Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

B7-H3 confers stemness characteristics to gastric cancer cells by promoting glutathione metabolism through AKT/pAKT/Nrf2 pathway / 中华医学杂志(英文版)

BACKGROUND@#Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.@*METHODS@#GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.@*RESULTS@#B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).@*CONCLUSIONS@#B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.

Expression and Clin ical Significance of B7-H5 in Ulcerative Colitis / 胃肠病学

Background: The incidence of ulcerative colitis (UC) has gradually increased in China in recent years. The pathogenesis of UC is related to the dysfunction of immune system. B7-H5 is an important immune checkpoint molecule and is significant for the regulation of immune function. Ainis: To investigate the expression and clinical significance of B7-H5 in UC. Methods: A total of 65 UC tissue specimens were collected from Jan. 2010 to Dec. 2020 at the First Affiliated Hospital of Soochow University, and 5 healthy subjects were served as controls. Immunohistoehemistry and immunofluorescence were used to detect the expression of B7-H5, and its relationship with elinieopathologieal characteristics of UC patients was analyzed. Results: Expression of B7-H5 was significantly increased in UC patients than in controls (P 0. 05). Conclusions; The expression of B7-H5 in UC patients is significantly increased and is correlated with ESR and CRP, and can be used as a new marker for reflecting the severity of inflammation in UC patients.

Advances in Study on Anti-inflammatory Effect of Exercise on Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease(IBD)is a chronic non-specific intestinal inflammatory disease,including ulcerative colitis(UC)and Crohn's disease(CD). Changing lifestyle can improve patients'symptoms to a certain extent and enhance the efficacy of drugs. The anti-inflammatory effect of exercise in IBD has been confirmed,but its specific mechanism is not clear. This article reviewed the advances in study on the anti-inflammatory effect of exercise on IBD.

Immunomodulatory effects of 1,25 dihydroxyvitamin D3 in the treatment of experimental colitis / 中华消化杂志

Objective To explore the immunomodulatory effects of 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) in the treatment of experimental colitis induced by dextran sulfate sodium (DSS) in mice.Methods According to random number table,thirty BALB/c mice were randomly divided into control group,model group,low dose,moderate dose,and high dose intervention group.Mice of model group,low dose,moderate dose and high dose intervention group drank 5％ DSS solution for seven days to create colitis model.On the 1st,3rd,5th,7th day,the mice of low dose,moderate dose and high dose intervention group were intraperitoneal injected with low,moderate,and high dose of 1,25(OH)2D3 (50,100 and 200 ng/each mouse,respectively).Mice of control group and model group were intraperitoneal injected with sterile soybean oil as control.The observed indicators included disease activity index (DAI) and colonic histopathological score (HPS).On the 8th day,all mice were sacrificed.The expression of interferon (IFN)-γ,interleukin (IL-17) and IL-21 in mice colon tissues and spleens at mRNA and protein level were measured by reverse transcription-polymerose chain reaction (RT-PCR) and flow cytometry,respectively.The data were analyzed by one way ANOVA.LSD-test or Tamhane test were performed for comparison in groups.Results Compared with the control group,the DAI and colitis HPS of mice in the model group significantly increased (0.33±0.52 vs 7.33±1.03,0.17±0.41 vs 12.00±0.63).Compared with the model group,the DAI and colonic HPS of intervention groups treated with 1,25 (OH)2 D3 declined with varying degrees (2.83 ± 0.40,2.83±0.75,2.33±0.52 and 10.83±0.98,7.50±0.84,6.67±0.52,LSD-t=0.39 and 0.41,all P＜0.01).The expression of IFN-γ,IL-17 and IL-21 of the model group were significantly higher than those of the control group.The expressions of IFN-γ,IL-17 and IL-21 of intervention group were signifiantly lower than that of the model group (mRNA:LSD-t =0.12,0.13,0.09; protein:F =20.61,22.46,4.80,all P＜0.01).Conclusion 1,25 (OH)2D3 might have a direct role on T-cell phenotype,down-regulate effective cytokines IFN-γ,IL-17 and IL-21 and then play an interventional role.