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BACKGROUND: This study aims to compare the clinical outcomes after performing radical prostatectomy (RP) or low-dose-rate brachytherapy (LDR) for patients with intermediate-risk prostate cancer (IRPC). METHODS: We performed a retrospective analysis on 361 IRPC patients who underwent treatment in Peking Union Medical College Hospital from January 2014 to August 2021, of which 160 underwent RP and 201 underwent Iodine-125 LDR. Patients were followed in clinic monthly during the first three months and at three-month intervals thereafter. Univariate and multivariate regression analyses were conducted to predict biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS), and overall survival (OS). Biochemical recurrence was defined using the Phoenix definition for LDR and the surgical definition for RP. The log-rank test was applied to compare bRFS between the two modalities, and Cox regression analysis was performed to identify factors associated with bRFS. RESULTS: Median follow-up was 54 months for RP and 69 months for LDR. According to log-rank test, the differences of 5-year bRFS (70.2% vs 83.2%, P = 0.003) and 8-year bRFS (63.1% vs 68.9%, P < 0.001) between RP and LDR groups were statistically significant. Our results also indicated that there was no significant difference in terms of cRFS, CSS, or OS between the two groups. With multivariate analysis of the entire cohort, prostate volume ≤ 30 ml (P < 0.001), positive margin (P < 0.001), and percentage positive biopsy cores > 50% (P < 0.001) were independent factors suggestive of worse bRFS. CONCLUSIONS: LDR is a reasonable treatment option for IRPC patients, yielding improved bRFS and equivalent rates of cRFS, CSS and OS when compared with RP.

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Introduction: Fear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation. Methods: Foot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition. Results: Fear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced. Discussion: These results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.

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Fear memory is critical for individual survival. However, the maladaptive fear response is one of the hallmarks of fear-related disorders, which is characterized by the failure to discriminate threatening signals from neutral or safe cues. The biological mechanisms of fear discrimination remain to be clarified. In this study, we found that the nucleus accumbens (NAc) was indispensable for the formation of cued fear memory in mice, during which the expression of DNA methyltransferase 3a gene (DNMT3a) increased. Injection of Zebularine, a nonspecific DNMT inhibitor, into NAc immediately after conditioning induced a maladaptive fear response to neutral cue (CS-). Using whole-genome bisulfite sequencing (WGBS), differentially methylated sites and methylated regions (DMRs) were investigated. 16,226 DMRs in the genenome were identified, in which, 214 genes with significant differences in their methylation levels and mRNA expression profiles were identified through correlation analysis. Notably, 15 genes were synaptic function-related and 8 genes were enriched in the cGMP-PKG signaling pathway. Moreover, inhibition of PKG impaired fear discrimination. Together, our results revealed the profile and role of genome-wide DNA methylation in NAc in the regulation of fear discrimination.

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INTRODUCTION: Since conflicting evidence from systematic reviews and meta-analyses (SRs/MAs) on the effectiveness of acupuncture in the treatment of postpartum depression is observed. To systematically collate, appraise and synthesize the evidence from these SRs/MAs, an overview will be performed, and this study is an overview protocol. METHODS AND ANALYSIS: Eight databases will be searched: Medicine, Web of science, Cochrane Library, Embase, China National Knowledge Infrastructure, SinoMed, VIP, and Wanfang Data. SRs/MAs of acupuncture on postpartum depression will be included. Literature screening, data extraction, and evaluation of the review quality will be performed by 2 independent reviewers. The methodological quality, reporting quality, and evidence quality will be assessed using the assessment of multiple systematic reviews-2 tool, the preferred reporting items for systematic reviews and meta-analyses checklists, and the grading of recommendations, assessment, development, and evaluation system, respectively. The results will be presented in the context of the topic and the objects of the overview. This study will help bridge the implementation gap between clinical evidence and its translation in clinical application, identify flaws in research and guide future high-quality study.

