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Abstract Background Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear. Methods Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models. Results We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA. Conclusions Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.

Abstract The correlation between lower psoas mass and the prognosis of osteoporotic vertebral compression fractures (OVCF) is still unclear. This study aims to investigate the impact of lower psoas mass on the prognosis of patients undergoing percutaneous vertebroplasty (PVP). One hundred and sixty-three elderly patients who underwent single-segment PVP from January 2018 to December 2021 were included. The psoas to L4 vertebral index (PLVI) via MRI were measured to assess psoas mass. Patients were divided into high PLVI (> 0.79) and low PLVI (≤ 0.79) groups based on the median PLVI in the cohort. The basic information (age, gender, body mass index (BMI) and bone mineral density (BMD)), surgical intervention-related elements (duration of operation, latency to ambulation, period of hospital stay, and surgical site), postoperative clinical outcomes (Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, Japanese Orthopaedic Association (JOA) scores), and incidence of secondary fractures) were compared. Patients showed no statistically significant differences in terms of age, gender, surgical sute, BMI, BMD and preoperative VAS, ODI, JOA scores (P > 0.05) between the two groups. However, there were significant differences in terms of latency to ambulation, period of hospital stay (P

Abstract The goal of blind image super-resolution (BISR) is to recover the corresponding high-resolution image from a given low-resolution image with unknown degradation. Prior related research has primarily focused effectively on utilizing the kernel as prior knowledge to recover the high-frequency components of image. However, they overlooked the function of structural prior information within the same image, which resulted in unsatisfactory recovery performance for textures with strong self-similarity. To address this issue, we propose a two stage blind super-resolution network that is based on kernel estimation strategy and is capable of integrating structural texture as prior knowledge. In the first stage, we utilize a dynamic kernel estimator to achieve degradation presentation embedding. Then, we propose a triple path attention groups consists of triple path attention blocks and a global feature fusion block to extract structural prior information to assist the recovery of details within images. The quantitative and qualitative results on standard benchmarks with various degradation settings, including Gaussian8 and DIV2KRK, validate that our proposed method outperforms the state-of-the-art methods in terms of fidelity and recovery of clear details. The relevant code is made available on this link as open source.

Abstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. Methods In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP–RIPK1–NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model. Results In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. Conclusions These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.

Abstract Central sarcopenia is associated with the prognosis of various orthopedic surgeries in the elderly. This study aims to investigate its impact on the outcomes of single-segment lumbar fusion surgery in elderly patients. Retrospective analysis was conducted on 314 patients aged 60 to 80 who underwent single-segment posterior lumbar fusion surgery due to degenerative lumbar diseases. Patients were categorized into high psoas and L4 vertebral index (PLVI) and low PLVI groups according to the MRI-measured PLVI for central sarcopenia. Basic patient data, surgery-related parameters, functional assessments at preoperative and postoperative 3, 6, and 12 months, and X-ray-based fusion status were compared. The basic data of the two groups showed no significant differences. Parameters including the operative segment, preoperative hemoglobin levels, surgical duration, and intraoperative blood loss exhibited no significant variances. However, notable differences were observed in postoperative initial hemoglobin levels, transfusion requirements, and length of hospital stay between the two groups. During the postoperative follow-ups at 3, 6, and 12 months, the VAS scores for lower back pain and ODI scores in the lower PLVI group were significantly higher compared to the high PLVI group. Additionally, the EuroQoL 5D scores were notably lower in the low PLVI group. There were no significant differences between the groups in terms of leg pain VAS scores at each time point and the fusion status at 12 months postoperatively. MRI-based central sarcopenia has a negative impact on the therapeutic effectiveness following single-segment lumbar fusion surgery in elderly patients.

