Demographic distribution analysis of different glomerular diseases in Southwest China from 2008 to 2022.

BACKGROUND: Environmental and lifestyle factors play an etiological role in the pathogenesis of different glomerular diseases. Thus, exploring the epidemic characteristics of renal disease in different nationalities and regions is important. MATERIALS AND METHODS: Patients who underwent renal biopsy from October 2008 to October 2022 were included. The proportion and change tendency of glomerular diseases and the differences between the sexes and different ages and races were analyzed. RESULTS: There were 15,146 cases of glomerular diseases (98.5%), involving 7538 males (49.8%) and 7608 females (50.2%). The mean age was 37.0 years (range 0-80 years). The proportion of membranous nephropathy (MN) and diabetic nephropathy (DN) showed an increased trend. The most common primary glomerulonephritis (PGN) was IgA nephropathy (IgAN, 44.6%), followed by minimal-change disease (MCD, 24.3%) and MN (15.4%). Lupus nephritis (LN, 30%) accounted for the largest proportion of SGNs, followed by Henoch-Schonlein purpura nephritis (HSPN, 20.9%) and DN (19.8%). Compared with adults aged 18-60 years old, MCD and HSPN were more common in children and MN and DN in elderly individuals, statistically significant differences. Additionally, the sex and age distribution of PGN and SGN between the Tibetan and Han populations differed significantly, whereby LN was higher in the Han population and HSPN in the Tibetan population. CONCLUSION: The distribution of glomerular diseases showed age, sex and race differences. This research will be beneficial for providing epidemiological evidence for clinical diagnosis, disease prevention and public health decision-making.

Drug Repositioning Based on Deep Sparse Autoencoder and Drug-Disease Similarity.

Drug repositioning is critical to drug development. Previous drug repositioning methods mainly constructed drug-disease heterogeneous networks to extract drug-disease features. However, these methods faced difficulty when we are using structurally simple models to deal with complex heterogeneous networks. Therefore, in this study, the researchers introduced a drug repositioning method named DRDSA. The method utilizes a deep sparse autoencoder and integrates drug-disease similarities. First, the researchers constructed a drug-disease feature network by incorporating information from drug chemical structure, disease semantic data, and existing known drug-disease associations. Then, we learned the low-dimensional representation of the feature network using a deep sparse autoencoder. Finally, we utilized a deep neural network to make predictions on new drug-disease associations based on the feature representation. The experimental results show that our proposed method has achieved optimal results on all four benchmark datasets, especially on the CTD dataset where AUC and AUPR reached 0.9619 and 0.9676, respectively, outperforming other baseline methods. In the case study, the researchers predicted the top ten antiviral drugs for COVID-19. Remarkably, six out of these predictions were subsequently validated by other literature sources.

Green fabrication of high-performance silver nanoparticles/reduced Ti3C2TxMXene nanocomposite catalyst for 4-nitrophenol reduction.

The outstanding electrical conductivity of transition metal carbides Ti3C2Tx(MXene) makes it as an excellent electron transfer medium for fabrication of efficient catalysts. However, the poor stability of MXene may restrict its application. Herein, a novel silver nanoparticles/reduced MXene nanocomposite (AgNPs/rMXene) catalyst was prepared by using L-arginine (L-Arg) as a green reducing agent. In the AgNPs/rMXene catalyst, the silver nanoparticles (AgNPs) and reduced MXene (rMXene) acted as catalytic active species and electron transfer medium, respectively. The composite catalyst exhibited superior catalytic activity in the conversion of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP), and the conversion frequency (TOF) was high up to 1109.4 h-1. Notably, the composite catalyst also showed high stability due to the reduction of L-Arg (i.e. the repair of defect groups on MXene surface). The conversion efficiency for 4-NP reduction by AgNPs/rMXene was high up to 90% after five recycles. This present study offers a simple and green approach for the design and development of efficient MXene-based catalysts.

Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis.

Introduction: Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. Methods: Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. Results: Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the ε3/ε3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with α-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. Conclusion: LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.

The role of kurtosis and kurtosis-adjusted energy metric in occupational noise-induced hearing loss among metal manufacturing workers.

Background: Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. Methods: A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (ß), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Results: Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (ß ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (ß < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when ß ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Conclusion: Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY / 药物分析学报

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Network Analysis of Meaning in Life and Coping Styles among College Students / 中国医学伦理学

【Objective:】 To explore the network structure characteristics and core items of meaning in life and coping styles among college students, and provide a basis for understanding their relationships and related interventions. 【Methods:】 A survey was conducted among college students using the Simplified Coping Style Questionnaire and Meaning in Life Questionnaire . The network analysis method was used to construct a network of college students’ meaning in life and coping styles, and R software was used for statistical analysis and visualization. 【Results:】 In the network of college students’ meaning in life and coping styles, "believing that time will change the status quo, and the only thing to do is to wait" and "trying to forget the whole thing" had the closest connection. "Learning from others to handle similar difficult situations" had the highest expected impact. "Seeking the meaning in life" and "pursuing hobbies and actively participating in cultural and sports activities" had the highest bridge expected influence. The average predictability value of all nodes was 0.775. 【Conclusions:】 Interventions aimed at "learning from others to handle similar difficult situations", "changing one’s own ideas and rediscovering what is important in life" and "changing some of the original practices or problems" may maximize the coping effect of college students. "Seeking the meaning in life" can furthest influence the coping styles, and "pursuing hobbies and actively participating in cultural and sports activities" can maximize the improvement of meaning in life.

