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BACKGROUND: Teleradiology has become one of the most important approaches to virtual clinical diagnosis; its importance has only grown during the coronavirus 2019 pandemic. In developing countries, asking patients to take photographs of their images using a smartphone can facilitate the process and help keep its costs down. However, the images taken by patients with smartphones often are of poor quality, and there is no regulation or standard instruction about how to use smartphones to take photographs of medical examination images effectively. These problems limit the use of smartphones in remote diagnosis and treatment. QUESTIONS/PURPOSES: To formulate a set of guidelines for the most appropriate and effective use of smartphones to capture images (radiographs, CT images, and MR images), and to determine whether these guidelines are more effectively adopted by patients of differing ages and genders. METHODS: In this prospective study, a set of step-by-step instructions was created with the goal of helping patients take better smartphone photographs of orthopaedic diagnostic images for transfer to telemedicine services. Following the advice of surgeons, experts in smartphone technology, imaging experts, and suggestions from patients, the instructions were modified based on clinical experience and finalized with the goals of simplicity, clarity, and convenience. Potentially eligible patients were older than 18 years, had no cognitive impairment, and used smart phones. Based on that, 256 participants (patients or their relatives and friends) who visited the orthopaedic department of our hospital from June to October 2020 potentially qualified for this study. A total of 11% (29) declined to participate, leaving 89% (227) for analysis here. Their mean age was 36 ± 11 years, 50% were women (113 of 227), and the patient himself/herself represented in 34% (78 of 227) of participants while relatives or friends of patients made up 66% (149 of 227) of the group. In this study, the diagnoses included spinal stenosis (47% [107 of 227]), disc herniation without spinal stenosis (31% [71 of 227]), vertebral fractures (14% [32 of 227]), and other (7% [17 of 227]). Each study participant first took photographs of their original medical images based on their own knowledge of how to use the smartphone camera function; each participant then took pictures of their original images again after receiving our instructional guidance. Three senior spine surgeons (YZ, TQL, TCM) in our hospital analyzed, in a blinded manner, the instructed and uninstructed imaging files based on image clarity (the content of the image is complete, the text information in the image is clearly visible, there is neither reflection nor shadow in the image) and image position (it is not tilted, curled, inverted, or reversed). If either of these conditions was not satisfied, the picture quality was deemed unacceptable; two of three judges' votes determined the outcome. Interobserver reliability with kappa values for the three judges were 0.89 (YZ versus TQL), 0.92 (YZ versus TCM), and 0.90 (TQL versus TCM). RESULTS: In this study, the overall proportion of smartphone medical images deemed satisfactory increased from 40% (91 of 227) for uninstructed participants to 86% (196 of 227) for instructed participants (risk ratio 2.15 [95% CI 1.82 to 2.55]; pi¼œ0.001). The proportion of acceptable-quality images in different age groups improved after instruction, except for in patients aged 51 years or older (3 of 17 uninstructed participants versus 8 of 17 instructed participants; RR 2.67 [95% CI 0.85 to 8.37]; p = 0.07). The proportion of acceptable-quality images in both genders improved after instruction, but there was no difference between the genders. CONCLUSION: We believe our guidelines for patients who wish to take smartphone photographs of their medical images will decrease image transmission cost and facilitate orthopaedic telemedicine consultations. However, it appears that patients older than 50 years are more likely to have difficulty with this approach, and if so, they may benefit from more hands-on assistance from clinic staff or younger relatives or friends. The degree to which our findings are culture-specific should be verified by other studies in other settings, but on the face of it, there is little reason to believe our findings would not generalize to a reasonable degree. Other studies in more heterogeneous populations should also evaluate factors related to levels of educational attainment and wealth differences, but in the meantime, our findings can give clinical teams an idea of which patients may need a little extra assistance. LEVEL OF EVIDENCE: Level II, therapeutic study.

Introduction Blinatumomab, a bi-specific T cell engager (BiTE®) combining the VH and VL domains of two antibodies against human CD19 and CD3, has been approved by U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed or refractory B precursor ALL (r/r B-ALL) for its clinical benefit demonstrated in different clinical trials. Clinical trials have also shown that there are still patients refractory to blinatumomab. It is thus important to understand the resistance mechanisms. Blinatumomab connects patients' autologous T cells and target cells to form immunologic synapse which potently triggers the activation signaling cascades in T cells and guides T cells to recognize and induce perforin/granzyme-mediated lysis of CD19+ B-ALL cells. Previous studies showed blinatumomab-mediated cytotoxicity involves different T cell subpopulations. But response of each T cell subpopulation to blinatumomab treatment remained largely unknown. Methods and Results In this study, we used 10X Genomics based single cell RNA sequencing to analyze the transcriptome of single T cells before and after blinatumomab treatment. First, ex vivo blinatumomab cytotoxicity model was established, in which healthy PBMCs were used as effector cells and cocultured with target cells (RS4;11 cells or SUP-B15 cells) at an effector-to-target cell ratio of 10:1 with 0.1 ng/mL blinatumomab. Then, PBMCs and BMMCs from 2 B-ALL patients were cultured with 10 ng/mL blinatumomab. Cells from both ex vivo model and patient samples were sequenced using 10X Genomics platform. In total, transcriptome of 17920 single T cells from the ex vivo model and 2271 single T cells from patient sample were analyzed. Based on T cell trajectory analysis, we identified four distinct populations of blinatumomab-activated T cells, which were derived from CD8+ effector memory T (TEM) cells, CD4+ central memory (TCM) cells, naïve T cells and Tregs, respectively. The differentially expressed genes in activated clusters were analyzed to reflect T cell activation mechanisms. The result showed blinatumomab induced the upregulation of aerobic glycolysis pathway (PKM, PGAM1, ENO1, GAPDH and LDHA), cytoskeleton dynamics pathway (ACTD1, ACTB, NME1 and TUBA1B), IFN-responsive pathway (GBP1, PSME2, WARS, CXCL10 and STAT1), and the upregulation of well-known immune-related genes (TNFRSF4, TNFRSF18, LAG3, CD69, IL2RA, MIR155HG, BATF, SH2D2A, LTA, NFKBIA and NDFIP2). We found blinatumomab-activated CD8+ TEM cells showed stronger cytotoxic capability than other activated populations with specific production of cytotoxic factors (PRF1, IFNG and FASLG) and cytokines (CCL2, CCL3, CCL3L1, CCL4, CCL4L2, CCL8, XCL1, XCL2, TNFSF9 and TNFSF14). Last, differential gene expression analysis revealed that co-stimulatory (TNFRSF4,TNFRSF9 and TNFRSF18) and co-inhibitory receptors (LAG3 and TIGIT) were similarly up-regulated in clusters activated from memory and naïve T cells, indicating ligand dependent T cell functional outcomes induced by blinatumomab. Conclusion In summary, we used single cell sequencing to map the blinatumomab-mediated T cell activation state transition and reveal the molecular changes in different T cell subpopulations. Memory T cells, naïve T cells and Tregs were identified functional populations after blinatumomab treatment. CD8+ TEM accounted for the majority of blinatumomab-induced cytotoxicity. Furthermore, T cell co-regulatory receptors were identified as potential targets accountable for blinatumomab sensitivity or resistance mechanisms. The study demonstrated that the collected cellular transcriptional profiles can serve as resource to explore novel strategies to enhance the efficacy of blinatumomab. Disclosures Yin: Amgen: Employment. Huo:Amgen: Employment. Sheng:Amgen: Employment. Li:Amgen: Employment. Ellwanger:Amgen: Employment. Lu:Amgen: Employment. Homann:Amgen: Employment. Wang:Amgen: Employment. Ren:Ruijin hospital: Employment.

