OBJECTIVETo discover and identify differentially expressed genes associated with colorectal adenoma formation and the role of RegIV in colorectal adenoma differentiation.

METHODSA subtracted cDNA library was constructed with cDNAs that were isolated from either the normal mucosa or adenoma tissue of a single patient. Suppressive subtractive hybridization (SSH) combined with virtual northern blotting was used to characterize differentially expressed genes and contigs were assembled by electronic cloning (in silico cloning) with the EST database. Semi-quantitative RT-PCR was performed in 9 colorectal adenomas.

RESULTSThe amino acid sequence was determined with open reading frame (ORF) prediction software and was found to be 100% homologous to the protein product of RegIV (a novel gene isolated from a large inflammatory bowel disease library). RegIV was found to be highly expressed in all of the adenoma samples (9/9) compared with the normal mucosa samples, while 5/6 cases showed RegIV to be more strongly expressed in adenocarcinoma.

CONCLUSIONRegIV may play an important role in the initiation of colorectal adenoma differentiation, and its detection may be useful in the early diagnosis of colorectal adenoma formation.

Adenoma ; genetics ; metabolism ; Blotting, Northern ; Colorectal Neoplasms ; genetics ; metabolism ; Humans ; Lectins, C-Type ; biosynthesis ; genetics ; Nucleic Acid Hybridization ; Pancreatitis-Associated Proteins ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction

Objective To investigate the molecular mechanism of YingZhongXiao Ointment(YZXO)in the treatment of goiter based on network pharmacology and experimental validation.Methods TCMSP,TCMID,BATMAN-TCM,TCM-MESH,were used to screen the effective active ingredients and targets of YZXO.GeneCards,OMIM,Pharm GKB and Drug Bank databases were used to obtain goiter disease targets.After mapping the drug targets to the disease targets,the intersecting targets were screened,and then the intersecting targets were used to construct a PPI network and screen the core targets,which were subjected to GO and KEGG enrichment analysis.Results In this study,227 active ingredients,314 targets and 847 goiter targets were screened,and 78 potential targets for goiter treatment were obtained after mapping.449 biological processes were obtained from GO enrichment analysis,and 118 pathways were identified from KEGG enrichment analysis,including PI3K-Akt,mitogen-activated protein kinase(MAPK),tumor necrosis factor(TNF)and other signalling pathways.The results of animal experiments showed that compared with the model group,the gene expression of PI3K/Akt/m TOR signalling pathway in thyroid tissue of rats in each dose group and LT4 group was decreased(P<0.01 or P<0.05),p-PI3K/PI3K、p-Akt/Akt was decreased(P<0.01),the protein content of VEGF and PCNA was decreased(P<0.01 or P<0.05),and the protein content of Fas and FasL was increased(P<0.05 or P<0.01).Conclusion This study suggests that the mechanism of YZXO treated goiter by Resolving the Fire may be related to downregulation of PI3K/Akt/m TOR signalling pathway,inhibition of abnormal thyroid cell proliferation and promotion of thyroid cell apoptosis.

Nitric oxide(NO)is a vital signal messenger in human and generated by nitric oxide synthase including endothelial nitric oxide synthase(eNOS), inducible nitric oxide synthase(iNOS)and neuropathic nitric oxide synthase(nNOS). NO has important regulatory function on the immune system, nervous system and many other physiological systems. Endogenous NO can enhance the function of the vascular system and endothelial cell survival, and inhibit platelet accumulation and leukocyte infiltration. Excessive production of NO may damage tissues by cytotoxic and cytostatic effects. Thus, NO plays a dual role in physiology and pathology. This paper gives a brief review on regulatory effects of NOS-NO system by traditional Chinese medicine during the recent five years, so as to provide some clues or references for the treatment of related diseases and scientific evidene for reasonable and effective clinical application.

