Contribution of AMPA Receptor-Mediated LTD in LA/BLA-CeA Pathway to Comorbid Aversive and Depressive Symptoms in Neuropathic Pain.

Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.SIGNIFICANCE STATEMENT Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPAR endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.

lncRNA HAND2-AS1 overexpression inhibits cancer cell proliferation in hepatocellular carcinoma by downregulating RUNX2 expression.

BACKGROUND: The long non-coding RNA HAND2 antisense RNA 1 (HAND2-AS1) acts as a tumor suppressor in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we aimed to investigate the function of HAND2-AS1 in HCC. METHODS: The expression levels of HAND2-AS1 and runt-related transcription factor 2 (RUNX2) were determined in patients with HCC and HCC cell lines using quantitative real-time polymerase chain reaction and western blot analyses. Cell proliferation was determined using Cell Counting Kit-8 assay, and the correlation between HAND2-AS1 and RUNX2 expression was also investigated. RESULTS: The plasma level of HAND2-AS1 was downregulated and that of RUNX2 was upregulated in patients with early-stage HCC compared with those in healthy controls. No significant differences in the plasma levels of HAND2-AS1 and RUNX2 were found among hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)-positive, and HBV- and HCV-negative patients with HCC. The plasma levels of HAND2-AS1 and RUNX2 were inversely correlated in the patient groups but not in the control group. HAND2-AS1 overexpression led to the downregulation of RUNX2 expression in human HCC cells, whereas RUNX2 failed to significantly affect HAND2-AS1 expression. HAND2-AS1 overexpression inhibited and RUNX2 overexpression promoted the proliferation of HCC cells. RUNX2 overexpression attenuated the inhibitory effects of HAND2-AS1 overexpression on cancer cell proliferation. CONCLUSION: HAND2-AS1 overexpression inhibits cancer cell proliferation in HCC by downregulating RUNX2 expression.

Spatio-temporal expression of miRNA159 family members and their GAMYB target gene during the modulation of gibberellin-induced grapevine parthenocarpy.

Grapevine, Vitis vinifera, is an important economic fruit crop that is highly sensitive to gibberellin (GA), and the exogenous application of GA can efficiently induce grapevine parthenocarpy. However, the molecular mechanisms underlying this process remain elusive. In this study, morphological changes during flower development in response to GA treatments were examined in the 'Zuijinxiang' cultivar. To obtain insights into the roles of miRNA159s in GA-induced grapevine parthenocarpy, VvmiR159a, VvmiR159b, VvmiR159c, and their target gene VvGAMYB were isolated, sequenced and characterized. Spatial-temporal expression analyses showed that VvmiR159c exhibited the highest expression levels at 4 d before flowering, followed by a gradual decrease, while VvGAMYB displayed an opposite pattern of expression with the lowest expression at the corresponding stage in response to GA treatment. A cleavage interaction between VvmiR159s and VvGAMYB and variations of their cleavage roles were confirmed in grapevine floral development. In addition, the potential roles of VvmiR159s in GA signaling were investigated through DELLA-protein repressors, indicating that GA-DELLA (SLR1)-VvmiR159c-VvGAMYB is the key signaling regulatory module in grapevine. Our findings provide novel insights into the GA-responsive roles of VvmiR159s in modulating grapevine floral development, which have important implications for the molecular breeding of high-quality seedless grapevine berry.

Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats.

Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of tBHQ (0.8µg/day), or oxygen free radical scavenger tempol (20µg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of tBHQ or tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition, tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore, tBHQ attenuated PVN levels of ROS, the expression of proinflammatory cytokines and restored the imbalance of neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated small interfering RNA abrogated the protective effects of tBHQ on hypertension. These findings suggest that PVN administration of tBHQ can attenuate hypertension by activation of the Nrf2-mediated signaling pathway.

[Expression of Tcf-4, MMP7 and Survivin in Colorectal Cancer and Its Clinical Significance].