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Stress-induced neuroepigenetic programming gains growing more and more interest in the studies of the etiology of posttraumatic stress disorder (PTSD). However, seldom attention is focused on DNA demethylation in fear memory generalization, which is the core characteristic of PTSD. Here, we show that ten-eleven translocation protein 3 (TET3), the most abundant DNA demethylation enzyme of the TET family in neurons, senses environmental stress and bridges neuroplasticity with behavioral adaptation during fear generalization. Foot shock strength dependently induces fear generalization and TET3 expression in nucleus accumbens (NAc) in mice. Inhibition of DNA demethylation by infusing demethyltransferase inhibitors or AAV-Tet3-shRNA virus in NAc enhances the fear generalization and anxiety-like behavior. Furthermore, TET3 knockdown impairs the dendritic spine density, PSD length, and thickness of neurons, decreases DNA hydroxymethylation (5hmC), reduces the expression of synaptic plasticity-related genes including Homer1, Cdkn1a, Cdh8, Vamp8, Reln, Bdnf, while surprisingly increases immune-related genes Stat1, B2m, H2-Q7, H2-M2, C3, Cd68 shown by RNA-seq. Notably, knockdown of TET3 in NAc activates microglia and CD39-P2Y12R signaling pathway, and inhibition of CD39 reverses the effects of TET3 knockdown on the fear memory generalization and anxiety. Overexpression of TET3 by Crispr-dSaCas9 virus delivery to activate endogenous Tet3 in NAc increases dendritic spine density of neurons in NAc and reverses fear memory generalization and anxiety-like behavior in mice. These results suggest that TET3 modulates fear generalization and anxiety via regulating synaptic plasticity and CD39 signaling pathway.

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Objective @#To screen differentially expressed miRNAs and explore its effect and mechanism on cell mi- gration in lung adenocarcinoma (LUAD) ．@*Methods @#Differentially expressed miRNAs in LUAD tissues and normal lung tissues were screened by miRNA microarrays，and then bioinformatics analysis was used to predict their poten- tial biological functions and signaling pathways．The cancer genome atlas (TCGA) analysis and quantitative real- time PCR (qRT-PCR) verified the expression level of hsa-let-7e-5p in LUAD tissues and cell lines．The effect of hsa-let-7e-5p cell migration in LUAD was examined by would healing experiment．After screening the underlying target genes by bioinformatics analysis ，the targeting relationship between hsa-let-7e-5p and DTX2，NME6， C8orf58，GATM and DHX57 were verified by qRT-PCR. @*Results @#The miRNA microarray results showed that 347 miRNAs were down-regulated while 229 miRNAs were up-regulated in lung adenocarcinoma tissues．Compared with normal lung tissue and cells，the expression level of hsa-let-7e-5p was significantly down-regulated．Besides，over- expression of hsa-let-7e-5p inhibitedLUAD cell migration．@*Conclusion @#Non-coding RNA hsa-let-7e-5p is down- regulated in LUAD and inhibits the migration of lung adenocarcinoma cells．DTX2，NME6，C8orf58，GATM and DHX57 are the potential target genes of hsa-let-7e-5p.

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Objective To investigate the effect of incremental load training on AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle satellite cells of aged mice. Methods Experimental mice were divided into 3 groups: young control group (YC group, n=12), old control group (OC group, n=12) and old training group (OT group, n=12). The mice in OT group received incremental load training, and CD45-/CD31-/Sca1-/VCAM (CD106) + cells were isolated by flow cytometry sorting. Desmin, Myod myogenic staining and myogenic differentiation culture were used for identification of muscle satellite cells, and the p-AMPK level of muscle satellite cells was detected by immunohistochemistry combined with Western blotting method. Results The expression levels of AMPK and p-AMPK in skeletal muscle satellite cells in YC group were significantly higher than those in OC group (P0.05), while p-AMPK expression level in OT group was significant higher than that in OC group (P<0.05). Conclusions Incremental load training can promote AMPK phosphorylation of skeletal muscle satellite cells in aged mice, and improve energy metabolism of skeletal muscle in aged mice.

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Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30 mg/kg, i.p.) 1 h before, 1 week before, immediately after, or 22 h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22 h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2 weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22 h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.

