OBJECTIVES: To investigate the effect of ecliptasaponin A (ESA) for alleviating dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice and the underlying mechanism. METHODS: Twenty-four male C57BL/6 mice (8-10 weeks old) were equally randomized into control group, DSS-induced IBD model group, and DSS+ESA (50 mg/kg) treatment group. Disease activity index (DAI), colon length and spleen index of the mice were measured, and intestinal pathology was examined with HE staining. The expressions of inflammatory mediators (TNF-α, IL-6, and iNOS) in the colon mucosa were detected using ELISA and RT-qPCR, and intestinal barrier integrity was assessed using AB-PAS staining and by detecting ZO-1 and claudin-1 expressions using immunofluorescence staining and Western blotting. In cultured RAW264.7 macrophages, the effects of treatment with 50 μmol/L ESA, alone or in combination with 20 μmol/L RO8191 (a JAK2/STAT3 pathway activator), on M1 polarization of the cells induced by LPS and IFN-γ stimulation and expressions of JAK2/STAT3 pathway proteins were analyzed using flow cytometry and Western blotting. RESULTS: In the mouse models of DSS-induced IBD, ESA treatment significantly alleviated body weight loss and colon shortening, reduced DAI, spleen index and histological scores, and ameliorated inflammatory cell infiltration in the colon tissue. ESA treatment also suppressed TNF‑α, IL-6 and iNOS expressions, protected the goblet cells and the integrity of the mucus and mechanical barriers, and upregulated the expressions of ZO-1 and claudin-1. ESA treatment obviously decreased CD86⁺ M1 polarization in the mesenteric lymph nodes of IBD mice and in LPS and IFN-γ-induced RAW264.7 cells, and significantly reduced p-JAK2 and p-STAT3 expressions in both the mouse models and RAW264.7 cells. Treatment with RO8191 caused reactivation of JAK2/STAT3 and strongly attenuated the inhibitory effect of ESA on CD86⁺ polarization in RAW264.7 cells. CONCLUSIONS ESA alleviates DSS-induced colitis in mice by suppressing JAK2/STAT3-mediated M1 macrophage polarization and mitigating inflammation-driven intestinal barrier damage.
Animals ; Mice ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice, Inbred C57BL ; Male ; Dextran Sulfate ; Macrophages/cytology* ; Colitis/metabolism* ; Saponins/pharmacology* ; Signal Transduction/drug effects* ; RAW 264.7 Cells ; Triterpenes/pharmacology* ; Interleukin-6/metabolism*

OBJECTIVES: To investigate the mechanism through which pinostrobin (PSB) alleviates dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomized into control group, DSS model group, and PSB intervention (30, 60, and 120 mg/kg) groups. Colitis severity of the mice was assessed by examining body weight changes, disease activity index (DAI), colon length, and histopathology. The expressions of tight junction proteins ZO-1 and claudin-1 in the colon tissues were examined using immunofluorescence staining, and macrophage infiltration and polarization were analyzed with flow cytometry. ELISA and RT-qPCR were used for detecting the expressions of inflammatory factors (TNF‑α and IL-6) and chemokines (CCL₂, CXCL₁₀, and CX₃CL₁) in the colon tissues, and PI3K/AKT phosphorylation levels were analyzed with Western blotting. In cultured Caco-2 and RAW264.7 cells, the effect of PSB on CCL₂-mediated macrophage migration was assessed using Transwell assay. Network pharmacology analysis was performed to predict the key pathways that mediate the therapeutic effect of PSB. RESULTS: In DSS-induced mouse models, PSB at 60 mg/kg optimally alleviated colitis, shown by reduced weight loss and DAI scores and increased colon length. PSB treatment significantly upregulated ZO-1 and claudin-1 expressions in the colon tissues, inhibited colonic macrophage infiltration, and promoted the shift of macrophage polarization from M1 to M2 type. In cultured intestinal epithelial cells, PSB significantly inhibited PI3K/AKT phosphorylation and suppressed chemokine CCL₂ expression. PSB treatment obviously blocked CCL₂-mediated macrophage migration of RAW264.7 cells, which could be reversed by exogenous CCL₂. Network pharmacology analysis and rescue experiments confirmed PI3K/AKT and CCL₂ signaling as the core targets of PSB. CONCLUSIONS PSB alleviates DSS-induced colitis in mice by targeting intestinal epithelial PI3K/AKT signaling, reducing CCL₂ secretion, and blocking macrophage chemotaxis and migration, highlighting the potential of PSB as a novel natural compound for treatment of inflammatory bowel disease.
Animals ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Colitis/drug therapy* ; Dextran Sulfate ; Proto-Oncogene Proteins c-akt/metabolism* ; Macrophages ; Chemokine CCL2/metabolism* ; Humans ; Signal Transduction/drug effects* ; Caco-2 Cells ; RAW 264.7 Cells ; Epithelial Cells/drug effects* ; Intestinal Mucosa/metabolism*

