Objective·To explore the relationship between abdominal fat area and the first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes,and to establish predictive models of nomogram.Methods·From October 2020 to February 2024,a total of 120 patients with type 2 diabetes,who were hospitalized in the Department of Endocrinology,Zhongshan Hospital,Fudan University,and underwent the arginine stimulation test,were recruited for the study.Patients were categorized into an insulin secretion function-preserved group(i.e.preserved group)and a depleted group according to the results of the arginine stimulation test.General information and laboratory parameters were collected.Subcutaneous fat area(SFA)and visceral fat area(VFA)were non-invasively measured by abdominal fat detector.The variables were screened by univariate analysis,and multivariate Logistic regression was used to identify the influencing factors,followed by the establishment of predictive models of nomogram.The area under the receiver operating characteristic curve(ROC curve)and concordance index(C-index)were used to evaluate the predictive performance of the models.Results·Seventy-four patients(61.7%)were assigned to the preserved group,and 46 patients(38.3%)to the depleted group.Patients in the depleted group had a longer diabetes duration,lower waist circumference,hip circumference,body mass index(BMI),uric acid,free triiodothyronine(FT3),adipose tissue insulin resistance(Adipo-IR),ankle brachial index(ABI),SFA and VFA,and higher brachial ankle pulse wave velocity(baPWV).Multivariate Logistic regression showed that SFA,VFA,FT3,baPWV,and ABI were independent risk factors for the depleted insulin secretion function.Nomogram models were constructed based on the above risk factors.Among them,the model comprising VFA,FT3,ABI,and baPWV showed the best predictive performance with a C-index of 0.81.Conclusion·SFA and VFA are lower in patients with depleted first-phase insulin secretion function of pancreatic β-cells.The nomogram model,including SFA or VFA,can be used to predict first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes.

OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Objective Hypobaric chamber and simulated weightless bed are essential methods for aerospace medical research,and conducting state assessment of volunteers before and after hypobaric chamber and simulated weightless bed tests is an essential guideline for aerospace implementation medicine.To further improve the efficiency of human condition assessment,in addition to the conventional biochemical and physiological indicators,the human oral exhaled gas can be used for condition assessment,and the olfactometry acquisition equipment and analysis software can collect and detect most volatile gases to complete the human oral exhaled gas data acquisition.Conducting comparative analysis of olfactory mapping data from different populations may be a means to assess the status of the body.Methods The olfactometry acquisition equipment was used to collect the oral exhaled breath olfactometry profiles of the general population,hypobaric cabin volunteers,and ambulatory volunteers.The olfactometry analysis software was used to calculate the 12 eigenvalues of the olfactometry profiles and the t-SNE downscaling,and the radar plots were used to analyze the olfactometry profiles of the general population,low-pressure cabin volunteers,and ambulatory volunteers respectively.A comparative analysis of different populations was conducted.Results(1)The t-SNE mapping data of the general population and the ambulatory volunteers were almost indistinguishable;(2)the t-SNE mapping data of the hypobaric cabin volunteers and the general population had a slight overlap,but the distinguishability of the vast majority of the t-SNE mapping data was obvious;(3)the t-SNE mapping data of the hypobaric cabin volunteers and the ambulatory volunteers were distinguishable with no overlap,and the ambulatory t SNE data are highly aggregated,and the distribution of t-SNE data in low-pressure cabin is more discrete;(4)there are 2-3 sensors with large eigenvalues and a large range of variation for both low-pressure cabin volunteers and recumbent volunteers after training activities,and the common sensor with a large range of variation is S6.Conclusion Olfactory diagnostic analysis mapping may be a means to assess the health status of the body and may be useful for spaceflight health status assessment in the future.The analysis and application of flight health state assessment can be a reference in the future.