Abstract The characteristics of floor failure and stress changes during the mining process of protective layers are crucial for determining the effectiveness of pressure relief. Three boreholes were designed in the 21104 fully mechanized mining face of Hulusu Coal Mine to implant optical fibers into the floor of the working face. A fiber optic monitoring system was established to monitor the dynamic evolution of stress in the floor rock mass at different mining distances. Based on the information entropy in information theory, the monitoring results in the fiber optic monitoring system are calculated to obtain the stress information entropy at different mining distances. A quantitative dynamic analysis is conducted on the stress change process of the mining floor rock layer, and the stress change law of the protective layer after mining is verified through numerical calculation and similar simulation experiments. The results indicate that the evolution of stress information entropy can be divided into four stages, namely the original rock stress stage, stress concentration stage, stress release stage, and stress recovery stage. The stress information entropy shows a fluctuating upward trend, indicating that coal seam mining leads to a decrease in the orderliness of the overlying rock system and an increase in disorder. In different spatial evolution processes, there are also significant differences in stress information entropy. In the vertical direction, the entropy value of shallow rock layers changes greatly, while the entropy value of deep rock layers changes slightly. Mining leads to a decrease in the orderliness of the entire overlying rock system, an increase in stress information entropy, and a fluctuating upward trend in stress information entropy. The information entropy of overlying rock deformation and re compaction increases, but the degree of change of the former is greater than that of the latter. The Brillouin fiber optic sensing technology provides a new method for monitoring the stress changes in the protective layer mining floor, achieving quantitative analysis of floor rock failure.

Abstract The tripartite motif (TRIM) 22 and mitogen-activated protein kinase (MAPK) signaling pathways play critical roles in the growth of glioblastoma (GBM). However, the molecular mechanism underlying the relationship between TRIM22 and MAPK signaling remains unclear. Here, we found that TRIM22 binds to exon 2 of the sphingosine kinase 2 (SPHK2) gene. An ERK1/2-driven luciferase reporter construct identified TRIM22 as a potential activator of MAPK signaling. Knockout and overexpression of TRIM22 regulate the inhibition and activation of MAPK signaling through the RING-finger domain. TRIM22 binds to Raf-1, a negative regulator of MAPK signaling, and accelerates its degradation by inducing K48-linked ubiquitination, which is related to the CC and SPRY domains of TRIM22 and the C1D domain of Raf-1. In vitro and in vivo, an SPHK2 inhibitor (K145), an ERK1/2 inhibitor (selumetinib), and the nonphosphorylated mutant Raf-1S338A inhibited GBM growth. In addition, deletion of the RING domain and the nuclear localization sequence of TRIM22 significantly inhibited TRIM22-induced proliferation of GBM cells in vivo and in vitro. In conclusion, our study showed that TRIM22 regulates SPHK2 transcription and activates MAPK signaling through posttranslational modification of two critical regulators of MAPK signaling in GBM cells.

Abstract Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R tool and the Venny platform. Protein–protein interaction information was obtained by inputting the intersection targets into the STRING database. The PPI network was constructed by Cytoscape v3.6.0 software again, and the key genes were screened out according to the degree value. Gene function enrichment of DEGs was performed by Webgestalt online tool. One hundred and thirty CG patients were finally included in this study. Univariate correlation analysis showed that age, gender, BMI and coffee were the potential influencing factors for the comorbidity (P

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, a PPARα/γ target gene involved in tumor progression and chemoresistance, was significantly downregulated. Clinical analysis demonstrated a strong correlation between the protein levels of CES1 and SCD in HCC. Interference with lipid signaling by targeting the CES1-PPARα/γ-SCD axis sensitized HCC cells to cisplatin treatment. As a result, the growth of HCC xenograft tumors in NU/J mice was potently slowed by coadministration of cisplatin and CES1 inhibition. Our results, thus, suggest that CES1 is a promising therapeutic target for HCC treatment.

Abstract Breast cancer (BC) is considered the second commonest human carcinoma and the most incident and mortal in the female population. Despite promising treatments for breast cancer, mortality rates of metastatic disease remain high. Gasdermin C (GSDMC) is an affiliate of the gasdermin (GSDM) family, which is involved in the process of pyroptosis. Pyroptosis is implicated in tumorigenesis, but the role of GSDMC in cancer cells is yet to be fully elucidated. In this study, we investigated the role and mechanism of GSDMC in breast cancer. We conducted a pan-cancer analysis of the expression and prognosis of GSDMC utilizing multidimensional data from The Cancer Genome Atlas (TCGA). We investigated GSDMC expression levels in 15 BC tissues and matched adjacent normal tissues by immunohistochemistry (IHC). Further verification was performed in the Gene Expression Omnibus (GEO) database. We discovered that elevated GSDMC expression was considerably linked to a worse prognosis in breast invasive carcinoma (BRCA). Next, we identified noncoding RNAs (ncRNAs) which contributing to higher expression of GSDMC by a series of expression, survival, and correlation analysis. We finally identified LINC00511/hsa-miR-573 axis to be the most promising ncRNA-associated pathways that account for GSDMC in BRCA. Furthermore, we demonstrated the significant correlations between GSDMC expression and immune infiltrates, immune checkpoints, and immune markers in BRCA. This study illustrated that ncRNAs-mediated upregulation of GSDMC linked to dismal prognosis and also exhibited a correlation with tumor immune cell infiltration in BRCA. It is anticipated to offer novel ideas for the link between pyroptosis and tumor immunotherapy.

