthenia gravis(PTMG).The Toredo acetylcholine receptor(AChR)induced EAMG model aligns well with Western diagnostic criteria,but poorly matches secondary symptoms in TCM.The synthetic AChR peptide model is widely used,but shows low conformity with TCM syndromes.Models induced by muscle-specific tyrosine kinase(MuSK),low-density lipoprotein receptor-related protein 4(LRP4),and transgenic models demonstrate high innovation but exhibit low clinical conformity.Evaluation of these models requires integration of behavioral,electrophysiological,and immunological indicators.However,a systematic framework for modelling TCM syndromes is still lacking.Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models.Additionally,it is crucial to establish a TCM syndrome evaluation system based on"validation by prescription",as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies.This review provides a theoretical foundation for optimizing MG animal model design,advancing the research on the combination of Chinese and Western medicine,and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

Objective:To investigate the laboratory diagnostic value of 5 new blood routine indexes in chronic hepatitis B (CHB), liver cirrhosis and hepatocellular carcinoma (HCC).Methods:The retrospective study included 65 patients with chronic HBV infection, 72 patients with liver cirrhosis and 163 patients with HCC recruited at Liver Disease Center in First Affiliated Hospital of Fujian Medical University, as well as 52 healthy controls recruited from the Physical Examination Center of the First Affiliated Hospital of Fujian Medical University from October 2022 to April 2023. Five new parameters [early granulated cell percent (EGC%), early granulated cell absolute count (EGC#), microcytic anemia factor (MAF), leukocyte estimate(corrected)from the DIFF optical channel (WDOP) and leukocyte estimate(corrected)from the NRBC optical channel (WNOP)] were detected by UniCel DxH 900 blood cell analyzer. Univariate analysis of the expression levels of the 5 new parameterswere compared among CHB, liver cirrhosis and HCC groups. Pearson correlation analysis was used to explore the correlation between the 5 new parameters and HBV-related markers in CHB and Child-Pugh score in liver cirrhosis. Receiver operating characteristic (ROC) curve and AUC were used to estimate the diagnostic capacity of the 5 new blood routine indexes in CHB, liver cirrhosis and HCC.Results:In patients with CHB, the levels of EGC% ( Z=4.613, P<0.001) and EGC# ( Z=4.220, P<0.001) were higher than those of healthy controls; EGC# was positively correlated with HBsAg and HBeAg (both P<0.05). In patients with cirrhosis, the level of MAF ( Z=-4.928, P<0.001) was lower than that of healthy controls, and Child-Pugh score was found to be negatively correlated with MAF ( r=-0.349, P<0.05). In HCC patients, WDOP ( Z=2.45, P=0.017) and WNOP ( Z=2.90, P=0.017) levels were higher in patients with tumor volume>3 cm 3 than those in patients with volume ≤3 cm 3. The AUCs of combination of 5 new parameters to diagnose CHB, liver cirrhosis and HCC were 0.901 (95% CI 0.830-0.973, P<0.001), 0.946 (95% CI 0.909-0.984, P<0.001), and 0.904 (95% CI 0.858-0.950, P<0.001). Conclusions:The 5 new parameters based on peripheral blood cell analysis have good clinical value in the diagnosis of CHB, liver cirrhosis and HCC diseases.