OBJECTIVE: To explore the clinical and pathological significance and correlations among the xpressions of Tcf-4, MMP7 and survivin in colorectal cancer. METHODS: The expressions of Tcf-4, MMP7 and survivin mRNA in tumor tissues and adjacent normal mucosa from 50 colorectal cancer patients were detected by reverse transcription PCR (RT-PCR). The expressed proteins of Tcf-4, MMP7 and survivin were measured using mmunohistochemistry staining technique (Elivision) in 100 colorectal cancer samples and 60 normal mucosa tissue samples. We analyzed the correlations between those measurements and their associations with clinical and pathological characteristics. RESULTS: Positive expressions of Tcf-4, MMP7 and survivin mRNA were found in both cancer and adjacent mucosa tissues, despite a higher level of expression in the cancer tissues (P < 0.01). Expressed proteins were detected in cancer tissues of 69.00% (69/100) of those with a positive Tcf-4 expression, 77.00% (77/100) of those with a positive MMP7 expression, and 65.00% (65/100) of those with a positive survivin expression. Compared with cancer tissues, lower levels of protein expression were found in normal mucosa tissues [16.67% (10/60) for Tcf-4, 13.33% (8/60) for MMP7 and 15.00% (9/60) for survivin, P < 0.01]. The expressions of Tcf-4, MMP7 and survivin were all associated with lymphatic metastasis and Dukes staging (P < 0.05). MMP7 expression was associated with depth of tumor invasion (P < 0.05). Survivin expression was associated with tumor differentiation. The Spearman rank correlation analyses showed that protein expressions in colorectal cancer tissues in those with a positive Tcf-4 were correlated with those with a positive MMP7 (r = 0.302) and those with a positive survivin (r = 0.279) (P < 0.01), but not in those with a positive MMP7 and those with a positive survivin (r = 0.097, P > 0.05). CONCLUSION: The expression levels of Tcf-4, MMP7 and survivin are high in colorectal cancer, all being linked to lymph node metastasis and Dukes stages of patients. This suggests that they may be involved in the occurrence, development, malignant growth and clinical progression of colorectal cancer.

[Expression of secreted frizzled related protein 1, ß-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances].

OBJECTIVE: To investigate the expression of secreted frizzled-related protein 1 (SFRP1), ß-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significance. METHODS: The expression of SFRP1, ß-catenin and E-cadherin mRNA and protein in tumor and pericancerous tissue samples from 60 cases of colorectal cancer was assayed by reverse-transcription PCR and immunohistochemistry, respectively. The correlation of their expression with clinicopathological factors of colorectal cancer was analyzed. RESULTS: In 52/60 cases the relative mRNA expression of SFRP1 in cancer tissue and pericancerous tissue was 0.4837±0.1532 and 0.7170 ±0.1830; for ß-catenin was 0.9293± 0.3705 and 0.6469±0.3166; and for E-cadherin was 0.5556±0.2535 and 0.9422±0.2372 (P<0.01), respectively. SFRP1 mRNA expression was associated with lymphatic metastasis (P<0.05). The positive rate of SFRP1 in colorectal cancer was 31.67% (19/60), and was significantly lower than that in pericancerous colorectal mucosa (75.00%, 45/60). No relationship between SFRP1 protein expression and clinical pathology was found. Abnormal expression rates of ß-catenin and E-cadherin in colorectal cancer were 75.00% (45/60) and 58.33% (35/60), respectively, which were significantly higher than that in pericancerous colorectal mucosa (1.67% and 6.67%), respectively. Abnormal ß-catenin and E-cadherin expression was associated with tumor differentiation, lymphatic metastasis and Duke's staging. SFRP1 protein expression was negatively correlated with ß-catenin and E-cadherin expression (r=-0.517, -0.442, Ps<0.01). CONCLUSION: Down-regulation of SFRP1 in colorectal cancer may cause abnormal Wnt signaling and induce abnormal ß-catenin and E-cadherin expression, indicating that SFRP1 might be involved in the development and progression of colorectal cancer, and could be a novel therapeutic target for colorectal cancer.

Characterization of grapevine microR164 and its target genes.

