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.

The teaching of radiology in standardized residency training needs a large number of case data to strengthen the subjective understanding and awareness of residents. The database built by residency training bases can meet the needs of teaching to a certain extent, but the conditions of training bases vary across regions, which makes it difficult to achieve homogeneity in the teaching of radiology. This article discusses the application of Eurorad database in the teaching of radiology in standardized residency training. This database is free of charge, reliable, and comprehensive and provides a large number of free reliable cases and images for teaching, covering both common and rare diseases. Moreover, it can also be used to cultivate the English ability and comprehensive quality of residents and help to establish a hierarchical training system for radiology and non-radiology residents, thereby promoting the improvement in the quality of standardized residency training. This article shows the potential value of Eurorad database in the teaching of radiology in standardized residency training, and comparative studies are needed in the future to further prove its effectiveness.

Mutations in the SAMD9 and SAMD9L genes are associated with MIRAGE syndrome and ATXPC syndrome, respectively. This study reports the clinical characteristics and genetic analysis of one case with SAMD9 mutation (c.3809T > A, p.F1270Y) and two cases with SAMD9L mutations (c.2675T > G, p.M892R; c.1096T > G, p.F366V and c.4517T > C, p.L1506p), none of which have been previously reported. All patients presented with recurrent infections, growth retardation, and myelodys-plasia, with varying degrees of involvement of multiple systems, including respiratory, gastrointestinal, immune, endocrine, neurological, and reproductive systems. In terms of treatment, two patients underwent regular intravenous immunoglobulin and their clinical symptoms improved, while one patient had a favorable recovery following hematopoietic stem cell transplantation at the age of 1 year and 5 months of age. SAMD9/SAMD9L gene mutations, therefore, chould be considered in children with recurrent infections, myelodysplasia, pancytopenia, and growth retardation. Early genetic testing is crucial for timely diagnosis and treatment, which may improve patient outcomes.

Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract that includes Crohn's disease and ulcerative colitis.IBD may be caused by complex interactions between genetic susceptibility,environmental factors,and alterations in the gut microbiota,resulting in dysregulated innate and adaptive immune responses.Recent studies have identified macrophages in the intestinal inflammatory response as having the plasticity to not only regulate inflammation,but also to promote tissue repair and healing.As aberrant macrophage polarization occurs during the development of IBD,the balance between the phenotype and function of pro-inflammatory M1 and anti-inflammatory M2 macrophages is regulated by extracellular and intracellular stimuli,and this process is therefore expected to be a potential target for new therapeutic approaches.This article reviewed the progress of research on macrophage polarization in IBD.

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. 001). B7-H5 expression in UC patients was positively correlated with ESR and CRP (P < 0. 01), but not related to gender, age, extent of lesion, Mayo score and UCEIS score (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.

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.

Objective To investigate the effect of Ⅲ-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment.Methods The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats.Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group,therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group,differentiated by 24 hours and 48 hours after ROSC.Each group had 10 rats at each time point.The anal temperature in the normothermia group was maintained at (37.0 ± 0.2) ℃,and the rats in the hypothermia group were given cooling treatment immediately after ROSC,and the target rectal temperature was 32-34 ℃.In the 3-MA pretreatment group,10 mmol/L 3-MA 5 μL was injected into the ventricle 20 minutes before asphyxia,and other groups were given the same amount of normal saline.Ten rats without CPR were included in Sham group only received anesthesia and catheterization.The rats were sacrificed at 24 hours and 48 hours after ROSC respectively,and the brain tissues were harvested,the brain water content (BWC) was measured by dry-wet weight method.Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3),apoptosis related proteins Bcl-2 and caspase-3,and the Ⅲ-type PI3K pathway proteins Vps34 and Atgl4.Ultrastructural changes in brain tissue were observed with transmission electron microscope.Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC.Results Compared with Sham group,the cortex at 24 hours after ROSC in normothermic group showed obvious edema,apeptosis and autophagy began to appear under transmission electron microscope,and the expressions of autophagy,apoptosis and Ⅲ-type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner,and the neurological function at 48 hours after ROSC was significantly damaged.After hypothermia intervention,brain edema of rats was significantly reduced,no obvious apoptosis was found,but autophagy was increased,the expressions of autophagy-related proteins Vps34,Atg14 and Ⅲ-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH:0.25±0.03 vs.0.15±0.04,Atg14/GAPDH:0.12±0.03 vs.0.05±0.04,Beclin-1/GAPDH:0.060±0.002 vs.0.018±0.002,LC3-Ⅱ/GAPDH:0.160±0.010 vs.0.050± 0.010,all P ＜ 0.05),the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH:0.05±0.03 vs.0.20±0.04,caspase-3/GAPDH:0.050±0.002 vs.0.140±0.015,both P ＜ 0.05),neurological function was significantly improved (NDS:157±85 vs.343± 198,P ＜ 0.05).Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues.The expressions of Vps34,Atg14,Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothennia group (Vps34/GAPDH:0.18±0.03 vs.0.25±0.03,Atg44/GAPDH:0.07±0.04 vs.0.12±0.03,Beclin-1/GAPDH:0.015±0.003 vs.0.060±0.002,LC3-Ⅱ/GAPDH:0.045±0.030 vs.0.160±0.010,all P ＜ 0.05),the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH:0.15±0.04 vs.0.05±0.03,caspase-3/GAPDH:0.120±0.015 vs.0.050±0.002,both P ＜ 0.05),and NDS score was significantly increased (341±208 vs.157±85,P ＜ 0.05).Conclusion Hypothermia treatment reduced brain edema and ameliorated brain function after CPR,which might be related to increase autophagy and inhibit apoptosis adjustment by activating Ⅲ-type PI3K pathway.

Objective To investigate the association between the level of polymorphism of APOE gene and cognitive impairment in patients with CNS demyelinating diseases. Methods 56 patients with central nervous system demyelinating disease were applied APOE genotyping,MoCA and expanded disability status (EDSS) scale score. Patients with MOCA scores <26 were divided into cognitive impairment group, and those with MOCA scores ≥26 were divided into normal cognitive preserved group. Results The probability of cognitive dysfunction in patients with central nervous system demyelinating diseases was 53.57%. There was no significant difference in age, gender, and disease duration between the CI group and the CP group(P>0.05), the difference in age and education among groups is statistically significant (P<0.05). There was no statistical significance in the difference in age, sex, education years and EDSS score between APOEε4 gene positive group and APOEε4 gene negative group (P<0.05). The difference of visual space and attention between different cognitive domains is statistically significant(P<0.05). Years of schooling is a risk factor for cognitive dysfunction in patients with central nervous system demyelinating disease(P<0.01). Conclusion The central nervous system demyelinating disease is impaired cognitive function. Patients with APOEε4 gene positive are more severely impaired in visual space and attention than patients with negative APOEε4 gene.Years of education are the risk factors of cognitive dysfunction in patients with central nervous system demyelinating disease. The course of disease and disabled function may not be significant related to cognitive impairment.