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OBJECTIVE: Roxadustat is used to treat renal anemia. The renoprotective effect of roxadustat needs to be further confirmed, and the mechanism of action is unknown. This study aims to evaluate the effect and mechanism of roxadustat in hypoxia-related nephropathy with the renal tubular epithelial cell line NRK-52E. MATERIALS AND METHODS: The cell Counting Kit-8 (CCK-8) assay was employed to assess cellular proliferation in the current investigation. Flow cytometry was used to conduct cell apoptosis analysis. The utilization of electron microscopy facilitated the identification of changes in cellular ultrastructure. Immunofluorescence was used to detect the expression trend of hypoxia-inducible factor-1α (HIF-1α). The connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), Smad family member 3 (Smad3), p-Smad3, α-smooth muscle actin (α-SMA), collagen I, and HIF-1α were assessed by western blotting. Real-time fluorescent quantitative PCR (RT-qPCR) was used to measure TGF-β1 and Smad3 mRNA. RESULTS: Significant growth inhibition and increased apoptosis were observed in NRK-52E cells cultured under hypoxic conditions (1% and 5% O2), which can be rescued by roxadustat. From a morphological perspective, it has been observed that roxadustat can counteract cellular damage features produced by hypoxia. These features include the contraction of the nuclear envelope and an increase in the formation of apoptotic bodies. Roxadustat increases HIF-1α expression acutely at 24 h, followed by a gradual reduction of HIF-1α expression to levels significantly below that of the hypoxia group by 72 h. Roxadustat can also inhibit hypoxia-induced increased expression of CTGF, TGF-β1, p-Smad3, α-SMA, collagen I, and HIF-1α. Combined treatment with roxadustat and siRNA against TGF-β1 synergistically reduced the expression of CTGF and HIF-1α, while the effect on TGF-β1 and p-Smad3 were comparable to that of the individual treatment alone. Comparably, the combined administration of roxadustat and siRNA targeting Smad3 had a synergistic impact on diminishing the expression of CTGF. CONCLUSIONS: These findings indicate that roxadustat attenuates experimental renal fibrosis likely by inhibiting the TGF-β1/Smad3 pathways, while its effect on CTGF and HIF-1α may involve other signaling pathways. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. MATERIALS AND METHODS: This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. RESULTS: We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CONCLUSIONS: CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL. [ABSTRACT FROM AUTHOR]

Endoscope-assisted surgery is becoming a preferred technique in salivary gland surgery. However, this technique has not yet been applied in submandibular gland (SMG) preservation surgery. This retrospective study was performed to evaluate the outcomes of endoscope-assisted gland-preserving surgery through a hairline incision in patients with benign SMG tumours. The study included 38 patients with benign SMG tumours who underwent tumour excision with gland preservation: 19 who underwent local excision of the tumour through an endoscope-assisted hairline approach and 19 who received the conventional cervical approach. The feasibility of the surgical procedure, perioperative patient variables, and postoperative appearance and functional outcomes were evaluated. Patients in both groups had their tumours removed successfully with tumour-free margins. The intraoperative blood loss, postoperative amount of drainage, mean length of the incision, and unstimulated saliva flow rate did not differ between the two groups. There was no difference in the stimulated saliva flow rate between the preserved gland and unaffected SMG. The aesthetic result was better in the endoscope-assisted hairline incision group. No tumour recurrence occurred during follow-up (range 12–52 months). Thus, gland-preserving tumour dissection appears to be a safe method for benign SMG tumours, with good functional results. Furthermore, the endoscope-assisted hairline incision is a feasible method with excellent cosmetic results. