Intracerebral hemorrhage (ICH) is a hemorrhagic cerebrovascular disease with high incidence and mortality. Oxidative stress response plays an important role in the pathological and physiological processes of ICH, and is also a potential effective target for clinical treatment. In this paper, the pathogenesis of oxidative stress after ICH, mechanism of nerve and vascular injury in oxidative stress, and detection and treatment of oxidative stress are reviewed in order to provide references for basic research and clinical practice in ICH.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Objective:To evaluate the clinical feasibility and image quality of three-dimensional breath-hold gradient and spin-echo (3D BH-GRASE) sequence in magnetic resonance cholangiopancreatography (MRCP).Methods:In this prospective study, 59 patients with clinically suspected pancreaticobiliary duct disease performed MRCP with both 3D BH-GRASE and 3D respiration-triggered turbo spin-echo (3D RT-TSE) sequences on 3.0 T scanner in the Affiliated Zhangjiagang Hospital of Soochow University from November 2017 to December 2018. The overall image quality was scored independently by 3 experienced radiologists based on the visibility of different anatomical features of the pancreaticobiliary duct. For comparing the 2 sequences, the statistical difference in scan time was assessed with a paired t test; while subjective scores, signal-to-noise ratios (SNR), contrast ratios (CR) and contrast noise ratios (CNR) were compared with Wilcoxon signed rank test. Results:The scan time of 3D BH-GRASE sequence was 16.4 s while that of 3D RT-TSE was (258.6±42.2) s. Their difference was statistically significant ( t=44.073, P<0.001), with the scan time for 3D BH-GRASE shortened by 94%. The overall quality scores of 3D BH-GRASE images were better than those of 3D RT-TSE ( Z=-6.595, P<0.001). There was no statistical difference ( P>0.05) in the scores regarding the visibility of the upper, middle and lower parts of common bile duct and the first and second branches of left and right hepatic ducts. For visualizing the bottom, body, neck and duct of gallbladder, the 3D BH-GRASE sequence received a higher score than the 3D RT-TSE sequence ( P<0.001). For displaying the proximal, middle and distal segments of main pancreatic duct, the 3D RT-TSE sequence was scored higher than the 3D BH-GRASE sequence ( P<0.05). There was no significant difference of SNR between the two sequences ( Z=0.403, P=0.687), whereas CR and CNR of 3D RT-TSE MRCP were better than those of 3D BH-GRASE MRCP ( Z=6.215, P<0.001 and Z=3.046, P=0.002, respectively). Conclusion:Under the prerequisite of ensuring image quality, a proper use of 3D BH-GRASE sequence can significantly shorten the scan time and thus greatly improve the working efficiency of MRCP examination.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

OBJECTIVETo observe the multiple symptom distribution, severity and quality of life of female pelvic floor dysfunction(FPFD) patients with constipation as chief complaint.

METHODSOne hundred FPFD patients with constipation as chief complaint from Speciaty Outpatient Clinic, Pelvic Floor Center of Nanjing Municipal Hospital of Traditional Chinese Medicine between September 2015 and February 2017 were retrospectively enrolled in this study. A comprehensive medical history questionnaire survey and systematical evaluation of severity and quality of life of these patients with constipation was conducted. Constipation scoring system scale (CSS) and patient-assessment of constipation quality of life questionnaire (PAC-QOL) were applied to evaluate the constipation. Other scales included: (1)pain visual analogue scale (VAS) and short form-36 questionnaire (SF-36): if combined with chronic functional anal rectal pain; (2) international consultation on incontinence questionnaire-short form (ICIQ-SF) and urinary incontinence quality of life questionnaires (I-QOL):if combined with urinary incontinence; (3) fecal incontinence severity score scale (Wexner-FIS) and fecal incontinence quality of life questionnaire (FI-QOL):if combined with fecal incontinence.

RESULTSThe mean age of 100 FPFD patients was (57.9±13.9) (24-89) years and the mean disease course was (7.0±8.2)(0.5-40.0) years. Seventy-five cases (75%) were complicated with anal pain, 70 with urinary incontinence, 37 with rectocele, 19 with nocturia, 11 with urinary frequency, 10 with defecation incontinence. Complication with only one symptom was observed in 20 cases (20%), and with two or more symptoms was observed in 80 cases (80%). Pelvic floor relaxation syndrome patients were dominant (58 cases, 58%). The severity of constipation (CSS) was 6-22 (13.89±3.79) points and the quality of life (PAC-QOL) was 45-133 (87.13±18.57) points in FPFD patients. VAS and SF-36 of patients combined with chronic functional anal rectal pain were 1-8 (3.0±1.9) points and 14.4-137.0(71.5±31.4) points respectively. ICIQ-SF and I-QOL of patients combined with urinary incontinence were 1-17 (6.1±3.6) points and 52-110 (90.0±15.8) points respectively. Wexner-FIS and FI-QOL of patients combined with fecal incontinence were 1-11 (4.4±3.0) points and 52-116 (83.4±23.3) points respectively.