Abstract Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we demonstrate an unreported autosomal dominant LRP6 heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominant LRP6 heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern of LRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report that LRP6 mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum of LRP6-related disorders, and provide valuable information on the characteristics of LRP6-related tooth agenesis.

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

Introduction The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

Abstract Investigation of the prevalence and diversity of Bartonella infections in small mammals in the Qaidam Basin, western China, could provide a scientific basis for the control and prevention of Bartonella infections in humans. Accordingly, in this study, small mammals were captured using snap traps in Wulan County and Ge’ermu City, Qaidam Basin, China. Spleen and brain tissues were collected and cultured to isolate Bartonella strains. The suspected positive colonies were detected with polymerase chain reaction amplification and sequencing of gltA, ftsZ, RNA polymerase beta subunit (rpoB) and ribC genes. Among 101 small mammals, 39 were positive for Bartonella, with the infection rate of 38.61%. The infection rate in different tissues (spleens and brains) (χ 2 = 0.112, P = 0.738) and gender (χ 2 = 1.927, P = 0.165) of small mammals did not have statistical difference, but that in different habitats had statistical difference (χ 2 = 10.361, P = 0.016). Through genetic evolution analysis, 40 Bartonella strains were identified (two different Bartonella species were detected in one small mammal), including B. grahamii (30), B. jaculi (3), B. krasnovii (3) and Candidatus B. gerbillinarum (4), which showed rodent-specific characteristics. B. grahamii was the dominant epidemic strain (accounted for 75.0%). Furthermore, phylogenetic analysis showed that B. grahamii in the Qaidam Basin, might be close to the strains isolated from Japan and China. Overall, we observed a high prevalence of Bartonella infection in small mammals in the Qaidam Basin. B. grahamii may cause human disease, and the pathogenicity of the others Bartonella species needs further study, the corresponding prevention and control measures should be taken into consideration.

African swine fever (ASF) has spread to many countries in Africa, Europe and Asia in the past decades. However, the potential geographic extent of ASF infection is unknown. Here we combined a modeling framework with the assembled contemporary records of ASF cases and multiple covariates to predict the risk distribution of ASF at a global scale. Local spatial variations in ASF risk derived from domestic pigs is influenced strongly by livestock factors, while the risk of having ASF in wild boars is mainly associated with natural habitat covariates. The risk maps show that ASF is to be ubiquitous in many areas, with a higher risk in areas in the northern hemisphere. Nearly half of the world’s domestic pigs (1.388 billion) are in the high-risk zones. Our results provide a better understanding of the potential distribution beyond the current geographical scope of the disease.

Background: Accurate predictions of distant metastasis (DM) in locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT) are helpful in developing appropriate treatment plans. This study aimed to perform DM prediction through deep learning radiomics. Methods: We retrospectively sampled 235 patients receiving nCRT with the minimum 36 months’ postoperative follow-up from three hospitals. Through transfer learning, a deep learning radiomic signature (DLRS) based on multiparametric magnetic resonance imaging (MRI) was constructed. A nomogram was established integrating deep MRI information and clinicopathologic factors for better prediction. Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) were used as performance metrics. Furthermore, the risk of DM in patients with different response to nCRT was evaluated with the nomogram. Findings: DLRS performed well in DM prediction, with a C-index of 0·747 and an area under curve (AUC) at three years of 0·894 in the validation cohort. The performance of nomogram was better, with a C-index of 0·775. In addition, the nomogram could stratify patients with different responses to nCRT into high- and low-risk groups of DM (P < 0·05). Interpretation: MRI-based deep learning radiomics had potential in predicting the DM of LARC patients receiving nCRT and could help evaluate the risk of DM in patients who have different responses to nCRT. Funding: The funding bodies that contributed to this study are listed in the Acknowledgements section.