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of the combined transplantation of a bilateral anterolateral thigh perforator (ALTP) flap for the repair of large-area skin and soft tissue defects of the extremities. PATIENTS AND METHODS: Twelve patients who had received bilateral ALTP flap reconstructions for large-area skin and soft tissue defects of the extremities were retrospectively analyzed. The areas of the skin and soft tissue defects were measured preoperatively (18.0×11.0 - 38.0×15.0 cm2). The wounds were on the forearm, elbow, upper arm, foot, and lower leg. Color Duplex Sonography (CDS) was used to localize the site where the perforator artery of the bilateral thighs penetrated the deep fascia. The selected area was evaluated according to the number of perforating branches and the range of supply. The flap areas and repairable range were further evaluated according to the number of perforating branches detected during the operation to determine whether to retain the deep fascia. It is important to design and adjust the anastomosis of the vascular pedicle according to the specific situation on transfer of the flap to the recipient site. The donor sites of all the patients in the study were closed in the first stage. The amount of bleeding and the blood supply to the flap after vascular anastomosis were evaluated during the operation. The postoperative survival of the flap and complications, such as bleeding, infection, and arteriovenous crisis, were closely monitored. All patients were followed-up at one, three, and six months after surgery to assess their satisfaction with the appearance of the flap transplantation and the recovery of limb function. RESULTS: The bilateral ATLP flaps survived successfully in all 12 cases and all donor sites were closed in the first stage. No post-surgery complications, including hematoma, wound dehiscence, and infection, were observed at the donor sites, resulting in high patient satisfaction. CONCLUSIONS: Combined transplantation of bilateral ALTP flaps can repair large-area skin and soft tissue defects in one stage, which not only reduces the number of operations and hospitalization costs but also reduces the damage to the limbs caused by the cutting of large-area flaps from only one side. The accuracy of the surgery was improved by ultrasound-assisted localization. In summary, combined transplantation of bilateral ALTP is a rational yet effective way to repair large-area skin and soft tissue defects of the extremities. [ABSTRACT FROM AUTHOR]

In order to intercept a highly manoeuvering target with an ideal impact angle in the three-dimensional space, this paper promises to probe into the problem of three-dimensional terminal guidance. With the goal of the highly target acceleration and short terminal guidance time, a guidance law, based on the advanced fast non-singular terminal sliding mode theory, is designed to quickly converge the line-of-sight (LOS) angle and the LOS angular rate within a finite time. In the design process, the target acceleration is regarded as an unknown boundary external disturbance of the guidance system, and the RBF neural network is used to estimate it. In order to improve the estimation accuracy of RBF neural network and accelerate its convergence, the parameters of RBF neural network are adjusted online in real time. At the same time, an adaptive law is designed to compensate the estimation error of the RBF neural network, which improves the convergence speed of the guidance system. Theoretical analysis demonstrates that the state and the sliding manifold of the guidance system converge in finite time. According to Lyapunov theory, the stability of the system can be guaranteed by online adjusting the parameters of RBF neural network and adaptive parameters. The numerical simulation results verify the effectiveness and superiority of the proposed guidance law. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Despite advances in plastic and reconstructive surgery, repairing soft tissue defects of the foot remains a complex surgical challenge when conventional methods cannot cover defects. We presented a case in which a free flap was used for reconstruction and reviewed the literature. PATIENTS AND METHODS: A 75-year-old woman with an acral melanoma history had a large exophytic mass on her right foot. Using PubMed, we found that reconstructive options in the literature include local flaps, fascial flaps, muscle flaps, and free flaps. RESULTS: Melanoma recurred four times at the same site after complete excision of the compound nevi in the present case. Melan A, Vimentin (+), S-100 (+), and HMB-45 positivity were found in immunohistochemical staining and increased Ki-67 proliferation. The defects in soft tissue are repaired using a free anterolateral thigh perforator flap. No complications were raised in the patient. CONCLUSIONS: Foot melanoma is difficult to be resected because it necessitates a wide excision, which can result in large defects. The free