A 36-year-old male patient presented with repeated myocardial infarction. Despite regular dual-antiplatelet therapy and intensive lipid-lowering therapy, he still experienced restenosis after coronary stent implantation. He then transferred to the Zhongshan Hospital, Fudan University. According to the disease history, combined with coronary artery inflammation observed by PET/CT and effective anti-inflammatory treatment, he was finally diagnosed with Behçet’s disease (BD) combined with isolated coronary arteritis. BD has been included in the Chinese Second Catalog of Rare Diseases, and the disease that only involves the coronary arteries is even rarer, which makes it very easy to misdiagnose and underdiagnosis in clinical practice. Strengthening the understanding of the complex clinical phenotypes of various vasculitis, attaching importance to multidisciplinary consultation, and dynamically following up are of great value for the early diagnosis of this disease.

OBJECTIVE To explore the potential mechanisms of astragalin （AG） in allevating ulcerative colitis （UC） in mice through modulation of the intestinal flora. METHODS Male C57BL/6 mice were randomly divided into normal group （CON group）， model group [dextran sodium sulfate （DSS） group]， 5-aminosalicylic acid group （5-ASA group）， AG low-dose group and high-dose group （AGL and AGH groups）， with 8 mice in each group. The mice UC model was established by drinking 3% DSS solution continuously for 7 days in all groups except the CON group. After that， 3% DSS solution was replaced by water， and the mice of each drug group were gavaged with the corresponding drug solution. Mice in the CON and DSS groups were gavaged with an equal volume of normal saline， once a day， for 7 days. After the last gavage， the body weight change index， disease activity index （DAI） score， colon length and spleen index， and levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） were compared among the mice in each group； pathological changes in colonic tissues of the mice were observed in each group， and the pathological score and the percentage of goblet cells were compared； mRNA expressions of barrier-related factors [occludin and ZO-1] and inflammation-related factors [silencing information regulatory factor 1 （SIRT1）， c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK）] were detected in each group of mice； the changes in the intestinal flora of mice in each group were analyzed and the contents of intestinal metabolites short-chain fatty acids （SCFAs） was determined. Using DSS and AG-treated fecal bacterial liquid as an intervention， the mechanism of anti-UC effect of AG was further verified by a fecal microbiota transplant experiment. RESULTS Compared with the CON group， the intestinal mucosal structure of mice in the DSS group was severely damaged， with obvious infiltration of inflammatory cells collapsing the wall； their body weight change index， colon length， the percentage of goblet cells， mRNA expressions of occludin， ZO-1 and SIRT1， Chao1 and Shannon indexes， and contents of acetic acid and butyric acid were significantly reduced， shortened or down-regulated （P＜0.05）； however， DAI score， spleen index， levels of inflammatory factors， pathological score， as well as mRNA expressions of p38 MAPK and JNK， were all significantly increased or up-regulated （P＜0.05）. Compared with the DSS group， colon tissue lesions of AG mice in all dose groups showed different degrees of improvement， and the above quantitative indexes were generally regressed （P＜0.05）， and the intervention effect of AG-treated fecal bacterial fluid was basically the same as that of AG. CONCLUSIONS AG can improve relevant symptoms in UC mice and reduce their inflammatory response and colonic histopathological changes. The above effects may be related to regulating the diversity of intestinal flora in mice， increasing the contents of butyric acid and propionic acid， and promoting the repair of the colonic mucosal barrier， thus regulating the expressions of genes related to the SIRT1/p38 MAPK inflammatory pathway.

Objective To investigate the effects and underlying mechanisms of a spray prepared from exosomes derived from M2 macrophages induced by interleukin-4 （IL-4） and tantalum particles （Ta） on the healing of pressure ulcers. Methods Bone marrow-derived macrophages were polarized into M2 macrophages using IL-4 or Ta, and exosomes （Exo-IL-4/Exo-Ta） were extracted. The regulatory effects of Exo-IL-4/Exo-Ta on M1 macrophage phenotypes and fibroblast matrix secretion were evaluated in vitro. Proteomic analysis was conducted to explore the biological processes and regulatory networks associated with Exo-Ta. A rat pressure ulcer model was used to assess the effects of Exo-IL-4/Exo-Ta spray on wound healing rate, inflammatory cell infiltration, and collagen deposition. Results In vitro, Exo-IL-4/Exo-Ta induced the polarization of M1 macrophages to M2 macrophages, reduced the secretion of pro-inflammatory factors, and promoted the expression of anti-inflammatory substances. Additionally, Exo-IL-4/Exo-Ta enhanced the production of collagen and fibronectin in fibroblasts. Proteomic analysis revealed that Exo-Ta primarily participated in biological processes such as energy metabolism and macromolecule biosynthesis. In vivo, Exo-IL-4/Exo-Ta spray accelerated wound healing, reduced inflammatory infiltration, and improved tissue remodeling in the rat pressure ulcer model. Conclusion Exosome sprays derived from M2 macrophages could accelerate pressure ulcer healing by modulating inflammation and promoting tissue regeneration, which demonstrated excellent clinical application potential.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

Sj?gren′s syndrome is a chronic autoimmune inflammatory disease characterized by exocrine gland and extraglandular involvement. Cases of Sj?gren′s syndrome-associated aseptic meningitis (SS-AM) are relatively rare, and a case of recurrent aseptic meningitis with leukopenia and mild anemia associated with primary Sj?gren′s syndrome is reported, whose symptoms basically disappeared after treatment with prednison and hydroxychloroquine. The purpose of reporting this case is to raise awareness of SS-AM among fellow clinicians.