Objective·To explore the relationship between abdominal fat area and the first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes,and to establish predictive models of nomogram.Methods·From October 2020 to February 2024,a total of 120 patients with type 2 diabetes,who were hospitalized in the Department of Endocrinology,Zhongshan Hospital,Fudan University,and underwent the arginine stimulation test,were recruited for the study.Patients were categorized into an insulin secretion function-preserved group(i.e.preserved group)and a depleted group according to the results of the arginine stimulation test.General information and laboratory parameters were collected.Subcutaneous fat area(SFA)and visceral fat area(VFA)were non-invasively measured by abdominal fat detector.The variables were screened by univariate analysis,and multivariate Logistic regression was used to identify the influencing factors,followed by the establishment of predictive models of nomogram.The area under the receiver operating characteristic curve(ROC curve)and concordance index(C-index)were used to evaluate the predictive performance of the models.Results·Seventy-four patients(61.7%)were assigned to the preserved group,and 46 patients(38.3%)to the depleted group.Patients in the depleted group had a longer diabetes duration,lower waist circumference,hip circumference,body mass index(BMI),uric acid,free triiodothyronine(FT3),adipose tissue insulin resistance(Adipo-IR),ankle brachial index(ABI),SFA and VFA,and higher brachial ankle pulse wave velocity(baPWV).Multivariate Logistic regression showed that SFA,VFA,FT3,baPWV,and ABI were independent risk factors for the depleted insulin secretion function.Nomogram models were constructed based on the above risk factors.Among them,the model comprising VFA,FT3,ABI,and baPWV showed the best predictive performance with a C-index of 0.81.Conclusion·SFA and VFA are lower in patients with depleted first-phase insulin secretion function of pancreatic β-cells.The nomogram model,including SFA or VFA,can be used to predict first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes.

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

Objective To explore the diagnostic value of alkaline phosphatase on the surface membrane of neutrophils(mNAP)in bloodstream infections(BSI)of Gram-negative bacteria(GNB)and Gram-positive bacteria(GPB).Methods A total of 418 patients diagnosed with BSI at Donghai People's Hospital from January 2022 to December 2023 were enrolled in the study.Based on the results of Gram staining from positive blood cultures,the patients were divided into GNB bacteremia(n=329)and GPB bacteremia(n=89).Additionally,35 hospitalized patients with systemic inflammatory response syndrome(SIRS)during the same period were selected as the control group.Their clinical data,routine laboratory test results,blood cultures and venous blood samples were collected,and the expression levels of mNAP were detected by flow cytometry.The receiver operating characteristics(ROC)curve was used to evaluate the diagnostic performance of mNAP for BSI of GNB and GPB.Results The expression levels of mNAP in the GPB infection,GNB infection and SIRS groups were 9 588(5 677,11 343)AB/C,16 616(11 853,22 035)AB/C,and 5 738(2 613,9 178)AB/C,respectively,and the difference among them was statistically significant(H=43.95,P＜0.000 1).Further pairwise comparisons showed that the expression levels of mNAP in the GNB infection group were significantly higher than those in the GPB infection group(U=203.0,P＜0.000 1)and the SIRS group(U=445.0,P＜0.000 1).Meanwhile,the expression levels of mNAP in the GPB infection group were significantly higher than that in the SIRS group(U=583.0,P＜0.000 1).The area under the ROC curve(AUCROC)of mNAP for predicting the BSI of GNB was 0.91(95%CI:0.85-0.96).When the cut-off value was 10 820 AB/C,its sensitivity and spe-cificity were 80.00%and 88.57%,respectively.The AUCROC of mNAP for predicting the BSI of GPB was 0.69(95%CI:0.55-0.83).When the cut-off value was 10 859 AB/C,its sensitivity and specificity were 33.00%and 88.13%,respectively.Conclusion The di-agnostic efficiency of mNAP for the BSI of GNB is significantly higher than that for the BSI of GPB,which may become a novel biologi-cal marker for distinguishing the BSI of GNB and GPB.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To explore the effect and the possible mechanism of knockdown acetyl CoA carboxylase 1(ACC1)on the migration of KYSE450 cells.Methods KYSE450 cells during the logarithmic phase were randomly divided into the shNC group,shACC1 group,shNC+AEB071 group,and shACC1+AEB071 group.The KYSE450 cells in the shNC group were transfected with empty plasmid;the KYSE450 cells in the shACC1 group were transfected with lentiviral plasmid;the KYSE450 cells in the shNC+AEB071 group were transfected with empty plasmid and then added with 5 μL of 2 mmoL·L-1 protein kinase C(PKC)inhibitor AEB071(final concentration 5 μmoL·L-1);The KYSE450 cells in the shACC1+AEB071 group were transfected with lentiviral plasmid and then added with 5 μL of 2 mmoL·L-1 PKC inhibitor AEB071(final concentration 5 μmoL·L-1).The migration of KYSE450 cells was detected by Transwell assay.The morpho-logical changes of KYSE450 cells were observed under the microscope.The expression levels of ACC1,histone H3(H3),histone H3 lysine 9 acetylation(H3K9Ac),and epithelial-mesenchymal transition(EMT)markers such as β-catenin,Vimentin and Snail were measured by Western blot.Results The migration of KYSE450 cells in the shACC1 group was significantly higher than that in the shNC group(P＜0.05);there was no significant difference in the migration ability of KYSE450 cells between the shNC+AEB071 group and the shNC group(P＞0.05);the migration of KYSE450 cells in the shACC1+AEB071 group was significantly lower than that in the shACC1 group(P＜0.05).The KYSE450 cells in the shNC group revealed an elliptical epithelial-like cell morphology;the KYSE450 cells in the shACC1 group exhibited a spindle-like interstitialcell morphology;the KYSE450 cells in the shNC+AEB071 and shACC1+AEB071 groups showed an elliptical epithelial-like cell morphology.The relative expression level of ACC1 in KYSE450 cells in the shACC1 group was significantly lower than that in the shNC group(P＜0.05),while the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 were significantly higher than those in the shNC group(P＜0.05);the relative expression levels of ACC1,β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 showed no significant difference between the shNC+AEB071 group and the shNC group(P＞0.05);the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 in the shACC1+AEB071 group were significantly lower than those in the shACC1 group(P＜0.05);there was no significant difference in the relative expression level of ACC1 in KYSE450 cells between the shACC1+AEB071 group and the shACC1 group(P＞0.05).Conclusion Knockdown of ACC1 promotes migration of KYSE450 cells and thus aggravates the tumor,which may be mediated by PKC-related signaling pathways.

