Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.

BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.

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In December 2022, the American Academy of Pediatrics released a clinical guideline for point-of-care ultrasonography (POCUS) in the neonatal intensive care unit (NICU). The guideline outlined the development and current status of POCUS in the NICU, and summarized the key elements and implementation guidelines for successful implementation of POCUS in the NICU. This article provides an overview of the key points of the clinical guideline and analyzes the current status of POCUS in China, providing a reference for the implementation of POCUS in neonatal care in China.

Prognostic model for predicting overall survival in patients with glioblastoma: an analysis based on the SEER database.

Predicting the prognosis of glioblastoma (GBM) has always been important for improving survival. An understanding of the prognostic factors for patients with GBM can help guide treatment. Herein, we aimed to construct a prognostic model for predicting overall survival (OS) for patients with GBM. We identified 11,375 patients with pathologically confirmed GBM from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The 1-, 2-, and 3-year survival probabilities were 48.8%, 22.5%, and 13.1%, respectively. The patients were randomly divided into the training cohort (n = 8531) and the validation cohort (n = 2844). A Cox proportional risk regression model was used to analyze the prognostic factors of patients in the training cohort, and a nomogram was constructed. Then concordance indexes (C-indexes), calibration curves, and receiver operating characteristic (ROC) curves were used to assess the performance of the nomograms by internal (training cohort) and external validation (validation cohort). Log-rank test and univariate analysis showed that age, race, marital status, extent of surgical resection, chemotherapy, and radiation were the prognostic factors for patients with GBM (p < 0.05), which were used to construct nomogram. The C-index of the nomogram was 0.717 (95% confidence interval (CI), 0.710-0.724) in the training cohort, and 0.724 (95% CI, 0.713-0.735) in the validation cohort. The nomogram had a higher areas under the ROC curve value. The nomogram was well validated, which can effectively predict the OS of patients with GBM. Thus, this nomogram could be applied in clinical practice.

Myeloid-derived suppressor cells cross-talk with B10 cells by BAFF/BAFF-R pathway to promote immunosuppression in cervical cancer.

Immunosuppression induced by myeloid-derived suppressor cells (MDSCs) is one of the main obstacles to the efficacy of immunotherapy for cervical cancer. Recent studies on the immunosuppressive ability of MDSCs have primarily focused on T cells, but the effect of MDSCs on B cells function is still unclear. In a study of clinical specimens, we found that the accumulation of MDSCs in patients with cervical cancer was accompanied by high expression of B cell activating factor (BAFF) on the surface and high expression of interleukin (IL)-10-producing B cells (B10) in vivo. We found that the absence of BAFF could significantly inhibit tumor growth in a cervical cancer model using BAFF KO mice. Further studies showed that abundant MDSCs in cervical cancer induced B cells to differentiate into B10 cells by regulating BAFF which acted on the BAFF receptor (BAFF-R) of them. In this process, we found that a large amount of IL-10 secreted by B10 cells can activate STAT3 signaling pathway in MDSCs, and then form a positive feedback loop to promote the differentiation of B10 cells. Therefore, this study reveals a new mechanism of BAFF-mediated mutual immune regulation between MDSCs and B cells in the occurrence and development of cervical cancer.

A case report of lymphangioleiomyomatosis with retroperitoneal masses in pregnancy.

