GINS1 promotes the initiation and progression of bladder cancer by activating the AKT/mTOR/c-Myc signaling pathway.

Bladder cancer(BC) is one of the most prevalent cancers in the urinary tract, with high recurrence and fatality rates. Research indicates that go-ichi-ni-san complex subunit 1 (GINS1) crucially influences cancer progression by regulating DNA replication through cell cycle modulation. Thus, suppressing the active proliferation of cells in tumor tissues may require silencing GINS1. However, the consequences of GINS1 in bladder cancer aren't to be determined. In this paper, we examine the role and mechanism of GINS1 in the development of bladder cancer. GINS1 expression levels and prognostic relevance in bladder cancer were validated using Western blotting, immunohistochemistry, and Kaplan-Meier survival analysis. The influence of GINS1 on bladder cancer was investigated using a variety of approaches, including cell transfection, cell counts, transwell migrations, colony formation, and flow cytometry. Immunohistochemistry studies demonstrate that GINS1 expression is increased in bladder cancer tissues. GINS1 silencing resulted in an arrest of the cell cycle at the phase of G0/G1, which inhibited BC cell growth both in vitro and in vivo. GINS1 knockdown also hindered the AKT/mTOR pathway. Furthermore, increased GINS1 expression affects the cell cycle and stimulates the AKT/mTOR pathway, allowing BC to develop more quickly. Consequently, GINS1 occurs as a latent therapeutic target, particularly for individuals with BC.

Advancing Ultrasonic Defect Detection in High-Speed Wheels via UT-YOLO.

In the context of defect detection in high-speed railway train wheels, particularly in ultrasonic-testing B-scan images characterized by their small size and complexity, the need for a robust solution is paramount. The proposed algorithm, UT-YOLO, was meticulously designed to address the specific challenges presented by these images. UT-YOLO enhances its learning capacity, accuracy in detecting small targets, and overall processing speed by adopting optimized convolutional layers, a special layer design, and an attention mechanism. This algorithm exhibits superior performance on high-speed railway wheel UT datasets, indicating its potential. Crucially, UT-YOLO meets real-time processing requirements, positioning it as a practical solution for the dynamic and high-speed environment of railway inspections. In experimental evaluations, UT-YOLO exhibited good performance in best recall, mAP@0.5 and mAP@0.5:0.95 increased by 37%, 36%, and 43%, respectively; and its speed also met the needs of real-time performance. Moreover, an ultrasonic defect detection data set based on real wheels was created, and this research has been applied in actual scenarios and has helped to greatly improve manual detection efficiency.

NCAPG promotes tumorigenesis of bladder cancer through NF-κB signaling pathway.

The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer.

Nondestructive analysis of rolling contact fatigue cracks using induced scanning thermography.

Rolling contact fatigue (RCF) produced by wheel-rail interaction is now considered to be a critical factor that causes failure. Throughout this work, induced scanning thermography (IST) for detecting RCF defects at different depths is investigated. The original thermal sequences could not utilize the features at the heat dissipation stage; thus, a data reconstruction method, including principal component analysis (PCA) and Tucker factorization, was employed to extract the spatial and time patterns. In addition, detectability was evaluated across a range of speed studies. The Tucker-PCA combination algorithms obtained defects with improved quality, showing a clear boundary over the velocity range of 1-4km/h, which dramatically suppressed background noise. A unique gradient response characteristic in the cooling phase was summarized and utilized through experimental verification in order to recognize defect width.

Analysis of the RCF crack detection phenomenon based on induction thermography.

Eddy current pulsed thermography (ECPT) is used to detect rolling contact fatigue (RCF) cracks on the rail. It is observed that some of the cracks disappear in the thermal image with the increase of heating time. Based on the finite element method, with double cracks as the basic unit, three different crack models are established, and the mutual disturbance relationship between the double cracks is discussed based on the eddy current distribution and thermal diffusion process. The simulation and experimental results show that different crack models are affected by thermal diffusion in different heating stages to different degrees, and the time of the crack thermal image disappearance is obtained. According to the above conclusions, the RCF cracks are extracted and classified based on the influence of thermal diffusion. The possibility of rail condition assessment and maintenance based on the disappearance time is explained.