The phenotypic transformation of hepatic myofibroblasts (MFs) is involved in the whole process of the progression and regression of liver fibrosis. Notch signaling has been demonstrated to modulate the fibrosis. In this study, we found that Notch signaling in MFs was overactivated and suppressed with the progression and regression of hepatic fibrosis respectively, by detecting Notch signaling readouts in MFs. Moreover, we inactivated Notch signaling specifically in MFs with Sm22αCreER-RBPjflox/flox mice (RBPjMF-KO), and identified that MFs-specific down-regulation of Notch signaling significantly alleviated CCl4-induced liver fibrosis during the progression and regression. During the progression of liver fibrosis, MFs-specific blockade of Notch signaling inhibited the activation of HSCs to MFs and increases the expression of MMPs to reduce the deposition of ECM. During the regression of fibrosis, blocking Notch signaling in MFs increased the expression of HGF to promote proliferation in hepatocytes and up-regulated the expression of pro-apoptotic factors, Ngfr and Septin4, to induce apoptosis of MFs, thereby accelerating the reversal of fibrosis. Collectively, the MFs-specific disruption of Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression, which suggests a promising therapeutic strategy for liver fibrosis.

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLR(W483X) in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.

Objective To investigate the efficiency of anterior decompression on the proximal‐type cervical spondylotic amyotrophy patients. Methods This was a retrospective analysis. From January 2014 to November 2017, 21 patients with proximal‐type cervical spondylotic amyotrophy (CSA) underwent anterior decompression. There were 15 males and 6 females, aged 35–73 years with an average of 51.62 years. All the patients underwent surgery of anterior decompression (ACDF or ACCF). Among them, 12 patients underwent C4/5 single level ACDF, eight patients underwent C4/5 and C5/6 double level ACDF, and one patient underwent C5 anterior cervical corpectomy decompression and fusion surgery. Preoperative and postoperative clinical and radiologic parameters were assessed. The clinical examinations were reviewed, including muscle strength, neck disability index (NDI) score, cervical Japanese Orthopaedic Association (JOA) score, and improvement rate of manual muscle test (MMT) at the last follow‐up. Preoperative spinal cord or nerve impingement was assessed by magnetic resonance imaging (MRI) or computed tomography (CT) myelography. Postoperative lateral X‐ray radiographs were performed every 3 months after the surgery. Results Severe preoperative muscle atrophy of the deltoid or biceps muscles occurred in 21 patients included in the study. All of them involve impingements of the ventral nerve root and/or the anterior horn according to MRI and CT myelography. The preoperative duration of symptoms averaged 8.4 months. The average follow‐up for all patients was 13.2 months. At the final follow‐up, all patients showed statistically significant improvements in muscle strength and NDI scores (P

BackgroundDesigning combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.MethodsWe here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells. Then, selective coinhibitors of NF-κB and c-JUN were tested demonstrating similar synergistic antiproliferation activity.ResultsConsistent with in vivo experiments of zebrafish, coinhibitors were found to significantly reduce tumor growth by 79% and metastasis by 96% compared to blank control, accompanied by anti-angiogenic activity. In an analysis of 365 HCC individuals, the low expression group showed significantly lower malignancies and better prognosis, with the median survival time increased from 67 to 213%, compared to the rest of the groups.ConclusionTogether, NF-κB and c-JUN were identified as promising synergistic inducers in developing anti-HCC therapies. Also, our method may provide a feasible strategy to explore new targeting space from natural compounds, opening opportunities for the rational design of combinational formulations in combatting malignant cancers.

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice.

This review aims to compile recent advances regarding the significance of Notch signaling in different types of intrahepatic cells during liver injury and repair. The functions of Notch signaling in regulating cell development, fate decisions, and organ homeostasis have been widely acknowledged. Notch is also expressed and activated in hepatocytes, macrophages, liver sinusoidal endothelial cells, endothelial progenitor cells, and hepatic progenitor cells during the process of development, injury, inflammation, fibrosis, and carcinoma. During acute/chronic liver injury, Notch interacts with many signaling pathways that are involved in liver repair. Recent research, including ours, has confirmed the crucial role of Notch signaling in modulating the function of diverse intrahepatic cells during liver injury and reconstruction. Thus, Notch signaling may serve as a potential therapeutic target for liver diseases. Key words: hepatocytes; liver injury; liver sinusoidal endothelial cells; macrophages; Notch signaling

Signaling through interleukin (IL)-7 is essential and required for development, differentiation, proliferation, and homeostasis of T cells. However, the role of IL-7 in regulation of CD4+ T cells in chronic viral infections was not fully elucidated. Thus, the aim of the current study was to investigate the immunomodulatory activity of IL-7 to T follicular helper (Tfh) cells and its contribution to pathogenesis of chronic HCV, hepatitis C virus (HCV) infection. A total of 47 patients with chronic hepatitis C and 19 normal controls were enrolled. Serum IL-7 and proportion of Tfh cells was measured. The regulatory function of IL-7 to Tfh cells was also investigated in CD4+ T cells and CD4+ T/HCVcc-infected Huh7.5 cell cocultured system. Serum IL-7 concentration was significantly downregulated in patients with chronic hepatitis C, and was negatively correlated with HCV RNA level. Tfh frequency and Tfh-associated cytokines (IL-21 and IL-6) were also reduced in chronic HCV-infected patients. Moreover, recombinant IL-7 stimulation elevated proportion of Tfh cells and IL-21/IL-6 secretion in both HCV-specific and nonspecific manners. Furthermore, IL-7-treated CD4+ T cells exhibited elevated antiviral activities without killing infected hepatocytes, which presented as inhibition of HCV RNA, induction of antiviral proteins, and promotion of cytokine production (especially IL-21) in cocultured system. This process might be dependent on IL-6 secretion. The current data revealed that IL-7 regulated HCV-specific and nonspecific activated Tfh cells, which might contribute to viral clearance. IL-7 could be a potential therapeutic agent for the treatment of chronic hepatitis C.

Tantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated the healing and fusion efficacy of this scaffold in lumbar vertebral defects after corpectomy in rabbits. The results showed that BMSCs on the surface of the Ta-coated Ti scaffolds proliferated better than BMSCs on Ti scaffolds. Histomorphometry showed better bone formation when using Ta-coated TEAVBs than that with Ti TEAVBs at both 8 and 12 weeks after implantation. In addition, the vertical and rotational stiffness results showed that, compared with uncoated TEAVBs, Ta-coated TEAVBs enhanced rabbit lumbar vertebral defect repair. Our findings demonstrate that Ta-coated TEAVBs have better healing and fusion efficacy than Ti TEAVBs in rabbit lumbar vertebral defects, which indicates their good prospects for clinical application.

Background Embolization of thrombus fragments in new or downstream vascular territories is a potential adverse event in neurothrombectomy, requiring additional repeated thrombectomy attempts. This study aims to describe technical results of the thrombectomy with clamping embolus technique (TCET) method in acute ischemic stroke. This study also aims to evaluate the efficiency of mechanical thrombectomy by TCET, and to compare it with conventional stent retriever thrombectomy (CSRT). Materials and Methods A retrospective analysis was performed in 52 consecutive patients treated between January 2015 and October 2016 for intracranial large vessel occlusion by stent retriever thrombectomy. Recanalization rates, procedure durations, and thrombectomy attempts were compared between the TCET and the CSRT groups. Results Successful recanalization (thrombolysis in cerebral infarction [TICI] 2b or 3) with TCET was achieved in 91.7% (22 of 24) versus 92.9% (26 of 28) in the CSRT group (P = .921). To preserve the restored patency of severely affected atherosclerotic intracranial vessels, 7 and 8 patients received angioplasty or stenting in the TCET and CSRT groups, respectively. In embolic cases, the number of thrombectomy attempts with TCET was significantly lower than that obtained with CSRT (1.7 ± .2 versus 2.6 ± .5, respectively; P = .001); the one-pass thrombectomy rate was significantly higher in the TCET group than in the CSRT-treated patients (58.8% versus 25.0%, respectively; P = .014). Procedure duration was significantly shorter by TCET than by CSRT (35.8 ± 5.8 minutes versus 55.5 ± 7.2 minutes, respectively; P = .001). Conclusions The efficiency of mechanical thrombectomy by TCET in acute ischemic stroke might be improved compared with CSRT.

Background4-1BB (CD137) is a co-stimulatory receptor that stimulates the function of multiple immune cells. Its ability to induce potent anti-tumor activity makes 4-1BB an attractive target for immuno-oncology. However, clinical development of a monospecific 4-1BB agonistic antibody has been hampered by dose-limiting hepatic toxicities. To minimize systemic toxicities, we have developed a novel Claudin18.2 (CLDN18.2) x 4-1BB bispecific antibody, TJ-CD4B (ABL111) that stimulates 4-1BB pathway only when it engages with Claudin 18.2, a tumor-associated antigen specifically expressed in gastrointestinal cancers. TJ-CD4B (ABL111) is now being evaluated in patients with advanced solid tumors in a first-in-human trial (NCT04900818).MethodsTJ-CD4B (ABL111) was evaluated in vivo using the human 4-1BB knock-in mice bearing CLDN18.2 expressing MC38 tumor cells. Pharmacodynamic effects upon treatment were characterized in tumor tissue and blood. Immunophenotyping of the tumor microenvironment (TME) and peripheral blood was performed by flow cytometry. Soluble biomarkers were measured using Luminex-based multiplex assay. In-depth gene expression analysis was performed on primary human CD8+ T cells that were co-cultured with CLDN18.2 expressing cells in the presence of anti-CD3 using NanoString nCounter®. Pharmacokinetic (PK) and toxicity study were performed in cynomolgus monkeys.ResultsTJ-CD4B (ABL111) elicited complete tumor regression in 13 out of 18 MC38 tumor bearing mice given at a dose above 2 mg/kg. Dose-dependent anti-tumor activity was associated with enhanced T cell activation in TME and expansion of memory T cells in the peripheral blood. Increased CD8+ T cells number and proliferation were observed in both tumor nest and surrounding stroma while the level of soluble 4-1BB in the serum was also elevated in response to the treatment. In vitro gene expression analysis by Nanostring revealed TJ-CD4B(ABL111) effectively activated immune pathways characterized by IFN?-signaling and T cell inflammation. Preclinically, TJ-CD4B was well tolerated at the repeated doses up to 100 mg/kg/wk in cynomolgus monkeys without the adverse influence on the liver function which is generally affected by 4-1BB activation. Besides, no cytokine release or immune activation was observed in the periphery.ConclusionsTJ-CD4B (ABL111) is a novel CLDN18.2 dependent 4-1BB bispecific agonist antibody that induced T cell activation and memory response in tumor with CLDN18.2 expression, leading to a strong anti-tumor activity in vivo. TJ-CD4B did not induce systemic immune response nor hepatic toxicity due to the CLDN18.2 dependent 4-1BB stimulation. These data warrant the current clinical development in phase I trial to validate the safety properties and tumor specific responses.

Aim of Study: Results on the association of Vitamin D receptor (VDR) gene polymorphism with renal cell carcinoma (RCC) susceptibility from the present reports are still debating. This meta-analysis was conducted to assess the association of VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphisms with RCC risk. Materials and Methods: The association studies were recruited from PubMed on May 1, 2016, and eligible reports were extracted and data were synthesized using meta-analysis method. Result: Six investigations were included into this meta-analysis for the relationship between VDR gene polymorphism and RCC susceptibility. In this meta-analysis, the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, VDR BsmI and TaqI gene polymorphisms were not associated with the RCC risk in Asians, Caucasians, and overall populations. Furthermore, Fok1 gene polymorphism was not associated with the RCC risk in Caucasians and overall populations. Conclusion: ApaI gene polymorphism and Fok1 FF genotype were associated with RCC susceptibility in Asians.