flap, in our experience, can easily be performed while preserving function and improving cosmesis. This flap is an appealing option for concealing defects in the distal extremities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the mechanism of action of protein phosphatase 2A (PP2A) in the recovery of spinal cord injury (SCI) in rats by down-regulating matrix metalloproteinase 9 (MMP-9) via the mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: A model of SCI was first successfully established in rats. A total of three groups were set, including: sham operation group (A group), SCI group (B group) and PP2A group (C group). The Basso, Beat-tie and Bresnahan (BBB) motor function score and inclined plane test were adopted to evaluate the motor ability and limb muscle strength of rats in each group. The water content in spinal cord tissues was detected as well. Quantitative Polymerase Chain Reaction (qPCR) assay was performed to analyze the messenger ribo-nucleic acid (mRNA) expression levels of MAPK, MMP-2, and MMP-9 in spinal cord tissues. The expressions of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-iβ (IL-1β) and IL-6 in each group of rats were determined via enzyme-linked immunosorbent assay (ELISA). Western blotting (WB) was employed to measure the protein expression levels of MAPK, MMP-2 and MMP-9 in each group of rats. Additionally, the apoptosis of nerve cells in spinal cord tissues was analyzed through terminal deoxynu-cleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The BBB score was 8.8 points in C group at 5 d after operation, which was significantly different from that in B group (p<0.05). The slope in B and C groups was clearly lower than that in A group at each time point (p<0.001). Meanwhile, it was significantly higher in C group than that in B group at 5, 7 and 9 d (p<0.05). The edema rate rose notably in B group compared with A group (p<0.001). However, spinal cord edema was remarkably relieved after treatment with FRY720 (p<0.01), suggesting that PP2A agonist could treat SCI in rats. The levels of cytokines TNF-α, I L-1β and IL-6 were markedly higher in B group than those in A group (p<0.01). However, they were significantly reduced after treatment with PP2A agonist (p<0.01). In comparison with A group, B group exhibited remarkably decreased mRNA expression of MAPK and elevated mRNA expressions of MMP-2 and MMP-9 (p<0.01). However, C group exhibited an up-regulated mRNA expression of MAPK (p<0.05), a downregulated mRNA expression of MMP-9 (p<0.01), and an undifferentiated mRNA expression of MMP-2 (p>0.05). Compared with B group, the protein expression level of MAPK significantly increased (p<0.05), while that of MMP-9 evidently decreased in C group (p<0.05). Besides, no statistically significant difference was observed in the protein expression level of MMP-2 between C group and B group (p>0.05). Compared with that in A group, the apoptosis rate significantly increased in B group (p<0.001). In addition, the apoptosis rate was significantly lower in C group than that in B group, showing a statistically significant difference (p<0.01). CONCLUSIONS: PP2A downregulates MMP-9 through the MAPK signaling pathway, thereby conducing to the recovery of SCI in rats. [ABSTRACT FROM AUTHOR]

To identify the potential risk factors for bad splits, we calculated the incidence of bad splits from 484 patients with 964 cases of sagittal split ramus osteotomy (SSRO) and investigated the association between the occurrence of bad splits and risk factors such as gender, patients' age, class of occlusion, unimaxillary or bimaxillary surgery, presence of the lower third molar, thickness of the ascending ramus, and the distance from the mandibular canal to the buccal cortical bone. The results showed that 40 sides (4.149%) with bad splits occurred in 36 patients (7.438%). The mean (SD) gap width from the canal to the buccal cortex for the bad split group, at 4.02 (1.20) mm, was narrower (p = 0.003; OR = 0.689; 95% CI = 0.538 to 0.882) than the normal split group 4.80 (1.72) mm. On the contrary, no statistical significance (p > 0.05) was detected between the patients with bad splits and those with normal splits for the other factors. In conclusion, SSRO patients with narrower distances from the mandibular canal to the buccal cortex were more prone to bad splits. More attention should be paid to patients with this risk factor during future surgeries. [ABSTRACT FROM AUTHOR]