Patients with skeletal ClassⅡ often show symptoms such as protrusion of maxillary anterior teeth,mandibular retraction,open lips and teeth,deep overbite,and deep overjet,which seriously affect the facial appearance.This article reports a case of an ado-lescent male patient with skeletal Class Ⅱ combined with impacted teeth treated by one-stage early correction and two-stage fixation.After treatment,the patient's skeletal Class Ⅱ symptoms improved significantly,including the improvement of mandibular retraction.The problem of open lips and teeth was solved;the facial appearance tended to be straight,and there was no obvious abnormality of the temporomandibular joint.This case shows that early correction can achieve good therapeutic effects on this kind of patients and can avoid or reduce the possibility of orthognathic surgery for these patients in adulthood.

Objective To explore the effects and mechanism of Baitouweng Decoction in intestinal mucosal healing in mice with ulcerative colitis(UC)based on RIPK1/RIPK3/MLKL signaling pathway.Methods Totally 30 C57BL/6 male mice were randomly divided into control group,model group,Baitouweng Decoction group,infliximab group and combination group(Baitouweng Decoction+infliximab),with 6 mice in each group.A mouse model of UC was established by free administration of 3.5%sodium gluconate sulfate solution for 7 days.After modeling,Baitouweng Decoction group was given 8 g/kg Baitouweng Decoction solution by gavage daily,while the infliximab group was given 5 mg/kg infliximab intraperitoneal injection,the combination group was given synchronous gastric and intraperitoneal injection,while the control group and model group were given equal volume of normal saline by gavage for 7 consecutive days.The body mass of mice was recorded daily,fecal characteristics were observed,and disease activity index(DAI)score was performed,colon length was measured after intervention,ELISA was used to detect the contents of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),RT-qPCR was used to detect mRNA expressions of RIPK1,RIPK3 and MLKL in colon tissue,Western blot and immunofluorescence staining were used to detect the expressions of RIPK1,RIPK3 and MLKL protein in colon tissue.Results Compared with the control group,the model group mice showed a decrease in body mass(P<0.01),an increase in DAI score(P<0.01),a shortened colon length(P<0.01),and an increase in serum IL-6 and TNF-α content(P<0.01);colonic mucosal was destructed,with disappearance of crypts and glandular structures,extensive infiltration of inflammatory cells,and increased pathological score of colon tissue(P<0.01);the mRNA and protein expressions of RIPK1,RIPK3 and MLKL in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the body mass of mice in each treatment group increased(P<0.01),and the DAI score decreased(P<0.01),colon length increased(P<0.01),and the contents of serum IL-6 and TNF-α decreased(P<0.05,P<0.01);the destruction of the colonic mucosal barrier was reduced,the pathological score of colon tissue was reduced(P<0.05);the expressions of RIPK1,RIPK3 and MLKL mRNA and protein in colon tissue decreased(P<0.05,P<0.01).Conclusion Baitouweng Decoction can alleviate intestinal mucosal damage and inflammation in UC mice,and its mechanism may be related to the inhibition of the RIPK1/RIPK3/MLKL signaling pathway.

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Objective:To investigate the influencing factors for inadequate bowel preparation of colonoscopy.Methods:A total of 677 patients who underwent colonoscopy at Peking Union Medical College Hospital from December 2021 to January 2023 were recruited, and all patients underwent standardized bowel preparation by using 3 L polyglycol electrolyte powder with fractional dose. The quality of bowel preparation was assessed by Boston bowel preparation scale, and the influencing factors for inadequate bowel preparation were analyzed by logistic regression analysis.Results:The rate of inadequate bowel preparation was 31.5% (213/677). Among the patients with inadequate bowel preparation, 85.4% (182/213) inadequate bowel preparation was only in proximal colon, 14.1% (30/213) was in both proximal and distal colon, and 0.5% (1/213) was only in distal colon. Inadequate bowel preparation in distal colon and total colon were combined into inadequate bowel preparation in distal colon. The results of logistic regression analysis showed that inadequate bowel preparation in proximal colon was more likely to occur in men ( P=0.001, OR=2.253, 95% CI: 1.399-3.629), outpatients ( P<0.001, OR=4.175, 95% CI: 2.410-7.231), those with no family history of colorectal cancer ( P=0.001, OR=2.117, 95% CI: 1.365-3.284), and diagnostic colonoscopy ( P=0.003, OR=1.978, 95% CI: 1.261-3.102). And spinal disease ( P=0.044, OR=7.430, 95% CI: 1.051-52.511), outpatients ( P<0.001, OR=135.577, 95% CI: 29.135-630.883),non-compliance of dietary requirements ( P=0.006, OR=4.772, 95% CI: 1.576-14.453), adverse reaction during bowel preparation ( P=0.015, OR=4.341, 95% CI: 1.329-14.179), no family history of colorectal cancer ( P=0.003, OR=7.110, 95% CI: 1.912-26.438), and poor last stool character ( P=0.001, OR=25.922, 95% CI: 3.779-177.832) were risk factors for inadequate bowel preparation in distal colon. Conclusions:The inadequate bowel preparation of colonoscopy mainly occurs in proximal colon, and the risk factors for the inadequate bowel preparation vary in different colonic segments. Therefore, the specific interventions should be performed according to the character of different colon segments to improve the quality of bowel preparation.