CONCLUSIONSThe symptoms of FPFD patients with constipation as chief complaint are complex. They are mainly complicated with anal diseases, then urinary incontinence, and mostly with more than 2 symptoms. Their quality of life is poor.

Adult ; Aged ; Aged, 80 and over ; Constipation ; etiology ; Fecal Incontinence ; etiology ; Female ; Humans ; Middle Aged ; Pelvic Floor ; Pelvic Floor Disorders ; complications ; diagnosis ; Quality of Life ; Retrospective Studies ; Surveys and Questionnaires ; Young Adult

Behavioral adjustment plays an important role in the treatment and relapse of drug addiction. Nonetheless, few studies have examined behavioral adjustment and its plasticity following error commission in methamphetamine (METH) dependence, which is detrimental to human health. Thus, we investigated the behavioral adjustment performance following error commission in long-term METH addicts and how it varied with the application of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty-nine male long-term METH addicts (for > 3 years) were randomly assigned to high-frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two-choice oddball task. Twenty-six age-matched, healthy male adults participated in the two-choice oddball task pretest to establish normal performance for comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly decreased the post-error slowing effect in response times of METH addicts. In addition, the 10 Hz rTMS intervention remarkably reduced the reaction times during post-error trials but not post-correct trials. While the 10 Hz rTMS group showed a more pronounced post-error slowing effect than the healthy participants during the pretest, the post-error slowing effect in the posttest of this sample was similar to that in the healthy participants. These results suggest that high-frequency rTMS over the left DLPFC is a useful protocol for the improvement of behavioral adjustment after error commission in long-term METH addicts.
Adjustment Disorders ; etiology ; therapy ; Adult ; Amphetamine-Related Disorders ; complications ; therapy ; Case-Control Studies ; Central Nervous System Stimulants ; adverse effects ; Choice Behavior ; physiology ; Functional Laterality ; Humans ; Male ; Methamphetamine ; adverse effects ; Middle Aged ; Prefrontal Cortex ; physiology ; Reaction Time ; physiology ; Transcranial Magnetic Stimulation ; methods ; Young Adult

AIM:R-spondin 2 (Rspo2), one member of R-spondin family which contains four secreted proteins , plays an important role in skeletal muscle development .However, the impact of Rspo2 on vascular smooth muscle cell ( SMC) differentiation is little known . This study aims at revealing the role and mechanism of Rspo 2 on SMC differentiation from embryonic stem cells (ESCs).METHODS:A well-established model for studying SMC differentiation from ESCs were used , in which mouse embryonic stem cells ( ES-D3) were seeded on collagen IV-coated flasks and cultured in differentiation medium (DM) for 2, 4, 6 and 8 days.Smooth muscle specific markers, includingα-smooth muscle actin (α-SMA), SM22 and smooth muscle myosin heavy chain (SM-MHC), were detected to in-sure the successful model by qRT-PCR and Western blot .After 3-day pre-differentiation, ESCs were treated with recombinant Rspo 2 protein, overexpression plasmid or shRNA plasmid for 96 h, and the mRNA and protein expression of smooth muscle markers was detected.To explore the role of Rspo2 on SMC differentiation in vivo, 3-day predifferentiated ESCs (106 in 50μLα-MEM) incubated with Rspo2-overexpression plasmid were mixed with 50 μL of Matrigel ( Becton Dickinson Labware ) and then subcutaneously injected into C57BL/6J mice.After 12 days, mice were sacrificed and the implants were harvested for immunofluorescence staining , qRT-PCR and Western blot.Furthermore, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation assay (ChIP) and lucif-erase reporter assay were performed to investigate the transcriptional activity of SMC differentiation related transcription factors , inclu-ding serum response factor (SRF), myocardin (MYO), myocyte-specific enhancer factor 2C (MEF-2C).Involvement of Rspo2 re-ceptor, leucine-rich repeat-containing, G-protein-coupled receptors (Lgr)4,5,6, and β-catenin pathway during Rspo2-induced MSC differentiation were also uncovered by overexpression or inhibition of the respective protein .RESULTS:Our results showed that Rspo 2 mRNA and protein expression was significantly and consistently increased during ESC differentiation towards SMCs .Recombinant Rs-po2 protein and enforced Rspo 2 expression in ESCs resulted in up-regulation of smooth muscle markers and transcription factors , while knockdown decreased the expression of these genes .Expectedly , Rspo2 overexpression also promotes SMC differentiation in vivo.
Mechanistically , our data showed that Rspo 2 could promote SRF binding to SM22 promoter region .Evidence also revealed that one of three Rspo2 receptors, LGR5, was up-regulated while the other two , LGR4 and LGR6, was down-regulated.Silencing of LGR5 inhibi-ted Rspo2-induced SMC differentiation, whereas knockdown of LGR4 had no impact.Finally, activation or inhibition of β-catenin could promote or inhibit SMC differentiation , respectively .CONCLUSION: Our findings demonstrate for the first time that Rspo 2 plays a positive role during smooth muscle cell differentiation from embryonic stem cells .We confirmed that Rspo 2 can up-regulate smooth muscle markers at transcription level .We also revealed Rspo promote smooth muscle cell differentiation through activation of LGR 5 re-ceptor and Wnt/β-catenin pathway .