The selection and implementation of a plan for maxillary surgery is of the utmost importance in achieving the desired outcome for the patient undergoing two-jaw orthognathic surgery. Some splint-based and splintless methods, accompanied by computer-assisted techniques, are helpful in improving surgical plan implementation. However, randomized controlled trials focused on this procedure are lacking. This study included 61 patients who underwent bimaxillary surgeries. The patients were randomly assigned to a conventional resin occlusal splint (CROS) group, a digital occlusal splint (DOS) group, or a digital templates (DT) group, in a 1:1:1 ratio. The mean linear distance between the planned and actual postoperative positions of eight selected points on the surfaces of the maxillary teeth was selected as the outcome measure. The distance was significantly smaller in the DT group (1.17 ± 0.66 mm) when compared to both the CROS group (2.55 ± 0.95 mm, P < 0.05) and DOS group (2.15 ± 1.12 mm, P < 0.05). However, the difference between the CROS group and DOS group was not statistically significant. These findings indicate that using digital templates results in the best performance in transferring the surgical plan to the operation environment as compared to the other two types of splints. This suggests that the application of digital templates could provide a reliable treatment option. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effects of dexmedetomidine (Dex) treatment administered at various times on acute lung injury (ALI). MATERIALS AND METHODS: Thirty Wistar rats were randomly divided into five groups (n = 6/group). Lipopolysaccharide (LPS) was intraperitoneally injected into the rats in the LPS, Dex1, Dex2, and Dex3 groups to induce ALI, while the control group (C) was left untreated. Rats in the Dex1 group were intraperitoneally administered with 50 µg/kg Dex 30 minutes before modeling. Rats in the Dex2 group were injected with 25 µg/kg Dex 30 minutes before modeling and two hours after. Rats in the Dex3 group received 50 µg/kg Dex two hours after modeling. The animals in the C and LPS groups were given an equal volume of saline. The wet-to-dry (W/D) weight ratio of the rats' lungs was calculated, and pathological alterations in lung tissues were observed. The concentrations of inflammation-related factors and the expression of Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and matrix metallopeptidase 9 (MMP9) were measured. RESULTS: The W/D ratio, expression of inflammatory factors, and expression of JAK1, STAT3, and MMP9 were significantly increased in the ALI rats (p < 0.05) compared with the C group. The level of anti-inflammatory factors in the Dex-treated groups was also significantly increased compared with the LPS group (p < 0.05). The concentration of anti-inflammatory factors in the Dex2 group was significantly higher than that recorded in the Dex1 and Dex3 groups (p < 0.05). CONCLUSIONS: Dex treatment administered at different times protects rats against LPS-induced ALI to varying degrees. The protective effects of Dex were most robust when administered both before and after LPS stimulation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to elucidate the regulatory role of microRNA- 324-5p (miRNA-324-5p) in inhibiting inflammatory response of diabetic vessels by regulating CPT1A level, thus alleviating the development of type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: Arterial vessels (splenic artery) and serum exosomes were extracted from 30 T2DM patients and 30 non-T2DM subjects treated in Binzhou People's Hospital from 2015 to 2019. Relative levels of miRNA-324- 5p and CPT1A in each subject were detected. Then, VSMCs were induced with high-glucose, followed by detection of inflammatory factor levels. Next, the regulatory effects of miRNA-324- 5p and CPT1A on viability, 5-Ethynyl-2'-deoxyuridine (EdU)-positive ratio, and release of inflammatory factors in VSMCs were determined. Finally, Dual-Luciferase reporter assay was conducted to verify the interaction between miRNA- 324-5p and CPT1A. RESULTS: T he r esults r evealed t hat c ompared with non-T2DM subjects, miRNA-324-5p was downregulated in splenic arteries and exosomes in T2DM patients. High-glucose treatment in VSMCs triggered the release of the inflammatory factors. In addition, the overexpression of miRNA-324-5p in VSMCs reduced viability and inflammatory factor levels, and the inhibited trends were partially reversed by overexpression of CPT1A. CPT1A was indicated to be the target gene binding miRNA-324-5p. CONCLUSIONS: MiRNA-324-5p exerts an inhibitory effect on T2DM-induced inflammation in blood vessels by negatively regulating CPT1A level and reducing the release of inflammatory factors. MiRNA-324-5p might be a promising therapeutic target for T2DM. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: Thyroid cancer (TC) is a common malignant tumor of the endocrine system, and its morbidity and mortality are in the high places. Recent studies have focused on exploring biological markers and targeted therapy for TC. This research aims to elucidate the role of LINC00106 in the progression of TC and the regulatory mechanisms. PATIENTS AND METHODS: Differential level of LINC00106 in a downloaded profile containing TC and normal tissues from GEPIA database was analyzed. Subsequently, its level in TC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRTPCR). The relationship between LINC00106 level and clinical data of TC patients was assessed, including age, tumor staging, lymphatic metastasis, and overall survival. After transfection of si-LINC00106, TC cell metastasis was evaluated by wound healing and transwell assay. Relative levels of E-cadherin, N-cadherin, β-catenin, and Vimentin regulated by LINC00106 were determined using qRT-PCR and Western blot. RESULTS: LINC00106 was downregulated in TC tissues than normal ones. Its level was correlated to tumor staging, lymphatic metastasis and overall survival in TC patients. The knockdown of LINC00106 in BCPCP and TPC-1 cells enhanced migratory and invasive abilities and triggered the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: LINC00106 is lowly expressed in TC specimens, which attenuates migratory and invasive abilities in TC by inhibiting EMT as a tumor suppressor. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to investigate the expression characteristics of circular RNA circ_0061140 in bladder cancer (BCa), and to further explore its effects on invasiveness and migration capacity of BCa cells, as well as its possible potential mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRTPCR) was performed to examine the expression level of circ_0061140 in tumor tissue samples and paracancerous ones collected from 42 patients with BCa, and the interplay between circ_0061140 level and the clinical indicators, as well as the prognosis of BCa patients were analyzed. Meanwhile, qRT-PCR was also used to verify circ_0061140 expression in BCa cell lines. In addition, a circ_0061140 knockdown model was constructed using Lentiviral in BCa cell lines, including T24 and 253j, and the effect of circ_0061140 on BCa cell functions and its underlying mechanisms were explored using Cell Counting Kit-8 (CCK-8), transwell, and cell wound healing assays. RESULTS: qPCR results showed that the expression level of circ_0061140 in tumor tissues of BCa patients was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of circ_0061140, patients with high expression of circ_0061140 had worse prognosis and higher incidence of lymph node or distant metastasis. Compared with those in the negative control group, the proliferation and invasion, as well as the metastasis ability of BCa cells in the sh-circ_0061140 group, were remarkably attenuated. In addition, bioinformatics and Luciferase reporter gene assay demonstrated that circ_0061140 can specifically bind to microRNA-1236. At the same time, the results of qPCR revealed that the expression levels of circ_0061140 and microRNA- 1236 were negatively correlated in the tumor tissues of BCa patients. Finally, cell recovery experiment indicated that silencing microRNA- 1236 reversed the impact of the knockdown of circ_0061140 on the ability of BCa cells to proliferate and invade, suggesting that the two may regulate each other. CONCLUSIONS: Circ_0061140 level was found remarkably elevated in BCa tissues, as well as in cell lines, which was closely relevant to the incidence of lymph node or distant metastasis of BCa patients. In addition, circ_0061140 may enhance the proliferation rate and invasion ability of BCa cells through the modulation of microRNA- 1236. