Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Parkinson′s disease (PD) is a neurodegenerative disorder that significantly impacts speech and voice, leading to hypokinetic dysarthria, a motor speech disorder. The advent of artificial intelligence (AI) has opened new avenues for the assessment, diagnosis, and rehabilitation of PD-associated speech impairments. This review explores the application of AI in the study of PD speech disorders, focusing on automated speech analysis, machine learning algorithms, and the development of speech pathology databases. This review also discusses the methodologies and technologies employed, such as speech signal processing, feature extraction techniques, classification algorithms, and the symptoms they can detect, including voice quality, articulation, speech rate, and prosody. The role of AI in early diagnosis, disease progression monitoring, treatment evaluation, and remote rehabilitation is highlighted. The review concludes with a discussion on the potential and challenges of AI in this field and recommendations for future research.

Objective The influencing factors of skin pruritus in patients with maintenance hemodialysis(MHD)were identified by systematic evaluation and Meta-analysis.Methods The PubMed,Web of Science,CINAHL,Medline,Embase,Cochrane of Library,China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,and Chinese Biomedical Literature Databases were searched from the database establishment until February 2024.After independent screening of literature,data extraction and evaluation of risk of bias by two fellows,Meta-analysis of the influencing factors of pruritus in MHD patients was performed by Stata 18.0,and the remaining influencing factors were performed by descriptive analysis.Results A total of 14 articles involving 5285 cases,totaling 30 influencing factors,were summarized into two themes:Socio-demographic factors and disease-related factors.The results of Meta-analysis showed that C-reactive protein(OR=1.44,95%CI:1.04-2.00)was the influencing factor of skin pruritus in MHD patients(P<0.05);Blood phosphorus(OR=1.75,95%CI:1.02-2.99)was the disease-related factor(P<0.05).Conclusion The complex causes of skin pruritus in MHD patients are limited by the quantity and quality of studies,and other influencing factors still need to be verified by high-quality studies.

Objective The influencing factors of skin pruritus in patients with maintenance hemodialysis(MHD)were identified by systematic evaluation and Meta-analysis.Methods The PubMed,Web of Science,CINAHL,Medline,Embase,Cochrane of Library,China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,and Chinese Biomedical Literature Databases were searched from the database establishment until February 2024.After independent screening of literature,data extraction and evaluation of risk of bias by two fellows,Meta-analysis of the influencing factors of pruritus in MHD patients was performed by Stata 18.0,and the remaining influencing factors were performed by descriptive analysis.Results A total of 14 articles involving 5285 cases,totaling 30 influencing factors,were summarized into two themes:Socio-demographic factors and disease-related factors.The results of Meta-analysis showed that C-reactive protein(OR=1.44,95%CI:1.04-2.00)was the influencing factor of skin pruritus in MHD patients(P<0.05);Blood phosphorus(OR=1.75,95%CI:1.02-2.99)was the disease-related factor(P<0.05).Conclusion The complex causes of skin pruritus in MHD patients are limited by the quantity and quality of studies,and other influencing factors still need to be verified by high-quality studies.

Enamel formation is a complex physiological process that depends on the coordinated regulation of multiple mechanisms. This process is quite sensitive to various local and systemic interference factors. Therefore, during the long period from the embryonic stage to adolescence or even adulthood, various interference factors may lead to enamel developmental defects. Among them, early life is the most sensitive stage to environmental factors exposure, while it is also the critical period of enamel development of deciduous and permanent teeth. Environmental factors exposure during this period often leads to varying degrees of enamel development defects. In this review, we generalize the research progress of environmental factors affecting enamel developmental defects, summarize the potential mechanisms of environmental factors leading to enamel developmental defects, and conclude the clinical management strategies based on tertiary prevention. This work hopes to provide a theoretical basis for preventing abnormal teeth development from the critical time window of early life, propose eugenics health consultation and promote children ′s oral health management.