Cervical MRI is the standard diagnostic imaging technique for patients with cervical myelopathy. However, the utility of conventional cervical MRI as a predictive biomarker for surgical recovery remains unclear, partly because of the limited information obtained from this anatomically small area. Brain resting-state functional MRI (rs-fMRI) may help identify candidate predictive biomarkers. Two analytical methods that assess local spontaneous brain activity are widely used for rs-fMRI: functional connectivity between two brain regions and amplitude of low-frequency fluctuation (ALFF). In our previous analysis of functional connectivity, we discovered that brain functional connectivity may be a predictive biomarker for neurologic recovery in patients with cervical myelopathy; however, the functional connectivity analysis identified a correlation with only one clinical outcome (the 10-second test). To establish a comprehensive prediction measure, we need to explore other brain biomarkers that can predict recovery of other clinical outcomes in patients with cervical myelopathy.We aimed to (1) elucidate preoperative ALFF alterations in patients with cervical myelopathy and how ALFF changes after surgery, with a focus on postoperative normalization and (2) establish a predictive model using preoperative ALFF by investigating the correlation between preoperative ALFF and postoperative clinical recovery in patients with cervical myelopathy.Between August 2015 and June 2017, we treated 40 patients with cervical myelopathy. Thirty patients met our prespecified inclusion criteria, all were invited to participate, and 28 patients opted to do so (93%; 14 men and 14 women; mean age: 67 years). The 28 patients and 28 age- and sex-matched controls underwent rs-fMRI (twice for patients with cervical myelopathy: before and 6 months after cervical decompression surgery). We analyzed the same study population that was used in our earlier study investigating functional connectivity. Controls had none of the following abnormalities: neck or arm pain, visual or auditory disorders, cognitive disorder, structural brain disorder, a history of brain surgery, mental and neurologic disorders, and medications for the central nervous system. We performed ALFF comparisons between preoperative patients with cervical myelopathy and controls, analyzed postoperative ALFF changes in patients with cervical myelopathy, and performed a correlation analysis between preoperative ALFF and clinical recovery in these patients. Clinical outcomes in the cervical myelopathy group were assessed using the 10-second test, the Japanese Orthopaedic Association upper-extremity motor (JOA-UEM) score, JOA upper-extremity sensory score (JOA-UES), and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire for upper-extremity function (JOACMEQ-UEF) score before and 6 months after surgery, which is when we believe these scores generally reach a plateau. A total of 93% of those enrolled (26 of 28 patients) were analyzed both preoperatively and postoperatively; the other two were lost to follow-up.The cervical myelopathy group had an increase in ALFF in the bilateral primary sensorimotor cortices (right, cluster size = 850 voxels, t-value = 6.10; left, cluster size = 370 voxels, t-value = 4.84) and left visual cortex (cluster size = 556 voxels, t-value = 4.21) compared with the control group. The cervical myelopathy group had a decrease in ALFF in the bilateral posterior supramarginal gyrus (right, cluster size = 222 voxels, t-value = 5.09; left, cluster size = 436 voxels, t-value = 5.28). After surgery, the bilateral sensorimotor cortices (right, cluster size = 468 voxels, t-value = 6.74; left, cluster size = 167 voxels, t-value = 5.40) and left visual cortex (cluster size = 3748 voxels, t-value = 6.66) showed decreased ALFF compared with preoperative ALFF, indicating postoperative normalization of spontaneous brain activities in these regions. However, the bilateral posterior supramarginal gyrus did not show an increase in ALFF postoperatively, although ALFF in this region decreased preoperatively. Greater levels of ALFF at the left and right frontal pole and left pars opercularis of the inferior frontal gyrus before surgery in the cervical myelopathy group were correlated with larger improvements in the JOACMEQ-UEF score 6 months after surgery (r = 0.784; p0.001, r = 0.734; p0.001 and r = 0.770, respectively; p0.001). The prediction formula, based on preoperative ALFF values in the left frontal pole, was as follows: the predicted postoperative improvement in the JOACMEQ-UEF score = 34.6 × preoperative ALFF value - 7.0 (r = 0.614; p0.001).Our findings suggest that preoperative ALFF may be a biomarker for postoperative recovery in that it predicted postoperative JOACMEQ-UEF scores. To establish a comprehensive prediction measure for neurologic recovery in patients with cervical myelopathy, a multicenter study is underway.Level II, diagnostic study.

Increasing number of studies have shown growing incidence of lumbosacral tuberculosis and its complications. However, the treatment options for this disorder are still limited. To evaluate the long-term therapeutic effect and prognosis of minimally invasive puncture catheter drainage and Isoniazid local chemotherapy for the treatment of lumbosacral tuberculosis without neural symptoms under the guidance of computed tomography (CT). A total of 45 patients with asymptomatic lumbosacral tuberculosis were treated by minimally invasive catheter drainage under CT guidance. Forty-two cases had been followed up, which included 22 women and 20 men with an average age of 36.45 years old. Isoniazid was injected locally and antituberculotic drugs were administered for postoperative treatment. Oswestry Disability Index (ODI), visual analogue scale (VAS) evaluation and Cobb angle were recorded before and after operation. Forty-two patients had been followed up and the follow-up term was from 1.2 to 8.5 years (average 60 months). All patients were healed without recurrent cases. The ODI were improved from 14.86 ± 2.02 before operation to 1.48 ± 1.55 after operation. The post-operative (4.19 ± 1.17) VAS score was improved compared to the pre-operative VAS score (0.55 ± 0.55). The post-operative Cobb angle (6.19° ± 3.85°) was also improved relatively to the preoperative Cobb angle (5.90° ± 3.71°). Minimally invasive puncture catheter drainage combined with Isoniazid local chemotherapy is an effective method for lumbosacral tuberculosis without neural symptom. Meanwhile, it can be applied for the treatment of spinal tuberculosis before open surgery.

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p

To build a mathematical model which could calculate the desired laminoplasty opening size (LOS) based on the target sagittal canal diameter (SCD) before single-door cervical laminoplasty (SDCL) when taking the effects of surgery drill into consideration. The model was based on geometric analysis on deformation of spinal canal; the formula was derived and characterized as: y (mm) = 2 $$ \overline{\text{CD}} $$ × sin(β/2) = c − d (y is the size of LOS, $$ \overline{\text{CD}} $$ the size of transverse canal diameter, β the size of laminoplasty opening size, c the size of mini-plate and d the diameter of the drill bit used during the surgery operation). The parameters of pre- and postoperative computed tomography scans of 20 patients who had undergone SDCL were measured by the picture archiving and communication system (PACS) software and a new instrument named as Lei’s ruler, respectively. The effects of surgery SDCL were very significant; for each patient, the SCD was enlarged dramatically after the surgery (P 0.05). According to the derived formula, the 95% confidence intervals of SCD after the surgery were within the range of 14 mm and 14.5 mm. Applying the mathematical model and derived formula, the desired LOS could be calculated according to the target SCD which could help the surgeon select an optimum mini-plate before SDCL. At the same time, a new measuring device named Lei’s ruler is designed for the convenience of the derived formula. These slides can be retrieved under Electronic Supplementary Material.

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit‑8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH‑knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth‑ and apoptosis‑associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c‑Myc, proliferating cell nuclear antigen and B‑cell lymphoma 2 (Bcl‑2) protein in HCT116 cells, and the expression of p53 and Bcl‑2‑associated X protein was significantly increased compared with the negative control shRNA group (P

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.

