Objective:To retrospectively analyze the pathogenic factors of retrograde peri-implantitis (RPI) and assess the effectiveness of treatment, and to provide clinicians evidence for the prevention and treatment of RPI.Methods:A total of 2 731 patients with missing teeth (4 016 implants) who underwent implant restoration in the Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University between January 2004 and December 2022 were included in the study. According to the diagnostic criteria of RPI, a total of 20 cases (23 implants) of RPI were collected, including 4 female (5 implants) and 16 male (18 implants), and the treatment medical records, intraoral photos and cone beam CT or oral panoramic radiographs records of each patient were collected. Each patient with RPI was treated accordingly and followed up regularly to evaluate its efficacy.Results:After treatment, the follow-up time for 20 patients with clinical symptoms of RPI was 13 (6, 40) months (1 month to 13 years), and the survival rate of the treated implants was 91% (21/23). There were 7 patients (8 implants) with inactive RPI, no clinical symptoms, no loosening of the implant, with normal occlusal load, and the disease was at the inactive stage and was not treated. The pulp vitality of the natural tooth adjacent to the implant was normal, and the implant could function normally. There were 13 patients (15 implants) with infected RPI, 1 patient (1 implant) had no loosening of the implant, and the periapical radiolucency of the implant disappeared after endodontic treatment of the natural tooth adjacent to the implant; 12 patients (14 implants) had clinical symptoms such as implant loosening, pus discharge, etc. Among them, 10 patients (12 implants) were successfully implanted in situ or in adjacent sites after removing the implants, and were successfully implanted after 3 to 20 months. Two patients(2 implants) were removed and no further implants were placed. Among them, 2 implants with infected RPI had cystic lesions, which was similar to natural root apex cysts.Conclusions:The etiology of RPI is related to inflammation of adjacent tooth root tips or bacterial residues from inflammatory lesions in the alveolar bone and bone augmentation. RPI can be treated by perfect root canal treatment of adjacent teeth, removal of inflammatory tissue, or simultaneous guided bone regeneration techniques.

Objective:To explore the application value of the integrated situational simulation teaching model based on the "Internet+"in obstetrics and gynecology clinical clerkship.Methods:Fifty-eight undergraduate students enrolled in 2019 who participated in the clinical clerkship at the Chengdu Fifth People's Hospital from June to September 2023 were selected and divided into a research group ( n=29) and a control group ( n=29) using the random number table method. The research group received the integrated situational simulation teaching model based on "Internet+", while the control group received traditional teaching methods. After clinical clerkship, theoretical tests, teacher evaluation, and questionnaire surveys were conducted to evaluate and compare the teaching effectiveness of the two groups of students. SPSS 23.0 was used for t test and chi-square test. Results:After receiving the integrated situational simulation teaching model based on "Internet+" for clinical clerkship, the research group achieved significantly higher theoretical test scores than the control group [(83.62±4.95) vs. (72.93±4.70), t=8.43, P<0.001]. The scores of all items in the mini-clinical evaluation exercise of the research group were higher than those of the control group ( P<0.01). According to the teaching feedback questionnaire, all students were satisfied with this new teaching model and reported that this model increased their interest in learning. Moreover, 86.21% (25/29) and 96.55% (28/29) of the students believed that the new model not only improved learning efficiency but also facilitated the integration of theory and practice. Conclusions:The integrated situational simulation teaching model based on "Internet+" is feasible in obstetrics and gynecology clinical clerkship and contributes to enhancing the quality of clinical clerkship teaching. This model is worthy of further research and promotion.