Objective:To analyze the efficacy and safety of splenic artery occlusion combined with microwave ablation (MWA) in the treatment of hepatocellular carcinoma (HCC) complicated with liver cirrhosis and hypersplenism.Methods:Clinical data of 24 patients with HCC complicated with cirrhosis and secondary hypersplenism admitted to Airport Hospital of Tianjin Cancer Hospital from August 2023 to May 2024 were retrospectively analyzed, including 13 males and 11 females, aged (57.4±7.8) years. All patients were treated with splenic artery occlusion combined with MWA of spleen. Spleen volume measured by MRI before and after MWA, blood routine changes and postoperative complications (fever, bleeding, pain, renal failure and thrombosis) were analyzed.Results:The splenic volume of 24 patients measured by MRI before MWA was 692.4 (504.7, 1023.7) cm 3, and decreased to 225.0 (186.4, 285.6) cm 3 after treatment for 60 days ( Z=-3.23, P=0.001). The red blood cell counts were comparable before and after microwave ablation. The white blood cell count before MWA was 4.3 (3.2, 5.3)×10 9/L, which increased to 11.0 (8.6, 15.8)×10 9/L three days after treatment, and to 5.0 (3.3, 6.1)×10 9/L 90 days after treatment ( Z=-4.70, -0.34, P<0.001, P=0.732). The platelet count of the patients was 47.0 (39.0, 67.0)×10 9/L before MWA, which increased to 155.0 (120.3, 214.3)×10 9/L seven days after Treatment, and to 77.0 (63.0, 125.0)×10 9/L 90 days after treatment ( Z=-5.29, -2.51, P<0.001, P=0.012). None of the patients had obvious bleeding and no death occured. One patient (4.2%) developed renal failure, one patient (4.2%) had splenic venous thrombosis, 4 patients (16.7%) had pain of different degrees, and 5 patients (20.8%) had low fever. Conclusion:Splenic artery occlusion combined with MWA in the treatment of HCC complicated with liver cirrhosis and hypersplenism can significantly reduce spleen volume and increase platelet level with acceptable complications.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

OBJECTIVE: To compare clinical efficacy between side-opening and front-opening bone cement injectors in percutaneous kyphoplasty(PKP) for the management of thoracolumbar osteoporotic vertebral compression fractures(OVCFs). METHODS: A retrospective cohort study was conducted, comprising 62 patients with single-segment thoracolumbar OVCFs (T₁₁-L₂), who underwent bilateral PKP at our department during the period from June 2020 to October 2021. Patients were categorized into two groups based on the specific bone cement injector employed during the surgical procedure: the side-opening group (n=29) and the front-opening group (n=33). Among them, the side-opening group consisted of 6 male and 23 female patients, with a mean age of (73.32±9.11) years. The front-opening group included 7 male and 26 female patients, with a mean age of (71.29±10.39) years. The variables encompassed essential patient characteristics were recorded, such as gender, age, bone mineral density (BMD), and fracture level (T₁₁-L₂), as well as procedural aspects, including operation duration, cement injection volume, cement distribution type (lobular or diffuse), occurrence of cement leakage, pre-and post-operative visual analogue scale (VAS) pain scores, and vertebral compression ratio. RESULTS: All patients underwent successful surgery, with a mean follow-up duration of (15.37±3.03) months. There were no statistically significant differences in gender, age, BMD, fracture level, preoperative vertebral compression degree, and VAS scores between the side-opening group and the front-opening group (P>0.05). The operation time, the mean cement injection volumes, the distribution of bone cement within the vertebrae has no statistically significant difference between two groups(P>0.05). Both the side-opening and front-opening groups showed significant improvements in VAS scores at 3 days and 6 months after operation (P<0.05). However, there was no significant difference in VAS scores between the two groups at both 3 days and 6 months after the operation (P>0.05). CONCLUSION Side-opening bone cement injectors in bilateral PKP surgery for single-segment thoracolumbar OVCF achieve similar clinical efficacy as front-opening injectors, without significant improvement in cement distribution and containment.
Humans ; Female ; Male ; Kyphoplasty/instrumentation* ; Aged ; Bone Cements ; Fractures, Compression/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Thoracic Vertebrae/injuries* ; Lumbar Vertebrae/injuries* ; Osteoporotic Fractures/surgery* ; Middle Aged ; Aged, 80 and over

Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)％,(2.40±0.25)％,(3.65±0.25)％,(5.43±0.29)％,(6.97±0.36)％and(9.38±0.49)％;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P＜0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP＜0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.