Objective To evaluate the effectiveness of micro-clamping stent-retriever thrombectomy (MSRT) in patients with acute ischemic stroke with intracranial large vessel embolism (ILVE), and compare it with that of conventional stent-retriever thrombectomy (CSRT). Methods We retrospectively evaluated 108 patients with ILVA treated by MSRT (n = 52) or CSRT (n = 56) from the 2 participating institutions between January 2016 and November 2017. The rates of successful (Modified Thrombolysis in Cerebral Infarction [mTICI] grade 2b or 3) and complete reperfusion (mTICI grade 3), time from guide catheter placement to reperfusion, rates of first-pass success, and the number of passes for reperfusion were compared between the MSRT and CSRT groups. Results The complete reperfusion (mTICI 3) rates by MSRT were significantly higher than those achieved with CSRT (78.8% [41/52] vs. 57.1% [32/56], respectively; P = 0.016). Successful reperfusion (mTICI 2b or 3) rates were 92.3% (48/52) in the MSRT group and 83.9% (47/56) in the CSRT groups (P = 0.181). The mean number of passes for reperfusion was significantly lower with MSRT compared with CSRT (1.5 ± 0.2 vs. 2.5 ± 0.5, respectively; P = 0.001). The first-pass success rates were significantly higher in the MSRT group than in the CSRT group (65.4% [34/52] vs. 28.6% [16/56]; P = 0.0001). The mean time from guide catheter placement to reperfusion was significantly shorter in the MSRT group (20.5 ± 6.6 minutes vs. 46.3 ± 7.6 minutes; P = 0.001). Conclusions These findings suggest that the complete reperfusion rates and mechanical thrombectomy efficiency in patients with ILVE are better after MSRT compared with CSRT.

Chitosan coated porous titanium alloy implant (CTI) is demonstrated a promising approach to improve osseointegration capacity of pure porous titanium alloy implant (TI). Since chitosan has been demonstrated to exhibit antioxidant activity, we propose CTI may ameliorate the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. Primary rat osteoblasts incubated on the TI and the CTI were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + LY294002 (a PI3K/AKT-specific inhibitor). In vivo study was performed on diabetic sheep implanted with TI or CTI into the bone defects on crista iliaca. Results showed that diabetes-induced ROS overproduction led to osteoblast dysfunction and apoptosis, concomitant with the inhibition of AKT in osteoblasts on the TI substrate. While CTI stimulated AKT phosphorylation through ROS attenuation, thus reversed osteoblast dysfunction evidenced by improved osteoblast adhesion, increased proliferation and ALP activity, and decreased cytotoxicity and apoptotic rate, which exerted same effect to NAC treatment on the TI. These effects were further confirmed by the improved osseointegration within the CTI in vivo evidenced by Micro-CT and histological examinations. In addition, the aforementioned promotive effects afforded by CTI were abolished by blocking PI3K/AKT pathway with addition of LY294002. These results demonstrate that the chitosan coating markedly ameliorates diabetes-induced impaired bio-performance of TI via ROS-mediated reactivation of PI3K/AKT pathway, which elicits a new surface functionalization strategy for better clinical performance of titanium implant in diabetic patients.

Generalized anxiety disorder (GAD) is common in patients with asthma. High levels of GAD may lead both to exacerbation of the condition and poor management. However, the physiological mechanisms of GAD in asthma patient is unclear. This study investigated the associations between the diurnal rhythm of sputum cytokines, salivary cortisol, α-amylase and GAD in asthma patients. Patients with co-morbid GAD and asthma showed higher sputum IL-1 AUC, sputum IL-6 AUC and sAA AUC. And there were positive correlations between Hamilton anxiety scale (HAMA) scores and sputum IL-1 AUC concentrations (r=0.37, P=0.002), HAMA scores and sputum IL-6 AUC (r=0.56, P

Notch signaling enhanced the response of interleukin (IL)-22-producing CD4+ T cells that were defined as T helper 22 (Th22) cells, and Notch-aryl hydrocarbon receptor (AhR)-IL-22 axis fine-tuned inflammatory response. Previous studies have demonstrated that both Notch signaling and Th22 cells took part in the pathogenesis of chronic hepatitis C virus (HCV) infection. Thus, in this study, we aimed at examining the regulatory role of Notch signaling in Th22 cells in HCV infection. A total of 59 patients with chronic hepatitis C and 22 normal controls (NCs) were enrolled in this study. The percentage of Th22 cells and mRNA expression of related transcriptional factors and cytokines were analyzed in response to γ-secretase inhibitor. Th22 cell frequency was significantly elevated in chronic hepatitis C in comparison with that in NCs. Inhibition of Notch signaling downregulated HCV-specific Th22 cells and IL-22 production, which was accompanied by the reduction of AhR and modulatory cytokines (IL-6 and tumor necrosis factor-α). Moreover, the suppression of Notch signaling also decreased the IL-22-mediated antimicrobial response in both normal and HCV-infected HepG2 cells/Huh7.5 cells. This process was also accompanied by the depression of signal transducers and activators of transcription 3 signaling. In conclusion, the current results suggested that Notch signaling acted as a critical pathway in determining the response to IL-22 in chronic hepatitis C. Thus, Notch-Th22 axis might be considered a new therapeutic target for HCV-infected patients.

Objective This study aimed to investigate the correlation between the functional magnetic resonance imaging (fMRI) pattern and the motor function recovery of an affected limb during the passive movement of the affected limb at an early stage of the striatocapsular infarction (SCI). Methods A total of 17 patients with an acute stage of SCI and 3 healthy volunteers as controls were included in this study. fMRI scans of passive movement were performed on the affected limbs of stroke patients within 1 week of onset. Follow-ups were carried out for the motor functions of the affected limbs (before fMRI scan, 1 month, and 3 months after the scan). Results The control group showed that the activation was mainly located in the contralateral sensorimotor cortex (SMC) and the bilateral supplementary motor area (SMA). The fMRI scan region of interest for stroke patients can be divided into 3 types: type I includes mainly the affected side, bilateral SMC, and SMA with activation; type II includes SMC on the affected side and SMA with activation; type III includes only SMC on the affected side or M1 with activation. The recovery of type I patients was better and faster, while the recovery of type II patients was better but slower, but recovery of type III patients was poorer and slower. Conclusions Multiple cortical activation patterns were noted during the passive movement of the affected limbs at an early stage of SCI, and a correlation was found between the different activation patterns and the clinical prognosis of patients.

Six purple corn grains were chosen to investigate their antioxidant activities and the relationships between anthocyanins and phenolics contents with antioxidant activities. Purple grains were screened for their antioxidant potentials using various in-vitro models such as superoxide anion radical scavenging activity and reducing power at various concentrations. The result showed that ZS39 and FS11 exhibited the highest anthocyanins and total phenolics contents. ZS39 and FS11 also exhibited the highest superoxide anion radical scavenging activity. There was no significant difference among the reducing power of six different purple corn grain extracts. It was found that there were positive correlations between anthocyanins and superoxide anion radical scavenging activity or reducing power, R2=0.9911, R2=0.9873, respectively. Whereas the correlations between total phenolics and superoxide anion radical scavenging activity or reducing power, R2=0.9863, R2=0.9826, respectively. It suggested that purple corn appeared to be a rich and interesting source of natural antioxidants.