At present, artificial intelligence (AI) has already been applied in cardiovascular imaging (e.g., image segmentation, automated measurements, and eventually, automated diagnosis) and it has been propelled to the forefront of cardiovascular medical imaging research. In this review, we presented the current status of artificial intelligence applied to image analysis of coronary atherosclerotic plaques, covering multiple areas from plaque component analysis (e.g., identification of plaque properties, identification of vulnerable plaque, detection of myocardial function, and risk prediction) to risk prediction. Additionally, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging of atherosclerotic plaques, as well as lessons that can be learned from other areas. The continuous development of computer science and technology may further promote the development of this field.

Objective(s): -methyl-D-aspartate NMDA receptor (NMDAR) and aquaporin 4 (AQP4) are involved in the molecular cascade of edema after traumatic brain injury (TBI) and are potential targets of studies in pharmacology and medicine. However, their association and interactions are still unknown.Materials and Methods: We established a rat TBI model in this study. The cellular distribution patterns of AQP4 after inhibition of NMDAR were determined by Western blotting and immunoreactive staining. Furthermore, the regulation of NMDA receptor 1 by AQP4 was studied by injection of a viral vector targeting AQP4 by RNAi into the rat brain before TBI.Results: The results suggest that AQP4 protein expression increased significantly (P

We report safety and efficacy of a combination therapy, comprising tamsulosin and phosphodiesterase type 5 inhibitors (PDE5-Is), relative to monotherapy, to ascertain its potential in treating lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) secondary to benign prostatic hyperplasia (BPH) after 3 months’ treatment. We screened MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases, for randomized controlled trials, and obtained eight articles comprising 1144 participants. Results showed that the combination group had superior outcomes with regard to International Prostate Symptom Score (IPSS) and Qmax, compared to the other two groups. The combination group also had superior efficacy with regard to International Index of Erectile Function (IIEF) than the tamsulosin group, but not over the PDE5-Is group. Further, the combination group showed better efficacy in IPSS voiding and quality of life (QoL) compared to the PDE5-Is group. An analysis of safety outcomes revealed extremely high adverse events (AEs) and pain in the combination group. However, therapy discontinuation due to pain and AEs did not increase with increase in AEs. Overall, our findings indicate that a combination of tamsulosin and PDE5-Is is superior to individual tamsulosin and PDE5-Is monotherapy, with regard to improving LUTS and ED secondary to BPH.

Objective: To investigate the long-term clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with human herpes virus 8 (HHV8)-positive multicentric Castleman’s disease (MCD). Methods: A 17-year-old female patient was admitted to Henan Provincial People’s Hospital with the complaint of febrile for half a month, headache, and enlarged superficial lymph nodes on October 5, 2010. HHV8-positive mixed cellular Castleman’s disease was found by pathological diagnosis of lymph nodes biopsy. After the administration of CHOP and Hyper-CVAD-B, the patient was still febrile, we administrated the followed COAP, two courses of VAD(Vincristine, Adriamycin, Dexamethasone), the patient received CR. Six months after CR, the patient relapsed, we administrated VAD and two courses of bortezomide+dexamethasone chemotherapy, and then the patient received PR. After that, the patient underwent allo-HSCT from his human leukocyte antigen (HLA)-matched unrelated donor after conditioning with Bu/Cy+Etoposide+Smoustin.graft-vs-host disease (GVHD) prophylaxis, which consisted of ATG (7.5 mg/kg, qd, ivdrip) from d-5 to d-2, cyclosporine (3 mg/kg/d, qd, ivdrip, for 24 h) started from day-1, MMF(0.5 g, tid, po.) started from day+1 to +28, and MTX (15 mg per time, ivdrip, d+1,+4,+7,+11). She received 3.5×10 6 /L CD34 + cells and 8.1×10 8 /LMNC. Results: Granulocyte engraftment occurred on day+12, platelet engrafted on day+14. Bone marrow biopsy showed normalization of trilineage hematopoiesis on day+33, chimerism: 97.6%. The transplantation was successful and followed up for 7 years with CR. Conclusion: Allo-HSCT might cure patients with refractory/relapsed HHV8+ MCD.

