Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Objective To screen mitochondria-targeting differential genes in alveolar macrophages of silicosis pa-tients and explore the role of mitochondrial homeostasis in alveolar macrophages of silicosis patients.Methods High-throughput sequencing dataset GSE174725 was downloaded,and differentially expressed genes were screened with R software and P＜0.05,|LogFC|＞1,and then intermixed with mitochondrial gene bank MitoCarta3.0 to obtain mitochondria-targeted differentially expressed genes.Then enrichment analysis was carried out to obtain the biological processes and pathways involved in differential genes,and the protein-protein interaction network was constructed.In addition,alveolar macrophages from silicosis patients and healthy controls were collected,the ex-pression levels of differential genes were detected by RT-qPCR,and the expressions of mitochondria-related factors mitochondrial fusion protein 1(MFN1),optic atrophy 1(OPA1)and dynamin-related protein 1(DRP1)in alveolar macrophages of silicosis patients were investigated by Western blot.Results A total of 204 differentially expressed genes were screened in silicosis patients,among which 62 differentially expressed genes were up-regulated,142 dif-ferentially expressed genes were down-regulated,and 22 differentially expressed genes were mitochondria-targeted.The concentration analysis of differentially expressed genes targeted by mitochondria showed that the cell compo-nents mainly enriched included mitochondrial membrane,endoplasmic membrane side components,etc.The bio-logical processes mainly enriched included mitochondrial electron transfer from NADH to ubiquinone,inflammatory response,immune response,etc.The main molecular functions enriched included the rotation mechanism of proton transport ATP synthase activity,NADH dehydrogenase activity,chemokine activity,etc.KEGG enrichment analy-sis mainly focused on the involvement in chemical carcinogenesis-ROS,IL-17 signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,TNF signaling pathway,etc.In addition,RT-qPCR results showed that the expressions of mitochondrial cytochrome coxidase 1,mitochondrial cytochrome coxidase 2,mito-chondrial cytochrome coxidase 3,mitochondrially encoded NADH dehydrogenase 1,mitochondrially encoded NADH dehydrogenase 3,mitochondrially encoded NADH dehydrogenase 5,superoxide dismutase and mitochondri-ally encoded ATP synthase 6 gene were down-regulated in silicosis patients(P＜0.05).Western blot and RT-qPCR results showed that,in silicosis patients,the expression of MFN1 and OPA1 decreased(P＜0.05),while the expression of DRP1 increased(P＜0.05).Conclusion Bioinformatics analysis and validation,eight mito-chondrial targeted differential genes(MT-CO1,MT-C02,MT-CO3,MT-ND1,MT-ND3,MT-ND5,SOD and MT-ATP6)were finally obtained,which were enriched in mitochondrial respiratory chain and oxidative stress pathways and might play an important role in the process of silicosis.

Objective:To analyze the association between visceral fat area (VFA) and fatty liver based on quantitative CT (QCT) in people receiving health examination with normal body mass index (BMI).Methods:A cross-sectional study. A total of 1 305 physical examiners who underwent chest CT and QCT examination in the Department of Health Management of Henan Provincial People′s Hospital from January to December 2021 were retrospectively selected as subjects. The physical components at the central level of the lumbar two cone were measured with QCT, including subcutaneous fat area (SFA), VFA and liver fat content (LFC). And the metabolic indexes, such as blood lipids and blood glucose, were collected. The t-test and χ2 test were used to analyze the correlation between the detection rate of fatty live and LFCr and age and gender. According to level of VFA (<100 cm 2, 100-150 cm 2 and≥150 cm 2), the subjects were divided into three groups, and one-way ANOVA and χ2 test were used in comparison between groups. Multiple linear regression was used to analyze the correlation between VFA and metabolic indexes and LFC. Results:Of the 1 305 subjects, there were 634 males and 671 females. The detection rate of fatty liver in normal BMI population was 65.67%, and it was 72.71% and 59.02% respectively in men and women ( χ2=27.12, P<0.001), and the detection rate of fatty liver and LFC increased with age (both P<0.05). With the increase of VFA, the age, BMI, SFA, LFC, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), blood uric acid and prevalence of fatty liver increased (all P<0.05), and the low-density lipoprotein cholesterol (HDL-C) decreased ( P<0.001). Multiple linear regression analysis showed that after adjustment for age factors, regardless of male or female, LFC was independently positively related with VFA, BMI, and ALT (male β=0.206, 0.145, 0.174, female β=0.194, 0.150, 0.184; all P<0.05). FBG was positively correlated with male independently ( β=0.134; P<0.001). The indicators related to female independently were TC, TG, and blood uric acid ( β=-0.121, 0.145, 0.141, all P<0.05) Conclusion:In the population receiving health examination with normal BMI, the VFA measured by QCT technique is closely related to fatty liver.

Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.

Objective:To analyze the distribution of body fat with quantitative computed tomography (QCT) in people with normal body mass index (BMI).Methods:A cross-sectional study was conducted in the physical examination population who underwent chest CT and QCT examination in the Department of Health Management, Henan Provincial People′s Hospital from January to December in 2021, and 1 395 physical examination subjects who met the inclusion criteria were selected as the research subjects. The subjects were divided into five groups according to their age. The general data of the subjects were collected. The total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), total abdominal muscle area (TMA) and muscle fat content (MFC) in the subjects were measured by QCT. One-way analysis of variance, Welch test and Kruskal-Wallis test were used to compare the above QCT measurement indexes between the two genders among different age groups with normal BMI. Pearson correlation analysis was used to analyze the correlation between VFA and sarcopenia indexes. Multivariate linear regression was used to analyze the relationship between VFA and linear correlation variables in the related indicators of sarcopenia.Results:There were significant differences in TFA, VFA, TMA and SMI among different age groups in subjects with normal BMI (all P<0.05). Pearson correlation analysis showed that VFA was negatively correlated with TMA in some age groups (male: 18-39 years group: r=-0.351; 40-49 years group: r=-0.278; 60-69 years group: r=-0.245; female:40-49 years group: r=-0.251; 50-59 years group: r=-0.270;≥70 years group: r=-0.391; all P<0.01); it was negatively correlated with SMI (male: 18-39 years group: r=-0.352; 40-49 years group: r=-0.340; 50-59 years group: r=-0.266; 60-69 years group: r=-0.316; female: 40-49 years group: r=-0.240; 50-59 years group: r=-0.284; all P<0.001); it was positively correlated with MFC (male: 18-39 years group: r=0.342; 40-49 years group: r=0.291; female: 50-59 years group: r=0.133; 60-69 years group: r=0.284; all P<0.05). Multivariate linear regression analysis showed that VFA was independently and negatively correlated with SMI in both men and women after adjusting for age interference factors (male B=-1.881, t=-6.025, P<0.001; female B=-0.603, t=-2.887, P=0.004), and it was independently positively correlated with MFC (male B=1.230, t=4.271, P<0.001;female B=0.893, t=3.836, P<0.001). There was an independent negative correlation between VFA and TMA in male subjects ( B=0.263, t=2.478, P=0.013). Conclusions:VFA is correlated with TMA, SMI and MFC in people with normal BMI. Regardless of gender, SMI has a negative effect on VFA, and MFC has a positive effect on VFA.

The blood flow in the aortic arch and branch vessels in vitro is simulated,and the blood model is optimized with a non-Newtonian model.A numerical simulation analysis is conducted based on bidirectional fluid-solid coupling to analyze the hemodynamic characteristics(blood flow velocity,vascular wall pressure and vascular wall stress)in a cardiac cycle,and discuss their relationships with the formation of aortic dissection.It is concluded that the long-term existence of"chaotic"blood flow distribution in the blood vessel and the sudden changes of wall pressure and wall stress are liable to cause changes in the structure and function of the cells of the arterial wall,and ultimately induce the formation of aortic dissection.The study provides a more reliable basis for medical diagnosis,and further protects the life,health and safety of patients.

Objective:To investigate the effects of personalized intermittent energy restriction (IER) diet on sleep related gut microbiome in obese patients.Methods:In this single-arm clinical trial, a total of 35 obese patients who visited Henan Provincial People′s Hospital from April to November 2018 were recruited as research subjects. They underwent a strict 32-day IER diet intervention, divided into 4 stages of 8 days each. Nutritional recipes were formulated and nutritious meals were provided to each obese patient with timed meals, including 55% carbohydrates, 15% protein, and 30% fat per meal. In stages 1, 2, 3, and 4, patients were provided with 2/3, 1/2, 1/3, and 1/4 of their previous calorie intake every other day, respectively, with meals at 8:00 and 16:00. During the remaining time, patients were allowed unrestricted eating at home. Physiological indicators (weight, body mass index, body fat percentage, waist circumference, hip circumference, fasting blood glucose, glycosylated hemoglobin, blood pressure, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and Pittsburgh Sleep Quality Index (PSQI) scores were observed before and after the intervention. Gut microbiota changes were analyzed using metagenomic sequencing technology, and Spearman′s correlation analysis was used to assess the correlation between significantly different bacterial species and PSQI scores.Results:After the intervention, the body weight, body mass index, and PSQI scores of obese patients were all significantly lower than before intervention [(89.92±14.98) vs (97.53±15.67) kg, (31.94±3.95) vs (34.64±4.05) kg/m 2, (3.43±1.16) vs (5.42±2.27)], the abundance of gut microbiota was significantly higher after the intervention (all P<0.05). There were 45 significantly different bacterial species before and after the intervention, of which 6 bacterial species ( Enterobacter cloacae, Escherichia coli, Odoribacter splanchnicus, Oribacterium sinus, Streptococcus gordonii, and Streptococcus parasanguinis) showed significantly positive correlations with PSQI scores ( r=0.476, 0.475, 0.369, 0.391, 0.401, 0.423) (all P<0.05), and they were mainly enriched in the glutamate and tryptophan synthesis pathways. Conclusions:The personalized IER diet intervention can improve the sleep of obese patients while reducing weight, possibly mediated by changes in gut microbiota through the glutamate and tryptophan pathways.

