[Advances in molecular mechanism and treatment of chronic mucus hypersecretion].

Chronic obstructive pulmonary disease (COPD) is one of the chronic diseases with high morbidity and mortality in China, which imposes heavy economic burden on society. Research has shown that chronic mucus hypersecretion (CMH) is an independent risk factor for persistent clinical symptoms, poor quality of life, rapid decline in lung function, acute exacerbation and increased hospitalization rate in COPD patients. CMH is a clinical phenotype of COPD with specific pathological and physiological changes. At present, the formation mechanism of CMH is not clear. There is a lack of specific and effective targeted treatments. This article aimed to review the latest research findings on CMH at home and abroad from the overview, impact on COPD patients, molecular mechanisms of formation, current treatment status and progress, and discuss potential targets for CMH treatment, to provide new ideas and directions for improving CMH and treating COPD.

[Treatment efficiency evaluation of left cardiac sympathetic denervation for patients with inherited arrhythmia by exercise-stress test].

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

[Perirectal fascial anatomy and pelvic autonomic nerve preservation during the transanal total mesorectal excision].

The difficulty of transanal total mesorectal excision (TME) is to find the correct dissection plane of perirectal space. As a complex new surgical procedure, the fascial anatomic landmarks of transanal approach operation are more likely to be ignored. It is often found that dissection plane is false after the secondary injury occurs during the operation, which results in the damage of pelvic autonomic nerves. Meanwhile, the mesorectum is easily damaged if the dissection plane is too close to the rectum. Thus, the safety of oncologic outcomes could be limited by difficulty achieving adequate TME quality. The promotion and development of the theory of perirectal fascial anatomy provides a new thought for researchers to design a precise approach for transanal endoscopic surgery. Transanal total mesorectal excision based on fascial anatomy offers a solution to identify the transanal anatomic landmarks precisely and achieves pelvic autonomic nerve preservation. In this paper, the authors focus on the surgical experience of transanal total mesorectal excision based on the theory of perirectal fascial anatomy, and discuss the feature of perirectal fascial anatomy dissection and technique of pelvic autonomic nerve preservation during transanal approach operation.

[Effect of high-titer plasma in pediatric patients with severe adenovirus pneumonia].

Objective: To explore the efficacy and safety of high-titer plasma in the treatment of pediatric patients with severe adenovirus pneumonia. Methods: The clinical data of 92 pediatric patients with severe adenovirus pneumonia admitted to pediatric intensive care unit (PICU) in Guangzhou Women and Children's Medical Center from January 2016 to October 2019 were retrospectively collected. According to the treatment with or without high-titer plasma, the patients were divided into plasma treatment group (n=41) and non-plasma treatment group (n=51). The 51 patients with chest radiograph showing more than half the lungs involved were divided into plasma treatment group (n=29) and non-plasma treatment group (n=22). According to fever duration before plasma treatment, patients were divided into early group (≤5 days, n=5), middle group (>5-10 days, n=14), and late group (>10 days, n=22). Baseline data, therapeutic effects, and prognosis of patients in each group were analyzed with t test, non-parametric rank sum test, one-way ANOVA and chi-square test. Results: Ninety-two patients were included. There were no significant differences in age, gender, body weight, fever duration, sequential organ failure assessment, and Murray lung injury score between plasma treatment group and non-plasma treatment group before admission (all P>0.05). The proportion of patients whose temperature drop to normal within 5 days was higher in plasma treatment group than that in non-plasma treatment group (88% (36/41) vs. 69% (35/51), χ(2)=4.745, P=0.029). However, there were no significant differences between the two groups in the proportions of invasive ventilator weaning within 14 days (63% (26/41) vs. 76% (39/51), χ(2)=1.868, P=0.172), transfer out from PICU within 14 days (49% (20/41) vs. 69% (35/51), χ(2)=3.724, P=0.054), discharge within 28 days (51% (21/41) vs. 61%(31/51), χ(2)=0.846, P=0.358) and survived patients (85% (35/41) vs. 76%(39/51), χ(2)=1.143, P=0.285). Among patients with severe chest radiograph, the proportions of patients whose temperature drop to normal within 5 days and survived patients were higher in plasma treatment group than those in non-plasma treatment group (86% (25/29) vs. 59% (13/22), χ(2)=4.843, P=0.028; 83% (24/29) vs. 55%(12/22), χ(2)=4.796, P=0.029, respectively). However, there were no significant differences between the two groups in the proportions of invasive ventilator weaning within 14 days (52% (15/29) vs. 59% (13/22), χ(2)=0.274, P=0.601), transfer out from PICU within 14 days (34% (10/29) vs. 45% (10/22), χ(2)=0.632, P=0.427), and discharge within 28 days (45% (13/29) vs. 45% (10/22), χ(2)=0.002, P=0.964). Among early, middle and late group, the proportions of invasive ventilator weaning within 14 days were 2/5, 13/14 and 50% (11/22), respectively, with statistically significant difference (χ(2)=8.119, P=0.017). There were no significant differences in the proportions of patients whose temperature drop to normal within 5 days (4/5, 14/14, 82% (18/22), χ(2)=2.965, P=0.227), transfer out from PICU within 14 days (2/5, 10/14, 36%(8/22), χ(2)=4.386, P=0.112), discharge within 28 days (2/5, 8/14, 50% (11/22), χ(2)=0.462, P=0.794) and survived patients (4/5, 13/14, 82% (18/22), χ(2)=0.966, P=0.617) in the three groups. Only one case with high-titer plasma therapy had rash in the course of infusing plasma and no other adverse reactions were observed. Conclusions: High-titer plasma can shorten the fever time and improve the proportion of survival patients in pediatric severe adenovirus pneumonia. The clinical effect of high-titer plasma is better in 5-10 days of fever course. High-titer plasma is an effective and safe treatment.

Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia.

Adenylyl cyclases are key points for the integration of stimulatory and inhibitory G protein-coupled receptor (GPCR) signals. Adenylyl cyclase type 5 (AC5) is highly expressed in striatal medium spiny neurons (MSNs), and is known to play an important role in mediating striatal dopaminergic signaling. Dopaminergic signaling from the D1 expressing MSNs of the direct pathway, as well as the D2 expressing MSNs of the indirect pathway both function through the regulation of AC5 activity, controlling the production of the 2nd messenger cAMP, and subsequently the downstream effectors. Here, we used a newly developed cell line that used Crispr-Cas9 to eliminate the predominant adenylyl cyclase isoforms to more accurately characterize a series of AC5 gain-of-function mutations which have been identified in ADCY5-related dyskinesias. Our results demonstrate that these AC5 mutants exhibit enhanced activity to Gαs-mediated stimulation in both cell and membrane-based assays. We further show that the increased cAMP response at the membrane effectively translates into increased downstream gene transcription in a neuronal model. Subsequent analysis of inhibitory pathways show that the AC5 mutants exhibit significantly reduced inhibition following D2 dopamine receptor activation. Finally, we demonstrate that an adenylyl cyclase "P-site" inhibitor, SQ22536 may represent an effective future therapeutic mechanism by preferentially inhibiting the overactive AC5 gain-of-function mutants.

[The efficacy of ansa cervicalis anterior root for unilateral recurrent laryngeal nerve injury].