Background: Patients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients. Methods: One thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization. Results: PCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23–0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18–0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19–0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14–0.93, P = 0.03, respectively). Conclusions: PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes. Trial Registration: ClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1

Abstract The broad clinical acceptance of intraoperative blood salvage and its applications in cancer surgery remain controversial. Until now, a method that can safely eliminate cancer cells while preserving erythrocytes does not exist. Here, we investigated whether X-ray generated from linear accelerator irradiation at a certain dose can kill hepatocarcinoma cells while preserving erythrocytes. HepG2, SK-Hep1 or Huh7 cells were mixed into the aliquots of erythrocytes obtained from healthy volunteers. After the mixed cells were exposed to 30 Gy and 50 Gy X-rays irradiation, the viability, clonogenicity, DNA synthesis and tumorigenicity of the tumor cells were determined by the MTT assay, plate colony formation, 5-ethynyl-2′-deoxyuridine incorporation, and subcutaneous xenograft implantation into immunocompromised mice. The ATP, 2,3-DPG, free Hb, osmotic fragility, blood gas variables in erythrocytes and morphology of erythrocytes at 0 h, 12 h, 24 h, 48 h, 72 h after irradiation were analyzed. X-ray irradiation at 30 Gy effectively inhibited the viability, proliferation, and tumorigenicity of HepG2, SK-Hep1 and Huh7 cells without noticeably damaging the ability of oxygen-carrying, membrane integrity and morphology of erythrocytes. Theses results suggest that X-ray at 30 Gy irradiation might be safe to eliminate hepatocarcinoma cells while preserving erythrocytes in salvaged blood.

Introduction : The present study aims to evaluate the utility of D-dimer testing for differentiating the causes of acute chest pain, including acute aortic dissection (AAD), pulmonary embolism (PE), acute myocardial infarction (AMI), unstable angina (UA), and other uncertain diagnoses of chest pain. Material and methods : Consecutive patients admitted for acute chest pain within 24 h from symptom onset were enrolled prospectively, and plasma D-dimer levels were measured on admission. Diagnoses of AAD, PE, AMI, and UA were confirmed by standard methods. Results : A total of 790 patients were enrolled, including 202 AAD, 43 PE, 315 AMI, 136 UA, and 94 cases of other uncertain diagnoses. D-dimer levels were significantly higher in patients with AAD and PE than in those with AMI, UA, and other uncertain diagnoses (p < 0.001), but they were comparable between patients with AAD and PE (p = 0.065). Moreover, patients with type A AAD had higher D-dimer levels than those with type B AAD (p = 0.022). Receiver operating characteristic (ROC) curve analysis showed that a D-dimer level < 0.5 µg/ml was a good predictor for ruling out AAD, with a sensitivity of 94.0% and a specificity of 56.8%. At a cut-off level of 0.5 µg/ml, the negative and positive likelihood ratios were 0.10 and 2.18, respectively, with a positive predictive value of 42.6% and a negative predictive value of 96.6%. Conclusions : The D-dimer level within 24 h after symptom onset might be helpful for differentiating AAD from other causes of chest pain.

In this paper, a wide-band low cross polarization antenna with a structure of microstrip line coupling to slot line as the balun is proposed. The radiation part of the antenna is fed by two pairs of parallel transmission line via a transition from a slot line which is coupled by a microstrip line. Because it is fed by parallel transmission lines, which is balanced-fed structure, the antenna can achieve an improved low cross-polarization performance. The height of the antenna is 0.146λ0 (λ0 is the wavelength of lowest frequency). The prototype antenna demonstrates a measured impedance bandwidth of 93.5% (2.7-7.44 GHz), a 3-dB-gain bandwidth of 77% (2.7-6.1 GHz), and a maximum gain of 10.5 dBi at 4.5 GHz.

Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide. Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur. Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets. Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV. We found that resveratrol could alleviate diarrhea induced by RV infection. Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response. The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets. It was found that resveratrol could alleviate diarrhea induced by RV infection. These results revealed that resveratrol dry suspension could be a new control measure for RV infection.

Background: The association of metabolic syndrome (MS) with left ventricular (LV) hypertrophy is controversial. The objective of our study was to investigate the influence of MS on LV mass and geometry in community-based hypertensive patients among Han Chinese. Materials and Methods: This study included 1733 metabolic syndrome patients according to the International Diabetes Federation (IDF) definition and 2373 non-MS hypertension patients. LV hypertrophy was diagnosed by the criteria of LV mass ≥49.2 g/m 2.7 for men and 46.7 g/m 2.7 for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LV hypertrophy and relative wall thickness. Logistic regression analysis was used to determine odds ratio (OR) and 95% confidence interval (CI) of MS for LV hypertrophy and LV geometry abnormality. Results: The LV mass and LV mass index were higher in the MS group than in the non-MS group. In multiple adjusted models. LV mass index, LV mass, interventricular septum, and post wall were raised with the increased number of MS disorders. MS was associated with increased LV hypertrophy risk (unadjusted OR 1.38; 95% CI 1.21-1.57); age, sex, and blood pressure (BP; adjusted OR 1.39; 95% CI 1.22-1.59). MS was also associated with increased risk of eccentric hypertrophy in male and female patients. MS was only associated with increased risk of concentric hypertrophy in female patients; and MS was not associated with concentric remodeling. Conclusion: LV mass and LV mass index were associated with the increased number of MS disorders in the Chinese community-based hypertensive population. MS was not only associated with increased LV hypertrophy risk, but also associated with concentric and eccentric LV geometry abnormality, especially in females.

