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.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

OBJECTIVE: To investigate the clinical characteristics and related risk factors of Clostridium difficile infection (CDI) in intensive care unit (ICU). METHODS: A retrospective study was conducted. Patients with diarrhea admitted to the ICU of the General Hospital of Ningxia Medical University from May 1 to August 30, 2023 were selected. Patients were divided into CDI group and non-CDI group based on the presence or absence of CDI. Clinical data from two groups of patients meeting the criteria were collected and compared, including gender, age, acute physiology and chronic health evaluation II (APACHE II), length of hospital stay, serum lactic acid, parenteral nutrition time, white blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP), coagulation indicators, albumin, antibiotic exposure, etc. Multivariate Logistic regression analysis was performed to analyze the risk factors for CDI in ICU diarrhea patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of each index for CDI in diarrhea patients. RESULTS: A total of 24 patients with diarrhea were enrolled, including 9 patients in the CDI group and 15 patients in the non-CDI group. The time of parenteral nutrition in the CDI group was significantly longer than that in the non-CDI group [days: 18.0 (13.5, 19.5) vs. 10.0 (4.0, 18.0)], the serum lactic acid level [mmol/L: 4.40 (3.00, 15.25) vs. 2.50 (1.90, 3.20)] and the ratio of serum lactic acid > 3.9 mmol/L [66.67% (6/9) vs. 6.67% (1/15)] were significantly higher than those in the non-CDI group, with statistical significance (all P < 0.05). Multivariate binary Logistic regression analysis showed that the serum lactic acid level of the patients was an independent risk factor for CDI [odds ratio (OR) = 3.193, 95% confidence interval (95%CI) was 1.011-10.080, P = 0.048]. ROC curve showed that serum lactic acid level had a high predictive value for CDI in ICU patients with diarrhea, and the area under the curve (AUC) was 0.815, respectively. When the cut-off value of serum lactic acid was 3.9 mmol/L, the sensitivity was 66.7% and the specificity was 93.3%. CONCLUSION Patients with diarrhea who have higher serum lactate levels (> 3.9 mmol/L) on admission are at increased risk of developing CDI.
Humans ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Clostridium Infections ; Clostridioides difficile ; Male ; Female ; Middle Aged ; Aged ; Diarrhea/microbiology* ; Logistic Models ; ROC Curve ; Adult

Transmembrane protein 16A(TMEM16A)is a voltage-dependent calcium-activated chloride channel that is widely expressed in cancer cells.In a variety of cancer types,TMEM16A regulates the proliferation,invasion,and metastasis of cancer cells and is corre-lated with the prognosis of cancer under treatment.In recent years,TMEM16A and its inhibitors have been intensively studied in cancer treatment.This review summarizes relevant studies conducted over the past 10 years,aiming to provide a novel therapeutic strategy for the clinical application of TMEM16A inhibitors in future cancer therapy.

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.

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 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 analyze the clinical and epidemiological features of human rhinovirus (HRV) infection in adult patients with upper respiratory tract infection (URTI) in Nanjing.Methods:Epidemiological data of adult patients with URTI in Nanjing from October 2021 to September 2022 were collected. Clinical specimens were collected and subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the detection of 14 common respiratory viruses. The VP4/VP2 genes in HRV-positive samples were amplified and sequenced. Then a phylogenetic tree was constructed.Results:A total of 399 pharyngeal swabs were collected from patients with URTI. The overall positive rate of respiratory viruses was 28.07% (112/399) with HRV accounting for most at 9.52% (38/399). Thirty-seven VP4/VP2 sequences were successfully obtained from the 38 HRV-positive specimens. Three genotypes involving 25 serotypes were identified with 13 strains belonging to HRV-A, 14 belonging to HRV-B, and 10 belonging to HRV-C. The three genotypes of HRV showed alternate prevalence or co-prevalence.Conclusions:HRV was the main pathogen causing URTI in adult patients in Nanjing from October 2021 to September 2022, and three genotypes of HRV-A, B and C were prevalent alternatively or together.

Objective:To investigate genetic characteristics of human rhinovirus (HRV) in adult inpatients with pneumonia in autumn and winter in Bengbu, Anhui province, 2021.Methods:The pharyngeal swabs of inpatients with pneumonia in Bengbu were collected for the detection of 14 common respiratory pathogens by Real-time PCR during September to December 2021. VP4/VP2 coding regions of HRV positive samples were amplified by nested PCR and phylogenetic tree was constructed using MEGA7.0.Results:A total of 146 samples were collected from inpatients with pneumonia; 35.62% (52/146) samples were positive with at least one pathogen. The four viruses with high detection rate were HRV, adenovirus, human coronavirus OC43 and influenza B virus. HRV positive samples accounted for 44.23% (23/52) of the positive samples, among which 9 cases (39.13%, 9/23) co-infected with HRV. Phylogenetic analysis found that HRV infection were dominated by HRV-A and HRV-B groups. The analysis based on clinical syndrome found that the white blood cells count and the proportion neutrophils of patients with HRV co-infection were higher that of HRV single infection. The proportion of patients with hypertension, diabetes, mechanical ventilation and poor prognosis in the HRV co-infection group were higher than that of HRV single infection group ( P<0.05). Conclusions:HRV is the predominant pathogen among the adult inpatients with pneumonia in Bengbu. HRV-A and HRV-B groups are common. Patients accompanied by hypertension, diabetes were easily co-infected with HRV. Patients coinfeted with HRV are more likely to be mechanical ventilation and poor prognosis.