OBJECTIVE To investigate the mechanism of gossypol acetic acid （GAA） in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations （5， 10， 20， 40， 80， 160 μmol/L） of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 （NDRG1）， epidermal growth factor receptor feedback inhibitor 1 （ERRFI1）， CXC chemokine ligand 3 （CXCL3）] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells （P＜0.05）. Proteomics results showed that a total of 921 differentially expressed proteins were obtained， including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria， nucleus， extracellular matrix， etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT （phosphoinositide 3-kinase/protein kinase B）， MAPK （mitogen-activated protein kinase）， TNF （tumor necrosis factor）， etc.， which mainly involved cell apoptosis， aging， and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 （P＜0.05）， but increased protein expression of ERRFI1 （P＜0.05）. CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT， MAPK， TNF， etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins， upregulating the expression of ERRFI1 protein， and affecting the proliferation and apoptosis of uterine fibroid cells.

BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

BACKGROUND:Diabetic foot patients with wound infections constitute a large patient population,and there is currently no satisfactory treatment approach. OBJECTIVE:To investigate the clinical efficacy of a modified tibial cortex transverse transport combined with antibiotic-loaded bone cement for treating refractory diabetic foot ulcers. METHODS:A total of 46 diabetic foot ulcers patients,27 males and 19 females,with an average age of 64.37 years,were selected from Beijing Chaoyang Hospital,Capital Medical University and Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from January 2020 to January 2023.All of them underwent the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement treatment.Ankle-brachial index,WIFi(Wound/Ischemia/Foot infection)classification,pain visual analog scale score,and ulcer area were recorded before and 3 months after surgery. RESULTS AND CONCLUSION:(1)The mean ulcer healing time for the 46 patients was(58.07±24.82)days.At 3 months postoperatively,there were significant improvements in ankle-brachial index,pain visual analog scale score,ulcer area,and WIFi classification in 46 patients,as compared to the preoperative values,with statistically significant differences(P<0.05).Two patients experienced pin-tract infections,without infection or ulcer recurrence during the follow-up period.(2)These findings indicate that the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement effectively alleviates patients'pain,improves lower limb circulation,controls infections,and promotes ulcer healing.

Objective To observe the expression of Galectin-3 in peritoneal dialysis (PD) fluid in patients with different dialysis ages, and to conduct correlation analysis with vascular endothelial growth factor (VEGF) , fi-bronectin (FN) and related clinical indicators.Methods A total of 109 PD patients who were regularly followed up in the department of nephrology were divided into four groups according to different peritoneal dialysis ages.The concentrations of Galectin-3, VEGF and FN were determined by enzyme-linked immunosorbent assay.The expres-sion of Galectin-3 in peritoneal dialysate of the 4 groups was compared, the correlation with VEGF, FN and clinical related indexes was analyzed, and the correlation was analyzed by Spearman test.Results The concentration of VEGF in peritoneal dialysis patients in group D significantly increased (P<0.05) .Galectin-3 expression levels were positively correlated with VEGF (r =0.358 , P =0.022) , but not significantly correlated with FN (r =0.121, P=0.452).Galectin-3 was positively correlated with clinical indicators parathyroid hormone (PTH) (r=0.201, P=0.037), C-reactive protein (CRP) (r=0.357, P<0.001), left ventricular posterior wall dimensions (LVPWD) (r=0.213, P=0.026), and negatively correlated with clinical indicators total cholesterol (TC) (r=-0.316, P=0.001).Conclusion The concentration of Galectin-3 in the dialysate of long-term peritoneal dialy-sis patients is significantly elevated, indicating that the expression of galectin-3 increases with the extension of peri-toneal dialysis time, suggesting that the detection of galectin-3 levels may be helpful for the evaluation of early peri-toneal fibrosis.The positive correlation with VEGF may suggest its role in promoting peritoneal angiogenesis and fi-brosis.Moreover, it is positively correlated with clinical indicators PTH, CRP and LVPWD, suggesting that it has certain clinical guiding significance on microinflammatory state and myocardial remodeling.

Radiotherapy is an important means to treat lung cancer,but it is easy to cause lung injury and reduce the quality of life of patients.Flash radiotherapy(FLASH-RT)has attracted attention due to its extremely short radiation duration and high dose rate,which can reduce toxicity of normal tissue while ensures treatment intensity of tumor.Whether Flash-RT can reduce radiation-induced lung injury has become an important research topic in recent years.Based on the literature analysis method,this review systematically assessed the effects and mechanisms of Flash-RT and radiotherapy with conventional dose rate on lung injury through searching relevant literatures at home and abroad,so as to provide scientific basis for the treatment of patients with lung cancer by reviewing the comparisons about the effects and mechanisms between Flash-RT and radiotherapy with conventional dose rate on lung injury.Compared with radiotherapy with conventional radiation rate,Flash-RT can significantly reduce lung injury and improve quality of life of patients.It is still demanded to explore the Flash-RT mechanism in future,so as to develop the Flash-RT instrument that is suitable for different tumors and to conduct larger-scale clinical researches.

