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Clinical studies have shown that there may be a certain relationship between pathological changes of the myodural bridge complex (MDBC) and chronic headaches of unknown cause. But there is still a lack of experimental evidence to explain the possible mechanism. This study aims to further confirm this relationship between MDBC and chronic headaches and explore its potential occurrence mechanism in rats. Bleomycin (BLM) or phosphate-buffered saline (PBS) was injected into the myodural bridge fibers of rats to establish the hyperplastic model of MDBC. After 4 weeks, the occurrence of headaches in rats was evaluated through behavioral scores. The immunohistochemistry staining method was applied to observe the expression levels of headache-related neurotransmitters in the brain. Masson trichrome staining results showed that the number of collagen fibers of MDBC was increased in the BLM group compared to those of the other two groups. It revealed hyperplastic changes of MDBC. The behavioral scores of the BLM group were significantly higher than those of the PBS group and the blank control group. Meanwhile, expression levels of CGRP and 5-HT in the headache-related nuclei of the brain were increased in the BLM group. The current study further confirms the view that there is a relationship between pathological changes of MDBC and chronic headaches of unknown cause. This study may provide anatomical and physiological explanations for the pathogenesis of some chronic headaches of unknown cause. [ABSTRACT FROM AUTHOR]

In the last two decades, many studies have focused on the muscles and dense connective tissues located in the suboccipital region. Our study investigated the existence of the second terminations originating from the suboccipital muscles, and the relationship between the variable types of the To Be Named Ligament (TBNL). Anatomical dissection was performed on 35 head-neck specimens. The existence of the second terminations of the suboccipital muscles was confirmed and various types of the TBNL were observed in this study. The second terminations originated from multiple suboccipital muscles including the rectus capitis posterior minor (RCPmi), rectus capitis posterior major (RCPma) and obliquus capitis inferior (OCI) muscles, merged and terminated at the TBNL. The overall incidence of the second terminations of the suboccipital muscles was 34.29% and it varied among the various suboccipital muscle origins. 28.57% of the second terminations originated from the RCPma; 11.43% was from the RCPmi and 8.57% was from the OCI. Furthermore, there was a significant relationship between the existence of second terminations and the particular type of the TBNL. 95% of the arcuate type of the TBNL was accompanied with the second terminations which attached to their turning part, whereas only 10% of all the radiate type of the TBNL was accompanied with the second terminations. This study for the first time described the second terminations originating from multiple suboccipital muscles and demonstrated the relationship with the various types of the TBNL. We speculated that the second terminations maintain the arcuate TBNL and transfer tensile forces to the Myodural Bridge (MDB), thereby modulating the physiological functions of the MDB. [ABSTRACT FROM AUTHOR]

Background: Salidroside is the major active component of Rhodiola rosea, a traditional Chinese herbal medicine used for protection against ultraviolet (UV) radiation. Objectives: This study investigated whether salidroside can protect skin from ultraviolet B (UVB)-induced oxidative damage in human immortalized HaCaT keratinocytes and the skin of guinea pigs. Methods: Using HaCaT cell models, the effects of salidroside on oxidative damage and possible regulatory factors [including NF-E2-related factor 2 (Nrf2), NAD(P)H-quinone oxidoreductase (NQO1), and heme oxygenase 1 (HO-1)] were examined. In addition, the regulatory effects of salidroside on apoptotic sunburn cells (SBCs) and 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive epidermal cells on UVB-exposed guinea pig skin were also investigated. Results: We found that salidroside pretreatment upregulated Nrf2 translocation to the nucleus and transcription activity in HaCaT cells, as reflected by the increased nuclear accumulation of Nrf2 as well as the gene and protein expression of downstream Nrf2 antioxidants, including NQO1 and HO-1. In addition, we also found that pretreatment with salidroside reactive oxygen species (ROS) in irradiated HaCaT cells. The oral administration of salidroside (0.1% w/w) to guinea pigs inhibited the UVB-mediated formation of apoptotic SBCs and 8-OHdG-positive epidermal cells in the skin of guinea pigs. Conclusions: Our results show that UVB-induced oxidative damage can be prevented by salidroside with upregulation of nuclear Nrf2 expression. [ABSTRACT FROM AUTHOR]