MicroRNAs (miRNAs) are an extensive class of newly identified small RNAs that regulate gene expression at post-transcription level by mRNA cleavage or translation. In our study, we used qRT-PCR and found that Vv-miR164 is expression in grapevine leaves, stems, tendrils, inflorescences, flowers and fruits. In addition, two potential target genes for Vv-miR164 were also found and verified by PPM-RACE and RLM-RACE. The results not only maps the cleavage site of the target mRNA but allowed for detection the expression pattern of cleaved fragments that can indicate the regulatory function of this miRNA on its target genes. These target genes were explored by qRT-PCR where some exhibited different expression patterns from their corresponding miRNA, indicating the cleavage mode of the miRNA on its target genes. The efficient and powerful approach used in this study can help in further understanding of how miRNAs cleaved their target mRNAs. Results from this study prove the importance of Vv-miR164 in regulating development and growth of grapes, and adds to the existing knowledge of small RNA-mediated regulation in grapes.

Analysis of expressed sequence tags from grapevine flower and fruit and development of simple sequence repeat markers.

A total of 6,230 EST sequences were produced from 7,561 clones in a cDNA library generated from grapevine (Vitis vinifera cv. 'Summer Black') flower and fruit tissues in this study. After cluster and assembly analysis of the datasets, 3,582 unigenes (GenBank accession numbers GW836604-GW840185) were established, among which 381 were new grapevine EST sequences. Out of the 381 new ESTs, 289 could be mapped on the 19 grapevine chromosomes. 913 unique ESTs with known or putative functions were assigned to 11 putative cellular roles. 540 potentially workable grapevine EST-SSRs were developed from 3,582 unigenes and about 42.6% of these unigenes were identified as true-to-type SSR loci and could amplify polymorphic bands from 22 individual plants of V. vinifera L, indicating that grapevine EST datasets are a valuable source for the development of functional simple sequence repeat (SSR) markers.

Computational identification of MicroRNAs in strawberry expressed sequence tags and validation of their precise sequences by miR-RACE.

MicroRNAs (miRNAs) are small, endogenously expressed, nonprotein-coding RNAs that regulate gene expression at the post-transcriptional level in both animals and plants through repressing translation or inducing mRNA degradation. A comprehensive strategy to identify new miRNA homologs by mining the repository of available strawberry expressed sequence tags (ESTs) was developed. By adopting a range of filtering criteria, we identified 11 potential miRNAs belonging to 5 miRNA families from 47 890 Fragaria vesca EST sequences. Using 2 specific 5' and 3' miRNA RACE PCR reactions and a sequence-directed cloning method, we accurately determined both end sequences of 5 candidate miRNAs. Meanwhile, qRT-PCR was used to detect the expression of these 5 miRNAs in different strawberry organs and tissues at several growing stages. These newly identified F. vesca miRNAs (fve-miRNAs) and their expression information can improve our understanding of possible roles of fve-miRNAs in regulating the growth and development of F. vesca.

Isolation and characterization of two YUCCA flavin monooxygenase genes from cultivated strawberry (Fragaria × ananassa Duch.).

UNLABELLED: In strawberry (Fragaria × ananassa Duch.), auxin has been recognized as the main signal molecule coordinating the growth and initiation of ripening of fruits. The molecular mechanism regulating auxin biosynthesis in strawberry remains unknown. This project reports two YUCCA flavin monooxygenase genes FaYUC1-2 isolated from cultivated strawberry. FaYUC1 and FaYUC2 are most homologous to AtYUC6 and AtYUC4, respectively. Significant expression of FaYUC1-2 is found in vegetative meristems and reproductive organs, with overlapping but distinct patterns. During fruit development, both transcripts of FaYUC1 and FaYUC2 in achenes reach a peak around large green fruit (G2) stage, but the sudden rise in FaYUC2 transcript level is much steeper and begins earlier than that in FaYUC1. FaYUC2 is also obviously expressed in the receptacles from green fruits, hinting another auxin source for receptacle development, other than achenes. FaYUC1 over-expression Arabidopsis exhibits typical auxin hyper-accumulation phenotype in many aspects, such as the narrow and downward curled leaves, strong apical dominance, short and hairy root. It is also severely sterile, due to the disruption of floral meristems initiation and floral organs development. Transgenic analysis indicates that strawberry YUC gene may hold conserved role in auxin biosynthesis like their homologs in other plants. Integrated with the spatiotemporal expression features, these results led us to propose that FaYUC1-2 may involve in many developmental processes including flower and fruit development in strawberry. KEY MESSAGE: This paper is the first report of isolation and characterization of strawberry auxin biosynthesis genes. And their conserved functions in auxin biosynthesis were confirmed after ectopic expression.

