Cow's milk allergy is mainly observed in infants and young children. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems. Conventional diagnosis is based on po-sitive allergy studies and evaluation of parameters including IgE and IgG1 levels, acute allergic skin response and anaphylactic shock reactions. We developed a cell membrane chromatographic (CMC) method based on human mast cells (HMC-1) for screening potential allergens in infant formula milk powders (IFMP). HMC-1 cell membranes were extracted and mixed with silica to prepare cell membrane chromatography columns (10 mm × 2 mm i.d., 5 mm). Under the conditions of 0.2 mL/min flow rate and 214 nm detection wavelength, human breast milk showed no retention. However, IFMP showed clear retention. The retained fractions were collected and analyzed through matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Four major milk proteins, i.e., α-casein, β-casein, α-lactalbumin, and β-lactoglobulin A, were identified. Furthermore, these proteins and β-lacto-globulin B showed clear retention on HMC-1/CMC columns. To test the degranulation effects of the five proteins, histamine and β-hexosaminidase release assays were carried out. All five proteins induced HMC-1 cells to release histamine and β-hexosaminidase. Also, we established a reversed phase liquid chromatographic (RPLC) method for the determination of the five proteins in IFMP and the results showed that 90％ proteins in IFMP were α-casein and β-casein. We concluded that cow's milk proteins may be potential allergens and caseins cause more β-casein allergic risk than other proteins. This con-clusion was consistent with other studies.

Objective To investigate the correlation between serum renal injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)in the remission of diabetic kidney disease(DKD)after gastric bypass surgery in obese DKD patients.Methods Seventy-nine obese patients with DKD who received gastric bypass surgery in our hospital from January 2021 to January 2022 were selected and divided into DKD remission group(n= 47)and DKD non-remission group(n=32)according to whether UACR decreased to normal level after surgery.Preoperative and postoperative general data were collected and biochemical indices,serum KIM-1 and NGAL levels were detected.Results None of the 79 obese DKD patients had intraoperative complications or switched to laparotomy.BMI,FPG,HbA1c,SBP,DBP,TC,TG,LDL-C,SUA,UACR,KIM-1 and NGAL were decreased after surgery,while HDL-C was increased after surgery(P＜0.05).SBP,DBP,Scr,BUN,UACR,KIM-1 and NGAL in remission group were lower than those in non-remission group(P＜0.05).Spearman correlation analysis showed that the levels of KIM-1 and NGAL were positively correlated with Scr,BUN and UACR(P＜0.05),but negatively correlated with eGFR(P＜0.05).Logistic regression analysis showed that SBP,UACR,KIM-1 and NGAL were influencing factors for DKD remission after gastric bypass surgery.The areas under ROC curve of serum KIM-1,NGAL and combined prediction of DKD remission were 0.801,0.757 and 0.863,respectively.Conclusion Serum KIM-1 and NGAL can predict DKD remission in obese DKD patients after gastric bypass surgery.

The traditional biological principle for developing bone biomaterials is to directly stimulate the osteogenic differentiation of osteoblastic lineage cells, the direct effector cells for osteogenesis. This strategy has been successful for the development of bone biomaterials. However, recent progress in bone biology has revealed the vital role of the local bone microenvironment, especially the immune environment, in controlling osteogenesis. Interdisciplinary osteoimmunology has found that the osteoimmune and skeletal systems are closely related, sharing numerous cytokines and regulators. In addition, immune cells play an important role in the physiological and pathological processes of the skeletal system, suggesting that neglecting the importance of the immune response is a major shortcoming of the traditional strategy. Based on this principle, we propose a novel “osteoimmunomodulation”-based strategy to meet the strict requirements of new-generation bone biomaterials: instead of directly regulating the osteogenic differentiation of osteoblastic lineage cells, we should focus more on manipulating the responses of immune cells and developing biomaterials to induce an immune environment that provides conditions that balance osteogenesis and osteoclastogenesis for optimal osseointegration. This article reviews the recent progress on osteoimmunology and immunomodulatory biomaterials for the generation of the “osteoimmunomodulation” concept. Additionally, the outcomes of “osteoimmunomodulation”-related studies have been summarized to guide the development of advanced “osteoimmune-smart” bone substitute materials.

Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.
Adenoviridae ; Aquaporins ; genetics ; Autoimmune Diseases ; therapy ; Catheters ; Genetic Therapy ; Genetic Vectors ; administration & dosage ; Humans ; Sjogren's Syndrome ; therapy

Objective To investigate the changes aad possible role of estrogen and its receptor ERα、ERβ、GPR30 in the pathogenesis of asymptomatic hyperuricemia.Methods The peripheral blood of 62 asymptomatic hyperuricemia patients (AH) and 68 healthy controls (HC) were collected.The expression of estradial (E2) in serum was detected by the chemilluminescent microparticle immunoassay (CMIA).The expression of ERα,ERβ,GPR30 mRNA in peripheral blood mononuclear cells (PBMCs) was measured using Real time quantitative polymerase chain reaction (RT-qPCR).Statistical Package form Soci-science (SPSS) 17.0 statistical software was used for data analysis.The measurement data were compared by t test,rank sum test or one factor analysis of variance test.The correlation between variables was used by Spearman correlation analysis.Results ① The expression of E2 in serum of the HC group was higher than that in the AH group [(38.7±10.2) pg/ml vs (33.7±8.6) pg/ml,Z=-0.356,P＜0.05].② The expression of ERα,GPR30 mRNA in PBMCs of HC group was increased,compared with that in the AH group (0.000 17±0.000 23 vs 0.000 12± 0.000 12,0.002 0±0.002 1 vs 0.001 5±0.000 8,Z=-2.112,-2.147,P＜0.05,respectively).No significant difference in PBMCs ERβ mRNA levels was found between HC group and AH group,while a slight but not significant increase was observed in HC group.③ The Spearman correlation analysis found that the expression of ERα and ERβ mRNA,E2 and GR,ERβ and GLU in the AH group were positively related (r=0.259,0.251,0.260,P＜0.05,respectively).Conclusion The expression of E2,ERα,ERβ,GPR30 mRNA in the peripheral blood of patients with AH is decreased,suggesting that the estrogen and its receptor may be involved in the patho-genesis of hyperuricemia.

OBJECTIVE: To detect metabolic changes of bilateral frontal lobe in patients with multiple system atrophy (MSA) and cognitive dysfunction by 1H-proton magnetic resonance spectroscopy (1H-MRS).
 METHODS: N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr, myoinositol (mI)/Cr in three sides of frontal lobe were detected by 1H-MRS in 48 healthy controls, 23 patients with MSA and cognitive dysfunction and 19 patients with MSA but without cognitive dysfunction.
 RESULTS: NAA/Cr of bilateral frontal lobes in patients with MSA and cognitive dysfunction was significantly decreased compared with MSA patients without cognitive dysfunction and healthy controls (P<0.05). mI/Cr of right frontal lobes was significantly increased in patients with MSA and cognitive dysfunction compared with healthy controls (P<0.05). There was a negative correlation between NAA/Cr of bilateral frontal lobes and duration while a positive correlation between NAA/Cr of bilateral frontal lobes and MoCA score in patients with MSA and cognitive dysfunction.
 CONCLUSION There is a decrease in NAA/Cr and an increase in mI/Cr in frontal lobes in patients with MSA and cognitive dysfunction, which may be associated with cognitive dysfunction in MSA patients.
Aspartic Acid ; analogs & derivatives ; metabolism ; Choline ; metabolism ; Cognition Disorders ; physiopathology ; Creatine ; metabolism ; Frontal Lobe ; metabolism ; Humans ; Inositol ; metabolism ; Multiple System Atrophy ; physiopathology ; Proton Magnetic Resonance Spectroscopy

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective: To systematically review the quality and reporting quality of colorectal cancer screening guidelines, and to provide reference for the update of colorectal cancer screening guidelines and colorectal cancer screening in China. Methods: "Colorectal cancer", "colorectal tumor", "screening", "screening", "guide", "consensus", "Colorectal cancer", "Colorectal neoplasms", "Screening", "Early Detection of Cancer", "Guideline" and "recommendation" were used as search keywords. The literature retrieval for all the Chinese and English guidelines published before April 2018 was conducted by using PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Biology Medicine disc (CBMdisc), Cochrane Library, Guideline International Network, China Guidelines Clearinghouse (CGC) and the official website of the US Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), International Agency for Research on Cancer (IARC), Australia Cancer Council (ACC) and Association of Coloproctology of Great Britain & Ireland (ACPGBI). The inclusion criteria were independent guidance documents for colorectal cancer screening. The language is limited to Chinese and English. The exclusion criteria were literature on interpretation, evaluation, introduction, etc., as well as the translated version of the guide and old guides. The quality and reporting norms of colorectal cancer screening guidelines were compared and evaluated using the European Guideline Research and Assessment Tool (AGREE Ⅱ) and the Practice Guideline Reporting Standard (RIGHT). Results: A total of 15 guides were included. The results of the AGREE Ⅱ quality evaluation showed that the overall quality of 15 guides was high. Among them, there were 9 guides with an overall score of 50 or more, 10 with a recommendation level of "A", and 2 with a rating of "B". There were 3 guides for "C"; each guide scores higher in scope and purpose, and clarity, and scores vary greatly in the areas of participants, rigor, applicability, and independence. The results of the RIGHT evaluation showed that 15 guides were insufficient in six areas except for background information, evidence, recommendations, reviews and quality assurance, funding and conflict of interest statements and management, and other aspects. Conclusion The overall quality of included guidelines for colorectal cancer screening is high, but the normative nature needs to be strengthened.