Objective·To construct truncations of CYLD,and to preliminarily analyze their effects on the proliferation of gastric cancer cells.Methods·TCGA,GTEx,and Kaplan-Meier Plotter databases were used to analyze the differences in the expression levels of CYLD between gastric cancer tissues and normal tissues,and their relationship with the prognosis of gastric cancer patients.Immunohistochemistry and Western blotting were used to detect the expression of CYLD in cancer tissues and adjacent noncancerous tissues.Western blotting and qRT-PCR were used to analyze the protein and mRNA expression levels of CYLD in gastric mucosal epithelial cells and gastric cancer cells.According to the sequence and structural characteristics of CYLD gene,primers were designed to construct its truncations.Their expression was detected and identified by agarose gel electrophoresis and Western blotting,and localization was observed by immunofluorescence.In the human gastric adenocarcinoma cells(AGS)with CYLD knockdown,blank NC was added to the control group,and the full-length CYLD,enzyme-inactivated mutant,and three truncated plasmids were added to the experimental group.The proliferation changes of cells in each group were detected by CCK-8 and plate cloning assays.Co-immunoprecipitation,deubiquitination,and Western blotting assays were performed to examine the binding ability of full-length CYLD,the enzyme-inactivated mutant,and the truncated variants to CAMK2A,the level of CAMK2A deubiquitination,and the expression of STAT3 and p-STAT3 proteins.Results·CYLD expression in normal gastric tissues and cells was significantly higher than in gastric cancer tissues and cells,and the prognosis of patients with high expression of CYLD was better.The truncations of human CYLD were successfully constructed,and full length CYLD,enzyme-inactivated mutant,and truncations were mainly localized in the cytoplasm.Knockdown of CYLD in gastric cancer cells significantly enhanced the proliferative ability of gastric cancer cells.Reconstitution of CYLD-knockdown cells with CYLD-WT,or truncated variants containing the CAP3 or USP domains significantly inhibited the proliferation of gastric cancer cells.In addition,CYLD bound to CAMK2A mediated K63 deubiquitination modification,and inhibited CAMK2A-induced phosphorylation of STAT3.Conclusion·The human CYLD truncation plasmids are successfully constructed,and the full length CYLD and its CAP3 and USP segments significantly inhibit the proliferation of gastric cancer cells.

Objective:To retrospectively analyze the pathogenic factors of retrograde peri-implantitis (RPI) and assess the effectiveness of treatment, and to provide clinicians evidence for the prevention and treatment of RPI.Methods:A total of 2 731 patients with missing teeth (4 016 implants) who underwent implant restoration in the Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University between January 2004 and December 2022 were included in the study. According to the diagnostic criteria of RPI, a total of 20 cases (23 implants) of RPI were collected, including 4 female (5 implants) and 16 male (18 implants), and the treatment medical records, intraoral photos and cone beam CT or oral panoramic radiographs records of each patient were collected. Each patient with RPI was treated accordingly and followed up regularly to evaluate its efficacy.Results:After treatment, the follow-up time for 20 patients with clinical symptoms of RPI was 13 (6, 40) months (1 month to 13 years), and the survival rate of the treated implants was 91% (21/23). There were 7 patients (8 implants) with inactive RPI, no clinical symptoms, no loosening of the implant, with normal occlusal load, and the disease was at the inactive stage and was not treated. The pulp vitality of the natural tooth adjacent to the implant was normal, and the implant could function normally. There were 13 patients (15 implants) with infected RPI, 1 patient (1 implant) had no loosening of the implant, and the periapical radiolucency of the implant disappeared after endodontic treatment of the natural tooth adjacent to the implant; 12 patients (14 implants) had clinical symptoms such as implant loosening, pus discharge, etc. Among them, 10 patients (12 implants) were successfully implanted in situ or in adjacent sites after removing the implants, and were successfully implanted after 3 to 20 months. Two patients(2 implants) were removed and no further implants were placed. Among them, 2 implants with infected RPI had cystic lesions, which was similar to natural root apex cysts.Conclusions:The etiology of RPI is related to inflammation of adjacent tooth root tips or bacterial residues from inflammatory lesions in the alveolar bone and bone augmentation. RPI can be treated by perfect root canal treatment of adjacent teeth, removal of inflammatory tissue, or simultaneous guided bone regeneration techniques.