Perigastric Hyaline-Vascular Variant Castleman's Disease.

Castleman disease (CD) is a rare chronic lymphoproliferative disease with unknown etiology and pathogenesis disease. When the lesion is located in the mediastinum, the diagnosis of CD is easy. However, if the lesion presents as a perigastric mass mimicking other subserosal gastric mesenchymal tumors, the diagnosis can be challenging. As few sonographic manifestations of hyaline-vascular variant CD, especially contrast-enhanced ultrasound (CEUS) imaging, as well as computed tomography (CT) and histopathological imaging, have been reported in literature, this case may provide a vivid example of a comprehensive CEUS and CT usage in the diagnosis and surgery with regard to CD. This report presents a case of a 50-year-old female diagnosed with hyaline-vascular variant CD in a random physical examination, the ultrasound examination first revealed a 24.3 mm × 15.4 mm hypoechogenic lesion abutting the stomach, esophagus, and liver, which was under the suspicion of gastrointestinal stromal tumor. Following a series of medical examinations, including CEUS, CT, postoperative histopathological examination, and immunohistochemical analysis, the patient was diagnosed with hyaline-vascular variant unicentric CD. After the mass was completely excised through laparoscopic surgery, the woman recovered very well without recurrence during a follow-up period of 15 months. Thus, mastering ultrasound and CT-imaging characteristics of CD and applying ultrasound and CT examination together would do help to preoperative diagnosis.

Wnt7a promotes muscle regeneration in branchiomeric orbicularis oris muscle.

BACKGROUND: The orbicularis oris muscle exhibits a deficiency in cleft lip patients. Compared with the somite-derived limb muscles, the regeneration performance of the branchiomeric orofacial muscle has seldom been investigated. OBJECTIVE: This study aims to explore the possibility of augmenting the orbicularis oris muscle through the stimulus of Wnt7a. METHODS: Adult rat orbicularis oris muscle and tibialis anterior muscle were injected with recombinant human Wnt7a protein. The muscles were harvested at different time points after Wnt7a delivery. Muscle regeneration-related activity, including cell proliferation, stem cell proportion, myofiber plasticity, and total fiber number, was examined. RESULTS: Adult rat orbicularis oris muscle and tibialis anterior muscle exhibit similar regeneration-related activities after Wnt7a administration. Recombinant human Wnt7a administration resulted in enhanced cell proliferation, stem cell expansion, and fiber type remodelling in rat orbicularis oris muscle. In addition, newly formed myofibers were detected, contributing to an increased total fiber number. CONCLUSION: Wnt7a induces vigorous regeneration in rat orbicularis oris muscle. This study helps lay a foundation for developing biotherapies to combat orofacial muscle deficiency.

Role of argon plasma coagulation in treatment of esophageal varices.

With the development of endoscopic therapy, argon plasma coagulation (APC) has been widely used by endoscopists. It has many advantages, such as simple to operate, low cost, and minimal invasiveness. Because of its capability of lesion ablation and hemostasis, APC has several indications in the gastrointestinal tract. One of them is esophageal varices. The aim of this review is to summarize the research on APC in this field to provide a reference for clinical practice.

Prevalence, Risk Factors, and Psychological Effects of Primary Nocturnal Enuresis in Chinese Young Adults.

PURPOSE: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China. METHODS: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included. RESULTS: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE. CONCLUSION: In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.

[Correlation of NK cell RIPK1 with Prognosis of Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].

