OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

Objective:Age-related cataract is the most common type of adult cataract and a leading cause of blindness.Currently,there are few reports on the establishment of animal models for age-related cataract.During the experimental breeding of Microtus fortis(M.fortis),we first observed that M.fortis aged 12 to 15 months could naturally develop cataracts.This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M.fortis. Methods:The 12-month-old healthy M.fortis were served as a control group and 12-month-old cataractous M.fortis were served as an experimental group.The lens transparency was observed using the slit-lamp biomicroscope.Hematoxylin and eosin staining was used to detect pathological changes in the lens.Biochemical detection methods were applied to detect blood routine,blood glucose levels,the serum activities of superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in both groups.Finally,real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. Results:Compared with the control group,the lens of cataract M.fortis showed severely visible opacity,the structure of lens was destroyed seriously,and some pathological damage,such as swelling,degeneration/necrosis,calcification,hyperplasia,and fiber liquefaction were found in lens epithelial cells(LECs).The fibrous structure was disorganized and irregularly distributed with morgagnian globules(MGs)aggregated in the degenerated lens fibers.There was no statistically significant difference in blood glucose levels between the experimental and control groups(P＞0.05).However,white blood cell(WBC)count(P＜0.05),lymphocyte count(P＜0.01),and lymphocyte ratio(P＜0.05)were significantly decreased,while neutrophil percentage(P＜0.05)and monocyte ratio(P＜0.01)were significantly increased.The serum activities of SOD and GSH-Px(both P＜0.05)were both reduced.The mRNAs of cataract-related genes,including CRYAA,CRYBA1,CRYBB3,Bsfp1,GJA3,CRYBA2,MIP,HspB1,DNase2B,and GJA8,were significantly downregultaed in the lenses of the experimental group(all P＜0.05). Conclusion:There are significant differences in lens pathological changes,peroxidase levels,and cataract-related gene expression between cataract and healthy M.fortis.The developed cataract spontaneously in M.fortis is closely related to age,the cataract M.fortis might be an ideal animal model for the research of age-related cataract.

Objective Liver cancer is the second leading cause of tumor-related death.The efficacy of local thermal ablation is comparable to surgical resection for the early hepatocellular carcinoma(HCC),and the ablation technique is minimally invasive,repeatable,and has a low complication rate.However,early recurrence((2 years)is the main cause of death after HCC ablation,but there is still a lack of accurate and reliable prediction models for early recurrence.Therefore,this survey intended to construct prediction models for early recurrence of HCC after ablation by using preoperative gadoxetic acid disodium-enhanced magnetic resonance(MR)images data combined with radiomics methods,evaluate and verify their predictive efficacy.To explore the application value of contrast-enhanced MRI imaging before ablation in the prognosis assessment of HCC patients,and to provide reliable data and theoretical basis for clinical treatment decisions.Methods A retrospective study was performed on 120 patients with HCC who underwent ablation and all the patients were underwent contrast-enhanced MRI examination within 1 month.A total of 1318 radiomic features were extracted from each patient by using preoperative T2-weighted sequence(T2WI)images of contrast-enhanced MRI.After feature selection,six machine learning algorithms would be used for construction of models and comparison.Finally,Logistic regression analysis was used to establish a clinical model,a radiomics model and a combined model which included the above risk factors and radiologic features.The nomogram was constructed based the combined model to evaluate the differentiation,accuracy and clinical benefit.Results Five radiomic features most closely related to early recurrence were identified and selected for model construction.The radiomic model had effective predictive performance,with AUC of 0.80 in the training sets.Two clinical risk factors associated with early recurrence,including tumor number and peritumoral hypodensity on the hepatobiliary phase,were selected to established a clinical-radiological-radiomics(CRRM)model,with AUC as high as 0.92 in the validation sets.The nomogram of CRRM model was constructed and the calibration curves indicated the goodness of fit.Decision curve analysis further confirmed the clinical usefulness of CRRM model.Conclusion The radiomics model of preoperatively contrast-enhanced MRI-T2WI image features was identified be effective to predict HCC early recurrence.In contrast,the CRRM model could be used as a more comprehensive and superior tool to predict individual probability of early recurrence.Patients at high risk of early recurrence could be identified and the appropriate and effective preoperative treatments could also be taken,to improve the prognosis and long-term survival rate of HCC patients the individualized treatment strategies should be formulated.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

BACKGROUND:It has been shown that in a mouse model of acute traumatic brain injury,the transcriptional and translational levels of silent information regulator 1(SIRT1)activated by drugs significantly elevates the expression of SIRT1 in brain tissue,reduces inflammatory and oxidative stress in brain tissue,and improves neurological function. OBJECTIVE:To investigate the mechanism of intraperitoneal injection of SRT1720,an activator of SIRT1,to alleviate acute traumatic brain injury in rats. METHODS:Ninety Sprague-Dawley rats were randomized into three groups(n=30 per group):a sham group(without modeling),a model group and an activator group.Animal models of acute traumatic brain injury were established in the latter two groups.At 6 hours after modeling,the sham,model and activator groups were injected intraperitoneally with dimethyl sulfoxide solution,methylsulfoxide solution and SRT1720 once a day for 28 days,respectively.The time points for sampling were set,and rats'neurological function,brain tissue water content,brain tissue oxidative stress and inflammatory response,brain tissue morphology,apoptosis and angiogenesis,and the protein expression of SIRT1 in brain tissue were detected and measured. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were increased in the model group at 7,14 and 28 days of injection(P<0.05);compared with the model group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were decreased in the activator group(P<0.05).Compared with the sham group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were increased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were increased(P<0.05),and the levels of superoxide dismutase in the serum were decreased in the model group at 7,14 and 28 days of injection(P<0.05).Compared with the model group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were decreased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were decreased(P<0.05),and the levels of superoxide dismutase in the serum were increased in the activator group at 7,14 and 28 days of injection(P<0.05).Immunohistochemical staining at 7,14 and 28 days of injection showed that the number of new vessels in the brain tissue was higher in the model group than the sham group(P<0.05)as well as higher in the activator group than the model group(P<0.05).Western blot assay indicated that at 7,14 and 28 days of injection,the expression of SIRT1 protein in the brain tissue was lower in the model group than the sham group(P<0.05)and higher in the activator group than the model group(P<0.05).Hematoxylin-eosin staining showed that at 7,14 and 28 days of injection,the degree of brain injury in the activator group was less than that in the model group.To conclude,intraperitoneal injection of the SIRT1 signal activator SRT1720 can significantly reduce oxidative and inflammatory stress in the brain tissue,inhibit neuronal apoptosis,promote angiogenesis,and alleviate brain injury in rats with acute traumatic brain injury.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.

Objective:Using primary care chronic disease management as a case,it aims to explore an economic incentive model for integrated primary healthcare services based on value pricing.Additionally,practical needs and implementation recommendations are proposed.Methods:With the help of the health technology assessment framework,it proposes that integrated health services can be priced through service effectiveness and service utility,and develops an economic incentive model with value pricing at its core based on the patient-centered incentive model for innovative healthcare services,including financing,payment,appraisal,and distribution,and puts forward feasible suggestions in the light of the needs and actuality of primary integrated services in China.Conclusion and Recommendation:The value-based pricing model for integrated health services serves as a theoretical foundation for the transformation of primary healthcare service functions and the enhancement of service dynamics,aligning with China's value-oriented service procurement strategy.This research contributes to the academic discourse by providing localized insights and a scholarly tone,contributing to the advancement of knowledge in the field.