The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

Mutations in the IARS1 gene are rare in clinical practice， and up to now， only ten cases with detailed clinical and genetic data have been recorded in the literature. This article reports a case of growth retardation， intellectual developmental disorder， hypotonia， and hepatopathy （GRIDHH） associated with single heterozygous mutations in the IARS1 gene and summarizes the clinical and genetic features of GRIDHH， thereby expanding the genetic spectrum of GRIDHH.

Objective: To compare the intervention effects of sitagliptin combined with metformin and insulin aspart combined with metformin among patients with type 2 diabetes mellitus (T2DM), so as to provide the reference for optimizing blood glucose control strategies among patients with T2DM. Methods: T2DM patients admitted to the department of endocrinology of Jinhua Central Hospital from January 2018 to December 2024 were selected as the research objects. According to the propensity score matching, T2DM patients were divided into sitagliptin combined with metformin group and insulin aspart combined with metformin group at a ratio of 1∶1. The basic information, capillary blood glucose, glycosylated hemoglobin blood glucose (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were collected by questionnaire survey, physical examination and laboratory test. The generalized estimating equation was used to analyze the changes of various indicators before and after treatment between the two groups of patients, and the intervention effect was compared. Results: There were 69 cases in the sitagliptin combined with metformin group. Among these 42 cases were males, accounting for 60.87%, and 27 cases were females, accounting for 39.13%.Forty-two cases were younger than 60 years, accounting for 60.87%. There were 69 cases in the insulin aspart combined with metformin group. Among these 47 cases were males, accounting for 68.12%, and 22 cases were females, accounting for 31.88%. Forty-five cases were younger than 60 years, accounting for 65.22%. There were no statistically significant differences in gender, age, education level, smoking, drinking, vegetable and fruit intake, and disease duration between the two groups (all P>0.05). After 6 months of treatment, there was an interaction between group and time in capillary blood glucose and HbA1c in the two groups (all P<0.05), and the reduction of capillary blood glucose and HbA1c in the sitagliptin combined with metformin group was greater than that in the insulin aspart combined with metformin group. There were no statistically significant differences between groups and time in TC, HDL-C, TG, BMI, SBP, and DBP, and no interaction effect was found between groups and time (all P>0.05). Conclusion Sitagliptin combined with metformin is more effective than insulin aspart combined with metformin in controlling blood glucose among patients with T2DM.

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

ObjectiveTo investigate the mechanism of astragaloside-Ⅳ （AS-Ⅳ） in regulating pyroptosis to alleviate intestinal ischemia-reperfusion injury （IRI） by combining network pharmacology and in vivo experiments. MethodFirstly， the corresponding target genes of AS-Ⅳ were obtained from TraditionalChineseMedicineSystemsPharmacology（TCMSP） database and Swiss Target Prediction database， and the target genes related to intestinal IRI and Pyroptosis were obtained from GeneCards database， and the common target genes of the three were obtained by drawing Venn diagrams through unspiralized website. Protein-protein interaction （PPI） network was constructed by STRING database and Cytoscape software to screen common target genes and imported into Cytoscape software to obtain core target genes. Microbiotics platform was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis and prediction of the mechanism of action of AS-Ⅳ in regulating Pyroptosis to alleviate intestinal IRI. Then C57/BL6J mice were randomly divided into 5 groups normal group， model group（IR）， drug administration group （IR+AS-Ⅳ）， nucleotide-binding oligomerization structural domain-like receptor protein 3 （NLRP3） agonist NSS group （IR+AS-Ⅳ+NSS）， and NLRP3 inhibitor MCC950 group （IR+AS-Ⅳ+MCC950） by using a randomized numerical table method. The intestinal IRI model was established by clamping the superior mesenteric artery for 45 min and resuming perfusion for 2 h in the model group， the drug administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group， and the normal group was only separated from the vessels without clamping. The administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group were gavaged with astragaloside dissolved in 0.1% dimethylsulfoxide （50 mg·kg^-1） for 3 consecutive days before modeling， with the last gavage 2 h before modeling， and the remaining two groups were gavaged with equal amounts of saline. The NLRP3 agonist NSS group was injected intraperitoneally with 4 mg·kg^-1 of NSS 1 h before modeling， and the NLRP3 inhibitor MCC950 group was injected intraperitoneally with 10 mg·kg^-1 of MCC950 1 h before modeling.The mice were put to death by reperfusion for 2 h， and intestinal tissues were obtained. The levels of IL-18 and IL-1β were detected by enzyme linked immunosorbent assay（ELISA）， and the protein expression of thioredoxin-binding protein （TXNIP）， NLRP3， Caspase-1 and pyrocatechin D （GSDMD） were detected by Western blot， and the pathological changes of intestinal tissues were evaluated by Chiu's score. ResultNetwork pharmacological analysis showed that there were 1599 targets of intestinal IRI， 199 targets of AS-Ⅳ action， 197 targets of pyroptosis， and 20 targets common to all three. There were 10 core targets， including NLRP3， TXNIP， silencing information regulator 1 （SIRT1）， high mobility group protein 1 （HMGB1）， interleukin-18 （IL-18）， GSDMD， and metallo matrix protease-9 （MMP-9），et al. The results of in vivo experiments showed that compared with the normal group， Chiu's score was elevated in the model group， the levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of TXNIP， NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the model group，Chiu's score was decreased in the administered group and NLRP3 inhibitor MCC950 group，the level of IL-18，IL-1β inflammatory factors in the intestinal tissue of mice was decreased（P<0.05）， and the level of TXNIP，NLRP3，Caspase-1，GSDMD protein expression was decreased（P<0.05）. Compared with the administered group， Chiu's score was elevated in the NLRP3 agonist NSS group， the levels of IL-18， IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the NLRP3 inhibitor MCC950 group， the NLRP3 agonist NSS group had elevated Chiu's scores， elevated levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues （P<0.05）， and elevated levels of TXNIP，NLRP3， Caspase-1， and GSDMD protein expression （P<0.05）. ConclusionNetwork pharmacological predictions were consistent with the results of in vivo experiments， and astragaloside attenuated intestinal ischemia-reperfusion injury by inhibiting cellular pyroptosis through the TXNIP-NLRP3 signaling pathway.