OBJECTIVE: To investigate the correlation of NK cell receptor-interacting serine/threonine kinase 1（RIPK1） activity and expression with prognosis of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. METHODS: A total of 132 AML patients with FLT3-ITD mutation and 136 AML patients with FLT3-WT were selected. Clinical data and the number, length and rearrangement ratio of FLT3-ITD mutations were collected. The ratio of CD4+ T cells, regulatory T cells（Tregs）, CD8+ T cells, B cells, natural killer cells（NK cells） and macrophage in peripheral blood（PB） were analyzed by flow cytometry. Correlation of NK cell ratio with FLT3-ITD mutation number, length and rearrangement ratio was analyzed by Pearson correlation analysis. Western blot and RT-qPCR were used to detect RIPK1 protein and mRNA levels in NK cells, respectively. Plasma RIPK activity was detected by ELISA, and Pearson corre-lation analysis was performed for the correlation of RIPK with FLT3-ITD mutation number, length and rearrangement ratio. Kaplan-Meier curve was used to analyze the survival rate of AML patients with FLT3-ITD mutation. RESULTS: Compared with AML patients with FLT3-WT, the white blood cell count in patients with FLT3-ITD mutation significantly increased, PB and BM blasts significantly decreased. There was no significant change in PB CD3+ T cells, Tregs, CD8+ T cells, B cells, M1 and M2 type macrophage of AML patients with FLT3-WT and FLT3-ITD mutation；Compared with AML patients with FLT3-WT, CD4+ T cells significantly decreased, NK cells significantly increased in AML patients wtih FLT3-ITD mutation. NK cells ratio in AML patients with FLT3-ITD mutation significantly positively correlated with the number of FLT3-ITD mutations and rearrangement bases. Plasma RIPK1 activity, RIPK1 protein and mRNA levels in NK cells of AML patients with FLT3-ITD were significantly lower than those of AML patients with FLT3-WT, and negatively correlated with the number of FLT3-ITD mutations, the length of rearranged bases (≥52 bp) and the ratio of rearranged bases. The survival rate of AML patients with FLT3-ITD mutation in low RIPK1 activity after Rydapt treatment was significantly higher than that in high RIPK1 activity. CONCLUSION: The prognosis of AML patients with FLT3-ITD mutation closely relates with plasma RIPK1 activity and RIPK1 expression in NK cells.

Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer.

This study aimed to identify significant immune microenvironment-related competing endogenous RNA (CeRNA) regulatory axis in gastric cancer (GC). Analysis of differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was performed for the microarray datasets. After abundance analysis of immune cell's infiltration, immune-related mRNAs and lncRNAs were obtained. Meanwhile, according to the Pearson correlation coefficient between immune-related mRNAs and lncRNAs, the co-expression mRNA-lncRNA pairs were screened. Furthermore, the target genes of co-existance miRNAs were predicted, and miRNA-lncRNA pairs were identified. Finally, the lncRNA-miRNA and miRNA-mRNA relationship regulated by the same miRNA was screened. Combining with the co-expression relationship between lncRNA and mRNA, the CeRNA network was constructed. In abundance analysis of immune cell's infiltration, a total of eight immune cells were obtained, in addition, 83 immune-related DElncRNAs and 705 immune-related DEmRNAs were screened. KEGG pathway enrichment analysis showed that these mRNAs were mainly involved in PI3K-Akt signaling pathway and human papillomavirus infection, while lncRNA were relevant to gastric acid secretion. A total of 25 miRNAs were significantly associated with immune-related mRNAs, such as hsa-miR-148a-3p, hsa-miR-17-5p, and hsa-miR-25-3p. From the mRNA-miRNA-lncRNA CeRNA network, we observed that AC104389.28─miR-17-5─SMAD5 axis and LINC01133─miR-17-5p─PBLD axis played a crucial role in the development of GC. Furthermore, resting memory CD4 T cells and plasma cells were closely associated with the pathogenesis of GC, and these immune cells might be affected by the key genes. The present study identified key genes that associated with immune microenvironment in GC, providing potential molecular targets for immunotherapy of GC.

Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

Upregulation of aryl hydrocarbon receptor nuclear translocator 2 in the hippocampi of post-stroke depression rats.

Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.

[Clinical efficacy of pishen bingbu recipe in patients with sympathetic cervical spondylosis and its impact on heart rate variability].