Background: Lymphangioleiomyomatosis (LAM) is a rare, gradually advancing tumor of unknown origin. It is distinguished by the anomalous proliferation of pulmonary smooth muscle cells and predominantly manifests in women of childbearing age. In this study, we aim to present a noteworthy case of LAM accompanied by lymphangioleiomyoma in the retroperitoneal space during pregnancy, a scenario susceptible to misdiagnosis. Case presentation: A 31-year-old woman, facing an unintended pregnancy, presented during the 13th week with a cystic-solid mass exhibiting abundant blood signals in the pelvic cavity, as revealed by routine obstetrical ultrasound. Concurrently, her chest CT disclosed diffuse thin-walled cavities in both lungs. Despite the absence of clinical symptoms, the patient abandoned pregnancy and underwent a complete curettage. However, 24 days post-operation, she was readmitted for further assessment, revealing an enlargement of the mass encompassing the abdominal aorta and inferior vena cava, along with compression on the middle and lower segments of the ureter. After a multi-disciplinary discussion and patient explanation, an exploratory laparotomy was performed, resulting in the complete removal of the tumor. Intraoperative pathological examination and immunohistochemical staining indicated a retroperitoneal mass devoid of malignant evidence. The comprehensive morphologic and immunophenotypic features substantiated the diagnosis of lymphangioleiomyomatosis. The postoperative course was uneventful, culminating in the patient's discharge. Conclusion: The consideration of Lymphangioleiomyomatosis (LAM) with a retroperitoneal tumor is crucial in the differential diagnosis of pelvic and abdominal masses. The preoperative diagnosis of this tumor poses a challenge, as ultrasound or CT scans may not yield definitive results. Accurate diagnosis necessitates not only a pathological examination of the retroperitoneal mass but also the correlation with the patient's chest High-Resolution Computed Tomography (HRCT) findings and corresponding clinical manifestations. Optimal management involves radical surgery, with surgeons comprehensively factoring in both fetal and maternal conditions when formulating a treatment plan.

Revisiting the immune landscape post spinal cord injury: More than black and white.

Spinal cord injury (SCI) induced catastrophic neurological disability is currently incurable, especially in elderly patients. Due to the limited axon regeneration capacity and hostile microenvironment in the lesion site, essential neural network reconstruction remains challenging. Owing to the blood-spinal cord barrier (BSCB) created immune cells and cytokines isolation, the immune elements were incorrectly recognized as innocent bystanders during the SCI pathological process traditionally. Emerging evidence demonstrated that the central nervous system (CNS) is an "immunological quiescent" rather than "immune privileged" area, and the CNS-associated immune response played mixed roles which dedicate beneficial and detrimental contributions throughout the SCI process. Consequently, coordinating double-edged immunomodulation is vital to promote tissue repair and neurological recovery post-SCI. The comprehensive exploration and understanding of the immune landscape post-SCI are essential in establishing new avenues for further basic and clinical studies. In this context, this review summarizes the recent significant breakthroughs in key aspects of SCI-related immunomodulation, including innate and adaptive immune response, immune organ changes, and holistic immune status modification. Moreover, the currently existing immune-oriented therapies for SCI will be outlined.

High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study.

Objective: This study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM). Methods: This is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0-2 points) and poor outcome groups (mRS scores of 3-6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model. Results: The CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age. Conclusion: High CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.

Development of a humanized HLA-A30 transgenic mouse model.

BACKGROUND: There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-A-restricted responses against infection in human. METHODS: A recombinant gene encoding the chimeric HLA-A30 monochain was constructed. This HHD molecule contains the following: α1-α2 domains of HLA-A30, α3 and cytoplasmic domains of H-2Db , linked at its N-terminus to the C-terminus of human ß2m by a 15-amino-acid peptide linker. The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination. Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed. RESULTS: We describe a novel human ß2m-HLA-A30 (α1α2)-H-2Db (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA-A01 gene locus including 49 kb 5'-UTR and 74 kb 3'-UTR of HLA-A01*01. Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30-18# and A30-19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice, and induced the rapid increase of cytokines, including IFN-γ, TNF-α, and IL-6, in both HLA-A30 humanized Tg mice and wild-type mice. The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9# line at 3 days post-infection (dpi). CONCLUSIONS: We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse, which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development, and support the study of HLA-A-restricted responses against infection in humans.