Objective:To study the application effect of prospective management based on failure cause analysis in optimizing the maintenance efficiency of digestive endoscope.Methods:The failure phenomena and causes of digestive endoscope were analyzed,basic management measures and common failure management countermeasures were formulated to carry out prospective management of digestive endoscope.The data of 43,866 operations of from 8 digestive endoscopes in clinically use from 2021 and 2022 in Department of Gastroenterology of The PLA Rocket Force Characteristic Medical Center were collected,and according to different management modes of digestive endoscope,the conventional management mode(21,737 times)and prospective management mode based on failure cause analysis(22,129 times)were adopted respectively.The differences in the incidence of digestive endoscope failure,maintenance grade(grade A,grade B,grade C,grade D and grade E)and the standardized evaluation(13 aspects in 3 dimensions)of the two management modes were compared.Results:The incidence rate of digestive endoscope failure in the prospective management mode was 0.15%(33/22,129),which was lower than that in the conventional management mode,the difference was statistically significant(x2=13.390,P<0.05).In the 33 times of digestive endoscope maintenance in the prospective management mode,the incidence rates of grade A,grade B,grade C,grade D and grade E maintenance were 12.12%(4/33),36.36%(12/33),27.27%(9/33),18.18%(6/33)and 6.06%(2/33),respectively,the maintenance grade data was better than that in the conventional management mode,the difference was statistically significant(Z=2.263,P<0.05).In the standardized evaluation of digestive endoscopes managed by the prospective management mode,the operation error rate was lower than that of conventional management mode,the difference was statistically significant(x2=4.110-34.909,P<0.05).Conclusion:The application of maintenance efficiency of digestive endoscopes by prospective management optimization based on fault cause analysis can reduce failure rate of digestive endoscopy and improve the standard use rate of digestive endoscopy.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective To investigate the anesthetic effects and adverse effects of cypropofol and propofol combined with alfentanil,respectively,for gastroenteroscopy.Methods A total of 162 patients who underwent elective gastroenteroscopy at the Gastrointestinal Endoscopy Center of the First Hospital of Lanzhou University from January to February 2024 were enrolled,including 86 males and 76 females,at an age of 18～65 years old,with a BMI value of 18～30 kg/m2,and ASA grade ≤ Ⅱ.They were randomly divided into propofol group(Group P)and cypropofol group(Group C),with 81 cases in each group.All patients were sedated with 0.7 μg/kg alfentanil,and in 30 s later,2 mg/kg propofol and 0.4 mg/kg cypropofol was intravenously dripped into Group P and Group C,respectively.When the modified alertness/sedation score(MOAA/S)≤1,a gastroscope was started to insert.The related indicators,including total procedure time,successful cases of sedation,induction time and awakening time,heart rate,blood pressure,and pulse oximetry saturation were recorded,occurrence of adverse reactions such as hypotension,respiratory depression,injection pain,intraoperative body movement,nausea and vomiting were observed,and the satisfaction of endoscopists and of patients to anesthesia were recorded and compared between the 2 groups.Results There were no statistical differences in the success rate of sedation,induction time and awakening time between the 2 groups.The patients of the Group C had more stable intraoperative vital signs,statistically lower incidences of injection pain,respiratory depression and hypotension(P＜0.05),and increased satisfaction for anesthesia(P＜0.05)when compared with those in Group P.No obvious difference were observed in the satisfaction of endoscopist to anesthesia between the 2 groups.Conclusion In combination with small-dose alfentanil,0.4 mg/kg cypropofol shows similar sedation effect as 2 mg/kg propofol in gastroenteroscopy,with comparable induction and awakening time.Cypropofol has more advantages in stable intraoperative vital signs,less adverse effects such as low blood pressure,respiratory depression and injection pain,higher the patient satisfaction,which is worthy of clinical promotion.

Colorectal cancer is a common malignant tumor.Revealing the interaction between tumor cells and tu-mor microenvironment(TME)can provide new targets for the prevention or therapy of colorectal cancer.Three-dimensional models such as cell spheroids,organoids,organ chips,and three-dimensional printing have been widely used to simulate TME in colorectal cancer,which can better reproduce the structure and heterogeneity of TME.This paper reviews the progress in the application of three-dimensional models in TME research of colorectal cancer to provide references for future research.