Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.
Humans ; Basophils ; Retrospective Studies ; Rhinitis/surgery* ; Eosinophils ; Sinusitis/surgery* ; Chronic Disease ; Nasal Polyps/pathology*

Chronic spontaneous urticaria (CSU) is a recurrent systemic inflammatory disease. At present, there are few biological indicators that can effectively reflect CSU activity in clinical practice, and some indicators have not been widely used. To identify sensitive and easy-to-check indicators may be helpful for the diagnosis and treatment of as well as prediction of therapeutic efficacy in CSU. This review comprehensively summarizes current clinical application of indicators related to CSU activity, in order to provide a reference for clinical practice and related scientific research.

In order to solve the difficulties and challenges in the implementation of the original blood distribution and collection regulations caused by the expansion of hospital area, the extension of blood transfer time, the changeability of blood transfer environment, and the strain of personnel due to the increase of workload, as well as to ensure the accuracy of the information throughout blood remote verification and distribution and the safety of clinical blood transfusion, , Shanghai experts related to clinical transfusion and blood management had made a systematic study on the applicable scope and management rules of remote verification of blood distribution and collection, and formulated this Expert Consensus combined with the development status of digital, intelligent and remote communication technologies, so as to provide corresponding guidance for clinical medical institutions in line with the changes in reality.

The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.

Objective: To investigate the incidence and risk factors of extraintestinal manifestations (EIMs) in children with inflammatory bowel disease (IBD). Methods: The clinical data of 161 children with IBD was collected from the electronic medical records in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine from January 2012 to December 2017. These patients were divided into Crohn′s disease (CD) group and ulcerative colitis (UC) group, accounting for 82.0% (132 cases) and 18.0%(29 cases), respectively. The incidence of EIMs in each group was analyzed. The potential risk factors of EIMs including the IBD phenotype, gender, age, location of the CD lesion, disease activity of CD, and the presence of perianal lesion were analyzed with logistic regression model. Results: Eighty-eight patients (54.7%) had EIMs. The main EIMs were immune-mediated EIMs and growth retardation, accounting for 41.0% (66/161) and 24.2% (39/161), respectively. Aphthous ulcer (39/161, 23.0%) was the most common symptom among immune-mediated EIMs, followed by arthropathy (20/161, 12.4%) and skin lesions (19/161, 11.8%). Forty-three patients (26.7%) had EIMs before being diagnosed as IBD. Fifty-eight (65.9%) patients had only one EIM during the whole course of IBD. By logistic regression analysis, CD (OR=5.536, 95%CI:1.825-16.788) and perianal disease (OR=1.969, 95%CI:1.035-3.746) were the risk factors of immune-mediated EIMs. Meanwhile, CD (OR=11.319, 95%CI: 1.487-86.179), younger than six-year-old at diagnosis (OR=8.556, 95%CI: 3.109-23.545), moderate to severe activity of CD (OR=3.447, 95%CI: 1.196-9.934) and perianal disease (OR=3.361, 95%CI: 1.720-7.793) increased the risk of growth retardation. Conclusions The children with IBD have a high incidence of EIMs, which were more common in CD than in UC. The risk factors of developing EIMs include CD, perianal diseases, younger than six-year-old at diagnosis and moderate to severe activity of CD.

BACKGROUND/AIMS: Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. METHODS: TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. RESULTS: Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. CONCLUSIONS: Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.
Abdominal Pain ; Animals ; Ankyrins ; Biopsy ; Calcium ; Cold Temperature ; Drinking ; Gene Deletion ; Humans ; Irritable Bowel Syndrome ; Models, Animal ; Neurons ; Nociception ; Phosphorylation ; Protein Kinases ; Rats ; Stress, Psychological ; Up-Regulation ; Vagus Nerve ; Visceral Pain ; Water