The myodural bridge was first described by Hack in 1995 and was thought to be related to chronic cervicogenic headaches. For a long time, few studies revealed the patterns of the myodural bridge considering the rectus capitis posterior minor muscle. In this study, P45 plastination technology and anatomical dissection were performed on head specimens, and four different terminal region types of the rectus capitis posterior minor muscle were observed, including the posterior atlanto-occipital interspace, posterior arch of the atlas and posterior atlanto-axial interspace. We propose that the myodural complex structures in the posterior atlanto-occipital and posterior atlanto-axial interspace have cooperative effects on cerebrospinal fluid and work together. This force might be an important source for the circulation of cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

Few studies have been conducted specifically on the dense connective tissue located in the posterior medial part of the cervical epidural space. This study was undertaken to examine the presence of this connection between the cervical dura mater and the posterior wall of spinal canal at the level of C1–C2. 30 head-neck specimens of Chinese adults were used. Gross dissection was performed on the suboccipital regions of the 20 specimens. Having been treated with the P45 plastination method, 10 specimens were sliced (9 sagittal and 1 horizontal sections). As a result, a dense fibrous band was identified in the nuchal ligament of 29 specimens (except for one horizontal section case). This fascial structure arose from the tissue of the posterior border of the nuchal ligament and then projected anteriorly and superiorly to enter the atlantoaxial interspace. It was termed as to be named ligament (TBNL). In all 30 specimens the existence of a fibrous connection was found between the posterior aspect of the cervical dura mater and the posterior wall of the spinal canal at the level of the atlas to the axis. This fibrous connection was identified as vertebrodural ligament (VDL). The VDL was mainly subdivided into three parts, and five variations of VDL were identified. These two structures, TBNL and VDL, firmly link the posterior aspect of cervical dura mater to the rear of the atlas-axis and the nuchal region. According to these findings, the authors speculated that the movements of the head and neck are likely to affect the shape of the cervical dural sleeve via the TBNL and VDL. It is hypothesized that the muscles directly associated with the cervical dural sleeve, in the suboccipital region, may work as a pump providing an important force required to move the CSF in the spinal canal. [ABSTRACT FROM AUTHOR]

Introduction: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited. Methods: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4+T, CD8+T, γδT, NK, and B cell frequencies using multi‐parameter flow cytometry. Results: Low frequencies of lymphocytes, T, CD4+T, and CD8+T cells were associated with significantly lower rates of one‐course complete remission (CR) (all p < 0.05). Moreover, the frequency of CD4+T cells independently predicted one‐course CR achievement (p = 0.021). Low frequencies of T and CD8+T cells were significantly associated with lower relapse‐free survival (RFS) rates (p = 0.032; 0.034), respectively, and a low frequency of CD8+T cells was associated with a significantly lower overall survival (OS) rate (p = 0.028). Combination of frequency of CD8+T cells and ELN risk stratification showed that patients with ELN‐intermediate/adverse risk + high CD8+T cell frequency had a similar RFS rate to those with ELN‐favorable risk + high CD8+T cell frequency and those with ELN‐favorable risk + low CD8+T cell frequency (p = 0.88; 0.76), respectively. The RFS rate of patients with ELN intermediate/adverse risk + low CD8+T cell frequency was significantly lower than that of all aforementioned patients (p = 0.021; 0.0007; 0.028), respectively. Conclusion: The frequencies of BM lymphocyte subsets at diagnosis predicted clinical outcomes and could help improve risk stratification in AML. [ABSTRACT FROM AUTHOR]

Many studies have confirmed that overexpressed WT1 exists in leukemic cells, especially in AML. However, the immunophenotypic features of this sort of leukemic cells remain to be unclarified. We retrospectively analyzed the immunophenotype of 283 newly diagnosed AML patients with intermediated and poor cytogenetic risk to evaluate the correlation between phenotype and WT1 overexpression. EVI1 transcripts, KMT2A-PTD, FLT3-ITD, and NPM1 mutations were simultaneously assessed. Our results revealed that overexpressed WT1 was significantly associated with the expression of CD117, CD13, and CD123. Besides, leukemic cells with WT1 overexpression also lacked lymphoid and myeloid differentiation-related markers. FAB subtype M2 patients had higher WT1 levels, compared with other FAB subtype. Multivariate analysis was proved that NPM1 mutation, M2 subtype, and the expression of CD123 were independently associated with WT1 overexpression. These indicated that AML with overexpressed WT1 was proliferated and blocked in the early stage of AML development. It presumably provided some clues to detect overexpressed WT1 cells via multiparameter flow cytometry. CD123-targeted drugs might become one of the alternative treatments for patients with WT1 overexpression. [ABSTRACT FROM AUTHOR]