Clinical features and long-term prognosis of diabetic patients with low or intermediate complexity coronary artery disease post percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.

Experimental Study on Seismic Performance of Precast Columns Repaired with CFRP Fabrics.

Earthquakes worldwide highlight the seismic vulnerability of reinforced concrete (RC) bridge columns. RC bridges are likely to collapse or lose service function due to damage to the bridge columns from strong earthquakes. Rapid repair of RC bridge columns is of great significance for maintaining traffic lines for emergency rescue work after earthquakes. In this study, an improved rapid repair method was developed to restore the bearing capacity of a damaged precast column after earthquake damage. A cyclic loading test was performed to simulate the seismic loading. The original column and the repaired column were both tested. The test results showed that the bearing capacity of the repaired columns was increased by 8%, and the energy dissipation capacity was 53% higher than that of the original column. The ductility decreased because the test for the repaired specimen ended in advance. The initial stiffness of the repaired columns was reduced, but the stiffness was significantly developed in the later loading stage. The rapid repair method proposed in this study exhibited an excellent effect on restoring the seismic resistance of the damaged columns.

Experimental and Numerical Evaluation on the Performance of Perfobond Leiste Shear Connectors in Steel-SFRCC Composite Beams.

The difference between the shear performances of Perfobond Leiste (PBL) shear connectors embedded in steel fiber-reinforced cementitious composite (SFRCC) structure and normal strength concrete (NC) structure was investigated by push-out tests and finite element (FE) simulations. Push-out tests were carried out on nine steel-SFRCC specimens and nine steel-NC specimens. The mechanical behavior of the PBL shear connector was examined according to the failure modes, load-slip curves, and strain distribution laws of the push-out specimens. Experimental results revealed that the extension of cracks in SFRCC was hindered by steel fibers, and the number and width of cracks in SFRCC were smaller than those in NC. The failure mode of the steel-SFRCC specimens and the single-hole steel-NC specimens was the shear failure of the penetrating reinforcement, whereas that of the multi-hole NC specimens was concrete slab cracking. The ultimate shear bearing capacity of PBL shear connectors in the steel-SFRCC specimens was 47.8% greater than that in the steel-NC specimens. Furthermore, an FE model verified by the test results was established to conduct parametric analyses. It was found that the hole diameter and thickness of the steel plate and the yield strength of the penetrating rebar greatly affected the shear bearing capacity of PBL shear connectors. Finally, based on the experimental and FE simulation results, an expression for calculating the ultimate shear bearing capacity of PBL shear connectors in the steel-SFRCC composite structure was developed by considering the bearing effects of concrete dowels, penetrating rebars, and end parts.

Abnormal decrement on high-frequency repetitive nerve stimulation in congenital myasthenic syndrome with GFPT1 mutations and review of literature.

Objectives: Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders characterized by neuromuscular junction defects. Mutations in GFPT1 have been shown to underlie CMS. An increasing number of patients with CMS due to mutations in GFPT1 have been reported. However, a comprehensive review of clinical and genetic analyses of GFPT-related CMS worldwide is lacking, especially, given that the common or hotspot mutations in GFPT1 have not been reported. Here, we described the clinical and genetic findings of three patients with GFPT1 mutations from southwestern China and reviewed the clinical and genetic features of patients with GFPT1-related CMS worldwide. Methods: Clinical, laboratory, electrophysiological, myopathological, and genetic analyses of three patients with GFPT1-related CMS from southwestern China were conducted, and a review of previously published or reported cases about congenital myasthenic syndrome with GFPT1 mutations in the PubMed database was made. Results: The clinical, laboratory, electrophysiological, and myopathological features by muscle biopsy of three patients with GFPT1-related CMS were consistent with those of previously reported patients with GFPT1 mutations. Additionally, an abnormal decrement in high-frequency RNS was found. Two different homozygous missense mutations (c.331C>T, p.R111C; c.44C>T, p.T15M) were detected by whole-exome sequencing (WES) or targeted neuromuscular disorder gene panels. Conclusion: A distinct decremental response to high-frequency RNS was found in three patients with GFPT1-related CMS from southwestern China, which has never been reported thus far. In addition, the location and degree of tubular aggregates (TAs) seemed to be associated with the severity of clinical symptoms and serum creatine kinase levels, further expanding the phenotypic spectrum of GFPT1-related CMS. Lastly, some potential hotspot mutations in GFPT1 have been found in GFPT1-CMS worldwide.