Objective:To analyze the correlation between quantified body fat distribution measured by computed tomography (CT) and blood lipids in overweight and obese individuals undergoing physical examinations.Methods:In this retrospective cohort study, a total of 3 463 physical examination subjects who underwent chest CT combined with quantified CT examination in the Department of Health Management at Henan Provincial People′s Hospital from January to December 2021 were selected using a comprehensive sampling method. The subjects were divided into three groups: normal group (1, 424 cases), overweight group (1, 531 cases), and obese group (508 cases) based on their body mass index: 18.5 to <24.0 kg/m 2, 24.0 to <28.0 kg/m 2, and≥28.0 kg/m 2, respectively. General information, blood lipid parameters, and different body fat distributions measured by quantified CT (subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, muscle fat content) were collected in the three groups. One-way analysis of variance was used to compare differences in body fat distribution and blood lipid parameters, and Pearson correlation analysis was performed to evaluate the correlation between body fat distribution and blood lipids. Results:In the obese group, compared to the normal and overweight groups, subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, muscle fat content, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were significantly higher [males: (152.80±49.27) vs (72.94±22.68), (103.79±28.30) cm 2; (287.95±57.55) vs (156.36±49.40), (224.67±53.10) cm 2; (440.75±72.44) vs (229.31±62.01), (328.46±62.77) cm 2; (12.92±8.61)% vs (6.82±3.31)%, (9.39±4.88)%; (9.06±9.34)% vs (4.55±5.06)%, (6.70±6.73)%; (6.52±0.94) vs (4.87±1.03), (6.27±0.96) mmol/L; (3.05±0.76) vs (2.92±0.86), (2.97±0.77) mmol/L; (2.34±1.42) vs (1.53±0.82), (1.99±1.28) mmol/L; females: (213.82±46.87) vs (104.69±30.62), (155.05±34.90) cm 2; (184.88±46.54) vs (90.67±34.09), (138.92±42.06) cm 2; (398.71±71.28) vs (195.37±55.32), (293.97±57.05) cm 2; (11.36±6.34)% vs (5.51±3.02)%, (7.98±4.77)%; (7.44±7.60)% vs (3.70±3.90)%, (5.56±5.94)%; (5.27±0.96) vs (5.04±0.86), (5.11±0.96) mmol/L; (3.26±0.84) vs (2.92±0.79), (3.01±0.74) mmol/L; (1.74±0.69) vs (1.27±0.65), (1.57±0.77) mmol/L], while high-density lipoprotein cholesterol (HDL-C) was significantly lower [males: (1.17±0.19) vs (1.38±0.28), (1.25±0.25) mmol/L; females: (1.36±0.22) vs (1.59±0.32), (1.42±0.27) mmol/L] (all P<0.001). In males, the visceral fat area and total abdominal fat area in the overweight group were positively correlated with triglycerides ( r=0.175, 0.113) and negatively correlated with HDL-C ( r=-0.125, -0.113), while liver fat content was positively correlated with total cholesterol, LDL-C, and triglycerides ( r=0.083, 0.075, 0.206) and negatively correlated with HDL-C ( r=-0.093) (all P<0.05). In the obese group, the liver fat content was positively correlated with triglycerides ( r=0.170) and negatively correlated with HDL-C ( r=-0.166) in males (both P<0.05). In females, the visceral fat area and total abdominal fat area in the overweight group were positively correlated with total cholesterol, LDL-C, and triglycerides (visceral fat area: r=0.129, 0.160, 0.348; total abdominal fat area: r=0.121, 0.130, 0.283) and negatively correlated with HDL-C ( r=-0.264, -0.173), while liver fat content was positively correlated with triglycerides ( r=0.352) and negatively correlated with HDL-C ( r=-0.195) (all P<0.05). In the obese group, the visceral fat area was positively correlated with triglycerides ( r=0.213) and negatively correlated with HDL-C ( r=-0.223) in females (both P<0.05). Conclusion:Blood lipids are correlated with body fat distribution in overweight and obese individuals undergoing physical examinations, and the degree of correlation varies between different genders and body regions, with triglycerides showing the strongest correlation with liver fat content.