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

BACKGROUND:Ankylosing spondylitis is a progressive inflammation of spinal stiffness deformity caused by tissue ossification and fibrosis.The posture of ankylosing spondylitis patients is abnormal and their activities are limited that minor injuries can lead to thoracolumbar fractures.Traditional medical image observation limits doctors'preoperative decision planning and postoperative disease prevention for ankylosing spondylitis treatment. OBJECTIVE:Based on the spinal model of ankylosing spondylitis patients before and after posterior spinal cancellous ossification osteotomy("Y"osteotomy for short),to explore the biomechanical changes of"Y"osteotomy and fixation in the treatment of ankylosing spondylitis. METHODS:Based on the preoperative and postoperative CT images of an ankylosing spondylitis patient who went to the Second Affiliated Hospital of Inner Mongolia Medical University,a three-dimensional spine model(T11-S1)before and after"Y"osteotomy(L3 osteotomy)was reconstructed in Mimics 19.0 software.A 7.5 Nm torque was applied to the top of T11 vertebral body to simulate the movement of the spine under six conditions:flexion,extension,left bending,right bending,left rotation and right rotation.Finally,the range of motion of each vertebral body,the stress of each intervertebral disc,and the stress of the screw rod system were simulated. RESULTS AND CONCLUSION:(1)After"Y"type osteotomy and posterior fixation,the range of motion of all vertebrae in the spine decreased,and the loss rate of upper vertebrae was large(L1:77.95%).(2)The maximum stress of the spinal intervertebral disc before operation occurred at the L1-L2 segment(0.55 MPa),and the maximum stress of the spinal intervertebral disc after operation occurred at the T11-T12 segment(0.50 MPa),and the stress of intervertebral disc below T12 was far less than that before operation.(3)The maximum stress of the screw rod system(166.67 MPa)occurred in the upper and middle segments of the rod body and the root of the pedicle screw.(4)In conclusion,the"Y"type posterior fixation operation enhances the stability of the spine and reduces the range of motion of the spine.The vertebral body decompression of the fixed segment is great and the stress-shielding phenomenon of the lower vertebral body is significant.The stiffness of the rod body and the stress concentration area of the pedicle screw should be strengthened to avoid the fracture of the rod caused by stress fatigue.

Under the organization of Renji Hospital, Shanghai Jiao Tong University School of Medicine, a specialized disease database of inflammatory bowel disease (IBD) cohort was deployed, and a brief introduction of the database was made in this article. The IBD data set was established by referring to domestic and foreign standards. Through data extraction, cleaning, normalization and other information processing technologies, data from multi‑source heterogeneous platform were arranged to form a specialized major disease database of IBD cohort and the efficiency and quality of data collection in clinical practice, teaching and scientific research were guaranteed. The display and personalized export capacities of the database can promote the researches on IBD and assist the clinical decision‑making. It provides not only efficient, comprehensive and reliable research‑level data support for scientific research, but also a precise guidance for diagnosis and treatment of the disease. Furthermore, it can excavate the potential clinical principles based on medical big data.