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BACKGROUND: Fear renewal, the context-specific relapse of a conditioned fear after extinction, is a widely pursued model of post-traumatic stress disorder and phobias. However, its cellular and molecular mechanisms remain poorly understood. The dentate gyrus (DG) has emerged as a critical locus of plasticity with relevance to memory, anxiety disorders, and depression, and it contributes to fear memory retrieval. Here, we have identified the role of the DG in fear renewal and its molecular mechanism. MATERIALS AND METHODS: Muscimol (MUS), activator of cyclic adenosine monophosphate (cAMP) forskolin (FSK), inhibitor of protein kinase A (PKA), Rip-cAMP, and a phosphodiesterase inhibitor rolipram were infused into DG of standard deviation rats before renewal testing. cAMP levels after fear renewal was measured by enzyme-linked immunosorbent assay. The protein levels of phosphodiesterase 4 (PDE4) isoforms were tested by western blot. At last, the roles of cAMP signaling were also tested in the acquisition of fear conditioning, fear retrieval, and extinction. RESULTS: Intra-DG treatment of MUS and Rp-cAMP impaired fear renewal. FSK and rolipram exhibited the opposite effect, which also occurred in the retrieval of original fear memory. This change in fear renewal was regulated by PDE4 isoforms PDE4A, PDE4A5, and PDE4D. In addition, FSK and rolipram facilitated the acquisition of fear conditioning in long-term memory, but not short-term memory, while Rp-cAMP impaired long-term memory. For extinction, FSK and rolipram inhibited extinction process, while Rp-cAMP facilitated fear extinction. CONCLUSION: These findings demonstrated that fear renewal activated cAMP signaling in the DG through decreased PDE4 activity. Because of the role of cAMP signaling in the acquisition or retrieval of fear conditioning and encoding of extinction, it is speculated that initial learning and extinction may have similarities in molecular mechanism, especially fear retrieval and fear renewal may share cAMP signaling pathway in the DG.

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Objective To investigate the predictive value of protein C( PC) for long -term mortality of patients with community-acquired pneumonia(CAP).Methods A total of 657 patients with CAP were enrolled in Taian Central Hospital from January 2011 to December 2011.The patients were divided into short-term group(≤30 days),medium-term group(>30~90 days) and long-term group(>90 days).PC,high sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),pneumonia severity index(PSI) score and CURB-65 score were measured at the time of admission.The ROC curve was used to evaluate the independent risk factors.The Kaplan-Meier surviv-al function curve was used to analyze the difference of mortality between the short-term group and long-term group. Independent risk factors for CAP risk were analyzed by COX regression.Results A total of 597 cases were followed up,there were 49 cases(8.09% ) in the short-term group,11 cases(1.84% ) in the medium -term group,and 537 cases(89.93% ) in the long-term group.The PC levels in the short-term group,medium-term group and long-term group were (32.2 ± 10.6)% ,(43.1 ± 9.9)% ,(69.6 ± 23.0)% ,respectively.The level of PC was signifi-cantly increased in the short-term group compared with the medium-term group and long-term group ( short-term group vs.medium-term group,q =6.18,P <0.05,short -term group vs.long -term group,q=9.87,P <0.05).The hs-CRP levels in the short-term group,medium-term group and long-term group were (108.1 ± 22.4)mg/L,(68.2 ± 12.9 ) mg/L, ( 25.1 ± 17.1 ) mg/L, respectively. The level of hs - CRP was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q =5.23, P <0.05, short -term group vs. long -term group, q =12.95, P<0.05 ). Meanwhile,PC showed higher accuracy(AUC,0.889) than CURB-65( AUC,0.828) and hs-CRP( AUC,0.711) in the long-term group.The Kaplan-Meier survival function curve showed that the mortality rate was significantly higher in the high-value group compared with the low-value group(F=17.10,P<0.01).PC was an independent factor for long - term mortality and was associated with poorer survival by the COX regression analysis. Conclusion PC has a high predictive value for long-term mortality in CAP patients.