Objective: To discuss the long-term efficacy of laryngeal reinnervation using the anterior root of the ansa cervicalis in the treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery. Method: From January 2010 to January 2016, a total of 39 UVFP patients who underwent ansa cervicalis anterior root-to-recurrent laryngeal nerve (RLN) anastomosis and who had suffered nerve disfunction for 6 to 24 months were enrolled as UVFP group.Another 39 age and gender matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and laryngeal electromyography were performed preoperatively and postoperatively for assessing surgery efficacy. Paired sample t test was used for statistical analysis. Result: Videostroboscopic reports indicated that the glottic closure, vocal fold edge, vocal fold position, phase symmetry and regularity were significantly improved in the UVFP group (P<0.01, respectively, postoperative vs. preoperative)and showed no statistical differences compared to the control group (P>0.05, respectively). Both the postoperative GRBAS assessment and acoustic parameters were also significantly improved in the UVFP group, Pre-operative acoustic parameters/Post-operative acoustic parameters were 1.68±0.82/0.39±0.27, 10.08±2.56/4.58±2.96, 0.203±0.216/0.018±0.038, 5.96±1.92/17.42±4.11(P<0.01, respectively) and Pre-operative acoustic parameters/Post-operative acoustic parameters were 0.39±0.27/0.32±0.19, 4.58±2.96/3.32±1.27, 0.018±0.038/0.014±0.027, 17.42±4.11/18.76±5.29, which showed no statistical differences compared to the control group (P>0.05, respectively). Conclusion: Delayed laryngeal reinnervation with the anterior root of ansa cervicalis, it can restore the physiological laryngeal phonatory function to the normal or a nearly normal voice quality, which is a feasible and effective approach for the treatment of thyroid surgery-related UVFP.

Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder.

Hundreds of genes have been implicated in autism spectrum disorders (ASDs). In genetically heterogeneous conditions, large families with multiple affected individuals provide strong evidence implicating a rare variant, and replication of the same variant in multiple families is unusual. We previously published linkage analyses and follow-up exome sequencing in seven large families with ASDs, implicating 14 rare exome variants. These included rs200195897, which was transmitted to four affected individuals in one family. We attempted replication of those variants in the MSSNG database. MSSNG is a unique resource for replication of ASD risk loci, containing whole genome sequence (WGS) on thousands of individuals diagnosed with ASDs and family members. For each exome variant, we obtained all carriers and their relatives in MSSNG, using a TDT test to quantify evidence for transmission and association. We replicated the transmission of rs200195897 to four affected individuals in three additional families. rs200195897 was also present in three singleton affected individuals, and no unaffected individuals other than transmitting parents. We identified two additional rare variants (rs566472488 and rs185038034) transmitted with rs200195897 on 1p36.33. Sanger sequencing confirmed the presence of these variants in the original family segregating rs200195897. To our knowledge, this is the first example of a rare haplotype being transmitted with ASD in multiple families. The candidate risk variants include a missense mutation in SAMD11, an intronic variant in NOC2L, and a regulatory region variant close to both genes. NOC2L is a transcription repressor, and several genes involved in transcription regulation have been previously associated with ASDs.

[The role of NF-κB signaling pathway in laryngeal leukoplakia recurrent with laryngeal reflux].

Objective: To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway. Methods: The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software. Results: In PPI untreated group, the expressions of IL-1ß, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant (P>0.05). The difference of p65 expression between PPI-treated group and PPI pre-treatment group was statistically insignificant (P>0.05). The expression of p-p65 in the PPI-treated group was lower than that of the PPI pre-treatment group (P<0.05). The expressions of IL-1ß, TNF-α and IL-6 were positively related with that of NF-κB-p65. Immun of luorescence method revealed the entrance of p65 to cell nucleus in PPI pre-treatment group, which meant that NF-κB was activated. In the PPI-treated group, few activated p65 could be observed in the cell nucleu. Conclusion: The possible mechanism of vocal mucosal barrier damage in vocal leukoplakia accompanied with LPR maybe the vocal mucosal inflammation mediated by NF-κB and NF-κB-regulated signaling pathway activated with refluxed materials.

Remifentanil on T lymphocytes, cognitive function and inflammatory cytokines of patients undergoing radical surgery for cervical cancer.