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1. PATIENTS AND METHODS: The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development. RESULTS: MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. CONCLUSIONS: MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the molecular mechanism of micro ribonucleic acid- 34a (miR-34a) in promoting the apoptosis of myocardial cells in the rat model of myocardial infarction (MI). MATERIALS AND METHODS: Sprague-Dawley (SD) rats were ligated with a left anterior descending branch to construct the MI model. The rats were randomly divided into four groups: sham operation group (Sham group), MI group, MI + miR-34a inhibitor group (MI + miR-34a antagomir group) and MI + miR-34a inhibitor negative control group (MI + antagomir NC group). Echocardiography (ECG) and magnetic resonance imaging (MRI) were adopted to detect the ejection fraction [EF (%)] and fraction shortening [FS (%)] of SD rats. Polymerase chain reaction (PCR) and Western blotting were used to detect expression levels of the apoptotic marker Caspase-3 and genes in Wnt/β-catenin signaling pathway. Hematoxylin and eosin (H&E) staining was applied to detect cardiac injury. In in vitro experiments, the rat-derived myocardial cell line H9C2 was selected to simulate myocardial ischemia and hypoxia at the time of MI with an anoxic and serum-free injury model. C59, the Wnt/β-catenin signaling pathway inhibitor was applied in MI + miR-34a antagomir + C59 group, and the effect of miR-34a on the apoptosis of myocardial cells through regulating the Wnt/β-catenin pathway was measured with Real-Time quantitative PCR (qPCR) and 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyltetrazolium bromide (MTT) cell activity detection kits, respectively. RESULTS: It was found that after miR-34a antagomir reversed FS (%) and EF (%) in MI rats, the messenger RNA (mRNA) and protein levels of Caspase-3 in Sham group and MI + miR- 34a antagomir group were significantly lower than those in the MI group (p < 0.05), indicating that the addition of miR-34a antagomir inhibited myocardial cell apoptosis after infarction, while the mRNA and protein levels of Wnt/β-catenin were both higher than those in the MI group. Besides, H&E staining proved that miR- 34a reversed the myocardial injury after MI. Similarly, in vitro experiments showed that, compared with those in Hypoxia group, the level of Caspase-3 decreased in Hypoxia + miR-34a inhibitor group and Sham group, while the apoptosis level in Hypoxia + miR-34a inhibitor + C59 group increased (p < 0.05). The results of the MTT assay were consistent with those of PCR. CONCLUSIONS: MiR-34a affects myocardial cell apoptosis by regulating the activation and inactivation of the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was made to investigate and evaluate the safety and carcinogenicity of nitenpyram (NIT) in rats. MATERIALS AND METHODS: A totally 50 male and 50 female SD rats were treated with NIT at 0, 800, 2400, and 7200 ppm, respectively, for 104 w. The growth, clinical signs, and survival rates, as well as the body and organ weights of these animals, were analyzed. Histopathological examination was also performed. RESULTS: Compared with the control group, survival rates at 104 w were significantly decreased in the 7200 ppm dose group, for both the male and female animals. The occurrence of esophageal squamous papilloma (ESP) was significantly increased in the treated animals. The occurrences of ESP for the 0, 800, 2400, and 7200 ppm NIT treatment groups were 0/39, 0/39, 3/35, and 9/27 for the male animals, and 0/43, 0/43, 6/49, and 12/33 for the female animals, respectively. For pre-neoplastic lesion of ESP, the occurrences of esophageal squamous hyperplasia for the 0, 800, 2400 and 7200 ppm NIT treatment groups were 0/39, 1/39, 10/35, and 9/27 for the male animals, and 0/43, 2/43, 15/49, and 17/33 for the female animals, respectively. The basal cell hyperplasia from mild to severe degrees was observed in the treatment groups. CONCLUSIONS: NIT exhibits carcinogenicity of ESP in the male and female rats after the twoyear treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease, whereas its cause still remains elusive. Typical pathological manifestations of RA include persistent synovitis and bone degeneration in the surrounding joints. Although the incidence of RA is high in population, currently there have been no effective cures for it. The purpose of this study is to investigate the therapeutic effects and main mechanism of IKKε (inhibitor of nuclear factor kappa-B kinase ε) in collagen II induced-Rheumatoid Arthritis (CIA) mice model. MATERIALS AND METHODS: IKKε-/- and wild-type (WT) littermate control mice were intraperitoneally injected with 5 mg/kg collagen II monoclonal antibody cocktail (Cab) for 5 days. After that, the nociception threshold and clinical rheumatoid arthritis articular damage score of mice were evaluated. After 5 days-CAb treatment, serum levels of a series of inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and interferon (IFN) were detected with enzyme-linked immunosorbent assay (ELISA) in both groups. Besides, Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) was