Experimental and Numerical Analyses of Stud Shear Connectors in Steel-SFRCC Composite Beams.

To investigate the shear performance and failure mechanism of stud shear connectors in steel fiber-reinforced cementitious composite (SFRCC) beams, six steel-SFRCC and six steel-normal strength concrete (NC) push-out specimens with two heights (80 mm, 120 mm) and three diameters (14 mm, 18 mm, 22 mm) of stud connectors were prepared. The experimental results revealed that the stud shearing failure was the main failure mode of all push-out specimens. In comparison to the steel-NC specimens, the development of cracks in the SFRCC beams was efficiently restrained due to the existence of high-strength steel fibers added to the normal concrete. The shear resistance and stiffness of studs in the steel-SFRCC beams were, respectively, 22.3% and 15.1% greater than those in the steel-NC specimens; however, their ductility was reduced, and the stud shear connectors failed in advance. The finite element (FE) model was developed and verified by push-out test results. FE analysis results indicated that the shear resistance of stud shear connectors was significantly improved with the increase in the concrete compressive strength, the stud diameter and tensile strength, whereas the aspect ratio of studs had a small impact on the ultimate resistance of stud shear connectors. Based on the as-obtained push-out experiment and FE analysis results, empirical formulas were presented to predict the load-slip curves and ultimate shear resistance of stud shear connectors in the steel-SFRCC specimens, and higher accuracy and a wider application range were obtained than with previous formulas.

6'-O-galloylpaeoniflorin alleviates inflammation and oxidative stress in pediatric pneumonia through activating Nrf2 activation

Objective: To assess the therapeutic effect and mechanism of 6'-o-galloylpaeoniflorin (GPF) in pediatric pneumonia.Methods: The effects of lipopolysaccharide (LPS) and GPF on cell viability and apoptosis were examined by cell counting kit-8 assay and flow cytometry analysis. The oxidative stress and inflammatory response were assessed by detecting expression levels of superoxide dismutase, glutathione, r-glutamyl cysteingl+glycine, myeloperoxidase, and malondialdehyde as well as tumor necrosis factor-α, Interleukin-18, and Interleukin-10 by using enzyme-linked-immuno-sorbent serologic assay. Moreover, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was detected by immunoblot assay, and the influence of Nrf2-knockdown on cell viability, oxidative stress, and inflammation response was also investigated.Results: The results established that GPF increased the viability of LPS-induced pneumonia cells. In addition, GPF reduced LPS-induced oxidative stress in pneumonia cells. It was further discovered that GPF reduced LPS-induced inflammation in pneumonic cell. GPF improved the activity of Nrf2 in LPS-treated pneumonic cells, and therefore alleviated inflammation and oxidative stress in pediatric pneumonia.Conclusion: GPF could serve as a promising drug for treating pediatric pneumonia (AU)

Regorafenib-induced renal-limited thrombotic microangiopathy: a case report and review of literatures.

BACKGROUND: Regorafenib belongs to a sub-group of small-molecule multi-targeted tyrosine kinase inhibitors(TKIs). In various studies with respect to the side-effect of regorafenib, drug-associated proteinuria standardly qualified to be defined as nephrotic syndrome was rarely reported as well as the relation of regorafenib with the occurrence and development of thrombotic microangiopathy (TMA). CASE PRESENTATION: In this case report and literature review, we presented a 62-year-old patient receiving regorafenib for metastatic colon cancer, manifesting abundant proteinuria, in which TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the first reported in terms of regorafenib-induced TMA confirmed by renal biopsy. CONCLUSION: This case indicates that regorafenib, a kind of TKIs may result in TMA, which is a rare but life-threatening complication of cancer treatment drug. Insights from this case might help physicians diagnose rare forms of TMA and adjust treatment for patients in a timely manner.

Drug repositioning based on heterogeneous networks and variational graph autoencoders.

Predicting new therapeutic effects (drug repositioning) of existing drugs plays an important role in drug development. However, traditional wet experimental prediction methods are usually time-consuming and costly. The emergence of more and more artificial intelligence-based drug repositioning methods in the past 2 years has facilitated drug development. In this study we propose a drug repositioning method, VGAEDR, based on a heterogeneous network of multiple drug attributes and a variational graph autoencoder. First, a drug-disease heterogeneous network is established based on three drug attributes, disease semantic information, and known drug-disease associations. Second, low-dimensional feature representations for heterogeneous networks are learned through a variational graph autoencoder module and a multi-layer convolutional module. Finally, the feature representation is fed to a fully connected layer and a Softmax layer to predict new drug-disease associations. Comparative experiments with other baseline methods on three datasets demonstrate the excellent performance of VGAEDR. In the case study, we predicted the top 10 possible anti-COVID-19 drugs on the existing drug and disease data, and six of them were verified by other literatures.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4 / 中南大学学报(医学版)

OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction / 中国结合医学杂志

OBJECTIVE@#To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways.@*METHODS@#Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis.@*RESULTS@#The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1.@*CONCLUSION@#LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.