OBJECTIVE: To explore the effects of remifentanil on cognitive function, T lymphocyte subsets and inflammatory cytokines of patients undergoing radical surgery for cervical cancer. PATIENTS AND METHODS: A total of 70 patients undergoing radical surgery for cervical cancer in our hospital from August 2014 to January 2017 were selected. They were divided into control group (n=35) and experimental group (n=35). The patients in the control group received intravenous drip of fentanyl, while those in the experimental group received intravenous drip of remifentanil in the surgery. All the patients returned to the wards after surgery. The eye-opening time, extubation time and awaking time of the patients were collected and recorded by specialized surgical nurses. Moreover, the cognitive function of the patients was assessed at the beginning of the surgery and 3 h, 6 h, 12 h, and 24 h after surgery. Blood was drawn at 24 h after surgery, and quantitative analysis of T lymphocyte subsets and inflammatory cytokines of the patients was conducted. RESULTS: The eye-opening time, extubation time, and awaking time in the remifentanil group were significantly earlier than those in the fentanyl group after surgery (p<0.05). At the same time after surgery, the score of mini-mental state examination (MMSE) in the remifentanil group was higher than that in the fentanyl group. The difference was statistically significant (p<0.05). The patients in the experimental group had a relatively low occurrence of cognitive disorder after surgery (p<0.05). The impacts of remifentanil on each type of T lymphocytes and inflammatory cytokines of the patients after surgery were smaller than those of fentanyl. The differences were statistically significant (p<0.05). CONCLUSIONS: Remifentanil can wake patients up early after surgery. Meanwhile, it results in small inflammatory response and stress response, and low occurrence of postoperative cognitive dysfunction in patients. Therefore, it is worthy of being vigorously promoted for clinical application.

[Treatment of bilateral vocal cord paralysis by hemi-phrenic nerve transfer].

Objective: To investigate the surgical effect of reinnervation of bilateral posterior cricoarytenoid muscles(PCA) with left hemi-phrenic nerve and endoscopic laser arytenoid resection in bilateral vocal cord fold paralysis(BVFP) and to analyze the pros and cons of the two methods. Methods: One hundred and seventeen BVFP patients who underwent reinnervation of bilateral PCA using the left hemi-phrenic nerve approach (nerve group, n=52) or laser arytenoidectomy(laser group, n=65) were enrolled in this study from Jan.2009 to Dec.2015.Vocal perception evaluation, video stroboscopy, pulmonary function test and laryngeal electromyography were preformed in all patients both preoperatively and postoperative1y.Extubution rate was calculated postoperative1y. Results: Most of the vocal function parameters in nerve group were improved postoperatively compared with preoperative parameters, albeit without a significant difference(P>0.05), while laser group showed a significant deterioration in voice quality postoperative1y(P<0.05). The two groups showed significant difference in voice quality postoperative1y(P<0.05). Videostroboscopy showed that vocal fold on the operated side in both groups could abduct to various extent postoperatively, which showed significant difference when compared with preoperative abductive movements (P<0.05). But the amplitude in nerve group was larger than that in laser group (P<0.05). 89% of the patients in nerve group were inhale physiological vocal cord abductions. Postoperative glottal closure showed no significant difference in nerve group (P>0.05), while showed various increment in laser group(P<0.05). Differences between the two groups were statistically significant(P<0.05). The pulmonary function in both groups was better after operation, reaching the reference value. Postoperative laryngeal electromyography confirmed successful reinnervation of the bilateral PCA muscles. The decannulation rate were 88.5% and 81.5% in nerve group and laser group respectively. In both groups, patients presented aspiration symptoms postoperatively, and rdieved soon, except 2 patients in laser group suffered repeated aspiration. Conclusions: Reinnervation of bilateral PCA muscles using left hemi-phrenic nerve can restore inspiratory vocal fold abduction to a satisfactory extent while preserving phonatory function at the preoperative level without evident morbidity, and do not affect swallowing function, greatly improving the quality of life of the patients.

[Coblation and silicon stent implantation for recurrent laryngeal papilloma with extensive lesions].