Background Non-bronchial systemic arteries can be a significant source of massive hemoptysis in patients with marked pleural involvement. However, in some cases without pleural involvement, the pulmonary ligament artery (PLA) can also enter the abnormal lung parenchyma and be responsible for hemoptysis. Purpose To discuss the factors influencing the development of a blood supply from the PLA in patients with hemoptysis. Material and Methods Seventy-five consecutive patients who underwent bronchial artery embolization (BAE) for massive hemoptysis were evaluated between January 2006 and December 2011 retrospectively. Selective arteriography showed an enlarged and tortuous PLA in five patients. CT was done to determine the site and extent of the underlying diseases before BAE in all patients. Angiographic and CT images were analyzed to determine if there was a relationship between PLA supply and location of the underlying disease or mediastinal pleural involvement. Results The underlying lesions of six patients involved the basal segments of the lower lobe without marked mediastinal pleural thickening or adhesion, but diaphragmatic and lateral pleural thickening was observed in one case. Of these six patients, the PLA supplied blood to the lesions related to the hemoptysis in five patients. No patient with massive hemoptysis whose underlying lesions involved other segments of lung had a PLA supplying the lesions. Conclusion Even though pleural involvement is absent, underlying lesions involving the basal segments of the lower lobe could be a good indicator that the PLA is the cause of bleeding in patients with massive hemoptysis.

The peptide angiotensin IV (Ang IV) is a derivative of angiotensin II. While insulin regulated amino peptidase (IRAP) has been proposed as a potential receptor for Ang IV, the signalling pathways of Ang IV through IRAP remain elusive. We applied high-resolution mass spectrometry to perform a systemic quantitative phosphoproteome of Neura-2A (N2A) cells treated with and without Ang IV using sta ble-isotope labeling by amino acids in cell culture (SILAC), and identified a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1 (PP1) upon Ang IV treatment. In addition, spinophilin (spn), a PP1 regulatory protein that plays important functions in the neural system, was expressed at higher levels. Immunoblotting revealed decreased phosphorylation of p70S6 kinase (p70(S6K)) and the major cell cycle modulator retinoblastoma protein (pRB). These changes are consistent with an observed decrease in cell proliferation. Taken together, our study suggests that Ang IV functions via regulating the activity of PP1.

The preparation and storage of photonic entanglement are central to the achievement of scalable linear optical quantum computation (LOQC). The most widely used photonic entanglement source (a spontaneous parametric downconversion (SPDC) source) is not directly suitable for storage, because its working frequency bandwidth is significantly larger than any available quantum memory. To remedy this problem, cavity-enhanced narrow-band SPDC sources have been developed. However, the storage of cavity-enhanced narrow-band entangled photons has not yet been achieved. Also, the spectral correlations between the entangled photons can make them practically useless for scalable LOQC. Here, we report the preparation and storage of frequency-uncorrelated narrowband (5 MHz) entangled photons from a cavity-enhanced SPDC source. The frequency correlation between the entangled photons is eliminated by changing the continuous UV pumping beam to short pulses. The storage of the polarization state of a single photon, and of a photon entangled with another flying in the fibre, is demonstrated. Our work demonstrates a quantum interface between narrow-band entangled photons from cavity SPDC and atomic quantum memory, and thus provides an important tool towards the achievement of all-optical quantum information processing. © 2011 Macmillan Publishers Limited. All rights reserved.

Clinical evidence indicates a high failure rate for titanium implants (TiI) in diabetic patients, involving the overproduction of reactive oxygen species (ROS) at the implant/bone interface. Tantalum coating on titanium (TaTi) has exerted better tissue integration properties than TiI, but its biological performance under diabetic conditions remains elusive. To investigate whether TaTi may ameliorate diabetes-induced implant destabilization and the underlying mechanisms, primary rabbit osteoblasts cultured on 3-dimensional printed TiI and TaTi were exposed to normal serum (NS), diabetic serum (DS), DS+NAC (a potent ROS inhibitor), and DS+SB203580 (a specific p38 MAPK inhibitor). An in vivo study was performed on diabetic sheep implanted with TiI or TaTi. Diabetes induced mitochondrial-derived ROS overproduction and caused cellular dysfunction and apoptosis, together with the activation of p38 MAPK in osteoblasts on TiI surface. Importantly, TaTi significantly attenuated ROS production and p38 MAPK phosphorylation and exerted more osseointegrative cell behavior than TiI, as shown by improved osteoblast adhesion, increased cell proliferation and differentiation and decreased apoptosis. These results were confirmed in vivo by the enhanced bone healing efficacy of TaTi. Moreover, treatment with NAC or SB203580 on TiI not only inhibited the activation of p38 MAPK but also improved cell function and alleviated apoptotic injury, whereas TaTi combined with NAC or SB203580 failed to further improve osteoblast functional recovery compared with TaTi alone. These results demonstrated that the tantalum coating markedly improved diabetes-induced impaired osteogenesis of TiI, which may be attributed to the suppression of the ROS-mediated p38 MAPK pathway.

Regulatory T cells (Tregs) and interleukin-17-producing T helper (Th17) cells were mutually antagonistic in the pathogenesis of chronic hepatitis C virus (HCV) infection. However, the regulation of imbalance between Tregs and Th17 cells was poorly understood in HCV infection. A recent report revealed the immunomodulatory role of Toll-like receptor (TLR) 2 in regulating the balance of Tregs/Th17 functions in multiple sclerosis. Thus, the aim of the current study was to assess the effect of TLR2 stimulation on the suppressive function of Tregs and Th17 differentiation in chronic hepatitis C. A total of 65 patients with chronic hepatitis C receiving pegylated interferon-a2a and ribavirin therapy for 48 weeks, as well as 20 of normal controls (NCs) were enrolled. Cellular proliferation and cytokine production was tested in purified CD4(+)CD25(+)CD127(dim/-) Tregs in response to the stimulation of Pam3Csk4, an agonist of TLR2. In treatment-naive patients, Tregs, but not Th17 cells, from chronic hepatitis C patients expressed higher levels of TLR2 compared with NCs. Stimulation with Pam3Csk4 enhanced the suppressive function of Tregs and production of IL-10 in chronic hepatitis C more than in NCs. However, TLR2 stimulation did not promote Th17 differentiation of Tregs in chronic hepatitis C patients. Moreover, effective anti-HCV therapy resulted in the induction of IL-17-secreting phenotypic shift of Tregs without loss of inhibitive function upon TLR2 stimulation. These data provided a novel mechanism underlying modulating the balance of Tregs/Th17 cells in chronic hepatitis C. HCV infection shifted Tregs/Th17 cells through TLR2 stimulation by inducing Tregs to produce IL-10 and enhancing inhibitive function of effector T cells, resulting in viral persistence.