What Factors Are Associated With Postoperative Ischiofemoral Impingement After Bernese Periacetabular Osteotomy in Developmental Dysplasia of the Hip?

BACKGROUND: Any abnormal structures that contribute to the narrowing of the ischiofemoral space could induce ischiofemoral impingement. Bernese periacetabular osteotomy (PAO) medializes the hip center and, therefore, decreases contact stress on the cartilage in developmental dysplasia of the hip (DDH). However, medialization of the hip center might also narrow the ischiofemoral space, which may increase the risk of postoperative ischiofemoral impingement in patients with acetabular dysplasia who are undergoing PAO. Furthermore, the dysplastic hip has less ischiofemoral space and less space for the quadratus femoris. A few studies have focused on the amount of medialization of the hip center, but the proportion of postoperative ischiofemoral impingement after PAO has not been investigated. QUESTIONS/PURPOSES: (1) What proportion of patients develop ischiofemoral impingement after undergoing unilateral PAO for DDH? (2) What radiographic factors are associated with postoperative ischiofemoral impingement in patients who underwent PAO for DDH? (3) How much hip center medialization is safe so as to avoid postoperative ischiofemoral impingement during PAO? METHODS: Between 2014 and 2016, we treated 265 adult patients who had symptomatic residual acetabular dysplasia (lateral center-edge angle less than 20°) using PAO. During that time, we generally offered PAO to patients with acetabular dysplasia when the patients had no advanced osteoarthritis (Tönnis grade < 2). Of those, we considered only patients who underwent primary PAO without femoral osteotomy as potentially eligible. Based on that, 65% (173 of 265) were eligible; a further 9% (24 of 265) were excluded due to leg length discrepancy, spine disorders, or joint replacement in the contralateral side, and another 6% (17 of 265) of patients were lost before the minimum study follow-up of 2 years or had incomplete datasets, leaving 50% (132 of 265) for analysis in this retrospective study at a mean of 2.70 ± 0.71 years. The diagnosis of ischiofemoral impingement was defined by symptoms, MRI, and diagnostic ischiofemoral injection. We ascertained the percentage of patients with this diagnosis to answer the first research question. To answer the second question, we divided the patients into two groups: PAO patients with ischiofemoral impingement and PAO patients without ischiofemoral impingement. The demographic data and preoperative imaging parameters of patients in both groups were compared. There were statistical differences in acetabular version, ischial angle, neck-shaft angle, the presence of positive coxa profunda sign, McKibbin index, ischiofemoral space, quadratus femoris space, anterior acetabular section angle, and the net amount of hip center medialization. To investigate potential factors associated with postoperative ischiofemoral impingement in patients who underwent PAO, these factors underwent binary logistic regression analysis. To answer the third question, the cutoff value of the net amount of hip center medialization was evaluated using receiver operator characteristic curve and the Youden index method. RESULTS: We found that 26% (35 of 132) of PAO dysplastic hips had postoperative ischiofemoral impingement. After controlling for confounding variables such as acetabular version, ischial angle, femoral neck version, McKibbin index, and ischiofemoral space, we found that an increasing neck-shaft angle (odds ratio 1.14 [95% confidence interval 1.01 to 1.29]; p = 0.03), a positive coxa profunda sign (OR 0.13 [95% CI 0.03 to 0.58]; p < 0.01), and an increasing net amount of hip center medialization (OR 2.76 [95% CI 1.70 to 4.47]; p < 0.01) were associated with postoperative ischiofemoral impingement in patients with DDH who underwent PAO (R 2 = 0.73). The cutoff values of neck-shaft angle was 138.4°. The cutoff values of the net amount of hip center medialization was 1.9 mm. CONCLUSIONS: Postoperative ischiofemoral impingement could occur in patients with acetabular dysplasia who have undergone PAO after hip center medialization. An increasing neck-shaft angle, a positive coxa profunda sign on preoperative imaging, and excessive medialization of the hip center are factors associated with ischiofemoral impingement development in these patients. Therefore, we suggest that physicians measure the ischiofemoral space on a preoperative CT when patients with DDH have an increasing neck-shaft angle (> 138.4°) or a positive coxa profunda sign on radiological imaging. During PAO, the amount of hip center medialization should be carefully controlled to keep these patients from developing postoperative ischiofemoral impingement. LEVEL OF EVIDENCE: Level III, therapeutic study.