Objective To explore the effect of radiofrequency heating on type Ⅱ collagen expression in a rabbit model of osteoarthritis.Methods Knee osteoarthritis was induced in the right hind legs of 54 male rabbits using modified Hulth modeling.The rabbits were randomly divided into a model group which was not given any special treatment,a Lugua polypeptide group and a radiofrequency hyperthermia group.The Lugua polypeptide group was injected with Lugua polypeptide;the radiofrequency hyperthermia group was treated with radiofrequency irradiation.Six,12 and 18 days after the treatment,the morphological condition of the rats' right femoral medial condyle cartilages were evaluated using modified Mankins scoring and the type Ⅱ collagen content of the cartilage was detected using a quantitative PCR technique.Results At the same time points after treatment,the average Mankins scores were decreased in all the 3 groups,with that of the model group was significantly higher than those of both of the other groups,and the radiofrequency hyperthermia group's average score was significantly better than that of the Lugua polypeptide group.The average type Ⅱ collagen content was significantly increased in all the 3 groups to various extent (the radiofrequency hyperthermia group ＞ Lugua polypeptide group ＞ model group).For the radiofrequency hyperthermia group,the average Mankins score decreased significantly and the average type Ⅱ collagen content increased significantly as the treatment continued.Conclusion Radiofrequency hyperthermia is superior to Lugua polypeptide for treating knee osteoarthritis,at least in rabbits.Its therapeutic effectiveness may be related to a significant increase of type Ⅱ collagen in the cartilage.

Objective To explore the effect of radiofrequency-induced hyperthermia on the morphology of articular cartilage and any changes in serum-1 interleukin-1 (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the process of knee osteoarthritis in rabbits.Methods Fifty-four male rabbits were selected and knee osteoarthritis was introduced to their right hind limbs using the modified Huhh model.They were then randomly divided into a model group,a cervus and cucumis polypeptide (CCP) group and a radiofrequency thermotherapy (RT) group,each of 18.The CCP group was injected with deer melon peptide intramuscularly.The RT group was given radiofrequency hyperthermia treatment.The model group was not provided with any special treatment.On the 7th,13th and 19th day of the treatment,6 rabbits in each group were sacrificed to resect the right medial femoral condyle cartilage.The morphological characteristics of the cartilage were evaluated using the modified Mankins score,while the content of IL-1βand TNF-α in the serum were detected using enzyme-linked immuno-sorbent assays (ELISAs).Results At the same time points,the average Mankins score and the average content of IL-1βand TNF-α in the serum of the model group were significantly higher than in the CCP group,with the values in the latter group significantly higher than in the RT group.In the RT group,the average Mankins score,as well as the IL-1 beta and TNF-alpha levels in the serum,decreased significantly with longer treatment.Conclusion Radiofrequency-induced hyperthermia is superior to deer melon polypeptide in treating knee osteoarthritis,at least in rabbits.Its therapeutic mechanism may be related to the control of serum IL-1 beta and TNF-alpha levels.

Objective:Prepared the specific chicken egg yolk immunoglobulins (IgY) against the cell wall protein of Trichophyton mentagrophytes (tmCWP) and detected its biological activities,which was to establish the basis for the preventment and treatment in dermatophytes disease.Methods: In this work,tmCWP was extracted and purified by cold alkali method,and being used as immunogen to immunized healthy laying hens.The IgY was extracted from the egg yolk by polyethylene glycol method and purified by saturated ammonium sulfate method,respectively.The concentration of the extracted IgY was detected by Bradford method.The purity and molecular weight of the specific anti-tmCWP IgY were analysed by SDS-PAGE.The titer of IgY was obtained by ELISA.The immunoreactivity of IgY was performed by Western blot.Results: The purity of the extracted IgY reached to 87.27％.ELISA indicated that the titer of the specific anti-tmCWP IgY gradual rised 20 days after primary immunization and reached to the highest value (1∶32 000) after 45 days.Western blot revealed that the specific IgY showed a good immunoreactivity and a specifically combination capacity.Conclusion: In our work,the tmCWP could be regarded as the immunogen to prepare the specific anti-tmCWP IgY,which could provide a novel thought for the therapy of Trichophyton mentagrophytes infection.