Southwestern (SW) China is an area of active tectonism and erosion, yielding a dynamic, deeply eroded landscape that influences the genetic structure of the resident populations of plants and animals. Iron walnut (Juglans regia subsp. sigillata) is a deciduous tree species endemic to this region of China and cultivated there for its edible nuts. We sampled 36 iron walnut populations from locations throughout the species' range in SW China and genotyped a total of 765 individuals at five chloroplast DNA regions and 22 nuclear microsatellite loci. Species distribution models were produced to predict the evolution and historical biogeography of iron walnut and to estimate the impacts of climate oscillations and orographic environments on the species' demography. Our results indicated that J. regia subsp. sigillata had relatively low genetic diversity, high interpopulation genetic differentiation, and asymmetric interpopulation gene flow. Based on DIYABC analysis, we identified two lineages of J. sigillata in southwestern China. The lineages (subpopulations) diverge during the last glacial period (~1.34 Ma). Southwestern China was a glacial refuge during the last glacial period, but increasingly colder and arid climates might have fostered the fragmentation of J. regia subsp. sigillata within this refugium. Finally, we found that recent habitat fragmentation has led to a reduction in population connectivity and increased genetic differentiation by genetic drift in isolated populations. Our results support a conclusion that geological and climatic factors since the Miocene triggered the differentiation, evolutionary origin, and range shifts of J. sigillata in the studied region. [ABSTRACT FROM AUTHOR]

Highlights • A seven-color panel including CD34 and TdT was built to detect MRD in T-ALL. • The panel could be applied to >97% T-ALL patients independent of initial phenotype. • Only one MRD false-negative result occurred because of antigen shifts. • MRD positive detected by the panel at post-HSCT could effectively predict relapse. Abstract A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93.8% of patients at diagnosis and 86.7% of patients who relapsed. Although some of the immature markers had disappeared in 23 of 59 cases after therapy, only one case presented with a false negative MRD. Of the 74 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), MRD-positive patients showed a higher relapse rate, a higher cumulative incidence of relapse at 4 years and a shorter median relapse-free survival than MRD-negative patients at post-HSCT(72.7% vs 17.3%, P = 0.000; 100% vs 19.9%, P < 0.0001; and 16 months vs undefined, P < 0.0001). We demonstrated that this panel could be applied to>97% of T-ALL patients to detect MRD and predict relapse after allo-HSCT even in the absence of the initial immunophenotype. [ABSTRACT FROM AUTHOR]