【Objective】 To explore the effects of anti-inflammatory of short-chain fatty acids in human peripheral blood mononuclear cells （THP-1） and chronic obstructive pulmonary （COPD） mice. 【Methods】 We adopted the methods of qRT-PCR， ELISA， Western blotting， HE staining and Sirius staining to detect the changes of inflammatory factors in THP-1 cells and COPD with or without short-chain fatty acids. 【Results】 The ELISA and qRT-PCR experiments showed that the serum inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， were higher in clinical COPD patients than in healthy people. And the THP-1 cells expressed these inflammatory factors highly after LPS stimulation. Among three short-chain fatty acids treated， butyrate could reduce the levels of inflammatory factors better than acetate and propionate. After COPD mice were treated with butyrate in the drinking water， the mRNA expressions of inflammatory factors IL-6， IL-1β and TNF-α in the lung tissue decreased， and the concentrations of IL-6 and IL-1β in plasma decreased. The protein detection results showed that the phosphorylation expression of NF-κB decreased， and butyrate might inhibit the expressions of inflammatory factors by inhibiting the NF-κB signaling pathway. 【Conclusion】 The SCFA butyrate can inhibit LPS-induced inflammatory response of THP-1 cells and have an inhibitory effect on inflammation in COPD mice.

OBJECTIVE To establish HPLC finger print of Leonurus japonicus granules，and to determine the contents of 4 index components such as leonurine hydrochloride ，ferulic acid ，rutin，hyperoside. METHODS The determination was performed on Inertsil TM ODS-3 column with mobile phase consisted of acetonitrile （A）-0.1％ formic acid solution （B）in the form of gradient elution；the flow rate was 1.0 mL/min，the detection wavelength was 280 nm，the column temperature was 25 ℃，and the sample size was 5 µL. Similarity Evaluation System of Chromatogram Fingerprint of TCM （2012 edition）was used for establishing the HPLC fingerprints of 10 batches of L. japonicus granules and analyzing their similarities. By comparing with HPLC fingerprints of reference substance ，the common peaks were identified. SPSS 25.0 and SIMCA 13.0 software were used for cluster analysis and principal component analysis ；the above HPLC method was used for the content determination of 4 index components in L. japonicus granules such as leonurine hydrochloride ，ferulic acid ，rutin，hyperoside. RESULTS HPLC fingerprints of 10 batches of L. japonicus granules were established ，and 16 common peaks were matched ，and 4 peaks identified were leonurine hydrochloride （peak 6），ferulic acid （peak 13），rutin（peak 14），hyperoside（peak 16）；the similarities of 10 batches of samples were all higher than 0.970. The 10 batches of samples could be divided into four categories by cluster analysis and principal component analysis；the classification results were consistent. The contents of leonurine hydrochloride ，ferulic acid ，rutin and hyperoside were 122.10-138.82 μ g/g，9.33-10.45 μ g/g，14.12-18.95 μ g/g，5.87-8.06 μ g/g，respectively. CONCLUSIONS Established HPLC fingerprint of L. japonicus granules and the method for the content determination of 4 index components are simple and easy to operate，and have high precision and good repeatability ，which provide reference for the quality evaluation of L. japonicus granules.

Objective    To evaluate the effect of perioperative nebulization of ipratropium bromide on preoperative pulmonary function and incidence of postoperative pulmonary complications as well as safety in chronic obstructive pulmonary disease (COPD) patients who underwent lung resection in thoracic surgery. Methods    During November 18, 2013 to August 12, 2015, 192 COPD patients with a necessity of selective surgical procedures of lobectomy or right bilobectomy or segmentectomy under general anaesthesia in 10 centers were 1 : 1 randomized to an ipratropium bromide group (96 patients) and a placebo group (96 patients), to compare the effect on preoperative pulmonary function and incidence of postoperative pulmonary complications. The average age of treated patients was 62.90±6.50 years, with 168 male patients and 22 female patients. Results     The demographic and baseline characteristics were well-balanced between the two groups. The adjusted mean increase of forced expiratory volume in one second (FEV1) in the ipratropium bromide group was significantly higher than that in the placebo group (169.90±29.07 mL vs. 15.00±29.35 mL, P<0.05). The perioperative use of ipratropium bromide significantly decreased incidence of postoperative pneumonia (2.6% vs. 14.1%, P<0.05). There was no ipratropium bromide related adverse event (AE) observed in this trial. Conclusion    This trial indicates that perioperative nebulization of ipratropium bromide significantly improves preoperative lung function and reduces postoperative pneumonia in COPD patients undergoing lung resection in thoracic surgery, and has good safety profile.