Objective:To explore the application value of the integrated situational simulation teaching model based on the "Internet+"in obstetrics and gynecology clinical clerkship.Methods:Fifty-eight undergraduate students enrolled in 2019 who participated in the clinical clerkship at the Chengdu Fifth People's Hospital from June to September 2023 were selected and divided into a research group ( n=29) and a control group ( n=29) using the random number table method. The research group received the integrated situational simulation teaching model based on "Internet+", while the control group received traditional teaching methods. After clinical clerkship, theoretical tests, teacher evaluation, and questionnaire surveys were conducted to evaluate and compare the teaching effectiveness of the two groups of students. SPSS 23.0 was used for t test and chi-square test. Results:After receiving the integrated situational simulation teaching model based on "Internet+" for clinical clerkship, the research group achieved significantly higher theoretical test scores than the control group [(83.62±4.95) vs. (72.93±4.70), t=8.43, P<0.001]. The scores of all items in the mini-clinical evaluation exercise of the research group were higher than those of the control group ( P<0.01). According to the teaching feedback questionnaire, all students were satisfied with this new teaching model and reported that this model increased their interest in learning. Moreover, 86.21% (25/29) and 96.55% (28/29) of the students believed that the new model not only improved learning efficiency but also facilitated the integration of theory and practice. Conclusions:The integrated situational simulation teaching model based on "Internet+" is feasible in obstetrics and gynecology clinical clerkship and contributes to enhancing the quality of clinical clerkship teaching. This model is worthy of further research and promotion.

Objective·To construct truncations of CYLD,and to preliminarily analyze their effects on the proliferation of gastric cancer cells.Methods·TCGA,GTEx,and Kaplan-Meier Plotter databases were used to analyze the differences in the expression levels of CYLD between gastric cancer tissues and normal tissues,and their relationship with the prognosis of gastric cancer patients.Immunohistochemistry and Western blotting were used to detect the expression of CYLD in cancer tissues and adjacent noncancerous tissues.Western blotting and qRT-PCR were used to analyze the protein and mRNA expression levels of CYLD in gastric mucosal epithelial cells and gastric cancer cells.According to the sequence and structural characteristics of CYLD gene,primers were designed to construct its truncations.Their expression was detected and identified by agarose gel electrophoresis and Western blotting,and localization was observed by immunofluorescence.In the human gastric adenocarcinoma cells(AGS)with CYLD knockdown,blank NC was added to the control group,and the full-length CYLD,enzyme-inactivated mutant,and three truncated plasmids were added to the experimental group.The proliferation changes of cells in each group were detected by CCK-8 and plate cloning assays.Co-immunoprecipitation,deubiquitination,and Western blotting assays were performed to examine the binding ability of full-length CYLD,the enzyme-inactivated mutant,and the truncated variants to CAMK2A,the level of CAMK2A deubiquitination,and the expression of STAT3 and p-STAT3 proteins.Results·CYLD expression in normal gastric tissues and cells was significantly higher than in gastric cancer tissues and cells,and the prognosis of patients with high expression of CYLD was better.The truncations of human CYLD were successfully constructed,and full length CYLD,enzyme-inactivated mutant,and truncations were mainly localized in the cytoplasm.Knockdown of CYLD in gastric cancer cells significantly enhanced the proliferative ability of gastric cancer cells.Reconstitution of CYLD-knockdown cells with CYLD-WT,or truncated variants containing the CAP3 or USP domains significantly inhibited the proliferation of gastric cancer cells.In addition,CYLD bound to CAMK2A mediated K63 deubiquitination modification,and inhibited CAMK2A-induced phosphorylation of STAT3.Conclusion·The human CYLD truncation plasmids are successfully constructed,and the full length CYLD and its CAP3 and USP segments significantly inhibit the proliferation of gastric cancer cells.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