Is Tranexamic Acid Beneficial in Open Spine Surgery? and its Effects Vary by Dosage, Age, Sites, and Locations: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of tranexamic acid (TXA) in controlling blood loss during spine surgery remains unclear. With the publication of new randomized controlled trials (RCTs), we conducted a meta-analysis to determine the safety and efficacy of TXA in spine surgery. METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for relevant studies through 2022. Only RCTs were eligible for this study. The extracted data were analyzed using RevMan 5.3 software for meta-analysis. RESULTS: Twenty RCTs including 1497 patients undergoing spine surgery were included in this systematic evaluation. Compared with the control group, TXA significantly reduced total blood loss (mean difference [MD] = - 218.96, 95% confidence interval [CI] = - 309.77 to - 128.14, P < 0.00001), perioperative blood loss (MD = - 90.54, 95% CI = - 139.33 to - 41.75, P = 0.0003), postoperative drainage (MD = - 102.60, 95% CI = - 139.51 to - 65.70, P < 0.00001)，reduced hospital stay (MD = - 1.42, 95% CI = - 2.71 to - 0.14, P = 0.03), reduced total blood transfusion volume (MD = - 551.06, 95% CI = - 755.90 to - 346.22, P < 0.00001), and international normalized ratio (MD = -0.03, 95% CI = -0.04 to -0.02, P < 0.00001). CONCLUSIONS: Based on the meta-analysis of 20 RCTs, we demonstrated that TXA reduces blood loss in open spine surgery, decreases transfusion rates, and shortens hospital stays. The TXA administration during the perioperative period does not increase the incidence of postoperative complications.

Acbp is essential for decidualization during early pregnancy in mice.

Decidualization of uterine stromal cells plays an important role in the establishment of normal pregnancy. Previous studies have demonstrated that Acyl-CoA binding protein (Acbp) is critical to cellular proliferation, differentiation, mitochondrial functions, and autophagy. The characterization and physiological function of Acbp during decidualization remain largely unknown. In the present study, we conducted the expression profile of Acbp in the endometrium of early pregnant mice. With the occurrence of decidualization, the expression of Acbp gradually increased. Similarly, Acbp expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. We applied the mice pseudopregnancy model to reveal that the expression of Acbp in the endometrium of early pregnant mice was not induced by embryonic signaling. Moreover, P4 significantly upregulated the expression of Acbp, whereas E2 appeared to have no regulating effect on Acbp expression in uterine stromal cells. Concurrently, we found that interfering with Acbp attenuated decidualization, and that might due to mitochondrial dysfunctions and the inhibition of fatty acid oxidation. The level of autophagy was increased after knocking down Acbp. During induced decidualization, the expression of ACBP was decreased with the treatment of rapamycin (an autophagy inducer), while increased with the addition of Chloroquine (an autophagy inhibitor). Our work suggests that Acbp plays an essential role in the proliferation and differentiation of stromal cells during decidualization through regulating mitochondrial functions, fatty acid oxidation, and autophagy.

Remodeling Effects of the Combination of GGT Scaffolds, Percutaneous Electrical Stimulation, and Acupuncture on Large Bone Defects in Rats.

The regeneration defect of bone is a long-term physiological process after bone injuries. To accelerate the bone remodeling process, the combination of chemical and physical stimulations provides an efficient strategy to allow maturation and to functionalize osteoclasts and osteoblasts. This study aims to investigate the dual effects of a tricalcium phosphate (TCP)-based gelatin scaffold (GGT) in combination with electroacupuncture stimulation on the activation of osteoclasts and osteoblasts, as well as new bone regrowth in vitro and in vivo. We demonstrated that electrical stimulation changes the pH of a culture medium and activates osteoblasts and osteoclasts in an in vitro co-culture system. Furthermore, we showed that electroacupuncture stimulation can enhance osteogenesis and new bone regrowth in vivo and can upregulate the mechanism among parathyroid hormone intact (PTH-i), calcium, osteoclasts, and osteoblasts in the bone-defected rats. Those results showed the potential interest to combine the electroacupuncture technique with GGT scaffolds to improve bone remodeling after injury.

The Expression of CLDN6 in Hepatocellular Carcinoma Tissue and the Effects of CLDN6 on Biological Phenotypes of Hepatocellular Carcinoma Cells.

