Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

ObjectiveTo study the virulence and biofilm inhibition effect of Fufang Huangbai Fluid Paint （FFHBFP） on methicillin-resistant Staphylococcus aureus （MRSA）， and to explore the antibacterial effect of FFHBFP on MRSA， which provides a theoretical basis and reference for clinical medication. MethodFirstly， the microdilution method and time–growth curve were used to determine the minimum inhibitory concentration （MIC） of FFHBFP and vancomycin （VAN） against MRSA and the effect on bacterial growth. The effects of FFHBFP and VAN on the inhibition of MRSA virulence factor lipase and restoration of hydrogen peroxide （H₂O₂） sensitivity were detected under sub-minimum inhibitory concentration （sub-MIC）. The inhibitory effect of FFHBFP and VAN on MRSA biofilm formation and maturation was detected by the microplate method. The morphological changes of mature biofilms before and after administration were observed under a scanning electron microscope （SEM）. Real-time polymerase chain reaction （Real-time PCR） was utilized to detect the effect of 50.600 g·L^-1 concentration of FFHBFP on the expression of MRSA virulence gene crtM and biofilm-forming genes fnbA and icaA. Finally， molecular docking technology was used to predict the mechanism of potential antibacterial active ingredients of FFHBFP in inhibiting the virulence and biofilm of MRSA. ResultThe MIC of VAN was 2 mg·L^-1， and VAN below 1 mg·L^-1 exerted no effect on MRSA growth. The MIC of FFHBFP was not determined， while the 101.200-202.400 g·L^-1 original solution inhibited MRSA growth. Compared with the blank group and the VAN group， sub-MIC （25.300-50.600 g·L^-1 original solution） inhibited lipase and recovered MRSA sensitivity to H₂O₂ （P<0.01）. The results of the microplate method showed that FFHBFP （25.300-202.400 g·L^-1 original solution） inhibited biofilm formation and maturation （P<0.05， P<0.01）. The SEM exhibited that FFHBFP made the structure of biofilm loose and the size of the bacteria varied. FFHBFP at 50.600 g·L^-1 concentration can inhibit the expression of related virulence genes and biofilm-forming genes （P<0.05， P<0.01）， and molecular docking results also showed that the main antibacterial active ingredients in FFHBFP have good binding ability to the target. ConclusionFFHBFP that cannot directly kill MRSA exerts clinical efficacy by impairing virulence expression， biofilm formation， and other pathogenic properties.

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( CONCLUSIONS A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.
Birth Weight ; Bone Diseases, Metabolic/etiology* ; China/epidemiology* ; Female ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Risk Factors

Objective:To understand the iodine nutrition states of children in Dongtai City Jiangsu Province by analyzing the urinary iodine level of children aged 0 - 12 years old (prepubescent children), so as to provide scientific reference for prepubescent children's reasonable iodine nutrition intake.Methods:Under the guidance of the "National Iodine Deficiency Disorders Monitoring Program" (2016), Dongtai City was divided into 5 districts according to the east, west, south, north and middle locations. In each district, children aged 0 - 7 years old who underwent physical examination in township hospitals and prevention and health centers were selected to collect urine samples for urine iodine testing. One township was selected from each district, and one primary school was selected from each township. At least 90 children aged 8 to 12 (half boys and half girls) were selected from each primary school to collect urine samples for urine iodine testing. The urinary iodine levels of children of different genders, ages and regions were compared and analyzed.Results:A total of 2 934 urine samples were collected. The median of urinary iodine was 191.9 μg/L, ranging from 1.4 to 627.9 μg/L, the proportion of urine iodine content < 50 μg/L was 5.5% (162/2 934), the proportion of 50 - 99 μg/L was 10.9% (319/2 934), the proportion of 100 - 199 μg/L was 37.4% (1 096/2 934), the proportion of 200 - 299 μg/L was 28.3% (829/2 934), and the proportion of ≥300 μg/L was 18.0% (528/2 934). A total of 1 535 and 1 399 urine samples of boys and girls were collected. The medians urinary iodine of boys and girls were 202.3 and 177.7 μg/L, respectively, and the difference was statistically significant ( Z = - 5.487, P < 0.05). There were 106, 1 539, 753 and 536 cases of infants (0 - 12 months old), early childhood (1 - 3 years old), preschool children (4 - 6 years old), and school-age children (7 - 12 years old), the medians urinary iodine were 169.8, 189.6, 169.9 and 243.7 μg/L, respectively, the difference was statistically significant ( H = 127.395, P < 0.05). There were 642, 699, 422, 738 and 433 cases in different regions (east, west, south, north and middle) and the medians urinary iodine were 194.2, 172.7, 196.8, 200.5 and 196.6 μg/L, respectively, the difference was statistically significant ( H = 29.461, P < 0.05). Conclusions:Children aged 0 - 12 years old in Dongtai City are not deficient in iodine on the whole, but those with urinary iodine value higher than 200 μg/L account for a large proportion. Therefore, a reasonable iodine nutrition plan should be implemented according to the actual situation. In addition, individual iodine deficiency and excess should also be paid attention to.