ObjectiveTo investigate the possible mechanism of electroacupuncture at "Neiguan" （PC6） and "Zhongwan" （RN12） in the treatment of functional dyspepsia （FD）. MethodsSPF male SD rats were randomly divided into model group， Neiguan （PC6） group， Zhongwan （RN12） group， and Neiguan-Zhongwan （PC6-RN12） group， with 8 rats in each group. Except for the normal group， the other groups of rats were cogavaged with 0.1% sucrose iodoacetamide solution combined with small platform standing training to establish FD rat models. After successful modeling， the rats in the normal group and model group were tied up for 30 min/d for 7 days； the Neiguan group， Zhongwan group， and Neiguan-Zhongwan group were treated with electroacupuncture intervention at "Neiguan" （PC6）， "Zhongwan" （RN12）， and "Neiguan" - "Zhongwan" （PC6-RN12） acupoints， respectively， using continuous wave， frequency of 2 Hz， current intensity of 1 mA， 30 min/d， and continuous intervention for 7 days. The general condition of rats in each group was observed. After treatment， the body weight and food intake of rats were measured， and the gastric emptying rate was calculated； HE staining was performed on the gastric antrum tissue of rats to observe the histopathologic changes； the expressions of calcitonin gene-related peptide （CGRP） and Ghrelin protein in gastric antrum were detected by Western Blot； the metabolites in gastric antrum tissues were detected by liquid chromatography-mass spectrometry （LC-MS）， and differential metabolites were screened by correlation analysis， then Metabo Analyst 5.0 and KEGG databases were used for metabolic pathway analysis. ResultsUnder light microscope， the gastric antrum structure was complete and the glands were abundant. No obvious inflammation and edema were found in gastric mucosa. Compared with the normal group， the body weight， food intake， and gastric emptie rate of rats in model group decreased， the expression of Ghrelin protein decreased and the expression of CGRP protein increased in gastric antrum tissue （P＜0.01）. Compared with model group， the body weight， food intake， and gastric emptance rate of rats in Neiguan group， Zhongwan group and Neiguan-Zhongwan group all increased， CGRP protein expression decreased in Neiguan group， and Ghrelin protein expression increased and CGRP protein expression decreased in Zhongwan group and Neiguan-Zhongwan group （P＜0.01 or P＜0.05）. Compared with Neiguan-Zhongwan group， Ghrelin protein expression decreased and CGRP protein expression increased in Neiguan group and Zhongwan group （P＜0.05 or P＜0.01）. Metabolomics results showed that compared with normal group， the content of metabolites adenosine diphosphate ribose， adenosine monophosphate and adenosine diphosphate in gastric antrum tissue of model group decreased； compared with model group， the contents of adenosine diphosphate， adenosine diphosphate and citicoline in Neiguan group increased， the contents of nicotine adenine dinucleotide， cytidine diphosphate ethanolamine and citicoline in Zhongwan group increased， and the contents of adenosine diphosphate， cytidine diphosphate and citicoline in Neiguan-Zhongwan group increased （P＜0.05 or P＜0.01）. Compared with model group， the main metabolic pathways of different metabolites in PC6-RN12 group were glycerophospholipid metabolism， taurine and hypotaurine metabolism， purine metabolism， starch and sucrose metabolism. ConclusionElectroacupuncture at “Neiguan” and “Zhongwan” acupoints can effectively regulate gastrointestinal motility and improve FD symptoms in FD rats， and the effect is better than that of "Neiguan" or "Zhongwan" acupoints alone. The mechanism may be related to the influence of related metabolites on energy metabolism， glucose metabolism and nucleotide metabolism， thereby regulating gastrointestinal motility hormones.