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Objective@#To investigate the predictive value of protein C(PC) for long-term mortality of patients with community-acquired pneumonia(CAP).@*Methods@#A total of 657 patients with CAP were enrolled in Taian Central Hospital from January 2011 to December 2011.The patients were divided into short-term group(≤30 days), medium-term group(>30~90 days) and long-term group(>90 days). PC, high sensitivity C-reactive protein(hs-CRP), procalcitonin(PCT), pneumonia severity index(PSI) score and CURB-65 score were measured at the time of admission.The ROC curve was used to evaluate the independent risk factors.The Kaplan-Meier survival function curve was used to analyze the difference of mortality between the short-term group and long-term group.Independent risk factors for CAP risk were analyzed by COX regression.@*Results@#A total of 597 cases were followed up, there were 49 cases(8.09%) in the short-term group, 11 cases(1.84%) in the medium-term group, and 537 cases(89.93%) in the long-term group.The PC levels in the short-term group, medium-term group and long-term group were (32.2±10.6)%, (43.1±9.9)%, (69.6±23.0)%, respectively.The level of PC was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q=6.18, P<0.05, short-term group vs.long-term group, q=9.87, P<0.05). The hs-CRP levels in the short-term group, medium-term group and long-term group were (108.1±22.4)mg/L, (68.2±12.9)mg/L, (25.1±17.1)mg/L, respectively.The level of hs-CRP was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q=5.23, P<0.05, short-term group vs.long-term group, q=12.95, P<0.05). Meanwhile, PC showed higher accuracy(AUC, 0.889) than CURB-65(AUC, 0.828) and hs-CRP(AUC, 0.711) in the long-term group.The Kaplan-Meier survival function curve showed that the mortality rate was significantly higher in the high-value group compared with the low-value group(F=17.10, P<0.01). PC was an independent factor for long-term mortality and was associated with poorer survival by the COX regression analysis.@*Conclusion@#PC has a high predictive value for long-term mortality in CAP patients.

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Objective To explore the effectiveness of impulse oscillometry(IOS)in airway responsiveness measurement and to find out the positive threshold of IOS for asthma diagnosis. Methods Seventy-nine children aged 6-14 years who had suspicious asthma,were recruited into the study. The positive criteria of the methacholine bron-chial provocation test was a 20％ reduction in forced expiratory volume in the first second (FEV 1 )compared to base-line. Simultaneously measured changes in various parameters of IOS,including resonant frequency(Fres),impedance at 5 Hz(Zrs),resistances at 5 and 20 Hz(R5,R20),reactance at 5 Hz(X5),and area of reactance(AX). The results of the challenge test were divided into positive and negative groups according to the pulmonary ventilation function me-thod. The differences between the 2 groups of IOS parameters before and after the challenge test,and the correlation be-tween the change rate of FEV1 and the change rate of IOS parameters were compared,and the positive judgment criteria of IOS parameters in the determination of respiratory responsiveness were determined. Results The positive group of bronchial provocation test had 37 patients and negative group had 42 patients. There was no significant difference in the basic values of parameters between the positive group and the negative group (all P > 0. 05). Changes in Zrs,R5,X5 of IOS were correlated with changes in FEV1 (r = 0. 374,0. 310,0. 449,all P < 0. 05). By single factor analysis,the area under the receiver operating characteristic(ROC)carve (AUC)showed:basic value of Zrs increased by 45. 85％,R5 increased by 45. 72％,X5 increased by 80. 74％ respectively compared to the baseline showed the optimal combination of sensitivity and specificity. In multivariate Logistic regression models,when Zrs and R5 were combined to measure the airway responsiveness,the sensitivity and specificity were 73. 0％ and 81. 0％,respectively. Conclusions IOS and spirometry can be used to determine airway responsiveness in children during methacholine bronchial challenge. Zrs≥45. 85％,or R5≥45. 72％,or X5≥80. 74％,or Zrs and R5 of multiple regression formula can be used as the positive criteria for young children with airway heperresponsiveness,the combination of Zrs and R5 has higher sensitivity and specificity.