Objective:To evaluate the feasibility and long-term outcome of radiofrequency coblation combined with silicon stent implantation in the treatment of recurrent laryngeal papilloma with extensive lesions. Method:From March 2009 to April 2016, a total of 13 patients (8 males, 5 females; aged 28-67 years) who suffered recurrent laryngeal papilloma were enrolled in this retrospective study. All the cases had undergone at least one operation at other hospitals before this hospitalization. The recurrence interval (RI) of these cases ranged from 2 to 6 months. Video-laryngoscopy or stroboscopy were preformed preoperatively and postoperatively, as well as vocal function assessment. These cases underwent radiofrequency coblationin combination of different stent implantation (member, 7 cases; tube, 4 cases; T-shaped tube, 2 cases) under general anesthesia. The follow-up was 12 to 76 months. Result:Laryngoscopy revealed that the lesions mainly located in the vocal folds, anterior commissure, ventricular band, posterior commissure, epiglottis and even in subglottic area. Varying extent of mucosal adhesion of anterior or/and posterior commissure were observed in all cases, and two cases suffered mild subglottic tracheal stenosis. Two to six weeks after surgery, the silicon stent were removed and no mucosal adhesion were found except for 2 cases who suffered mucosal adhesion of anterior commissure again. Compared to preoperative scores, VHI-10 and G scores showed the significant improvement of voice quality postoperatively in all cases. The recurrence of papilloma was observed in 3 cases during 1-year follow-up, and 4 cases during 2-year follow-up, no recurrence in 6 cases. These recurrence lesions mainly located in ventricular band, subglottic area and trachea. However, no recurrence occurred in these cases who received ablation again. No serious complications were observed in these cases. Conclusion:Radiofrequency ablation may be an effective approach in the treatment of recurrent laryngeal papilloma with extensive lesions. One-stage application of suitable silicon stents can effectively prevent the adhesion of the wound and the onset oflaryngo-tracheal stenosis, and improve the quality of voice.

[Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature].

Objective: To report a case of the pulmonary surfactant protein(SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease(ILD), and review the related literature, to investigate the relationships of ABCA3 gene mutation associated with ILD in infants. Method: A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University. The clinical, radiological, histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed; 12 reports retrieved on literature search at Pubmed, OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed. Result: (1)The patient, a 6-months-old boy, had progressive tachypnea and dyspnea since 4 months old. Physical examination on admission revealed respiratory rate of 78 times/min , heart rate of 187 times/min, SpO2 0.93(mask oxygen-inspiration with 6 L/min), scattered fine moist crackles could be heard over the both lungs, clubbing fingers were found. High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity, interlobular and intralobular septal thickening. Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis. SP-A and SP-B were negative in immunohistochemical stainting. SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c. 1942A>G, c.2701-33G>C and c. 991-105C>A. (2)The review of related literature found that totally 12 cases were reported. The main manifestations were progressive tachypnea and dyspnea, age of onset was between birth and 4 years of age. The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung. PROGNOSIS: 6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.

Effects of calcitriol on experimental spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the effects of calcitriol on oxidative stress, apoptosis, autophagy and locomotor recovery in rats after spinal cord injury (SCI). SETTING: China. METHODS: Ninety female rats were randomly divided into three groups. Laminectomy only was performed in the control group. The SCI group received laminectomy as well as spinal cord compression injury. In the calcitriol group, SCI rats received an intraperitoneal injection of calcitriol (2 µg kg(-1)day(-1)). Oxidative stress was assessed by the tissue superoxide dismutase (SOD) activity and the contents of glutathione (GSH) and malondialdehyde (MDA). The extent of apoptosis was assessed by immunohistochemistry for C-caspase3, TUNEL staining and western blotting for C-caspase3, Bax and Bcl2. Transmission electron microscopy was used to examine autophagosomes in the injured spinal cord of calcitriol-treated rats. Autophagy was detected by western blotting for LC3-II, Beclin1 and p62. Histological changes were assessed by haematoxylin and eosin staining and Nissl staining. Functional recovery was reflected by the Basso, Beattie and Bresnahan locomotion rating scale and the inclined plane test. RESULTS: With calcitriol treatment, oxidative stress was decreased, SOD activity and GSH content were increased and MDA content was decreased. Moreover, apoptosis was inhibited in the SCI plus calcitriol group. However, a higher level of autophagy was detected in the lesions of the calcitriol group compared with the SCI group. Histological damage and neuron loss after SCI were reduced in calcitriol-treated rats, and functional recovery was significantly promoted in the calcitriol group compared with controls. CONCLUSIONS: Calcitriol promotes locomotor recovery after SCI by reducing oxidative stress and inhibiting apoptosis, as well as promoting autophagy.