Background:The purpose of this study was to analyze cases of AO31-A2 intertrochanteric fractures (ITFs) and to identify the relationship between the loss of the posteromedial support and implant failure.Methods:Three hundred ninety-four patients who underwent operative treatment for ITF from January 2003 to December 2017 were enrolled.Focusing on posteromedial support,the A2 ITFs were divided into two groups,namely,those with (Group A,n =153) or without (Group B,n =241) posteromedial support post-operatively,and the failure rates were compared.Based on the final outcomes (failed or not),we allocated all of the patients into two groups:failed (Group C,n =66) and normal (Group D,n =328).We separately analyzed each dataset to identify the factors that exhibited statistically significant differences between the groups,In addition,a logistic regression was conducted to identify whether the loss of posteromedial support of A2 ITFs was an independent risk factor for fixation failure.The basic factors were age,sex,American Society of Anesthesiologists (ASA) score,side of affected limb,fixation method (intramedullary or extramedullary),time from injury to operation,blood loss,operative time and length of stay.Results:The failure rate of group B (58,24.07％) was significantly higher than that of group A (8,5.23％) (x2 =23.814,P ＜ 0.001).Regarding Groups C and D,the comparisons of the fixation method (P =0.005),operative time (P =0.001),blood loss (P =0.002)and length of stay (P =0.033) showed that the differences were significant.The logistic regression revealed that the loss of posteromedial support was an independent risk factor for implant failure (OR =5.986,95％ CI:2.667-13.432) (P ＜ 0.001).Conclusions:For AO31-A2 ITFs,the loss of posteromedial support was an independent risk factor for fixation failure.Therefore,posteromedial wall reconstruction might be necessary for the effective treatment of A2 fractures that lose posteromedial support.

OBJECTIVE: To investigate the values of diffusion tensor imaging (DTI) and virtual reality (VR) techniques in design surgery program of gliomas near eloquent regions. METHODS: In this study, 35 cases were retrospectively analyzed with gliomas involved language areas or rolandic regions operated in Department of Neurosurgery, Peking University Third Hospital from January 2015 to January 2019. Surgery programs were performed by Dextroscope virtual reality system. The pre-operative data, such as the magnetic resonance imaging (MRI), magnetic resonance arteriography (MRA) and DTI was transferred into the VR computer for restitution,Tumors, neural fiber tracts and blood vessels were reconstructed to simulate operation and design individual surgical plan. Neurological function was evaluated 1 week, 1 month and 3 months after operation. RESULTS: Virtual reality three-dimensional images of the 35 cases were successfully achieved, including neural fiber tracts,blood vessels and the lesions. The displacement and destruction of fiber tracts, the anatomic relationship between tumor and important fiber bundle, artery and vein could be shown clearly. Surgical simulation and surgery program of VR of the 35 patients were successfully performed. The 3D images obtained from virtual reality near to the real surgery. Ten of the 35 cases were defined as rolandic regions tumors, 14 of the 35 cases were defined as language areas tumors and 11 of the 35 cases involved both language areas and rolandic regions. Complete resection of enhancing tumor (CRET) was achieved in 30 cases (85.7%), subtotal resection in 5 cases (14.3%), neurological function improved in 34 cases (97.1%) after operation,and 1 case had no improvement compared with that before(2.9%). Thirteen cases without neurological deficit pre-operation, showed transient neurological deficit ,which were recovered about 10 days post-operation, 12 of 22 cases with pre-operative neurologic deficit, improved one week postoperation, 9 of 22 cases with pre-operative neurologic deficit improved one month after operation, the rest 1 case was recurrent with glioblastoma with aggravated hemiplegia symptom after operation, who died of cerebral hernia 2 months later. CONCLUSION Dextroscope virtual reality system can clearly expose and quantify the 3D anatomic relationship of tumors, neural fiber tracts and blood vessels surrounding gliomas near eloquent regions, which is helpful to design the best individualized surgery program, to improve surgical effect.
Brain Neoplasms/diagnostic imaging* ; Diffusion Tensor Imaging ; Glioma/diagnostic imaging* ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Retrospective Studies ; Virtual Reality

The aim of this study was to investigate the mechanism by which a diet inducing high hyperhomocysteinemia (HHcy) leads to the deterioration of erectile function in rats and whether this is inhibited by expression of the human tissue kallikrein-1 (hKLK1) gene. We established a rat model of HHcy by feeding methionine (Met)-rich diets to male Sprague-Dawley (SD) rats. Male wild-type SD rats (WTRs) and transgenic rats harboring the hKLK1 gene (TGRs) were fed a normal diet until 10 weeks of age. Then, 30 WTRs were randomly divided into three groups as follows: the control (n = 10) group, the low-dose (4% Met, n = 10) group, and the high-dose (7% Met, n = 10) group. Another 10 age-matched TGRs were fed the high-dose diet and designated as the TGR+7% Met group. After 30 days, in all four groups, erectile function was measured and penile tissues were harvested to determine oxidative stress, endothelial cell content, and penis fibrosis. Compared with the 7% Met group, the TGR+7% Met group showed diminished HHcy-induced erectile dysfunction (ED), indicating the improvement caused by hKLK1. Regarding corpus cavernosum endothelial cells, hKLK1 preserved endothelial cell-cell junctions and endothelial cell content, and activated protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) signaling. Fibrosis assessment indicated that hKLK1 preserved normal penis structure by inhibiting apoptosis in the corpus cavernosum smooth muscle cells. Taken together, these findings showed that oxidative stress, impaired corpus cavernosum endothelial cells, and severe penis fibrosis were involved in the induction of ED by HHcy in rats, whereas hKLK1 preserved erectile function by inhibiting these pathophysiological changes.
Animals ; Apoptosis ; Diet ; Endothelial Cells ; Erectile Dysfunction/prevention & control* ; Fibrosis ; Humans ; Hyperhomocysteinemia/complications* ; Male ; Methionine ; Oxidative Stress ; Penis/pathology* ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; Signal Transduction/genetics* ; Tissue Kallikreins/genetics*