Despite many angiogenic factors playing crucial roles in metabolic homeostasis, effects of angiopoietin-2 (ANG-2) in adipose tissue (AT) remain unclear. Utilizing a doxycycline-inducible AT-specific ANG-2 overexpression mouse model, we assessed the effects of ANG-2 in AT expansion upon a high-fat diet (HFD) challenge. ANG-2 is significantly induced, with subcutaneous white AT (sWAT) displaying the highest ANG-2 expression. ANG-2 overexpressing mice show increased sWAT vascularization and are resistant to HFD-induced obesity. In addition, improved glucose and lipid metabolism are observed. Mechanistically, the sWAT displays a healthier expansion pattern with increased anti-inflammatory macrophage infiltration. Conversely, ANG-2 neutralization in HFD-challenged wild-type mice shows reduced vascularization in sWAT, associated with impaired glucose tolerance and lipid clearance. Blocking ANG-2 causes significant pro-inflammatory and pro-fibrotic changes, hallmarks of an unhealthy AT expansion. In contrast to other pro-angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), this is achieved without any enhanced beiging of white AT.

Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery.A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis.Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408).Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.

Peripheral neural sensory mechanisms play a crucial role in metabolic regulation but less is known about the mechanisms underlying vagal sensing itself. Recently, we identified an enrichment of liver X receptor alpha and beta (LXRα/β) in the nodose ganglia of the vagus nerve. In this study, we show mice lacking LXRα/β in peripheral sensory neurons have increased energy expenditure and weight loss when fed a Western diet (WD). Our findings suggest that the ability to metabolize and sense cholesterol and/or fatty acids in peripheral neurons is an important requirement for physiological adaptations to WDs.

HIV infection increases a woman's risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study's objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women.A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d'Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant.VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis-controlling for HIV status, location of the screening clinic, facility location, facility type, and country-compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P

Intraoperative blood salvage, an effective blood conservation strategy, has not been applied in onco-surgery, because of potential malignant cell contamination. In this study we tested effectiveness of a modified leukocyte depletion filter (M-LDF) for removal of tumor cells.The effects of M-LDF and regular LDF on removal of cells (HepG2 cell line) were compared. The safety of M-LDF was tested with blood (collected and washed during onco-surgery), the salvaged blood mixed with tumor cells from the solid tumor of the same patient, or mixed with HepG2 cells (n=30 in each protocol). Cancer cells were identified by flow cytometry, culture and bioassay with and without filtration.M-LDF removed 5-log of HepG2 and nucleated cells, which was much higher than regular LDF, and cells were destroyed when they passed through M-LDF. Cytokeratin-positive cells in all samples were removed by M-LDF. Invasive growth adherent cells were found in most of unfiltered samples and 67% of the inoculated nude mice developed tumors in LDF-treated sample. Neither adherent cells nor nude mice developed tumors were found in M-LDF-treated samples.Since M-LDF can effectively remove and destroy cancer cells in the salvaged blood, it has great potential for clinical application.

A phenanthrene-degrading endophytic bacterium, Pn2, was isolated from Alopecurus aequalis Sobol grown in soils contaminated with polycyclic aromatic hydrocarbons (PAHs). Based on morphology, physiological characteristics and the 16S rRNA gene sequence, it was identified as Massilia sp. Strain Pn2 could degrade more than 95% of the phenanthrene (150 mg · L(-1)) in a minimal salts medium (MSM) within 48 hours at an initial pH of 7.0 and a temperature of 30 °C. Pn2 could grow well on the MSM plates with a series of other PAHs, including naphthalene, acenaphthene, anthracene and pyrene, and degrade them to different degrees. Pn2 could also colonize the root surface of ryegrass (Lolium multiflorum Lam), invade its internal root tissues and translocate into the plant shoot. When treated with the endophyte Pn2 under hydroponic growth conditions with 2 mg · L(-1) of phenanthrene in the Hoagland solution, the phenanthrene concentrations in ryegrass roots and shoots were reduced by 54% and 57%, respectively, compared with the endophyte-free treatment. Strain Pn2 could be a novel and useful bacterial resource for eliminating plant PAH contamination in polluted environments by degrading the PAHs inside plants. Furthermore, we provide new perspectives on the control of the plant uptake of PAHs via endophytic bacteria.