CLDN6, a member of claudin (CLDN) family, was found to be a breast cancer suppressor gene in our early experiments. However, CLDN6 was highly expressed in human hepatocellular carcinoma (hHCC) (TCGA database), and the role of CLDN6 in hHCC is still unclear. To investigate the expression of CLDN6, immunohistochemical staining was performed in hHCC tissues. As a result, hHCC tissues highly expressed CLDN6, and the expression was related to the degree of tumor's differentiation. To research the role of CLDN6 in hHCC cells, CLDN6 was silenced in HepG2 and Hep3B cells which highly expressed CLDN6 through liposome transfection. Results showed that after silencing of CLDN6, the proliferation, migration and invasion abilities of hHCC cells were inhibited. Meanwhile, the expression of E-cadherin was upregulated, and the expression of N-cadherin and Vimentin was downregulated. All the results above indicated that CLDN6 promoted the development of hHCC, and could be a potential target for the treatment of it.

Generation and expression analysis of BAC humanized mice carrying HLA-DP401 haplotype.

Background: Human leukocyte antigen (HLA)-DP is much less studied than other HLA class II antigens, that is, HLA-DR and HLA-DQ, etc. However, the accumulating data have suggested the important roles of DP-restricted responses in the context of cancer, allergy, and infectious disease. Lack of animal models expressing these genes as authentic cis-haplotypes blocks our understanding for the role of HLA-DP haplotypes in immunity. Methods: To explore the potential cis-acting control elements involved in the transcriptional regulation of the HLA-DPA1/DPB1 gene, we performed the expression analysis using bacterial artificial chromosome (BAC)-based transgenic humanized mice in the C57BL/6 background, which carried the entire HLA-DP401 gene locus. We further developed a mouse model of Staphylococcus aureus pneumonia in HLA-DP401 humanized transgenic mice, and performed the analysis on the expression pattern of HLA-DP401 and immunological responses in the model. Results: In this study, we screened and identified a BAC clone spanning the entire HLA-DP gene locus. DNA from this clone was analyzed for integrity by pulsed-field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR primers for regional markers with an average distance of 15 kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA-DPA1/DPB1 gene. Transgene copy numbers were determined by real-time PCR analysis. HLA-DP401 gene expression was analyzed at the mRNA and protein level. Although infection with S aureus Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA-DP401-H2-Aß1 humanized mice. Increased expression of HLA-DP401 was observed in the thymus of the humanized mice infected by S aureus. Conclusions: We generated several BAC transgenic mice, and analyzed the expression of HLA-DPA1/DPB1 in those mice. A model of Saureus-induced pneumonia in the HLA-DP401-H2-Aß1-/- humanized mice was further developed, and S aureus infection upregulated the HLA-DP401 expression in thymus of those humanized mice. These findings demonstrate the potential of those HLA-DPA1/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC-associated immunological diseases.

Predictive risk factors for recollapse of cemented vertebrae after percutaneous vertebroplasty: A meta-analysis.

BACKGROUND: As one of the most common complications of osteoporosis, osteoporotic vertebral compression fracture (OVCF) increases the risk of disability and mortality in elderly patients. Percutaneous vertebroplasty (PVP) is considered to be an effective, safe, and minimally invasive treatment for OVCFs. The recollapse of cemented vertebrae is one of the serious complications of PVP. However, the risk factors associated with recollapse after PVP remain controversial. AIM: To identify risk factors for the recollapse of cemented vertebrae after PVP in patients with OVCFs. METHODS: A systematic search in EMBASE, MEDLINE, the Cochrane Library, and PubMed was conducted for relevant studies from inception until March 2020. Studies investigating risk factors for the recollapse of cemented vertebrae after PVP without additional trauma were selected for analysis. Odds ratios (ORs) or standardized mean differences with 95% confidence interval (CI) were calculated and heterogeneity was assessed by both the chi-squared test and the I-squared test. The methodological quality of the included studies was assessed according to the Newcastle-Ottawa Scale. RESULTS: A total of nine case-control studies were included in our meta-analysis comprising 300 cases and 2674 controls. The significant risk factors for the recollapse of cemented vertebrae after PVP in OVCF patients were fractures located at the thoracolumbar junction (OR = 2.09; 95%CI: 1.30 to 3.38; P = 0.002), preoperative intravertebral cleft (OR = 2.97; 95%CI: 1.93 to 4.57; P < 0.00001), and solid lump distribution pattern of the cement (OR = 3.11; 95%CI: 1.91 to 5.07; P < 0.00001). The analysis did not support that age, gender, lumbar bone mineral density, preoperative visual analogue scale score, injected cement volume, intradiscal cement leakage, or vertebral height restoration could increase the risk for cemented vertebra recollapse after PVP in OVCFs. CONCLUSION: This meta-analysis suggests that thoracolumbar junction fractures, preoperative intravertebral cleft, and solid lump cement distribution pattern are associated with the recollapse of cemented vertebrae after PVP in OVCF patients.