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The amygdala, a critical structure for both Pavlovian fear conditioning and fear extinction, receives sparse but comprehensive dopamine innervation and contains dopamine D1 and D2 receptors. Fear extinction, which involves learning to suppress the expression of a previously learned fear, appears to require the dopaminergic system. The specific roles of D2 receptors in mediating associative learning underlying fear extinction require further study. Intra-basolateral amygdala (BLA) infusions of a D2 receptor agonist, quinpirole, and a D2 receptor antagonist, sulpiride, prior to fear extinction and extinction retention were tested 24 h after fear extinction training for long-term memory (LTM). LTM was facilitated by quinpirole and attenuated by sulpiride. In addition, A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor glutamate receptor 1 (GluR1) subunit, GluR1 phospho-Ser845, and N-methyl-D-aspartic acid receptor NR2B subunit levels in the BLA were generally increased by quinpirole and down-regulated by sulpiride. The present study suggests that activation of D2 receptors facilitates fear extinction and that blockade of D2 receptors impairs fear extinction, accompanied by changes in GluR1, GluR1-Ser845 and NR2B levels in the amygdala.

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OBJECTIVES@#To explore the identification method of full sibling between two males with microdeletion and mutation of Y chromosome.@*METHODS@#DNA were extracted from two samples. The type testing of Y-STR and autosomal STR were performed. Full sibling between two individuals was calculated by IBS, ITO and discriminant functions methods.@*RESULTS@#There were 2 loci mutations existed in 33 Y-STR loci and one of the two samples had 19 loci deletions. The IBS of two samples was 53 and greater than the threshold which was 42; FSI was 1.36×10¹⁶ and far greater than 19. The discriminant function of full sibling-unrelated individual DFS2 was greater than DR2, which meant the two individuals tend to be full sibling.@*CONCLUSIONS@#The methods of IBS, ITO and discriminant functions of full sibling-unrelated individual can be used comprehensively to provide more reliable expert opinion in microdeletion and mutation of Y chromosome in full sibling identification.

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OBJECTIVE: To offer reference for Chinese pharmaceutical enterprises in formulating a physicians' prescription behavior-based marketing strategy. METHODS: A survey and analysis was carried out by reviewing pertinent literature and interviewing experts. RESULTS: Physicians' prescription behavior was influenced by many factors. Most pharmaceutical enterprises had inertia thinking in formulating marketing strategies in that they put an emphasis on the quantity rather than the quality of information available to physicians, which has caused the unsatisfactory sales performance. CONCLUSIONS: The pharmaceutical enterprises could improve the efficiency of sales performance by analyzing physicians' prescription behavior, getting rid off inertia thinking and taking corresponding strategies.

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AIM:To confirm the therapeutic effect of Zijin capsule on liver fibrosis in rat model.METHODS:Model group: Bovine serum albumin (BSA) Freund's incomplete adjuvant 0.5ml was injected subdermally at d(1) d(15) d(22) d(29) and d(36) for primary sensitization. Seven days after the fifth injection, BSA antibody in the serum was detected by double agar diffusion method. Normal saline of 0.4ml was injected through cauda vein to BSA antibody-positive rat twice a week for fifteen times. Traditional Chinese medicine (TCM) decoction group and Zijin capsule group: In the attack injection period, Chinese medicinal decoction or Zijin capsule was given ig, the others were the same as in the model group. NS was used in the control group. The collagen content of rat liver was determined by Bergman's method and expressed as x-±s.The liver pathological changes were divided into four grades and expressed as the avarage of the total rank sum.RESULTS:The collagen content (mg/g) of the liver in the control group (7.2± 1.9) was significantly lower than that in the other groups; it was higher in the model group (31.7± 16.6) than that in the two therapeutic groups; and lower in Zijin capsule group (9.7 ± 2.8) than that in the TCM decoction group (11.5± 5.3). The pathological changes were more aggravated in the model group (37.4) than those in the two therapeutic groups; and more severe in the TCM decoction group (30.2) than in the Zijin capsule group (22.9).CONCLUSION: The therapeutic effect of Zijin capsule on the model was confirmed.