Transalveolar technique for sinus floor elevation(TSFE)offers the advantages of minimal invasiveness,reduced postoperative reaction,and shorter operative time for vertical bone augmentation in the maxillary posterior region.The clinical data of one patient with severe deficiency of residual bone height(RBH)in the maxillary posterior region,a blood vessel visible in the lateral wall of the maxillary sinus and a visible septum at the floor of the maxillary sinus were reported,and two-stage flexible TSFE was used to improve the vertical bone height of the operated area while reducing trauma,the risk of Schneiderian membrane rupture and maxillary sinus infection,etc.,and the relevant literatures were reviewed.The patient,male,26 years old,complained of missing left maxillary posterior teeth for more than 1 year and requested restoration.The patient had 27 missing teeth,normal keratinized gingiva,full alveolar ridge,no elongation of the opposing teeth,fair width of the proximal and normal occlusal distance.The results of cone beam CT(CBCT)showed that the distance between the sinus crests at the site of the 27 teeth was about 3 mm,the width of the alveolar bone was about 12.8 mm,the bone density was normal,and there were no residual roots or other abnormalities;no cyst-like lesions were seen in the walls of the maxillary sinuses bilaterally,and separation was seen at the floor of the maxillary sinus on the left side and a blood vessel was seen in the lateral wall of the maxillary sinus.A diagnosis of Kennedy class Ⅱ maxillary tooth defects was made.After two stages of TSFE,the Schneiderian membrane was intact and the bone height of the implant area was elevated to 9.6 mm from 3 mm preoperatively after the completion of the restoration,with stable bone augmentation,good osseointegration,and restoration of normal occlusal function.For the patients with severe bone height deficiency in the maxillary posterior region,flexible two-stage TSFE should be considered,which can help to reduce the risk of maxillary sinus infection and Schneiderian membrane rupture while minimizing the damage and obtaining the ideal bone augmentation results.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

As a new type of model organism， zebrafish is gradually gaining prominence in the field of scientific research. The unique biological characteristics and advantages of zebrafish make them play an increasingly important role in the quality evaluation of traditional Chinese medicine. Compared with other common experimental animals， zebrafish have a fast reproductive and growth speed and high embryo transparency， making them an ideal model for evaluating the quality of traditional Chinese medicine. This provides a new perspective and method for research on traditional Chinese medicine. With the growing global interest in traditional Chinese medicine， it has become crucial to find scientific and accurate methods to evaluate the quality and effectiveness of traditional Chinese medicine. The introduction of the zebrafish model has brought new breakthroughs in the quality evaluation of traditional Chinese medicine. To further promote the application of zebrafish in evaluating the quality of traditional Chinese medicine， this article systematically searched and sorted out the previous studies related to the application of zebrafish for this purpose since 2023. The commonly used disease models and indicators of zebrafish in evaluating the effectiveness of traditional Chinese medicine， as well as the mechanism of zebrafish in exploring the active ingredients of traditional Chinese medicine， were primarily reviewed. The application of zebrafish in evaluating the safety of traditional Chinese medicine and the typical examples in ensuring the quality of traditional Chinese medicine were demonstrated. The limitations encountered by zebrafish models in evaluating the quality of traditional Chinese medicine were highlighted. The resolution of these problems will help further improve the accuracy and reliability of zebrafish in evaluating the quality of traditional Chinese medicine. The article discussed the evaluation of effectiveness， safety， and quality control of zebrafish applied in traditional Chinese medicine， so as to provide a reference for establishing standards for traditional Chinese medicine and promoting its modernization in the future.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