Objective To investigate the efficacy of methylprednisolone in preventing postoperative pulmonary infections in locally advanced esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy.Methods A total of 89 patients with locally advanced esophageal cancer treated at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023 were selected as the research subjects.All patients underwent thoracolaparoscopic radical esophagectomy for esophageal cancer.The patients were randomly divided into an observation group(n=45)and a control group(n=44)using a random number table method.In the observation group,one patient with intraoperative thoracotomy,two patients with extensive pleural adhesion,and one patient with preoperative upper respiratory tract infection were excluded.In the control group,one patient with extensive pleural adhesion and one patient with preoperative upper respiratory tract infection were excluded.As a result,a total of 83 patients were included in the study,with 41 in the observation group and 42 in the control group.Preoperatively,a neoadjuvant treatment regimen of paclitaxel(albumin-bound)+nedaplatin in combination with camrelizumab was given to patients in both groups for 2 cycles.Patients in the control group received conven-tional anti-infection treatment after surgery,while patients in the observation group were intravenously injected with methylpred-nisolone at a dose of 1 mg·kg-1 daily from the first to the third day after surgery.Postoperative inflammatory markers,incidence of postoperative pulmonary infections,incidence of anastomotic fistula,postoperative hospital stay,and total hospitalization costs were compared between the two groups.Results There were no statistically significant differences in leukocyte count,neutrophil ratio,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6)levels of patients between the two groups before treatment(P＞0.05).On day 1 and 4 after treatment,patients in the observation group had significantly higher leu-kocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels compared to those before treatment(P＜0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels were significantly lower than those on day 1 postopera-tively(P＜0.05).On postoperative days 1 and 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP and IL-6 levels of patients in the control group were significantly higher than those in the preoperative period(P＜0.05),and the leukocyte count,neutro-phil ratio and hs-CRP level were significantly lower on day 4 after surgery than on day 1 after surgery(P＜0.05);the differe-nces in PCT and IL-6 level of patients between day 4 after surgery and day 1 after surgery were not statistically significant(P＞0.05).On postoperative day 1,there were no statistically significant differences in leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels between patients in the observation group and the control group(P＞0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of pulmonary infections in patients in the control group and the ob-servation group was 30.9％(13/42)and 12.2％(5/41),respectively;the incidence of pulmonary infections in patients in the observation group was significantly lower than that in the control group(x2=4.298,P＜0.05).The incidence of anasto-motic fistula in patients in the observation group and the control group was 9.76％(4/42)and 21.43％(9/42),respectively;there was no statistically significant difference between the two groups(x2=2.140,P＞0.05).The postoperative hospital stay was significantly longer in the control group than in the observation group(P＜0.05),and the total hospitalization costs were significantly higher in the control group than in the observation group(P＜0.05).Conclusion Methylprednisolone can effec-tively reduce the levels of inflammatory markers and the incidence of postoperative pulmonary infections in esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy before surgery.It is a highly safe treatment thera-py without increasing the incidence of anastomotic fistula.

Background::The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).Methods::In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.Results::The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 μg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.Conclusions::The prevalence of hypertension increased significantly with the increase of plasma aluminum level.