This article studies plating bath preparation method of novel nano-composite plating technology to improve properties of coatings when repairing the wear of equipments surface with the application of composite plating technology. The Nanoparticles of plating bath use Al2O3, metal substrates use Fe-based nano-composite plating coatings of Fe. The liquids ingredients of plating bath are prepared with ferric chloride and hydrochloric acid. The experiments of mechanical properties indicate that this plating method is an advanced technology on repairing the surface wear, which can effectively enhance the coatings properties of hardness, strength and wear resistance, which especially is suitable for the restoration to the wear of the high accuracy metal components of important equipments

The aim of this study is to compare the rate of screw loosening and clinical outcomes of expandable pedicle screws (EPS) with those of conventional pedicle screws (CPS) in patients treated for spinal stenosis (SS) combined with osteoporosis. One hundred and fifty-seven consecutive patients with SS received either EPS fixation (n = 80) or CPS fixation (n = 77) to obtain lumbosacral stabilization. Patients were observed for a minimum of 24 months. Outcome measures included screw loosening, fusion rate, Japanese Orthopaedic Association (JOA) scores and Oswestry disability index (ODI) scoring system, and complications. In the EPS group, 20 screws became loose (4.1%) in 6 patients (7.5%), and two screws (0.4%) had broken. In the CPS group, 48 screws became loose (12.9%) in 15 patients (19.5%), but no screws were broken. The fusion rate in the EPS group (92.5%) was significantly higher than that of the CPS group (80.5%). The rate of screw loosening in the EPS group (4.1%) was significantly lower than that of the CPS group (12.9%). Six EPS (1.8%) screws were removed. In the EPS group, two screws had broken but without neural complications. Twelve months after surgeries, JOA and ODI scores in the EPS group were significantly improved. There were four cases of dural tears, which healed after corresponding treatment. EPS can decrease the risk of screw loosening and achieve better fixation strength and clinical results in osteoporotic lumbar spine fusion.

Objective To study the correlation between the airway dimensions from third to five generation of bronchi, and pulmonary function test(PFT) results in patients with chronic obstructive pulmonary disease(COPD) by using inspiratory and expiratory multisection computed tomography(MSCT). Materials and Methods The study included 19 patients with COPD who underwent both inspiratory and expiratory CT. For each patient, airway luminal areas and wall thickness from the third to fifth generations of RB1 and RB10 were measured. Correlations between these parameters and PFT results were evaluated. Results The correlation coefficients between airway luminal at expiratory CT and PFT results were higher than those for inspiratory CT, and improved as the airway size decreased from the third to the fifth generations. Conclusion Some parameters of airway luminal are significantly correlated with PFT. MSCT can be used to assess the pulmonary function of patients with COPD.

We have investigated whether mast cells are associated with bronchodilator responsiveness and airway vascular changes in chronic obstructive pulmonary disease (COPD) airways. We have previously shown that the reticular basement membrane is hypervascular and the lamina propria is hypovascular in COPD. Bronchial biopsies from 32 COPD subjects, 15 smokers with normal lung function and 17 controls, were immunostained for factor VIII, mast cell tryptase and chymase antibodies. Mast cells in the airway smooth muscle, the reticular basement membrane and the underlying lamina propria were quantitated. 41% of COPD subjects had significant bronchodilator responsiveness, but this was not related to smooth muscle mast cell numbers. The reticular basement membrane had greater mast cell density in all groups compared with controls (p

Tropical medicine is defined by an association with geographic location,and it is a branch of medicine integrating preclinical medicine,clinical medicine and preventive medicine and investigating the diagnosis,treatment and prevention of diseases of tropical and subtropical zones.Military tropical medicine is a new interdiscipline based on tropical medicine and military medicine.With the improvement of health condition and the development of global economy,some tropical infectious diseases have been gradually controlled.However,factors such as increasingly frequent international communication and extreme changes in global climate induced by overproduction activity of human are leading to a redistribution of infectious diseases,which inevitably has impact on military strategies and tactics.This article reviews the past and prospect of military tropical medicine.

Compact 48 × 48 and 23 × 23 arrayed waveguide grating (AWG) devices are realized by using SU-8 strip waveguides fabricated with the process of direct ultraviolet (UV) photolithography. The demonstrated 48-channel and 23-channel AWG devices operating around 1550 nm have a channel spacing of 0.8 nm (100 GHz) and 3.2 nm (400 GHz), respectively. Due to the high index-contrast of the SU-8 strip waveguide, the fabricated AWG has a very compact size of only about 0.22 × 0.47 cm2. For the fabricated 100 GHz-spaced AWG, the crosstalk between adjacent channels is less than -15 dB, and the polarization-dependent wavelength is about 0.72 nm (@1543.5 nm). The fabricated 400 GHz-spaced AWG device exhibits a crosstalk of less than -20 dB, a polarization-dependent wavelength of 0.02 nm (@1559.6 nm). Finally the temperature tenability of the present AWG device is also characterized. A 12 nm tuning range is observed as the temperature changes from 25°C to 115°C.

Study design Applying rotating rod techniques to reduce irreducible atlantoaxial dislocation. Objective To spare the occipital-C1 motion by the strategy in reduction of before surgery irreducible atlantoaxial dislocation with obvious neurologic symptoms and congenital odontoid aplasia. Summary of background data The treatment of atlantoaxial dislocation (AAD) is a challenging problem for most surgeons. Posterior surgical stabilization of C1 and C2 include C1-C2 transarticular screws, or C1 lateral with C2 pars screws. These constructs, however, are based on preoperative reductions. When preoperative skull reduction fails and myelopathic symptoms coexist, long-segment cervico-occipital fusion and decompression are usually the only practical choice. Methods The authors explored a different surgical technique to spare the axial occipital joints by rotating rods in polyaxial C1, C3 lateral mass, and C2 pars screws, functioning as a lever analogue. Three before surgery irreducible AAD cases with obvious neurologic symptoms and congenital odontoid aplasia were successfully reduced and fused with this procedure. The authors used intraoperative somatosensory-evoked potential monitoring and intraoperative fluoroscopy. Preoperative skull traction was employed to distract and help extend the atlantoaxial complexes. Results Three C1-C2 dislocations were reduced completely without any deterioration of neurologic signs. Cervical myelopathic symptoms recovered soon after the operation. No atlantoaxial subluxation recurred. They returned to their normal work and/or activities. Conclusion The rotating rod strategy is a viable option to reduce and fuse C1-C3 for AAD with odontoid aplasia. It spares the occipital-C1 motion.