Objective To explore the clinical features,treatment and prognosis of glioblastomas(GBM)in adults.Methods A retrospective cohort study was performed on 176 adult GBM patients admitted to our department from January 2015 to December 2021.Chi-square test was used to investigate the clinical differences between isocitrate dehydrogenase(IDH)mutant and wild-type GBM.Kaplan-Meier and Log-Rank tests were employed to plot survival curve and compute the survival analysis.Multivariate Cox regression model was applied to identify the independent prognostic factors.Results IDH wild-type GBM account for 89.2％and had significantly differences from the IDH-mutant GBM in terms of age of onset,Karnofsky(KPS)score at admission,symptoms of neurological deficit,and methylation status of O6-methylguanine-DNA-methyltransferase(MGMT)promoter(P＜0.05).For the IDH wild-type GBM patients receiving conventional therapy,univariate Cox hazard analysis showed gross total resection,methylation of MGMT promoter,initiation of radiation within the 5th to 6th week after surgery,and adjuvant temozolomide(TMZ)chemotherapy ≥6 cycles were favorable prognostic factors for overall survival(OS);GBMs in the left hemisphere,involvement of single lobe,methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery were favorable prognostic factors for progression free survival(PFS)(all P＜0.05).Moreover,multivariate Cox hazard regression analysis indicated that methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery,and adjuvant TMZ chemotherapy ≥6 cycles were independent protective factors for OS,and GBMs in the left hemisphere,involvement of single lobe and methylation of MGMT promoter were independent protective factors for PFS in the GBM patients(all P＜0.05).Conclusion The clinical and prognostic features are totally different between IDH mutant and wild-type GBM,and molecular detections are needed for the further pathological classification.Methylation of MGMT promoter is a primary marker of favorite prognosis for IDH wild-type GBM,and slightly delay in radiotherapy(the 5th to 6th week after surgery)can effectively improve the survival prognosis of IDH wild-type GBM.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Objective:To construct an estimating equation to accurately reflect the aging phenomenon of the glomerular filtration rate(GFR).Methods:Healthy subjects receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University between January 2017 and April 2018 were included in the study, and the aging phenomenon of renal function indicators such as serum creatinine(Scr)was used as the reference standard to evaluate the accuracy of four Scr-based GFR equations during GFR aging, including the full age spectrum(FAS)equation, the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)equation, the Osaka equation and the Xiangya equation.Results:Of 37 636 individuals receiving physical examinations, 6 534 met the criteria specified in this study.Scr, serum urea nitrogen, serum uric acid, and serum albumin showed a significant aging phenomenon( H=191.640, 196.693, 83.271, 414.585, P<0.001 for all).The GFR estimated by the four equations all decreased with aging, but the starting point and rate of decline were significantly different.The GFR aging phenomenon estimated by the FAS equation was closer to the trend of renal function indicators. Conclusions:The FAS equation may be more applicable to healthy people to understand the aging phenomenon of GFR.

Objective To assess the effectiveness of enhanced tibial transverse transport(TTT)in con-junction with vacuum-assisted closure(VAC)therapy for managing recalcitrant diabetic foot ulcers.Methods A retrospective analysis was conducted on data from diabetic foot patients with Wagner grade≥2 who were treated at Beijing Chaoyang Hospital and Beijing Chaoyang Hospital of Integrated Traditional Chinese and Western Medicine between July 2020 and December 2022.The patients were categorized into three groups based on their treatment regimen:VSD treatment(VSD group),modified TTT treatment(TTT group),and combined application of TTT and VSD(combined group).A one-year follow-up was performed to assess general data,ulcer area before and three months after surgery,ankle brachial index,visual analog pain score,as well as adverse events within one year post-surgery among the three groups.Results The VSD group consisted of 43 patients,while the TTT group consisted of 43 patients,and the combined group consisted of 42 patients.There were no statistically significant differences in baseline characteristics among the three groups(P＞0.05).Patients in the VSD group had longer ulcer healing time,higher pain scores,lower ankle brachial index(P＜0.05),larger ulcer area(P=0.029),and higher one-year ulcer recurrence rate compared to those in the TTT group.On the other hand,patients in the combined group had shorter ulcer healing time compared to those in the TTT group(P=0.046).However,there were no significant differences observed between these two groups regarding ulcer area(P=0.362),pain scores(P=0.932),ankle brachial index(P=0.671),and one-year ulcer recurrence rate(P=0.710).Conclusions The efficacy of modified TTT surpasses that of VSD in promoting ulcer healing,alleviating pain,and enhancing lower limb circulation.Furthermore,the combination of VSD with modified TTT demonstrates a potential to further expedite wound healing time.