Objective:To investigate the role of alkylation repair homolog 5(ALKBH5)-mediated N6-methyladenosine(m6A)modifi-cation in endometrial decidualization.Methods:The mouse models of pregnancy and pseudopregnancy were established,and quantita-tive real-time PCR and Western blot were used to measure the expression pattern of ALKBH5 in the endometrium.The mouse and cell models of artificially induced decidualization were established,and quantitative real-time PCR,Western blot,and immunohistochemis-try were used to measure the expression levels of decidualization-related markers.The EpiQuik m6A RNA methylation quantification kit was used to measure the level of m6A.The mouse and cell models of artificially induced decidualization with interference of ALKBH5 expression were established,and quantitative real-time PCR,Western blot,and immunohistochemistry were used to measure the expression levels of decidualization-related markers,cell proliferation marker molecules,and apoptosis molecules.Flow cytometry was used to measure cell apoptosis rate.Results:In the mouse model of pregnancy,the expression level of ALKBH5 at the uterine em-bryo implantation site was significantly higher than that adjacent to the implantation site,and in the mouse and cell models of artifi-cially induced decidualization,compared with the control group,the induction group had a significant increase in the expression level of ALKBH5 and a significant reduction in the level of m6A.Inhibiting the expression of ALKBH5 led to an increase in the level of m6A,which in turn inhibited the proliferation of stromal cells,induced cell apoptosis,and ultimately impaired the normal process of en-dometrial decidualization.Conclusion:ALKBH5 deficiency leads to an increase in the level of m6A and decidualization injury in the en-dometrium,which lays a foundation for the research on m6A modifi-cation in decidualization.

Objective:To observe the effects of electroacupuncture(EA)on gut microbiota and serum inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α in Crohn disease(CD)model rats. Methods:Thirty-six Sprague-Dawley rats were randomly divided into a normal control(NC)group with 10 rats and a modeling group with 26 rats.In the modeling group,the CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.After successful modeling,the rats were randomly divided into a CD model(CD)group,an EA group,and a Western medicine(WM)group.The NC and CD groups received no treatment;the EA group was treated with EA for 20 min each time,with 7 consecutive days'intervention;the WM group received mesalazine enteric-coated tablet solution by gavage once a day for 7 d.The changes in body mass and disease activity index(DAI)were observed.Serum IL-1β and TNF-α were determined by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the pathological changes of colon tissues,and 16S rDNA sequencing was used to analyze the structural changes of gut microbiota. Results:Compared with the NC group,the body mass of rats in the CD group decreased(P<0.01),and the DAI score increased(P<0.01);the colon tissue structure was disordered,and many inflammatory cells were present;also,IL-1β and TNF-α increased significantly(P<0.01).As a result,the diversity of gut microbiota decreased,and the abundance of some conditional pathogenic bacteria(such as Prevotella)increased,while the abundance of beneficial bacteria(such as Lactobacillus,Rochella,and Spirillum)decreased.After the intervention,compared with the CD group,the body mass of rats in the EA group and WM group increased(P<0.01);the DAI score decreased(P<0.01),the colon tissue structure improved,and the IL-1β and TNF-α levels decreased(P<0.01);the diversity of gut microbiota increased(P<0.05),and the abundance of some conditional pathogenic bacteria decreased while the abundance of beneficial bacteria increased in the EA group;whereas the diversity of gut microbiota in the WM group was not statistically different(P>0.05). Conclusion:EA can reduce the damage of colon mucosa,regulate the imbalance of gut microbiota,and inhibit the serum inflammatory factor IL-1β and TNF-α expression in CD rats.

Primary Sj?gren's syndrome(pSS)is a chronic inflammatory autoimmune disease involving a variety of exocrine glands.It is a common autoimmune disease in the department of rheumatology.However,the pathogenesis of pSS is still unclear,re-sulting in lack of treatment.While the international research on pSS is also increasing,we review the latest literature on the mecha-nism of Sj?gren's syndrome under different factors.In this paper,the process mechanism of Sj?gren's syndrome is summarized from the aspects of heredity,environment,autoimmune cells and autoantibodies.

Objective: To evaluate the correlation between electronic cigarette (e-cigarette) use and environmental e-cigarette exposure among residents living in Guangzhou City, so as to provide the evidence for the development of the e-cigarette control policy. Methods: Permanent university students living in Guangzhou City were recruited as investigators from July to October 2021, and the permanent adult residents in communities where the university students lived were randomly selected as participants. Subjects' demographic features, e-cigarette use, passive viewing of e-cigarette use and exposure to e-cigarette advertising were collected using both online and offline questionnaire surveys, and the association of e-cigarette use with passive viewing of e-cigarette use and exposure to e-cigarette advertising were examined using a multivariable logistic regression model. Results: A total of 948 questionnaires were allocated, and 874 valid questionnaires were recovered, with an effective recovery rate of 92.19%. The respondents had a mean age of ( 34.96±13.76 ) years. There were 420 men ( 48.05% ), and 426 married residents ( 48.80% ). The prevalence of e-cigarette use was 14.99%, and the rate of e-cigarette use was 23.81% in men and 6.83% in women. In addition, 27.27% of respondents at ages of 35 to 44 years used e-cigarette, 479 respondents viewed e-cigarette advertising ( 54.81% ) and 510 respondents had at least once passive viewing of e-cigarette use ( 58.35% ). Multivariable logistic regression analysis revealed that a higher frequency of exposure to e-cigarette advertising ( OR: 3.064-5.784, 95%CI: 1.683-12.620 ) and a higher frequency of passive viewing of e-cigarette use ( OR: 2.182-2.349, 95%CI: 1.094-4.526 ) led to a higher rate of e-cigarette use. Conclusions E-cigarette use is affected by passive viewing of e-cigarette use and exposure to e-cigarette advertising among community residents in Guangzhou City. Supervision and restriction is recommended for e-cigarette advertising, marketing, and use in public places.