used to evaluate the expression of these inflammatory cytokines in plantar tissues. In addition, Western blot was performed to investigate the protein levels of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B) signaling pathway. Moreover, WT mice receiving CAb were further applied with or without IKK inhibitor amlexanox (25 mg/kg) to investigate the expression of the above-mentioned inflammatory cytokines. RESULTS: Our work showed that IKKε-/- mice with CIA displayed less nociception and suppressed inflammatory response than WT mice. Meanwhile, the clinical rheumatoid arthritis articular damage scores were significantly decreased in IKKε-/- mice. The levels of TNF-α, IL-1β, IL-6 in serum and plantar tissues in IKKε-/- mice were significantly lower than those in WT mice. Besides, NF-κB expression in IKKε-/- mice was significantly decreased. Similarly, the same phenotype was observed in WT mice administrated with IKKε inhibitor amlexanox as that of IKKε-/- mice, indicating that inflammatory and nociception responses were remarkably decreased than those of the negative controls. CONCLUSIONS: IKKε plays an important role in promoting nociception and inflammatory response in CIA. Our research demonstrated that knockout of IKKε may serve as a new direction for clinical prevention and treatment of rheumatoid arthritis. IKKε inhibitor amlexanox may become a new drug for the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this study, the changes of insulin resistance (IR) and pancreatic β-cell function in GDM patients were observed; changes of CTRP3 level in fasting serum and relationships with plasma glucose (PG) and pancreatic β-cell function were explored at the same time, and the correlation between serum CTRP3 and body mass index (BMI) was preliminarily discussed, providing a new way to identify the pathogenesis of GDM. PATIENTS AND METHODS: Data of women from 24 to 28 weeks of pregnancy were collected. 100 women were selected to form gestational diabetes mellitus (GDM) group and another 100 women were chosen to constitute normal glucose tolerance (NGT) group according to the results of oral glucose tolerance test (OGTT). They were divided into GDM overweight/obesity (GDM + OW) group, GDM non-overweight/obesity (GDM + NW) group, simple overweight (OW) group and normal body weight (NW) group, according to whether the progestational body mass index (BMI) was higher than 24 kg/m2 before pregnancy. General information of all subjects, for example, age, last menstrual period, parity, diet, weight and height, were collected, and blood samples were taken from all subjects for use in detections of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and serum C1q/tumor necrosis factor-related protein-3 (CTRP3). RESULTS: The levels of FPG, 1 h PG, 2 h PG, fasting CP (FCP), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), TG and VLDL-C in the GDM group, were significantly higher than those in the NGT group. TC and LDL-C in the GDM group were greater than those in the NGT group. Compared with that in the NGT group, homeostasis model assessment of β (HOMA-β) index was lower in the GDM group. From the NGT group to the GDM group, FPG, 1 h PG, 2 h PG, FINS and FCP had rising tendencies, and the differences were of statistical significance. Pearson correlation analysis indicated that HOMA-IR was positively correlated with pre-pregnancy BMI, FPG, 2 h PG, FINS, 1 h INS, 2 h INS, FCP, 1 h CP and 2 h CP in the GDM group, HOMA-β was negatively related to FPG. In the NGT group, there was a positive correlation between HOMA-IR and pre-pregnancy BMI. The level of CTRP3 in fasting serum of the GDM group was distinctly lower than that of the NGT group. Pearson correlation analysis revealed that in the GDM group, fasting serum CTRP3 had positive correlations with HOMA-β and HDL-C, but negatively associated with pre-pregnancy BMI, FPG, 1 h PG, 2 h PG, FCP, HOMA-IR, TG and VLDL-C. In the NGT group, the fasting serum CTRP3 was negatively correlated with pre-pregnancy BMI. Multiple linear stepwise regression analysis showed FPG was an independent influencing factor for fasting serum CTRP3. CONCLUSIONS: With the increase of FPG, the progression of GDM IR patients is increased, and pancreatic β-cell function progressively declines. The decrease of CTRP3 level in fasting serum in GDM patients plays a metabolic role in the pathogenesis of GDM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the curative effects of two unilateral puncturation percutaneous vertebroplasty (PVP) for the pain caused by multiple-level osteoporotic