OBJECTIVE: To investigate the clinical effect of Pishen Bingbu Recipe (PBR) in treating patients with sympathetic cervical spondylosis (SCS) of qi-blood deficient syndrome type and its impact on heart rate variability (HRV). METHODS: Fifty patients were randomized into the control group and the treatment group equally. Both were treated with mecobalamin, vitamin B1, neurotropin, and occipital - jaw band traction in the sitting posture, but to patients in the treatment group, PBR was given additionally. The course of treatment was 60 days. Therapeutic effect and changes of HRV indexes were observed. RESULTS: After treatment, in the treatment group, 5 patients (20%) were clinically cured, treatment was markedly effective in 12 patients (48%), effective in 7 (28%) and ineffective in 1 (4%), while the corresponding data in the control group were 2 (8%), 4 (16%), 18 (72%) and 1 (4%) respectively, demonstrating the efficacy in the treatment group was superior to that in the control group (P <0.05). Before treatment, the HRV indexes in the two groups were insignificantly different respectively (P >0.05). But after treatment, difference between groups was observed in terms of either time domain or frequency domain. Those of time domain were: standard deviation of NN intervals (SDNN, ms) 133.41 +/- 8.61 vs 115.61 +/- 13.49, average standard deviation of 5 min NN intervals (SDANN, ms) 126.90 +/- 9.99 vs 106.20 +/- 8.84, HRV trigonometric index (HRVTI) 35.10 +/- 4.48 vs 25.51 +/- 2.24; and those of frequency domain: low frequency (LF, ms2) 379.90 +/- 159.07 vs 477.70 +/- 396.91 high frequency (HF, ms2) 157.10 +/- 28.18 vs 122.10 +/- 101.90, and LF/HF ratio 2.37 +/- 0.52 vs 4.27 +/- 2.84. All were superior in the treatment group (P < 0.05). CONCLUSION: PBR shows evidently clinical efficacy on SCS, it can significantly improve the functional activities of sympathetic nerve in patients.

[Analysis of reason for postoperative axial pain caused by unilaterally open-door cervical laminoplasty].

OBJECTIVE: To explore the reason of postoperative axial pain (PAP) complication caused by unilaterally open-door cervical laminoplasty with Centerpiece mini-plate fixations for the treatment of multilevel cervical spondylotic myelopathy(CSM). METHODS: The clinical data of 79 patients with CSM who underwent unilaterally open-door cervical laminoplasty from January 2010 to December 2013 were retrospectively analyzed. There were 45 males and 34 females, aged from 48 to 75 years old with an average of (58.7±4.4) years, complicated with ossified posterior longitudinal ligament(OPLL) of 42 cases. Courses of disease were from 2.1 to 3.9 years with an average of (3.0±0.4) years. Decompression segment occurred in C3-C6 of 31 cases, C3-C7 of 9 cases, C4-C7 of 39 cases. The condition of PAP was record. Cervical curvature index, cervical lordosis angle, the rate of cervical instability, the motion of flexion and extension between PAP group and non-PAP group were compared preoperatively. Multivariate non-linear regression analysis was used to verify relationship between aforementioned parameters and incidence of PAP. JOA score of preoperative, postoperative 6 months and initial onset of PAP, the improvement rate of JOA score and Odom criteria at final follow-up were used to evaluate curative efficacy. RESULTS: All the patients were followed up from 26 to 44 months with an average of (36±9) months. Among them, 12 patients occurred PAP who receive the conservative treatment. The rate of preoperative cervical instablility of PAP group were higher than that of non-PAP group(P<0.05). Preoperative cervical instability was the only independent risk factor in predicting occurrence of PAP. There were no significant differences in cervical curvature, cervical lordosis index, the motion of flexion and extension between PAP and non-PAP group before operation. There were no significant differences in the improvement of nerve function and clinical effect between PAP and non-PAP group after operation(P>0.05). CONCLUSIONS: Preoperative cervical instability is prone to inducing the respectively intervertebral motion disorder and imbalance of stress redistribution, which results in PAP after cervical unilateral laminoplasty. Correct treatment of preoperative cervical instability is a key factor to prevent the occurrence of PAP after cervical laminoplasty, which would not affect long-term nerve functional recovery pronouncedly.