What is the agreement between intraoperative fluoroscopy and postoperative radiographs in Bernese periacetabular osteotomy?

BACKGROUND: It is important to reorient the acetabular fragment into an optimal position and version to ensure a good long-term outcome after Bernese periacetabular osteotomy (PAO). Unfortunately, the intraoperative balance between overcorrection and undercorrection remains challenging for the surgeon. The purpose of this study was to answer two questions: (1) Does the femoral head coverage measured on intraoperative fluoroscopy agree with that measured on postoperative radiography? (2) What is the reliability of intraoperative fluoroscopy in identifying hip center correction in PAO? METHODS: A total of 173 patients (173 hips) who underwent PAO for developmental dysplasia of the hip (DDH) at our center from July 01, 2020, to December 31, 2020, were retrospectively reviewed. Imaging data from 111 patients (female/male, 98/13; right/left, 72/39; mean age, 28.93 years) were included in this study. The analysis included measurement of the lateral center-edge angle (LCEA), acetabular index (AI), anterior wall index (AWI), posterior wall index (PWI), extrusion index (EI), and medial offset distance (MO). These measurements were acquired from intraoperative fluoroscopic images and postoperative radiographs and compared by paired t test using SPSS (version 24.0). Significance was determined at a p value of < 0.05. Bland-Altman analysis, conducted using GraphPad Software (version 9), was used to quantify the agreement between intraoperative fluoroscopic images and postoperative radiographs. RESULTS: The means (standard deviations, SDs) of the LCEA, AI, AWI, PWI, EI, and MO obtained on intraoperative fluoroscopy were 32.86° (5.73°), 0.66° (5.55), 0.29 (0.10), 0.75 (0.17), 11.15% (6.50%), and 8.49 mm (3.68 mm), respectively. On postoperative radiography, the corresponding values were 32.91° (6.31°), 1.63° (5.22°), 0.29 (0.15), 0.85 (0.14), 11.27% (7.36%), and 9.60 mm (3.79 mm). The differences in the LCEA, AWI, and EI acquired from intraoperative fluoroscopic images and postoperative radiographs were not significant (p = 0.90, 0.95, and 0.83, respectively), but those in the AI, PWI, and MO were significant (p < 0.05). The mean biases (95% limits of agreement) of the LCEA, AI, AWI, PWI, EI, and MO were - 0.04 (- 6.85), - 0.97 (- 7.78), 0 (- 0.30), - 0.11 (- 0.36), - 0.12 (- 11.92), and - 1.11 (- 5.51), respectively. CONCLUSION: The LCEA, EI, and AWI can be used to reliably predict postoperative femoral head coverage at the level of 2D graphics. Acetabular inclination can be cautiously assessed using AI on intraoperative fluoroscopy. In the absence of intraoperative 3D image evaluation, the AWI and PWI demonstrate acceptable agreement between fluoroscopy and radiography in assessing the acetabular version. Although the MO shows slight bias, it can be helpful in properly positioning the acetabulum during PAO.

Characteristics of the patellofemoral joint of patients with DDH and the effects of Bernese periacetabular osteotomy on the patellofemoral joint.

