Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

Objective To study the endogenous glucocorticoid on rat femoral head microenvironment of 11 hydroxysteroid dehydrogenase expression ,and to discuss the influence of combined with femoral head pathological changes of the corresponding mechanism .Methods Sixty SD rats were divided into control group ,1‐month group ,3‐months group ,each 20 rats in group .1‐month group and 3‐months group inject cortisone acetate in the abdominal cavity intraperitoneal for 1‐month or 3‐months each .Im‐munohistochemical ,immunofluorescence ,Real‐time qPCR ,HE staining were employed in this study .Results From immunohisto‐chemical ,immunofluorescence ,Real‐time qPCR ,the 11 hydroxysteroid dehydrogenase content of 1‐month group and 3‐months group were higher than that of the control group(P<0 .05) .From HE staining we detected 1‐month group in the bone marrow cavity in‐creased in fat cells ,3‐months group subchondral trabecular bone density decreased ,compared with the control group(P< 0 .05) . Conclusion Supplement of corticosterone could promote rat femoral head microenvironment 11 hydroxysteroid dehydrogenase ex‐pression and subchondral trabecular bone density decrease .

OBJECTIVETo evaluate the results of autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL).

METHODSFrom January 2000 to December 2007, the clinical data of auto-HSCT in adults Ph-ALL with complete remession (CR) 1 according to BDHALL2000/02 protocol were analyzed.

RESULTSA total of 56 patients were enrolled and the probabilities of standard risk, intermediated risk and high-risk group were 41.1%, 33.9%, and 25.0%, respectively. After a median follow-up of 75 months (range 7-177 months), the 5-year overall survival (OS), events free survival (EFS) and relapse free survival (RFS) were (51.8 ± 6.7)%, (51.8 ± 6.7)%, and (60.5 ± 6.9)%, respectively. And the 5-year accumulative relapse rate was (39.1 ± 6.9)%. The 5-year OS of standard risk, intermediate risk, high-risk group were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 2.8)%, respectively. The 5-year RFS among three groups were (68.3 ± 9.9)%, (62.5 ± 12.1)%, and (44.9 ± 14.1)%, respectively. The 5-year EFS among three groups were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 12.8)%, respectively. The 5-year accumulative relapse rate among three groups were (31.7 ± 9.9)%, (37.5 ± 12.1)%, and (55.1 ± 14.1)%, respectively. There was no statistical significance of any survival rates between standard and intermediate risk groups, just as intermediate and high-risk groups. The OS and EFS in standard risk group were superior to those in high-risk group (P=0.040 and P=0.029, respectively), while there was no statistical significance of RFS and accumulative relapse rate between the two groups. The clinical factors listed below did not influenced the prognosis in the univariate analysis (P>0.05), including more than 5 weeks reaching to CR, WBC count at diagnosis, different immunophenotype (T or B cells), myeloid antigen expression, hyperdiploid chromosome karyotype, complex chromosome abnormality, conditioning regimen with or without TBI, duration between transplantation and diagnosis.

CONCLUSIONPh-ALL adults could achieve a satisfactory CR and better survial according to BDHALL2000/02 protocol followed by auto-HSCT, especially for the standard or intermediate risk group, and no-donors high-risk patients.

Adult ; Autografts ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunophenotyping ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Survival Rate

BACKGROUND:For reason of pathological particularity, treatments for young adult patients with lumbar disc herniation require more demanding procedures. Traditional discectomy and rigid fixation and fusion receive a lower clinical satisfaction rate because of their concomitant complications. Waveflex is a semi-rigid fixation system with non-fusion pedicle screws. Once combined with the technology of annulus repair, it can maintain the normal movement of the segments, and can thus raise clinical satisfaction rate. OBJECTIVE:To evaluate the short-term efficacy of the treatment of young adult lumbar disc herniation through the technology of the posterior Waveflex non-fusion pedicle screw elastic fixed smal window nucleus pulposus extirpation associated with annulus repair. METHODS: Thirty-eight patients with lumbar disc herniation were involved in this study, among which, 18 cases in the elastic fixation group were subjected to a posterior lumbar smal window nucleuspulposus extraction along with annulus repair together bound with Waveflex elastic fixation; the rest 20 cases in the nucleus pulposus removal group underwent simple nucleus pulposus extirpation. After these operations, a series of folow-up study was conducted, including: folow-up analysis of clinical efficacy and complications, colection of low-back pain visual analogue scores, colection of Japanese Orthopaedic Association scores (JOA), regular assessment of Oswestry dysfunction index, and reevaluation of the lumbar lateral radiographs related indicators. RESULTS AND CONCLUSION:Folow-up visits to the patients were conducted 12-20 months later since the operations. Both groups showed a better performance than before treatment in the pain visual analogue scale, low back pain JOA score, and Oswestry dysfunction index of low-back pain (P < 0.05) during the last visit. The pain visual analogue scale, low back pain JOA score, and Oswestry dysfunction index of low-back pain in the dynamic fixation group were superior to those in the nucleus pulposus removal group (P <0.05). Stil in the last folow-up, operative segment disc height in the dynamic fixation group was greater than that before treatment, and the operative segment range of motion was smaler than that before treatment (P <0.05). These results suggest that compared to nucleus pulposus removal, Waveflex system associated with nucleus pulposus excision annulus repair has a more satisfactory effect in the early recovery of lumbar spine function and exerts a positive effect on the stability of the operated segments in the treatment of lumbar protrusion of the intervertebral disc in young adults.