Morphologic analysis of Chinese lumbar endplate by three-dimensional computed tomography reconstructions for helping design lumbar disc prosthesis.

ABSTRACT: Lumbar disc prostheses have been used increasingly in recent years. The successful design of lumbar disc prostheses depends on accurate morphometric parameters. However, the morphologic dimensions of lumbar endplate area have not been investigated in Chinese population.A total of 1800 lumbar endplates were retrospectively accessed in 150 Chinese adults. Eighteen parameters of each lumbar segment were measured by three-dimensional computed tomography reconstructions from T12/L1 to L5/S1. These obtained parameters were compared between genders, bilateral sides, vertebral segments, and different populations.Endplate length and width increased in general, and there was a significant decrease for length/width ratio from T12 to S1 (P = .03). The average concavity depth of the lower lumbar endplate (2.09 ±â€Š0.93 mm) was usually larger than that of the upper lumbar endplate (1.61 ±â€Š0.74 mm) (P = .02). The percentage of the most concave point of the upper and lower lumbar endplate was 50.01 ±â€Š10.76% and 56.41 ±â€Š9.93%, respectively. Anterior, medium, or posterior intervertebral endplate height was severally 10.01 ±â€Š1.98 mm, 10.46 ±â€Š2.03 mm, and 6.41 ±â€Š1.74 mm, and increased among vertebral segments (P = .01).The intervertebral endplate angle significantly increased from T12-L1 to L5-S1 (P = .01). Parameters displayed significant difference between genders. The morphometric parameters of different populations also showed differences.In conclusion, there is a morphologic discrepancy in dimensions of lumbar endplate regarding genders, vertebral segments, and different populations. It is essential to design the lumbar disc prosthesis suited for Chinese patients specially, for which the morphometric parameters in our study can be utilized.

Unlocking the Recovery Potential: JMJD3 Inhibition-Mediated SAPK/JNK Signaling Inactivation Supports Endogenous Oligodendrocyte-Lineage Commitment Post Mammalian Spinal Cord Injury.

Spinal cord injury (SCI) induced catastrophic neurological disability is often incurable at present. The injury triggered immediately oligodendrocytes loss and overwhelming demyelination are regarded as an insurmountable barrier to SCI recovery. To date, effective strategy to promote the endogenous oligodendrocytes replacement post SCI remains elusive. Epigenetic modifications are emerging as critical molecular switches of gene expression in CNS. However, the epigenetic mechanisms underlying oligodendrogenesis post SCI yet to be discovered. In this study, we report that H3K27me3 demethylase JMJD3 exists as a pivotal epigenetic regulator which manipulates the endogenous oligodendrogenesis post SCI. We found that JMJD3 inhibition promotes the oligodendrocyte linage commitment of neural stem/progenitor cells (NPCs) in vitro and in vivo. Moreover, we demonstrated that JMJD3 inhibition mediated SAPK/JNK signaling inactivation is functionally necessary for endogenous oligodendrocyte-lineage commitment post SCI. Our results also suggested that JMJD3 is downstream of SAPK/JNK pathway, and capable of translates SCI induced SAPK/JNK signaling into epigenetic codes readable by spinal cord endogenous NPCs. Taken together, our findings provide novel evidence of JMJD3 mediated oligodendrocyte-lineage commitment orchestration post SCI, which would be a potential epigenetic approach to induce the mature mammalian endogenous recovery.