Major depressive disorder (MDD), is characterized by high incidence rate, high suicide rate, and high disability rate, however, the underlying pathogenesis of MDD is still unclear. Based on the diathesis-stress model of depression, epigenetic mechanisms strongly explain the integration of genes and environment in the development of depression. However, depression has a high degree of clinical heterogeneity, with individuals of different ages presenting different symptoms and epigenetic changes. As a dynamic molecular marker that varies with age and environmental experience, epigenetics helps to elucidate the unique and complex disease pathogenesis of depression at different ages. Therefore, this paper aims to review relevant epigenetic studies of depression at different ages of onset to explore its potential age-specific association mechanism, in order to provide a theoretical basis for the formulation of accurate intervention measures for patients with MDD at different ages.

Major depressive disorder (MDD), is characterized by high incidence rate, high suicide rate, and high disability rate, however, the underlying pathogenesis of MDD is still unclear. Based on the diathesis-stress model of depression, epigenetic mechanisms strongly explain the integration of genes and environment in the development of depression. However, depression has a high degree of clinical heterogeneity, with individuals of different ages presenting different symptoms and epigenetic changes. As a dynamic molecular marker that varies with age and environmental experience, epigenetics helps to elucidate the unique and complex disease pathogenesis of depression at different ages. Therefore, this paper aims to review relevant epigenetic studies of depression at different ages of onset to explore its potential age-specific association mechanism, in order to provide a theoretical basis for the formulation of accurate intervention measures for patients with MDD at different ages.

Objective:To explore the application effect and evaluation of virtual reality technology in oral implant therapy training.Methods:In November 2018, one adult patient (female, 36 years old) with missing right mandibular first molar was treated in the Department of Implantology, School and Hospital of Stomatology, Fujian Medical University. The three-dimensional virtual models of mandible and implant surgery tools were established, and the virtual reality software (Unity 3D 5.5.1) was imported. Combined with the virtual reality head mounted display, a virtual reality training system simulating the dental implant treatment process was independently developed. Ten refresher doctors and 20 graduate students in Department of Implantology, School and Hospital of Stomatology, Fujian Medical University from September 2018 to December 2019 were recruited as the experimental objects (no clinical experience was found). According to the level and seniority of doctors, they were randomly divided into virtual training group and conventional training control group, which made the two groups comparable, with 15 in each group. Subjective scores (including anatomical structure, surgical field of vision, cavity preparation, implant placement and process mastery) were given after the corresponding training in the two groups, and the virtual reality training system was used to test. The mesial and distal direction, buccolingual direction, depth and angle deviation of implants before and after the training were analyzed, and the differences between the two groups were compared.Results:The subjective scores of five dimensions in the virtual training group were significantly higher than those in the conventional training control group ( P<0.05). In the virtual training group, the mesial and distal, buccolingual, depth and angle deviation of implants were (0.73±0.33), (0.78±0.41), (0.61±0.32) mm and 6.66°±3.87°. All of them were significantly lower than those in the control group [(0.85±0.32), (1.12±0.38), (0.89±0.24) mm and 9.68°±3.74°] ( P<0.05). Conclusions:The self-developed virtual reality system of oral implant has good application effect, good operability and predictability. It can be effectively carried out in implant education and training, and it can strengthen skills of doctors, and is conducive to the practical operation.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

Objective To study preparation of micronized Shuanghuangpo hydrogel patch and its characteristics of transdermal penetration in vitro. Methods Micronized Shuanghuangpo hydrogel patch was prepared with some macromolecular water-soluble materials as gel base.The content of berberine was determined by HPLC method.Its transdermal penetration in vitro was determined according to the method of Chinese Pharmacopoeia 2010 edition. The rat skin penetration test in vitro was performed by modified Franz diffusion cell method. Results The hydrogel patch had constant content of berberine. Its release property in vitro conformed to Higuchi equation. The penetration of berberine in the hydrogel patch through the rat skin followed zero-order dynamics in 12 h.Its release rate was 7.934μg??(cm2)-1??h1/2 and percutaneous rate was 0.571μg??(cm2)-1??h-1. Conclusion The micronized Shuanghuangpo hydrogel patch is a new transdermal agent with sustained release property.