Objective:To systematically review research on the association between vitamin K and type 2 diabetes and diabetes-related biomarkers in humans, and evaluate the role of vitamin K in the prevention of type 2 diabetes.Methods:"Vitamin K", "type 2 diabetes" and related terms were searched in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang Med Online up to November 2018.Results:A total of 1 Chinese and 12 English articles were included. Among 6 observational studies, 5 of them showed that higher dietary vitamin K intake and plasma vitamin K level were associated with the decrease of the risk of type 2 diabetes. Among 6 clinical intervention studies, 5 of them indicated that the supplementation of vitamin K 1 or K2 could have positive influence on insulin metabolism. One Mendelian randomization study showed higher circulation vitamin K level might reduce the risk of type 2 diabetes. Conclusion:Vitamin K plays an important role in the prevention and control of type 2 diabetes, which may be related to the improvement of insulin metabolism and blood glucose level.

Objective:To systematically review research on the association between vitamin K and type 2 diabetes and diabetes-related biomarkers in humans, and evaluate the role of vitamin K in the prevention of type 2 diabetes.Methods:"Vitamin K", "type 2 diabetes" and related terms were searched in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang Med Online up to November 2018.Results:A total of 1 Chinese and 12 English articles were included. Among 6 observational studies, 5 of them showed that higher dietary vitamin K intake and plasma vitamin K level were associated with the decrease of the risk of type 2 diabetes. Among 6 clinical intervention studies, 5 of them indicated that the supplementation of vitamin K 1 or K2 could have positive influence on insulin metabolism. One Mendelian randomization study showed higher circulation vitamin K level might reduce the risk of type 2 diabetes. Conclusion:Vitamin K plays an important role in the prevention and control of type 2 diabetes, which may be related to the improvement of insulin metabolism and blood glucose level.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

ObjectiveTo investigate the current status and development needs of evidence-based medicine （EBM） capability in ethnic minority medicine， and explore effective strategies to enhance EBM capability in this field. MethodsThe questionnaire survey was conducted in various ethnic minority medical institutions and research organisations. The questionnaire covered three dimensions， firstly， perceptions and attitudes towards evidence-based medicine； secondly， advantages and challenges in the development of ethnic minority medicine； thirdly， demands and recommendations for enhancing evidence-based medicine capability in ethnic minority medicine. ResultsA total of 501 valid questionnaires were collected， of which 103 questionnaires were collected by re-sending to minority medicine regions with insufficient participation. The questionnaires included 354 responses （70.66%） from practitioners of minority medicine， including Tibetan medicine， Mongolian medicine， Uyghur medicine， Zhuang medicine， and Korean medicine. Among the 501 questionnaires， 146 respondents （29.14%） indicated that they knew about EBM， 355 respondents （70.86%） had either a "general understanding" or had "not heard about" EBM before， and 469 respondents （93.61%） believed that introducing ECM could promote the development of ethnic minority medicine. The primary challenge in promoting EBM in the field of ethnic minority medicine is the lack of professionals in EBM and a lack of understanding of how to apply it into clinical practice （442 respondents， 88.22%）. In the 9-point importance rating for enhancing evidence-based abilities， high scores were achieved in standardization of clinical practice guidelines （7.50±1.90） and methods for sample sizes in clinical research （7.45±1.90）. Regarding the demand for improving clinical research literacy， expert academic lectures， and experience sharing （404 respondents， 80.64%） and evidence-based methodology monographs on ethnic minority medicine （401 respondents， 80.04%） were emphasized. ConclusionsPractitioners in ethnic minority medicine hold a positive attitude towards integrating EBM. However， there remains substantial room for the education and dissemination of EBM. Enhancing evidence-based capabilities can be achieved through specific measures such as cultivating or recruiting talents in EBM， establishing evidence-based support platforms for clinical research， organizing regular academic lectures and exchanges， and strengthening the construction of theoretical frameworks and evaluation systems tailored to ethnic minority medicine， thereby following a path of evidence-based practices aligned with the unique characteristics of ethnic minority medicine.