BACKGROUND: Some patients with developmental dysplasia of the hip (DDH) complained of anterior knee pain (AKP) before and after Bernese periacetabular osteotomy (PAO) surgery. The purpose of this study was to (1) identify the characteristics of patellofemoral joint (PFJ) deformities in patients with DDH and (2) to determine the effects of PAO on the PFJ. METHODS: Seventy patients (86 hips) were included in the DDH group. Thirty-three patients (33 knees) without AKP and hip pain were included in the control group. All patients underwent simultaneous CT scans of the hip and knee joints before PAO and after hardware removal surgery. The distance from the anterior inferior iliac spine to the ilioischial line (DAI), was measured in DDH patients. Imaging parameters of knees, including the sulcus angle (SA), femoral trochlear depth (FTD), patellar width (PW), tibial tuberosity-trochlear groove (TT-TG), patellar tilt angle (PTA) and lateral shift of the patella (LSP) were measured in patients in both the DDH and control group. TT-TG, PTA, and LSP of DDH patients were measured before PAO and after hardware removal. The DAI, PTA, LSP and TT-TG of all DDH patients before and after Bernese PAO were compared using paired t-tests. The FTD, PW, and SA of the DDH patients and the control group were analyzed using independent t-tests. PTA, TT-TG, and LSP between the control group and preoperative DDH patients, between the control group and post PAO patients were compared using independent t-tests. RESULTS: The DAI changed from 4.04 ± 0.61 mm before PAO surgery to 5.44 ± 0.63 mm after PAO surgery. The SA of the DDH group (140.69 ± 11.30 degree) was greater than that of the control group (130.82 ± 6.43 degree). The FTD and the PW of the DDH group (5.45 ± 1.59 mm, 4.16 ± 0.36 mm) were smaller than that of the control group (7.39 ± 1.20 mm, 4.24 ± 0.38 mm). The changes in LSP, PTA, and TT-TG before and after surgery were not statistically significant. Both before and after PAO, there was no statistically significant difference in the parameters of LSP, PTA, and TT-TG compared with the control group. CONCLUSION: The knee joints of DDH patients presented a certain degree of femur trochlear groove dysplasia and patellofemoral instability. PAO surgery did not change PFJ stability, although the origination point of the rectus femoris muscle moved laterally during PAO surgery.

Variations in lower limb alignments indicate pelvic tilt after total hip arthroplasty.

OBJECTIVE: We sought to correlate various spinopelvic and lower limb alignments, and to examine the current spinopelvic theories on a Chinese cohort. METHODS: We retrospectively reviewed 166 patients undergoing THA. Among them, 138 patients with unilateral THA met the inclusion criteria. Sagittal alignments and cup orientations were measured on standing and sitting lateral EOS images. Patients were categorized into two groups with a scoring system for lumbar spine degeneration. Patients' demographics including age, sex, lumbar spine degeneration and radiographic measurements were studied. RESULTS: PT, SS, LL and TK differed significantly between standing and sitting within each group except for TK in degenerative group (32.8 ± 13.9 vs. 32.9 ± 14.2, p = 0.905). Compared with degenerative spine group, non-degenerative spine patients have great pelvic mobility (ΔPT, -24.4 ± 12.5° vs. -17.6 ± 10.7, p = 0.0008), greater lumbar mobility (ΔLL, -34.8 ± 15.2 vs. -21.7 ± 12.2, p = < 0.0001) and compensatory cup orientation changes (ΔRA, -15.5 ± 11.1 vs. -12.0 ± 8.4, p = 0.00920; ΔRI, -10.8 ± 11.5 vs. -5.6 ± 7.5, p = 0.0055). Standing PT and ankle dorsiflexion angle correlated positively (R2 = 0.236, p = 0.005). CONCLUSION: THA patients in this cohort showed a spinopelvic motion paradigm similar to that from previous studies on Caucasians. Ankle dorsiflexion indicate greater posterior pelvic tilt on standing. Surgeons should beware of risks of instability in patients with lower limb compensations. ADVANCES IN KNOWLEDGE: This study provides new insights into the clinical relevance of lower limb alignments to spinopelvic motion after THA in a relatively young Chinese population.

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway.

BACKGROUND: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. METHODS: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. RESULTS: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. CONCLUSION: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

Quantification of closed cracks in railway using eddy current pulsed thermography.

Rolling contact fatigue cracks are common defects in rail, and they are also the source of various rail defects. When such defects occur, crack closure is caused due to interaction forces between wheels and rails during train running. In this study, eddy current pulsed thermography was applied for quantitative closed crack detection based on the isotherm analysis of temperature distributions. The differences between point-contact crack and opening crack in eddy current and temperature profile were compared in the simulation study. The angle crack test blocks with different closure depths were tested, and the simulation conclusions were consistent with experimental results. Therefore, the proposed method is an effective approach to quantify closed crack.

