Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective:To evaluate the early assessment of hepatocardiac integration based on ultrasonic elasticity and blood flow vector imaging (VFM) technology, in conjunction with unsupervised cluster analysis and supervised machine learning methods.Methods:An observational research design without any intervention was adopted from December 2021 to September 2022, 45 patients with liver cirrhosis, 43 patients with liver fibrosis, and 42 healthy volunteers were selected from the First Affiliated Hospital of Harbin Medical University. Liver combined elasticity technology and VFM technology were used to obtain information on the liver and heart of the subjects, respectively. The acquired data were standardized, and then clustered using topological data analysis (TDA) technology on the processed data. Subsequently, the clustering results were evaluated based on statistical analysis, and finally, supervised multi-classification tasks were realized through machine learning methods.Results:Patients were stratified into five distinct groups based on a network of patient similarities. The average characteristics of each group were as follows: Group 1 exhibited the most severe hepatocardiac conditions relative to the other groups. Groups 2 and 3 displayed moderately severe conditions.In contrast, Group 4 comprised entirely of healthy controls, all of whom presented with normal hepatocardiac function. Group 5 presented a unique case among the categories.Participants in this group showed poor liver conditions. However, according to the guidelines for cardiac diastolic function assessment, their heart function was generally unremarkable, with only a minority of indicators deviating significantly. Support Vector Machine (SVM), Random Forest Tree (RFT), and Multilayer Perceptron (MLP) were employed for multi-classification tasks on the test dataset. The average accuracies achieved by these models were 70%, 81%, and 84%, respectively.Conclusions:By combining liver combined ultrasonic elasticity, cardiac VFM technology and TDA technology to construct a patient similarity network, we successfully identified patients with liver fibrosis who did not show abnormalities in conventional cardiac indicators but may have potential abnormal cardiac function, which has important implications for guiding the selection of clinical intervention measures, and optimizing patient management stratification.

In recent years, the risk of perioperative concurrent venous thromboembolism (venous thromboembolism, VTE) has been significantly increased in patients with pancreatic cancer. Early prediction of VTE and strengthening the quality evaluation and clinical management of pancreatic surgery are the key to promote the prevention and treatment of VTE in pancreatic cancer patients. In view of the particularity of pancreatic surgery and the risk of related complications, clinicians should not only focus on the prevention of VTE, but also take into account the occurrence of serious complications such as postoperative bleeding, and strive to balance the two. Based on the relevant guidelines and the clinical experience of the center, the author's team elaborated on the early prediction of VTE in patients with pancreatic cancer, the indication and timing of perioperative VTE prevention and treatment in pancreatic surgery, in order to provide beneficial reference for the clinicians of VTE prevention and treatment in such patients.

The step-up approach is the most important modality in the treatment of infected pancreatic necrosis (IPN) and has been recommended by several national and international guidelines. Screening patients with low success rates of percutaneous drainage for timely treatment using the step-up approach and selecting appropriate escalation approach based on IPN staging are expected to improve the overall cure rate of IPN. The open debridement in the step-up approach should be carried out under reasonable indications and timing. When the patient's overall condition is poor and the condition of disease is complex, it is not necessary to adhere to a fixed treatment mode and choose a leapfrogging treatment strategy in a timely manner after thorough evaluation.When following the step-up approach in the treatment of IPN, endoscopic and surgical interventions are advocated in parallel, and escalating and leapfrogging strategies are promoted to establish an integrated, disease-centric, multidisciplinary treatment platform, with the aim of improving clinical prognosis. The authors review relevant literature and combine with team's treatment experience to explore the escalating strategies of surgical intervention for IPN, with a view to further improving the overall cure rate of IPN patients.