Sex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM).A total of 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 to 2011. Compared to male patients, at baseline female patients were older at diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), and had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year follow-up period (range 2-7 years), survival analysis showed that the incidences of mortality from all causes, cardiovascular death and progression to chronic heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21-3.95, P = 0.010; HR 2.19, 95% CI 1.17-4.09, P = 0.014; HR 1.73, 95% CI 1.12-2.69, P = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was identified only in patients younger than 50 years old (P = 0.011, 0.011 and 0.009, respectively), but not for those 50 years or older.Our results suggest that female sex is associated with worse survival and heart failure in HCM patients. Further studies are required to determine whether female hormones modify the clinical expression and prognosis of HCM.

Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34(+) progenitor cells (fCB-CD34(+) cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34(+) cells were transplanted i.v. to mice while CD34(-) cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34(-) cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34(+) cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34(-) cell-treated controls. Importantly, lung inflammation in fCB-CD34(+) cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34(-) cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34(+) cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34(+) cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34(+) cells are an important source of stem cells for the treatment of acute lung injury.

Glioblastomas are the most aggressive forms of primary brain tumors due to their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. The water channel protein, Aquaporin-4 (AQP4) is a key molecule for maintaining water and ion homeostasis in the central nervous system and has recently been reported with cell survival except for its well-known function in brain edema. An increased AQP4 expression has been demonstrated in glioblastoma multiforme (GBM), suggesting it is also involved in malignant brain tumors. In this study, we show that siRNA-mediated down regulation of AQP4 induced glioblastoma cell apoptosis in vitro and in vivo. We further show that several apoptotic key proteins, Cytochrome C, Bcl-2 and Bad are involved in AQP4 signaling pathways. Our results indicate that AQP4 may serve as an anti-apoptosis target for therapy of glioblastoma.

In response to inflammation, mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodeling and wound healing. Tumors apply persistent mechanical and pathological stress to tissues and causes continual infiltration of MSCs. Here, we demonstrate that MSCs promote human hepatocellular carcinoma (HCC) metastasis under the influence of inflammation. The metastasis promoting effect could be imitated with the supernatant of MSCs pretreated with IFNγ and TNFα. Interestingly, treatment of HCC cells with the supernatant leads to epithelial-mesenchymal transition (EMT), an effect related to the production of TGFβ by cytokines stimulated MSCs. Importantly, the levels of MSCs expressing SSEA4 in clinical HCC samples significantly correlated with poor prognosis of HCC, and EMT of HCC was strongly associated with a shorter cancer-free interval (CFI) and a worse overall survival (OS). Therefore, our results suggest that MSCs in tumor inflammatory microenvironment could promote tumor metastasis through TGFβ-induced EMT.

BACKGROUND: There are a number of sound justifications for publishing nearly identical information in Chinese and English medical journals, assuming several conditions are met. Although overlap publication is perceived as undesirable and ethically questionable in Europe and North America, it may serve an important function in some regions where English is not the native tongue. There is no empirical data on the nature and degree of overlap publication in English and Chinese language journals. METHODS/PRINCIPAL FINDINGS: A random sample of 100 English manuscripts from Chinese institutions was selected from PubMed. Key words and institutions were searched in the China National Knowledge Infrastructure, a comprehensive Chinese language research database. Unacknowledged overlap was a priori defined according to International Committee of Medical Journal Editor (ICMJE) guidelines following examination by two individuals. 19% (95% CI 11-27) of English manuscripts from Chinese institutions were found to have substantial overlap with Chinese published work based on full text examination. None of the manuscripts met all of the criteria established by the ICMJE for an acknowledged overlap publication. Individual-level, journal-level, and institutional factors seem to influence overlap publication. Manuscripts associated with an institution outside of China and with more than one institution were significantly less likely to have substantial overlap (p