Objective To investigate the expression and clinical significance of multiple endocrine neoplasia type 1(MEN1)gene in breast cancer.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the relationship between MEN1 gene and clinicopathological characteristics of breast cancer.Kaplan-Meier method was used to observe the effect of MEN1 on survival of breast cancer patients.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis(GSEA)were used to predict the function and signaling pathways of MEN1 related and interacting genes.Tumor Immune Estimation Resource(TIMER)and single sample gene set enrichment analysis(ssGSEA)were used to investigate the correlation between the level of immune infiltration and MEN1 expression in breast cancer.Results MEN1 was highly expressed in breast cancer patients,and its expression level was related to PAM50 subtype and menopause status(both P＜0.05).Kaplan-Meier survival analysis showed that high MEN1 expression was associated with poor clinical outcome(P=0.019).GO and KEGG enrichment analysis showed that MEN1 related and interacting genes were involved in biological processes(histone modification,histone-lysine methylation),cell components(methyltransferase complex and histone methyltransferase complex),molecular functions(histone-methyltransferase activity),and functional pathways(transcriptional disorders in tumors).GSEA identified that the highly expressed MEN1 phenotype was involved in vesicle-mediated transport,complement cascade,B-cell receptor signaling,lymphocyte-non-lymphocyte interaction,interleukin signaling,and cytokine signaling pathways in the immune system.CancerSEA single cell sequencing results indicated that the expression of MEN1 was positively correlated with angiogenesis in MDA-MB-231 cells(P＜0.05).TIMER analysis found that MEN1 in breast cancer was negatively correlated with the infiltration levels of macrophages and CD8+T cells,and positively correlated with the infiltration level of CD4+T cells(all P＜0.05).ssGSEA showed that the infiltration levels of 18 types of immune cells were negatively correlated with MEN1 expression(all P＜0.05).Conclusion High MEN1 level is associated with poor survival and immune infiltration in breast cancer patients.

Pharmacovigilance impact research(PIR),as an important application field of pharmacoepidemiology,has attracted continuous attention in recent years from drug regulatory authorities,pharmaceutical manufacturers,and the academic community both domestically and internationally.This paper provides an interpretation of PIR based on the Guide for Methodology in Pharmacoepidemiologic Research(2nd edition).First,an overview of the implications of PIR will be provided,focusing on the pathways of pharmacovigilance activities and the significant importance of conducting PIR.Second,it reviews commonly used study designs and presents illustrative case examples.Building on this,the specific statistical considerations relevant to PIR were discussed.Finally,the challenges and prospects of conducting pharmacovigilance impact studies in a scientific and standardized manner are summarized.Compared with the previous edition,the 2nd edition has expanded the application scenarios of pharmacoepidemiology to include new areas such as PIR.Drawing on the guideline content and practical experience,this paper provides a detailed introduction and case analysis of PIR,serving as a reference for researchers engaged in this field.

Objective:To study the current status of transitional readiness from adolescence to adulthood of patients with inflammatory bowel disease（IBD）in China,analyze the factors affecting transitional readiness,and provide a basis for developing scientific and targeted transitional preparedness programmes.Methods:The IBD patients aged 12-24 years who were admitted to the Department of Gastroenterology,Beijing Children's Hospital Affiliated to Capital Medical University from January 1,2016 to January 15,2025 were enrolled.From November 1,2024 to January 15,2025,the survey was conducted through online distribution of the transition readiness assessment questionnaire (TRAQ)6.0 Chinese version scale to IBD patients by using the convenient sampling method.The scores of each dimension of TRAQ scale were calculated,and multiple linear regression analysis was used to analyze the factors influencing the scores of TRAQ during the transitional period.Results:A total of 184 patients were included and 184 questionnaires were collected.Male patients were slightly more than female(109:75),with an average age of (14.94±2.35) years.70.11% of patients had a disease duration of 1 to 5 years,with Crohn's disease accounting for the highest proportion(54.89%),and the severity of the disease was mostly mild to moderate.Family support was generally higher(84.24%).Parents were highly involved in patient disease management(94.02%).There were 52.72% of the patients received social support.The mean score of the TRAQ was 4.14 ± 0.89,and the mean scores of the four dimensions from high to low were following health problems(4.28±0.97),insisting on making an appointment and seeing a doctor on time(4.20±1.10),talking with medical staff(4.17±1.05) and drug management(4.14±0.99).Multiple linear regression analysis showed that family status,the encourage,supports and help from the family members,and the supports from the society were the independent influencing factors of IBD patients' readiness score for transition from adolescence to adulthood( P<0.05).Among them,family status had a positive effect on transition readiness score,and the degree of readiness score increased with the increase of harmony( P<0.05).Social support also had a positive effect on transition readiness score( P<0.05).Compared with no encouragement,support and help from family members,the situation of little encouragement had a certain improvement on the readiness score( P<0.05). Conclusion:Children with IBD have better overall performance during the transition from adolescence to adulthood.Family status,the encourage,supports and help from the family members,and the supports from the society are the important factors influencing transitional preparedness.