Objective:To compare the safety and efficacy of the " step-up approach" versus the " step-jump approach" in treatment of infected pancreatic necrosis (IPN).Method:The clinical data of IPN patients who underwent step-up strategy or step-jump strategy treatment at the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from December 2018 to November 2022 were analyzed retrospectively. Propensity score matching (PSM) was done based on the nearest neighbor matching method (1: 1 ratio). After matching the baseline data (the caliper value was 0.01), a total of 62 patients with IPN were included, including 41 males and 21 females, aged (41.1±13.1) years old. Patients who were treated with the step-up strategy were included in the step-up group, while patients who were treated with the step-jump strategy were included in the step-jump group. There were 31 patients in each group after PSM, and the treatment effect of the two groups were compared.Results:Of the 62 patients with IPN, 43 received surgical intervention, and 19 were managed successfully using symptomatic anti-inflammatory treatment or percutaneous catheter drainage. The total hospitalization cost of patients in the step-jump group was significantly higher than that in the step-up group [122 000 (73 000, 179 000) yuan vs. 88 000 (46 000, 144 000) yuan, P=0.034]. The overall cure rate of IPN patients in the step-jump group was 93.5%(29/31). The 2 patients who died had type Ⅲ IPN. In the IPN patients in the step-up group were all cured, and the overall cure rate was 100%(31/31), with no death. There were no statistical differences between the two groups in the rates of death, postoperative complications, residual infection, debridement ≥2 times, and positive bacterial culture in blood or drainage fluid (all P>0.05). A total of 19.4% (12/62) patients had postoperative complications, including 4 patients with abdominal bleeding, 3 patients with new organ dysfunction, 2 patients with gastrointestinal bleeding, 2 patients with gastrointestinal fistula, and 1 patient with venous thrombosis in both lower limbs. Conclusion:Both the step-up treatment strategy and the step-jump treatment strategy were safe and effective for treatment of IPN patients.

BACKGROUND: Standard two-dimensional (2D) culture has confirmed the mechanism of mast cells (MCs) in the pathogenesis of inflammatory bowel disease (IBD), but the regulation of signaling responses of MCs may well differ in three-dimensional (3D) microenvironments. The aim of the study was to develop a 3D culture model based on decellularized intestinal scaffolds (DIS) and verify how MCs influenced fibroblasts phenotype in the 3D model. METHODS: DIS were achieved using the detergent technique and extracellular matrix (ECM) components were verified by histologic analysis, quantification and scanning electron microscope. After human colon fibroblasts recellularized into the scaffolds and activated by MCs tryptase and TGFb1, the changes in genes and signaling pathways during fibroblasts activation in 3D were studied and compared with the changes in 2D cell culture on plastic plates. RESULTS: Decellularization process effectively removed native cell debris while retaining natural ECM components and structure. The engrafted fibroblasts could penetrate into the scaffolds and maintain its phenotype. No matter whether fibroblasts were cultured in 2D or 3D, MCs tryptase and transforming growth factor b1 (TGF-b1) could promote the differentiation of fibroblasts into fibrotic-phenotype myofibroblasts through Akt and Smad2/3 signaling pathways. Furthermore, the pro-collagen1a1 and fibronectin synthesis of myofibroblasts in 3D was higher than in 2D culture. CONCLUSION Our results demonstrated that the DIS can be used as a bioactive microenvironment for the study of intestinal fibrosis, providing an innovative platform for future intestinal disease modeling and screening of genes and signaling pathways.

Infected pancreatic necrosis (IPN) is a crucial reason for the poor prognosis of patients with acute pancreatitis,which is complicated and difficult to predict the outcomes. Surgery is an important way to cure IPN,and “step-up approach” is the mainstream mode of IPN treatment. In the era of minimally invasive surgery,the full course endoscopic treatment of IPN has been gradually hot and achieved good outcomes as endoscopic technology’ improvement. However,it is controversial that whether technique is better for IPN by surgery debridement or endoscopy drainage,and there is no consensus on the scope of applicability and the timing of intervention. The paper aims to explore the intervention methods,indications and timing of endoscopic and surgical treatment of IPN and elaborate the selection strategies of them in clinical practice,so as to develop individualized treatment options,accurately implement minimally invasive intervention and improve the prognosis.

Infected pancreatic necrosis (IPN) is a crucial reason for the poor prognosis of patients with acute pancreatitis,which is complicated and difficult to predict the outcomes. Surgery is an important way to cure IPN,and “step-up approach” is the mainstream mode of IPN treatment. In the era of minimally invasive surgery,the full course endoscopic treatment of IPN has been gradually hot and achieved good outcomes as endoscopic technology’ improvement. However,it is controversial that whether technique is better for IPN by surgery debridement or endoscopy drainage,and there is no consensus on the scope of applicability and the timing of intervention. The paper aims to explore the intervention methods,indications and timing of endoscopic and surgical treatment of IPN and elaborate the selection strategies of them in clinical practice,so as to develop individualized treatment options,accurately implement minimally invasive intervention and improve the prognosis.