vertebral body compression fractures (OVCF) in senile patients. PATIENTS AND METHODS: From June 2008 to November 2014, eighty-nine cases suffering from fresh multiple-level OVCF were randomly divided into experimental group (n=51) and control group (n=38). Patients underwent PVP guided by C-arm fluoroscopy in the prone position. We monitored and recorded the visual analgesic scale (VAS) at pre-operation and 2 days post-operation, operation time, exposure duration, bone cement injection amount and extraosseous cement leakages. RESULTS: PVP procedures were successful in both groups without serious complications. The VAS scores in both two groups at 2 days post-operation were significantly lower than VAS scores at pre-operation (p<0.05). The operation time and exposure duration in the observational group were significantly lower than those in the control group (p<0.05). However, bone cement injection amount and extraosseous cement leakages in the observing group were similar to those in control (p>0.05). CONCLUSIONS: The curative effects of two unilateral puncturation PVPs were satisfactory. However, puncturation method had lower operation time and lower X-ray exposure dose. We concluded that puncturation method was a suitable method to be considered for clinical application. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to explore the role of NF-κB/P65 signaling pathway in postoperative cognitive dysfunction (POCD) after sevoflurane anesthesia. MATERIALS AND METHODS: A total of 120 male Sprague-Dawley (SD) rats were selected and assigned into five groups (24 rats in each group): the control, sevoflurane, sevoflurane + splenectomy, pyrrolidine dithiocarbamate (PDTC, a specific inhibitor of NF-κB), and sevoflurane + splenectomy + PDTC groups. Electrocardiogram (ECoG) and behavior changes of rats were monitored before and after anesthesia/operation. Ionized calcium-binding adapter molecules 1 (Iba-1) in the hippocampal zones were observed by immunofluorescence staining. Blood-brain barrier (BBB) permeability was determined by immunohistochemistry. The mRNA and protein expressions of NF-κB/P65 signaling pathway-related proteins and inflammatory cytokines were detected by qRT-PCR assay and Western blotting. RESULTS: During the anesthesia/operation, the vital signs of rats were stable, but the ECoG in the sevoflurane and sevoflurane + splenectomy groups mainly presented slow waves. The ECoG arousal response in the sevoflurane + splenectomy + PDTC group was observed. At 24 h after the anesthesia/operation, the expressions of NF-κB and P65 in the hippocampal zone, the expressions of IκBα and inflammatory cytokines (IL-1β, IL-6 and TNF-α), the expression of Iba-1 in rat hippocampal dentate gyrus (DG) zone and CA3 zone, and the permeability of BBB were significantly increased and the behavior of rats changed dramatically (all p < 0.05), while PDTC treatments could eliminate these changes induced by the anesthesia/operation (all p < 0.05). No changes were observed in the expressions of NF-κB, P65, IκBα, Iba-1 and inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the permeability of BBB and the behavior of rats in the sevoflurane and the PDTC groups (all p > 0.05). CONCLUSIONS: These results suggest that the inhibition of NF-κB/P65 signaling pathway may relieve POCD after sevoflurane anesthesia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the effects of leptin (LEP) on the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and to explore the mechanism controlling the process. MATERIALS AND METHODS: Respectively cultivated the third-generation hBMSCs with 100 ng/ml bone morphogenetic protein (BMP) culture media containing 320, 160, 80 and 40 ng/ mL LEP, and regular medium. We administered alkaline phosphatase (ALP) dye (on the 7th day) and mineralized nodules alizarin red (on the 21st day) and tested the ALP activity as well as osteocalcin (OCN) level on 7th, 14th, 21st day in each group to establish the best inducing concentration of LEP. 7 days later, we tested bone differentiation related genes expression in the control, 160 ng/mL LEP and 100 ng/mL BMP groups using RT-PCR. RESULTS: The activity of ALP and OCN in the 160 ng/mL LEP group after 7, 14 and 21 days was lower than that of the BMP group but higher than that of other groups. However, LEP significantly promoted the expression of bone differentiation related genes, namely, Cbfal, ALP, COL-I and OCN. CONCLUSIONS: LEP promoted the bone differentiation in hBMSCs by promoting the expression of genes related to bone differentiation. [ABSTRACT FROM AUTHOR]