Objective:By using cognitive interviews,the interviewees' cognition and understanding of the inflammatory bowel disease(IBD) self-efficacy scale for adolescents and young adults (IBDSES-A) were evaluated,and the semantic content of IBDSES-A,which was initially translated into Chinese,was tested and revised.Methods:Using purposive sampling,15 IBD patients aged 12-18 were selected from Beijing Children's Hospital,Capital Medical University,between January and February 2025,stratified by age group and disease type.Two rounds of cognitive interviews were conducted.Feedback and suggestions from interviewees were analyzed using a question appraisal system for coding and integration.Based on expert panel discussions,ambiguous items were revised to finalize the Chinese version of the IBDSES-A.Results:In the first round,10 interviewees were interviewed,followed by 5 interviewees in the second round.There were no statistically significant differences ( P>0.05) between the interviewees of two rounds in terms of age,gender,and education level.During the first round of interview,interviewees expressed comprehension difficulties with 76.9% (10/13) of the items.Coding analysis revealed that the primary issue was "clarification",as unclear wording made it difficult for interviewees to fully grasp the intended meaning of certain items.Based on these findings,the expert panel revised 10 of the 13 items in the IBDSES-A.The second round of cognitive interview showed that the interviewees generally understood the revised items，achieving linguistic and semantic consistency with the original scale. Conclusion:The application of cognitive interviews in the translation process of the IBDSES-A helps reduce comprehension biases caused by inappropriate wording，ensuring that the localized version of the scale is more accessible and understandable to the target population.