Objective More early esophageal cancers are treated by endoscopy.However,whether submucosal patients are suitahle for endoscopic treatment is still controversial,and few domestic researches were conducted in this area.The present study investigated the impact of submucosal invasion depth on lymph node metastasis.Methods A total of 258 patients who underwent esophagectomy from November 2009 to March 2014 were studied.Submucosal invasion was equally categorized into inner one-third(sml),middle one-third(sm2),and deep one-third(sm3) invasion by pathologists.Demographics of patients,tumor characteristics,and surgical information were retrospectively collected through medical records.They were compared according to different submucosal invasions.Cancer characteristics and its association with LNM were analyzed by univariate and multivariate analysis.Results The study included 75 sml (29.1％),73 sm2(28.3％),and 110 sm3(42.6％) patients,and the rates of LNM were 12.0％ (9/75),11.0％ (8/73),20.9％ (23/110),respectively.sm3 might be associated with regional LN M (univariate analysis,P =0.041).Tumor volume ＞ 1.856 cm3 (P =0.022) and lymphovascular invasion (P =0.004) predicted LNM using multivariate analysis.Conclusion Submucosal ESCC showed a substantial rate of LNM and it seems that they are not suitable for endoscopic treatment.Depth of invasion was not an independent risk factor for LNM.

BACKGROUNDPulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD.

METHODSWe measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg.

RESULTSCompared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P < 0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P < 0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P < 0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P < 0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r = 0.477-0.589, P < 0.05).

CONCLUSIONThe increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Aged ; Breath Tests ; Female ; Humans ; Hypertension, Pulmonary ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Male ; Middle Aged ; Prostaglandins A ; blood ; metabolism ; Pulmonary Disease, Chronic Obstructive ; blood ; metabolism

Objective To evaluate two different MRI techniques , enhanced 3D STIR SPACE and unidirectionally-encoded DWIBS MR Neurography in visualizing the brachial plexus.Methods Twenty healthy volunteers underwent MR scanning by the procedures of unidirectionally -encoded DWIBS and enhanced 3D STIR SPACE sequence of the brachial plexus.Original images were reconstructed with coronal maximum intensity projection ( MIP ).The image quality was assessed by comparing the visualization of various parts of the brachial plexus and the suppression ratio of image background.The degree of visualization was compared via χ2-test of paired data , and comparison of background suppression scores was performed using a nonparametric Wilcoxon signed rank sum test.Results The successful rate of visualizing the brachial plexus supraclavicular section ( C5-T1 ) was 84% ( 167/200 ) and 99% ( 198/200 ) , respectively, for the DWIBS and enhanced 3D STIR SPACE, and the rate for the infraclavicular section was 33%( 13/40 ) and 95% ( 38/40 ).The differences between these two techniques were statistically significant (χ2 value was 28.18 and 31.15 respectively, P <0.01).In all images, the scores of grade (Ⅰ-Ⅳ) of background suppression were 0, 0, 4 and 16 for unidirectionally-encoded DWIBS, respectively;while they were 15, 4, 1 and 0 for enhanced 3D STIR SPACE.There was significant difference between the two techniques ( Z =3.96,P <0.01).Conclusions High-quality MR neurography of the brachial plexus can be obtained using the enhanced 3D STIR SPACE sequence.It offers a complete anatomical coverage of the brachial plexus , and thus demonstrates a better capacity in depicting the anatomy of brachial plexus as compared with the unidirectionally-encoded DWIBS.