LncRNA-CIR promotes articular cartilage degeneration in osteoarthritis by regulating autophagy.

Osteoarthritis (OA) is a common joint disease that is regarded as a local inflammatory response caused by joint instability and accompanied by the progressive degeneration of articular cartilage. However, the molecular mechanisms involved in the maintenance of articular cartilage remain a subject of debate and research. This study aims to analyze the roles of long noncoding RNA (lncRNA)CIR and autophagy in cartilages and determine their overall contribution to the degradation of extracellular matrix. Patients with OA possessed high levels of lncRNA-CIR and MMP3 and low level of COL2A1. The levels of autophagy-related proteins, including LC3BI/II and beclin-1, increased from 12 h to 48 h. The use of si-lncRNA-CIR reversed the trend compared with that in the OA group. The negative effect of lncRNA-CIR was assessed in vivo by establishing a model of surgically induced OA. Moreover, si-lncRNA-CIR-treated joints exhibited fewer OA changes than saline-treated joints. Results were confirmed by histopathological grading of the models by using the Osteoarthritis Research Society International Scoring System and the outcomes of immunohistochemistry for LC3B-II and MMP-3. Overall, lncRNA-CIR played a negative role in the OA process by activating autophagy.

The inhibition of RANKL expression in fibroblasts attenuate CoCr particles induced aseptic prosthesis loosening via the MyD88-independent TLR signaling pathway.

Periprosthetic osteolysis and aseptic loosening are mainly caused by wear particles (Ps) that are generated from friction interfaces. However, the mechanisms underlying the development of aseptic loosening remain unclear. Therefore, we aimed toclarify how the myeloid differentiation factor 88 (MyD88)-independent Toll-like receptor (TLR) signaling pathway mediates cobalt and chromium (CoCr)-Ps-induced osteolysis. We quantified the expression levels of TLRs, MyD88, RANKL, and inflammatory factors in patients experiencing aseptic loosening after primary total hip arthroplasty (THA) with metal-on-metal (MoM) bearings and hip osteoarthritis (hOA). We observed the in vitro and in vivo levels of RANKL, TLRs, and MyD88 in fibroblasts challenged with CoCr Ps by applying shMyD88 interference lentivirus vectors to block the MyD88-independent TLR pathway. The levels of TLRs, MyD88, RANKL, and inflammatory factors in the revision THA (rTHA) with MoM group were higher than those in the hOA group. Our data collectively revealed that inhibiting MyD88 expression could reduce osteoclastogenesis in vitro and CoCr-Ps-induced osteolysis in vivo. Our findings suggested that osteoclastogenesis is promoted by the CoCr-Ps-induced expression of RANKL in fibroblasts and that MyD88 is a potential target in the treatment of wear Ps-induced osteolysis.

Effects of 1,25-Dihydroxyvitamin D3 on the Prevention of Chronic Obstructive Pulmonary Disease (COPD) in Rats Exposed to Air Pollutant Particles Less than 2.5 Micrometers in Diameter (PM2.5).