Objective:To investigate the treatment and prognosis of esophageal cancer patients with pulmonary resection history.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 58 esophageal cancer patients with pulmonary resection history who were admitted to Chest Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Jiangxi Provincial People's Hospital from May 2019 to April 2024 were collected. There were 52 males and 6 females, aged (69±3)years. Observation indicators: (1) surgical and postopera-tive conditions; (2) postoperative pathological examination results; (3) follow-up; (4) stratified analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric rank sum test. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and the Log-rank test was used for survival analysis. Results:(1) Surgical and postoperative conditions. Of the 58 esophageal cancer patients, 49 patients underwent transthoracic approach (26 cases of ipsilateral approach and 23 cases of contralateral approach of pulmonary resection history), and 9 patients underwent mediastinoscopic-laparoscopic approach. There were 57 cases with R 0 resection and 1 case with R 2 resection because of tumor invading carina. The total operation time of 58 patients was (246±27)minutes, and the volume of intraoperative blood loss was (114±29)mL. There was no unplanned reoperation or perioperative death for all patients. The duration of postoperative hospital stay of 58 patients was (10.4±4.6)days, and time for intensive care unit stay was (1.4±0.5)days, and no patient readmitted to intensive care unit due to changes in conditions. The postoperative total incidence of complications of 58 patients was 41.4%(24/58). The Clavien-Dindo grading of complications for all patients was 1-2 grade. (2) Postoperative pathological examination results. Results of postoperative pathological examination showed there were 51 cases of squamous cell carcinoma, 6 cases of adenocarcinoma, and 1 case of melanoma. Number of lymph node dissected of 58 patients was 27±6. The ratio of patient with positive lymph node was 37.9%(22/58). One patient may experience more than 1 region of positive lymph node metastasis. Results of postoperative pathological staging showed 5 cases of ⅠA stage, 2 cases of ⅠB stage, 13 cases of ⅡA stage, 15 cases of ⅡB stage, 4 cases of ⅢA stage, 16 cases of ⅢB stage, and 3 cases of ⅣA stage. Thirteen of the 58 patients underwent neoadjuvant therapy, with the pathological staging as 6 cases of Ⅰ stage, 4 cases of Ⅱ stage, 3 cases of ⅢB stage after therapy. Results of postoperative tumor regression grade for the 13 patients with neoadjuvant therapy showed 4 cases of grad 0, 3 cases of grade 1, 6 cases of grade 2. (3) Follow-up. All 58 patients were followed for 24 (4, 50)months, and no patient died within 90 days after surgery. During the follow-up period, 19 patients experienced tumor recurrence and metastasis and 17 patients died. Twenty-one patients underwent postoperative adjuvant therapy, including 7 cases with chemoradiotherapy, 7 cases with chemotherapy, 3 cases with chemotherapy and immunotherapy, 2 cases with immuno-therapy, 2 cases with radiotherapy. The postoperative 1-, 2-year overall survival rates of the 58 patients were 91.3%, 78.7%, respectively, of whom undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery with postoperative 1-, 2-year overall survival rates as 89.2%, 83.1% and 85.7%, 53.6%, respectively. The postoperative 1-, 2-year esophageal cancer specific survival rates for patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery were 94.4%, 87.9% and 85.7%, 71.4%, respectively. There was no significant difference in postoperative 1-, 2-year overall survival rates and postoperative 1-, 2-year esophageal cancer specific survival rates between patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery ( P>0.05). (4) Stratified analysis. Of the 49 patients underwent transthoracic approach for esophageal cancer, there were significant differences in surgical method, surgical type, time of chest surgery, cases with upper mediastinal lymph node dissection, and duration of postoperative hospital stay between patients with pulmonary resection history as ipsilateral approach and contralateral approach ( χ2=11.74, 11.68, t=-2.25, χ2=8.45, t=-2.17, P<0.05), and there was no significant difference in total operation time, volume of intraoperative blood loss, the number of lymph node dissected, post-operative total complications, and postoperative pathological TNM staging ( P>0.05). For patients with pulmonary resection history as ipsilateral approach and contralateral approach, the postopera-tive 1-, 2-year esophageal cancer specific survival rates were 95.5%, 95.5% and 81.4%, 71.1%, showing a significant difference between them ( χ2=5.63, P<0.05). Conclusions:The transthoracic approach and mediastinoscopic-laparoscopic approach are safe and feasible for esophageal cancer patients with pulmonary resection history. Compared with patients with pulmonary resection history as contralateral approach, patients with pulmonary resection history as ipsilateral approach have a higher ratio of McKeown surgery, minimally invasive surgery and upper mediastinal lymph node dissection, shorter time of chest surgery and duration of postoperative hospital stay, better esophageal cancer specific survival rate. And there is no increase in perioperative risk.

It has been not been updated for nearly 5 years since the Pharmacoepidemiology Professional Committee of the Chinese Pharmaceutical Association released the Guide on Methodological Standards in Pharmacoepidemiology in China(1st edition)in 2019,and an update is urgently needed.This study adopts a systematic review approach to comprehensively search for global pharmacoepidemiology methodological guidelines and analyze their development status.By extracting the frameworks and key elements of the guidelines,the China's guide was compared with other included guidelines,its shortcomings were analysed,and pragmatic and feasible suggestions for improvement in line with China's national conditions,were proposed in order to provide references for updating China's guide.A systematic search was conducted by searching PubMed,Embase,CNKI,WanFang Data and 17 official websites of international academic organizations for pharmacoepidemiology and regulatory agencies from countries or regions including Europe,the United States,Japan,and China,etc.,and relevant guidelines or standards were screened based on predefined inclusion and exclusion criteria,resulting in the inclusion of 33 methodological guidelines or standards for pharmacoepidemiological studies.A qualitative synthesis approach was then employed to extract core elements from the guidelines through thematic categorization and content summarization,followed by a descriptive comparative analysis.The results indicate that the 1st edition of the China's guide provides relatively comprehensive guidance on adverse drug reaction reporting and publication of research findings.However,there are gaps in study protocol development,data analysis during study implementation,study reporting,and specific study scenarios.By integrating and drawing upon the latest international pharmacoepidemiology methodology guidelines while balancing comprehensiveness,practicality,and user-friendliness,this study provides recommendations for updating the China's guide.