Background Context: Studies over the past 20 years have revealed that there are fibrous connective tissues between the suboccipital muscles, nuchal ligament, and cervical spinal dura mater (SDM). This fibrous connection with the SDM is through the posterior atlanto-occipital or atlantoaxial interspaces and is called the myodural bridge (MDB). Researchers have inferred that the MDB might have important functions. It was speculated that the function of MDB might be related to proprioception transmission, keeping the subarachnoid space and the cerebellomedullary cistern unobstructed, and affecting the dynamic circulation of the cerebrospinal fluid. In addition, clinicians have found that the pathologic change of the MDB might cause cervicogenic or chronic tension-type headache. Previous gross anatomical and histologic studies only confirmed the existence of the MDB but did not reveal the fiber properties of the MDB. This is important to further mechanical and functional research on the MDB.Purpose: Multiple histologic staining methods were used in the present study to reveal the various origin and fiber properties of the MDB. Muscles and ligaments participating in forming the MDB at the posterior atlanto-occipital or atlantoaxial interspaces were observed, and the fiber properties of the MDB were confirmed. The present study provides a basis for speculating the tensile force values of the MDB on the SDM and a morphologic foundational work for exploring the physiological functions and clinical significances of the MDB.Study Design: Anatomical and histologic analyses of suboccipital structures that communicate with the SDM at the posterior atlanto-occipital or atlantoaxial interspaces were carried out.Methods: Multiple histologic staining methods were used to evaluate the histologic properties and composition of the MDB at the posterior atlanto-occipital or atlantoaxial interspaces in five formalin-fixed head-neck human specimens.Results: The results show that the MDB traversing the atlanto-occipital interspace originated from the rectus capitis posterior minor (RCPmi). The MDB traversing the atlantoaxial interspace originated mainly from the RCPmi, rectus capitis posterior major, and obliquus capitis inferior. These fibers form the vertebral dural ligament in the atlantoaxial interspace and connect with SDM. The MDB is mainly formed by parallel running type I collagen fibers; thus, suboccipital muscle could pull SDM strongly through the effective force propagated by the MDB during head movement.Conclusions: Myodural bridge is mainly formed by parallel running type I collagen fibers; thus, it can transmit the strong pull from the diverse suboccipital muscles or ligaments during head movement. The results of the present study will serve as a basis for further biomechanical and functional MDB research. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate the morphological changes and potential correlation between chronic headaches and the rectus capitis posterior minor muscle (RCPmi). Methods Comparison of RCPmi between patients with chronic headaches and healthy adult volunteers were collected using magnetic resonance imaging (MRI) and Mimics software. Results Among the 235 MRI images analyzed, the data between the two groups were considered statistically significant. The number of males was larger than that of females ( p < 0.001) and the headache group showed greater hypertrophy than the control group in both males ( p < 0.001) and females ( p = 0.001). Conclusions Chronic headaches were correlated with the RCPmi. Patients with chronic headaches suffered from more obvious hypertrophy than that of the control group. Additionally, it was supposed that RCPmi hypertrophy may be one pathogenesis of the chronic headaches. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin disease for which immunomodulating calcineurin inhibitors have been considered reasonable treatment. We searched the MEDLINE, Embase, and Cochrane central register of controlled trials databases for articles published prior to September 2014. Thirteen studies were included in the meta-analysis. After pooling the trials, we concluded that calcineurin inhibitors showed a better therapeutic effect on vitiligo than placebo, according to lesion report (RR=2.62, 95% CI, 1.39-4.93, p=0.003) and patient report (RR=1.42, 95%, 0.87-2.31, p=0.157). Subgroup analysis was performed to determine whether the combination with phototherapy was a source of heterogeneity. The trial sequence analysis indicated that the results of combined therapy by lesion report were reliable and conclusive. However, in the patient report trials, the frequency of lesions on the hand and foot was higher, and the effect of combined therapy was still not significant. Calcineurin inhibitors showed a better therapeutic effect than placebo in the treatment of vitiligo with phototherapy. However, the typical UV-resistant sites (i.e., hand and foot) were still difficult to cure even with combined therapy. Because of concerns about photocarcinogenesis, the clinical application of combined therapy should be explored with caution. [ABSTRACT FROM AUTHOR]

Heat is known as an environmental factor that causes significant skin pigmentation, but its effects on melanogenesis have been poorly studied. It has been shown that mitogen-activated protein kinase (MAPK) is involved in ultraviolet B (UVB) and stress-induced melanogenesis in melanocytes. In this study, we investigated the effects of heat and UVB, on melanocyte melanogenesis, differentiation, and MAPK phosphorylation. The results showed that heat (1 h at 40 °C for 5 days) increased cell dendrites, enlarged cell bodies, and induced extracellular signal-regulated kinases (ERK)/p38/MITF activation but did not influence melanogenesis of human epidermal melanocytes from skin phototype III. UVB irradiation (20 mJ/cm for 5 days) induced melanogenesis and c-jun N-terminal kinases (JNK)/p38/MITF/tyrosinase activation in melanocytes from skin phototype III. UVB combined with heat resulted in much more significant tyrosinase activation and melanogenesis as compared with UVB alone in melanocytes from skin phototype III. Furthermore, heat treatment and UVB irradiation induced JNK, ERK, and p38 activation but not melanogenic and morphological changes in melanocytes from skin phototype I. These findings suggested that heat promoted melanocyte differentiation, probably via heat-induced ERK/p38/MITF/activation. Furthermore, heat had an additive effect on the UVB-induced tyrosinase activation and melanogenesis. These results provide a new clue for dermatologists for the treatment of hypopigmented skin disease with heat combined with UVB irradiation. [ABSTRACT FROM AUTHOR]