Decoding epigenetic codes: new frontiers in exploring recovery from spinal cord injury.

Spinal cord injury that results in severe neurological disability is often incurable. The poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural circuits. Several intrinsic and extrinsic determinants contribute to this inability to reconnect. Epigenetic regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical genes. Recent studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration, glial activation and neurogenesis. These findings not only establish a theoretical foundation for further exploration of spinal cord injury, but also provide new avenues for the clinical treatment of spinal cord injury. This review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord injury. Together, these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.

Short-term exposure to noise on stroke volume and left ventricular contractility: A repeated-measure study.

Prolonged exposure to noise has been associated with cardiovascular disease, but the possible mechanism for its influence on cardiac activity is unknown. This study investigated the acute effects of noise exposure on 24-h ambulatory cardiac parameters among male workers. We recruited 75 volunteers in an aviation-industry cohort in 2009. Personal noise-exposure levels and individual cardiac parameters, including stroke volume (SV) and left ventricular contractility (LVC), were measured simultaneously over 24 h on working and nonworking days. Linear mixed-effects regression models were used to estimate transient and sustained effects on ambulatory SV and LVC among high-noise-exposure (≥80 A-weighted decibels [dBA]), low-noise-exposure (<80 dBA) and office workers. Every 1-dBA increase in noise exposure was significantly associated with transient changes of -1.50 (95% confidence interval [CI]: -2.18, -1.03) ml/beat in SV and -1.76 (-2.99, -1.03) L/sec in LVC at work on working days only among high-exposure workers. The 1-dBA increase in nocturnal noise exposure was also significantly associated with transiently decreased SV among high-exposure (-1.62 [-2.15, -1.22] ml/beat), low-exposure (-1.27 [-1.57, -1.03] ml/beat) and office workers (-1.09 [-1.18, -1.00] ml/beat), but only the high-exposure group had the transiently reduced LVC (-1.70, [-2.37, -1.22] L/sec) after the current noise exposure on nonworking days. Such decreasing effects persisted to become sustained decreases in 24-h ambulatory SV in high-exposure (-1.10 [-1.20, -1.01] ml/beat) and office workers (-1.13 [-1.22, -1.05] ml/beat) on working days and in all three groups (-1.19 [-1.36, -1.04]; -1.15 [-1.31, -1.02]; -1.08 [-1.13, -1.02] ml/beat, respectively) on nonworking days. No significant effect on 24-h ambulatory LVC was found in any group on working or nonworking days. Occupational and nocturnal noise exposure may have acute effects on 24-h ambulatory SV among male workers, directly influencing the cardiac function related to cardiovascular disease.

Behavior fusion for deep reinforcement learning.

For deep reinforcement learning (DRL) system, it is difficult to design a reward function for complex tasks, so this paper proposes a framework of behavior fusion for the actor-critic architecture, which learns the policy based on an advantage function that consists of two value functions. Firstly, the proposed method decomposes a complex task into several sub-tasks, and merges the trained policies for those sub-tasks into a unified policy for the complex task, instead of designing a new reward function and training for the policy. Each sub-task is trained individually by an actor-critic algorithm using a simple reward function. These pre-trained sub-tasks are building blocks that are used to rapidly assemble a rapid prototype of a complicated task. Secondly, the proposed method integrates modules in the calculation of the policy gradient by calculating the accumulated returns to reduce variation. Thirdly, two alternative methods to acquire integrated returns for the complicated task are also proposed. The Atari 2600 pong game and a wafer probe task are used to validate the performance of the proposed methods by comparison with the method using a gate network.