OBJECTIVE：To provide reference for improving medical insurance reimbursement for multi-indication drugs based on value-based pricing in China. METHODS：The theory and practice of value-based pricing for multi-indication drugs were sorted out，and the value standards and medical insurance reimbursement strategies based on value-based pricing in France，Germany，UK，Italy and Sweden were analyzed，so as to provide the suggestions for medical insurance reimbursement of multi-indication drugs in China. RESULTS & CONCLUSIONS：The realization of value-based pricing first needed to develop a value framework to define，measure and integrate value，and then established a model to convert the total value into price. The overall idea of value-based pricing for multi-indication drugs was consistent，but there were differences in the value standard. In the UK and Sweden， quality-adjusted life years （QALYs） and incremental cost-effectiveness ratios （ICERs） measured by pharmacoeconomicsare used as the value standard. France，Germany and Italy were more focused on the therapeutic value and clinical benefit improvement. As for medical insurance reimbursement strategies，France adopted single weighting method based on expected volume. Germany adopted combination weighting method based on value and volume. UK introduced the Patient Access Schemes and Italy introduced the Managed Entry reements，both based on the nominal reimbursement standard. Sweden adopted independent reimbursement for different indications by different brand names. It is suggested that China can explore the value-based pricing strategies of multi-indication drugs on the basis of the above international experiences，reference and use these variety of medical insurance reimbursement strategies comprehensively. Simultaneously，the information collection mechanism of patients and drug use should be improved to provide data support for the implementation of China’s value-based pricing and reimbursement strategies for multi-indication drugs.

Objective:To observe the clinical effect of hormone replacement therapy(HRT) on patients with cervical squamous cell carcinoma after operation and its effect on sex hormone, blood fat, bone content and tumor markers, and to evaluate the clinical significance of HRT therapy.Methods:From January 2016 to January 2019, a total of 100 patients with cervical squamous cell carcinoma admitted to Zhuhai Maternal and Child Health Hospital were analyzed retrospectively.After surgical treatment, 50 patients were willing to receive hormone replacement therapy as the experimental group and 50 patients received routine treatment as the control group, Kupperma score was used to evaluate the severity of perimenopausal symptoms, and the serum levels of sex hormones, blood fat, bone content and tumor markers in the two groups before and after treatment were detected and the occurrence of adverse reactions were evaluated.Results:Before treatment, there was no significant difference in kupperma score, estradiol, follicle-stimulating hormone, luteinizing hormone level, lipid level, bone content and tumor marker level between the two groups(all P>0.05). After HRT treatment, kupperma score in the experimental group was significantly lower than that before treatment((11.47±5.12) vs.(20.46±7.52), t=7.262). In the detection of sex hormones, the levels of estradiol in the experimental group was significantly increased((39.26±7.43) ng/L vs.(13.78±7.52) ng/L, t=12.345), and the levels of follicle stimulating hormone((34.25±7.61) U/L vs.(62.18±19.12) U/L, t=8.245)and luteinizing hormone((20.31±6.25) U/L vs.(35.08±6.27) U/L, t=5.452, P=0.004) in the experimental group were significantly decreased.In the detection of blood lipid level, bone content and tumor markers, high-density lipoprotein((1.62±0.33) mmol/L vs(1.34±0.26) mmol/L, t=4.592, P=0.008) and alkaline phosphatase levels((66.21±25.75) U/L vs.(46.88±9.06) U/L, t=5.912, P=0.001)was significantly increased, the low density lipoprotein((2.78±0.43) mmol/L vs.(2.87±0.78) mmol/L, t=4.265, P=0.012)and total cholestenone((4.02±0.45) mmol/L vs.(4.23±0.91) mmol/L, t=5.761, P=0.002) levels were significantly decreased in the experimental group, with statistically significant differences(all P<0.05). There was no significant difference in the level of serum SCC antigen between the experimental group and the control group before and after treatment ( P> 0.05); there was no significant difference in the above indicators between the experimental group and the control group before and after treatment ( P> 0.05); there was no significant increase in adverse reactions such as breast swelling and pain (3 cases), body mass increase (2 cases), bleeding (1 case), body pain (4 cases), vomiting (4 cases), etc. between the experimental group and the control group (2, 1, 2, 3, 1 case) There was no statistical significance ( P> 0.05). Conclusion:HRT treatment of cervical squamous cell carcinoma patients after surgery can significantly improve the peri menstrual syndrome caused by low estrogen level, and did not significantly increase the risk of recurrence of cervical cancer patients and adverse reactions.