The administration of certain fluoroquinolone antibacterials has recently been linked to QT interval prolongation, raising the clinical concerns over the cardiotoxicity of these agents. In this study, the effects of a novel fluoroquinolone, antofloxacin hydrochloride (AX) on human-ether-a-go-go-related gene (HERG) encoding potassium channels and the biophysical mechanisms of drug action were performed with whole-cell patch-clamp technique in transiently transfected HEK293 cells. The administration of AX caused voltage- and time-dependent inhibition of HERG K+ current (IHERG/MiRP1) in a concentration-dependent manner but did not markedly modify the properties of channel kinetics, including activation, inactivation, deactivation and recovery from inactivation as well. In comparison with sparfloxacin (SPX), levofloxacin lactate (LVFX), the potency of AX to inhibit HERG tail currents was the least one, with an IC50 value of 460.37 μM. By contrast, SPX was the most potent compound, displaying an IC50 value of 2.69 μM whereas LVFX showed modest potency, with an IC50 value of 43.86 μM, respectively. Taken together, our data suggest that AX only causes a minor reduction of IHERG/MiRP1 at the estimated free plasma level.

Background: Right heart failure is a frequent hemodynamic disturbance in pediatric cardiac patients. Besides inotropic and chronotropic drugs, fluid administration and inhaled nitric oxide, right ventricular mechanical assistance remains difficult to perform. A circulatory assist device adapted for the right heart biophysics and physiology might be more efficient. Materials and Methods: We are developing a prototype of a non-invasive cardiac assist device (CAD) for neonates and pediatrics. It is based on a pulsatile suit device covering and affecting all territories of the right heart circuit. It will be tested in a neonatal animal model of right ventricular (RV) failure. Experimental models will be matched and compared with control and sham groups. Expected results would be immediate hemodynamic improvement due to synchronized diastolic reduction of stagnant venous capacitance, increasing preload and contractility. On long term, increased shear stress with changing intrathoracic pressure in a phasic way would improve and remodel the pulmonary circulation. Future studies will be focused on: hemodynamic, biochemistry, endothelium function test, and angiogenesis. Comments: A non-invasive CAD guarantees better hemodynamics and endothelial function preservation with low morbidity and mortality. This is a physiological approach, cost-effective method, and particularly interesting in neonates and pediatrics with RV failure.

Malignant monoclonal B cells of chronic B cell lymphocytic leukemia (B-CLL) usually fail to be cleared, which indicates important costimulatory molecules may be lacking. Among those costimulatory signals, B7-1/CD80 and B7-2/CD86 caused utmost attention. In this study, B7-1 and B7-2 expression on B cells in chronic B cell lymphocytic leukemia patients were detected. Data showed that B7-2 expression in chronic B cell lymphocytic leukemia patients is significantly lower than in normal people, which suggests defective B7-2 expression may be one of the pathogenic mechanisms of chronic B cell lymphocytic leukemia. Further, we confirmed interferon-gamma could induce B7-2 expression slightly and promote T-cell response against chronic B cell lymphocytic leukemia cells, indicating interferon-gamma has clinical value in chronic leukemia immunotherapy based on modulating B7-2 expression.

No diploma for orthopaedic surgery is available in the current medical education and licensing system in China. The orthopaedist generally receives on-the-job training in a clinical practice after getting a license to practice surgery. There are multiple training pathways to and opportunities in orthopaedic surgery, and these vary from hospital to hospital and from region to region. These include on-the-job training, academic visits, rotation through different departments based on local medical needs, fellowship training in large general or teaching hospitals (locally, regionally, nationally, or internationally), English language training, postgraduate diploma training, and Internet CME. Due to the current training system, orthopaedic techniques and skill levels vary greatly from hospital to hospital.

Traditional continuing medical education (CME) depended primarily on periodic courses and conferences. The cost-effectiveness of these courses has not been established, and often the content is not tailored to best meet the needs of the students. Internet training has the potential to accomplish these goals. Over the last 10 years, we have developed a Web site entitled “Orthochina.org,” based upon the wiki concept, which uses an interactive, case-based format. We describe the development of online case discussions, and various technical and administrative requirements. As of December 31, 2007, there were 33,984 registered users, 9,759 of which passed the confirmation procedures. In 2007, an average of 211 registrants visited daily. The average number of first page clicks was 4,248 per day, and the average number of posts was 70 per day. All cases submitted for discussion include the patient’s complaint, physical examination findings, and relevant images based on specific criteria for case discussion. The case discussions develop well professionally. No spam posting or unauthorized personal advertisement is permitted. In conclusion, online academic discussions proceed well when the orthopaedic surgeons who participate have established their identities.

SUMMARY: The effects of Sairei-to and its active components on a model of irreversible mesangial proliferative glomerulonephritis induced by injecting monoclonal antibody (MoAb) 1-22-3 into uninephrectomized rats were examined. the significant suppressive effects of Sairei-to and its active components on proteinuria were demonstrated on days 7, 14, 21 after MoAb 1-22–3 injection compared with phosphate-buffered saline (PBS)-treated controls. On day 21, light microscopy revealed that the drugs reduced mesangial cell proliferation, mesangial matrix expansion (matrix score: 84.5 ± 41.6 for Sairei-to, 76.1 ± 31.9 for Syo-saiko-to, 66.7 ± 46.3 for its three components vs 162.4 ± 26.1 for PBS, P

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.

Herbal compounds that have notable therapeutic effect upon Alzheimer's disease (AD) have frequently been found, despite the recent failure of late-stage clinical drugs. Icariin, which is isolated from Epimedium brevicornum, is widely reported to exhibit significant anti-AD effects in in vitro and in vivo studies. However, the molecular mechanism remains thus far unclear. In this work, the anti-AD mechanisms of icariin were investigated at a target network level assisted by an in silico target identification program (INVDOCK). The results suggested that the anti-AD effects of icariin may be contributed by: attenuation of hyperphosphorylation of tau protein, anti-inflammation and regulation of Ca(2+) homeostasis. Our results may provide assistance in understanding the molecular mechanism and further developing icariin into promising anti-AD agents.

Overexpression of the Eph receptor tyrosine kinases in cancers is related to malignant transformation, metastasis, tumor differentiation, and prognosis. Down-regulation of EphA7 secondary to hypermethylation has been reported in colorectal cancer. In the present study, expression of EphA7 in gastric cancer cell lines and gastric carcinoma specimens was determined by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression of EphA7 was reduced in all tested gastric cancer cell lines; however, there is marked variability in expression among gastric carcinoma specimens. Overexpression was observed more often in younger patients (aged < or =65 years) (P = .03) and in patients with advanced cancer (P = .031). Hypermethylation of the EphA7 promoter-associated CpG island was found using methylation-specific polymerase chain reaction. Down-regulation of EphA7 was significantly related to hypermethylation (P = .001), and the level of hypermethylation was greater in moderately differentiated tumors than in poorly differentiated ones (P = .03). We also performed immunohistochemical staining for EphA7 in 52 gastric carcinoma specimens and found that expression of the protein was consistent with its transcript expression, with the protein being significantly overexpressed in younger patients (P = .016) and in patients with advanced tumors (P = .033). Our data indicate that EphA7 may have roles in the pathogenesis and development of gastric carcinomas.