BACKGROUND This study aimed to investigate the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on airway changes in chronic obstructive pulmonary disease (COPD) rats exposed to air pollutant particles less than 2.5 micrometers in diameter (PM2.5), and to evaluate the mechanisms. MATERIAL AND METHODS Three groups were included in this study: a normal group, a COPD model group, and a COPD with 1,25(OH)2D3 treatment group. In each group, the rats were divided into four subgroups: control and different doses of PM2.5 (1.6, 8 and 40 mg/kg body weight). Apoptosis in lung tissue was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of c-Jun N-terminal kinase 1 (JNK1) and mucin 5AC (MUC5AC) were detected by real-time polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence staining. RESULTS Compared with corresponding subgroups in normal group, the apoptotic rates in COPD group were significantly increased. By contrast, 1,25(OH)2D3 treatment group significantly reduced COPD-induced apoptosis in lung tissue. Upon the dose increase of PM2.5, the apoptotic rate was also elevated in each group. Compared with the corresponding control in each group, PM2.5 increased apoptosis in a dose-dependent manner. Importantly, 1,25(OH)2D3 also prevented apoptosis in COPD rats exposed to PM2.5. Mechanically, the expression of MUC5AC and JNK1 in COPD group was significantly upregulated, compared with corresponding subgroups in the normal group. Treatment with 1,25(OH)2D3 reduced expression of MUC5AC and JNK1 in COPD rats. It was found that the expression of MUC5AC and JNK1 was elevated with the dose increase of PM2.5 in each group. Consistently, 1,25(OH)2D3 also reduced the expression of MUC5AC and JNK1 in COPD rats exposed to PM2.5. CONCLUSIONS 1,25(OH)2D3 prevented lung injury in COPD rats with or without PM2.5 exposure. Our results suggest that 1,25(OH)2D3 is useful to mitigate the injury caused by COPD.

Design of the Fall-Block Sensing of the Railway Line Pantograph Based on 3D Machine Vision Sensors.

As an important part of the electric locomotive in railway transportation, the sensing and inspection of the pantograph has a significant effect on the safe operation of the train. In general, the pantograph carbon slip detection items include slide wear detection, slip strip crack detection, carbon slip fall-block detection and slip strip wear detection. The emergence and development of structured light measurement technology with 3D sensors provide new technical means for the acquisition of spatial 3D information. The three-dimensional data can not only obtain more information but also reduce the data deviation, thereby improving the measurement accuracy and work efficiency. At present, few studies have been conducted on the slide block and partial wear of the carbon slide. Therefore, this paper studies the detection of the pantograph slide block based on 3D sensor measurement technology. The experimental results indicate that it is feasible to adopt 3D measurement technology to detect the fall-block of the pantograph slide. In addition, a sound detection effect can also be obtained.

Hyperglycemia, p53, and mitochondrial pathway of apoptosis are involved in the susceptibility of diabetic models to ischemic acute kidney injury.

Patients with chronic kidney diseases, including diabetic nephropathy, are more susceptible to acute kidney injury (AKI) and have a worse prognosis following AKI. However, the underlying mechanism is unclear. Here we tested whether diabetic mice were more sensitive to AKI and show that renal ischemia-reperfusion induced significantly more severe AKI and higher mortality in the streptozotocin and Akita diabetic mouse models. The severity of AKI in the mice correlated with their blood glucose levels. In vitro, high glucose-conditioned renal proximal tubular cells showed higher apoptosis and caspase activation following ATP depletion and hypoxic injury, accompanied by a heightened mitochondrial accumulation of Bax and release of cytochrome c. In response to injury, both glucose-conditioned renal proximal tubular cells and diabetic kidney tissues showed markedly higher p53 induction. Suppression of p53 diminished the sensitivity of high glucose-conditioned cells to acute injury in vitro. Moreover, blockade of p53 by pifithrin-α, siRNA, or proximal tubule-targeted gene ablation reduced ischemic AKI in diabetic mice. Insulin reduced blood glucose in diabetic mice and largely attenuated their AKI sensitivity. Thus, our results suggest the involvement of hyperglycemia, p53, and the mitochondrial pathway of apoptosis in the susceptibility of diabetic models to AKI.

Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol trisphosphate receptor signaling.