[Comparing the free fasciocutaneous flap with free jejunium in reconstruction for hypopharyngeal and cervical esophageal defects].

Objective:To investigate the application of the reconstruction methods for hypopharyngeal and cervical esophageal defects due to the resection of hypopharyngeal cancer and advanced laryngeal cancer between free fasciocutaneous flaps and free jejunium transfer.We compared the superiorities and inferiorities of these two reconstruction methods. Method:Retrospective review of the archives of 56 patients from 2000 to 2010 who underwent pharyngoesophageal reconstruction with free flaps (n=32) or free jejunal transfer(n=24),comparison of indications,complications, hospitalization duration, swallowing function recovery and postoperative survival time. Result:The overall 3 year survival rate of free flap group and free jejunal transfer group was 59.3%,55.7% respectively; the overall 5 year survival rate was 38.5%,37.1% respectively. The overall rate of complication rate was 18.8%, 16.7% respectively. The patients with free flaps had higher incidence rate of fistula and scarring in the donor site and lower incidence rate of hues and stricture than the ones with free jejunal transfers. The mean hospitalization duration was (15.00±7.06) days and(13.00±6.75) days. The mean time of first oral food intake was(13.00±5.83)days and (11.00±6.67) days. The differences between two groups had no statistical significance(P>0.05). Conclusion:Free flaps and free jejunium transfer are the two most common reconstruction methods for the hypopharyngeal and cervical esophageal defects. Each has its own advantages and disadvantages respectively. We should choose reconstruction method according to the site and extent of the hypopharyngeal and cervical esophageal defects, preoperative and postoperative radiotherapy requirement.

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging.

Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM(-1) s(-1) from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM(-1) s(-1)) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

Programmable shunt valves for the treatment of hydrocephalus: a systematic review.

OBJECTIVE: To evaluate the clinical effectiveness of programmable valves compared with non-programmable valves of hydrocephalus. METHODS: In this paper, the authors report a systematic review and meta-analysis of complications and revision rate for programmable valves and non-programmable implantation. Randomized or non-randomized controlled trials of hydrocephalus treated by programmable and non-programmable valves were considered for inclusion. RESULTS: Seven published reports of eligible studies involving 1702 participants meet the inclusion criteria. Compared with non-programmable, programmable valves had no significant difference in catheter-related complications [RR = 0.88, 95%CI (0.66,1.19), p = 0.10] and infection rate [RR = 1.25, 95%CI (0.92,1.69), p = 1.00]. There were significant differences in overall complications [RR = 0.80, 95%CI (0.67,0.96), p < 0.01], over-drainage or under-drainage complications [RR = 0.44, 95%CI (0.31,0.63), p < 0.01] and revision rate [RR = 0.56, 95%CI (0.45,0.69), p < 0.01] in favor of programmable valves. CONCLUSION: Although the studies seem to demonstrate a small advantage for the programmable shunts, the probable bias and the difficulties in patient selection are too important to make a general conclusion.

LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and near-IR photothermal therapy of cancer cells.

In this study, LaB6 nanoparticles are used as a novel nanomaterial for near-infrared (NIR) photothermal therapy because they are cheaper than nanostructured gold, are easy to prepare and have an excellent NIR photothermal conversion property. Furthermore, the surface of LaB6 nanoparticles is coated with a carbon-doped silica (C-SiO2) shell to introduce a fluorescent property and improve stability and biocompatibility. The resulting LaB6@C-SiO2 nanoparticles retain the excellent NIR photothermal conversion property and exhibit a bright blue emission under UV irradiation or a green emission under visible irradiation. Using a HeLa cancer cell line, it is demonstrated that LaB6@C-SiO2 nanoparticles have no significant cytotoxicity, but their presence leads to remarkable cell death after NIR irradiation. In addition, from the observation of cellular uptake, the fluorescence labeling function of LaB6@SiO2 (LaB6 core/SiO2 shell) nanoparticles is also confirmed. These results suggest that LaB6@C-SiO2 nanoparticles may potentially serve as an efficient multifunctional nano-platform for simultaneous fluorescent imaging and NIR-triggered photothermal therapy of cancer cells.