Objective:To investigate the clinical characteristics and treatment of Beh?et′s disease complicated with cardiac valve involvement.Methods:We searched the wanfang medical database and Medline database to reviewed the domestic and foreign literature reports on cardiac Beh?et′s disease and analyzed their clinical features and therapeutic strategies. Chi-squared test was used for data analysis.Results:It was shown that Beh?et′s disease with cardiac valve involvement mainly affect men. The male to female ratio was 3.86∶1 in China and 2.50∶1 in foreign patients( χ2=1.32, P=0.251). The preoperative diagnosis rate was not high(60.3% in China, 57.1% abroad) ( χ2=0.13, P=0.716). Aortic valve and perivalvular lesions were the most common involved sites, of which aortic regurgitation was the most frequenty occurred, followed by mitral valve lesions. Glucocorticoids was still the main means treatment for medical(93/235 in China, 28/420 abroad), cyclophosphamide was more widely used in China(28/235), azathioprine was more widely used in foreign countries (12/42). Aortic replacement (AVR) was the mainly surgical approach, followed by artificial aortic valve replacement and left ventricular outflow tract plasty (Bentall).The incidence of postoperative perivalvular leakage or valve prolapse was higher with AVR than with Bentall(AVR 76.3%/Bentall 21.8% at home, χ2=32.60, P<0.001, AVR 71.4%/Bentall 0 abroad, χ2=13.84, P<0.001). Conclusions:Cardiac valve involvement is a severe complication of Beh?et′s disease. Heart involvement are more common, and the preoperative diagnosis rate is lower in China. The incidence of perivalve leakage (PVL) or valve prolapse (PD) after operation is higher with AVR than with Bentall surgery.The Bentall operation could improve prognosis and the postoperative complications abroad are lower than domestic.

Objective: To explore the potential mechanism of acupuncture and moxibustion in treating Crohn disease (CD) by evaluating the changes in histamine and inflammatory factors in the skin tissue at Tianshu (ST25) of rats.Methods: Fifty-eight Sprague-Dawley rats were randomly divided into a normal group (n=14) and a CD-modeling group (n=44). Rats in the CD-modeling group received enema with 2,4,6-trinitrobenzene sulfonic acid plus ethanol to establish CD models. The enema was repeated once every 7 d for a total of 4 times. After modeling, four modeled rats and four normal rats were randomly selected for model identification. After the CD model was successfully established, the remaining rats in the CD-modeling group were randomly divided into a model group, an acupuncture group, a moxibustion group, and a Western medication group, with ten rats in each group. The rats in the acupuncture and moxibustion groups were treated with acupuncture or moxibustion at Tianshu (ST25) and Shangjuxu (ST37); the rats in the Western medication group were treated with mesalazine enteric-coated tablets by gavage for continuous 7 d. After the intervention, the colon tissue of rats in each group was collected. After gross observation, hematoxylin-eosin (HE) staining was performed to further observe the pathological changes. The expression of histamine in the skin tissue at Tianshu (ST25) was detected by enzyme-linked immunosorbent assay. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, IL-10, and IL-6 in the skin tissue at Tianshu (ST25) was detected by Western blotting. Results: Compared with the normal group, the colonic wall of rats in the model group showed cobblestone-like changes, local ulcers, and polyps in dark red and thickening and hardening. HE staining showed local loss of mucosal epithelial layer and formation of slit-like ulcers, destruction of mucosal glands, edema, and infiltration of inflammatory cells in lamina propria and submucosa, and occasional formation of sarcoid-like granuloma. The levels of histamine and IL-6 were significantly up-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly down- regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the model group. Compared with the model group, the pathomorphological damage of the colon tissue of rats in the acupuncture group, moxibustion group, and Western medication group was significantly improved. The levels of histamine and IL-6 were significantly down- regulated (P<0.01, P<0.05), and the level of IL-10 was significantly up-regulated (P<0.01) in the skin at Tianshu (ST25) of rats in the acupuncture group. The levels of histamine and IL-6 were significantly down-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly up-regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the moxibustion group. The level of histamine was significantly down-regulated (P<0.01), and the levels of IL-18 and IL-10 were significantly up-regulated (P<0.05, P<0.01) in the skin tissue of rats in the Western medication group. Compared with the acupuncture group, the level of IL-10 in the skin tissue at Tianshu (ST25) of rats in the moxibustion group was significantly up-regulated (P<0.01). Conclusion: The inflammatory responses in the skin tissue at Tianshu (ST25) may be the external manifestation of CD. Significant differences in the regulation of inflammatory responses in the skin tissue at Tianshu (ST25) between acupuncture and moxibustion exist, which may be caused by the differences in the stimulation characteristics between acupuncture and moxibustion.