Intra-articular injection of glucocorticoids (GCs) has been widely used in the management of osteoarthritis and rheumatoid arthritis. Nevertheless, several studies showed that GCs had toxic effects on chondrocytes as well as synovial cells. Previously we reported the protective role of autophagy in the degeneration of meniscal tissues. However, the effects of GCs on autophagy in the meniscal cells have not been fully elucidated. To investigate whether GCs can regulate autophagy in human meniscal cells, the meniscal cells were cultured in vitro and exposed in the presence of dexamethasone. The levels of apoptosis and autophagy were investigated via flow cytometry as well as western blotting analysis. The changes of the aggrecanases were measured using real-time PCR. The role of autophagy in dexamethasone-induced apoptosis was investigated using pharmacological agents and RNA interference technique. An agonist of inositol 1,4,5-trisphosphate receptor (IP3R) was used to investigate the mechanism of dexamethasone-induced autophagy. The results showed that dexamethasone induced autophagy as well as apoptosis in normal human meniscal cells. Using RNA interference technique and pharmacological agents, our results showed that autophagy protected the meniscal cells from dexamethasone-induced apoptosis. Our results also indicated that dexamethasone increased the mRNA levels of aggrecanases. This catabolic effect of dexamethasone was enhanced by 3-MA, the autophagy inhibitor. Furthermore, our results showed that dexamethasone induced autophagy via suppressing the phosphorylation of IP3R. In summary, our results indicated that autophagy protected meniscal cells from GCs-induced apoptosis via inositol trisphosphate receptor signaling.

Total hip arthroplasty with a non-modular conical stem and transverse subtrochanteric osteotomy in treatment of high dislocated hips.

Conventional stems may be unsuitable for hypoplastic femurs associated with severe dysplasia, meanwhile, custom-made or modular stems in total hip arthroplasty are often complex and expensive. This series included 21 Crowe type IV dysplastic hips in which a non-modular cementless conical stem was implanted with transverse subtrochanteric femoral osteotomy. Follow up averaged 40months. Twenty hips survived with mean Harris hip score improved from 52 to 90. One hip failed for stem loosening. The average leg lengthening was 3.8cm with transient sciatic nerve palsy occurring in three hips. Femoral offset averaged 3.3cm postoperatively. The non-modular conical stem not only obviated the complexities, high medical cost and potential risk at the neck-stem interface associated with stem modularity, but also simplified surgical technique.

Effects of PM2.5 on mucus hypersecretion in airway through miR-133b-5p/EGFR/Claudin1/MUC5AC axis.

OBJECTIVE: To investigate the role of the EGFR/MAPK signaling pathway in PM2.5 in promoting the MUC5AC hypersecretion in airway and exacerbating airway inflammation. METHODS: By establishing rat model exposed to PM2.5, overexpressing miR-133b-5p and Claudin1, the content of IL-1 and TNF-α in serum were detected by ELISA, the pathology of lung tissue was observed by HE staining, p-EGFR, Claudin1, MUC5AC, p-ERK1/2, p-JNK, p-p38 in rats lung tissue were detected by immunohistochemical and WB, the expression level of miR-133b-5p in rats lung tissue were detected by qPCR. RESULTS: After the rats were exposed to PM2.5, the content of inflammatory factors in serum increased, the inflammatory damage of lung tissues occurred, the expression of miR-133b-5p was down-regulated, and the expression of MUC5AC protein was increased. The ELISA test results showed that the expression of IL-1 and TNF-α in the model group was significantly higher than that in the control group, and the model +AG1478 treatment group was down-regulated compared with the model group, and the +miR-133b-5p agomir treatment group was significantly lower than that in the control group, the model group and the model +Claudin1 overexpression blank load group, and the model +Claudin1 overexpression group was down-regulated compared with the model group and the model +Claudin1 overexpression blank load group. The protein detection results showed that the expression of p-EGFR, MUC5AC, p-ERK1/2, p-JNK and p-p38 proteins was increased and the expression of Claudin1 protein was decreased in the model group compared with the control group. In the model + AG1478 treatment group, model + miR-133b-5p agomir treatment group and model + Claudin1 overexpression group, compared with the model group, p-EGFR, MUC5AC, p-ERK1/2, p-JNK, p-p38 protein expression was down-regulated, and Claudin1 protein expression was up-regulated. CONCLUSIONS: PM2.5 inhibited the expression of miR-133b-5p to activate the EGFR/MAPK signal pathway, induce the hypersecretion of MUC5AC, thus aggravating PM2.5-related airway inflammation in rats.

Advanced Science and Technology of Polymer Matrix Nanomaterials.

The advanced science and technology of polymer matrix nanomaterials are rapidly developing fields that focus on the synthesis, characterization, and application of nanomaterials in polymer matrices [...].