Respiratory Distress Resulting from Gastroesophageal Reflux Is not Asthma,but Laryngotracheal Irritation,Spasm,even Suffocation

DESPITE the strong association between gastroesophageal reflux disease (GERD) and asthma has been undisputedly established and widely recognized by experts in advanced countries. Yet few topics in medicine are as controversial

Midterm outcome of stapled transanal rectal resection for obstructed defecation syndrome:A single-institution experience in China

AIM:To assess midterm results of stapled transanal rectal resection(STARR)for obstructed defecation syndrome(ODS)and predictive factors for outcome.METHODS:From May 2007 to May 2009,75 female patients underwent STARR and were included in the present study.Preoperative and postoperative workup consisted of standardized interview and physical examination including proctoscopy,colonoscopy,anorectal manometry,and defecography.Clinical and functional results were assessed by standardized questionnaires for the assessment of constipation constipation scoring system(CSS),Longo’s ODS score,and symptom severity score(SSS),incontinence Wexner incontinence score(WS),quality of life Patient Assessment of Constipation-Quality of Life Questionnaire(PAC-QOL),and patient satisfaction visual analog scale(VAS).Data were collected prospectively at baseline,12 and 30 mo.RESULTS:The median follow-up was 30 mo(range,30-46 mo).Late postoperative complications occurred in 11(14.7%)patients.Three of these patients required procedure-related reintervention(one diverticulectomy and two excision of staple granuloma).Although the recurrence rate was 10.7%,constipation scores(CSS,ODS score and SSS)significantly improved after STARR(P<0.0001).Significant reduction in ODS symptoms was matched by an improvement in the PAC-QOL and VAS(P<0.0001),and the satisfaction index was excellent in 25(33.3%)patients,good in 23(30.7%),fairly good in 14(18.7%),and poor in 13(17.3%).Nevertheless,the WS increased after STARR(P=0.0169).Incontinence was present or deteriorated in 8(10.7%)patients;6(8%)of whom were new onsets.Univariate analysis revealed that the occurrence of fecal incontinence(preoperative,postoperative or new-onset incontinence;P=0.028,0.000,and 0.007,respectively)was associated with the success of the operation.CONCLUSION:STARR is an acceptable procedure for the surgical correction of ODS.However,its impact on symptomatic recurrence and postoperative incontinence may be problematic.

Gastroesophageal reflux disease related asthma:From preliminary studies to clinical practice

The diagnosis of asthma requires the presence of episodic respiratory difficulties characterized by variable and reversible airway obstruction. It has a high prevalence worldwide and is traditionally considered to be an allergic disease. Most cases are responsive to treatment with bronchodilators and anti-inflammatories, as recommendedby national and international guidelines; however, appro-ximately 10% of asthmatic patients are refractory even to optimal therapy. Gastroesophageal reflux disease(GERD) is a common disorder in asthmatic patients and the two disorders may be linked pathophysiologically. Here we review data from preliminary studies that suggest asthma could be induced or exacerbated by gastroesophageal reflux. The optimal strategies for the diagnosis of GERDrelated asthma and its therapy are still debated. However, there is evidence to suggest that antireflux treatment is effective and practical for asthmatic patients with welldefined reflux disease.

A preliminary report on adjuvant analgesic efficacy of HANS in opioid tolerant patients with cancer pain

Objective： To observe the adjuvant analgesic efficacy of Han＇s Acupoint Nerve Stimulator （HANS） in opioid tolerant patients with cancer pain. Methods： A prospective non-controlled study was conducted. Opioid tolerant patients with cancer pain were enrolled and treated with both routinely analgesics and adjuvant HANS （2/100 Hz for 30 min/d, 5 d on and 2 d off for two weeks）. Cancer pain, quality of life （QOL）, anxiety and depression were assessed before enrollment and on d 8 and d 15 with the BPI-C, EORTC QLQ-C30, and self-rating anxiety scale （SAS）/ self-rating depression scale （SDS）, respectively; the therapeutic frequency of breakthrough pain （BP） and daily opioid dose were also recorded. Results： Totally 47 patients meeting the inclusion criteria participated in this study; 43 patients completed the two-week treatment and assessment. The mean scores of patient＇s ＂worst＂ and ＂least＂ pain intensity assessed with BPI-C decreased significantly on d 8 and d 15; the therapeutic frequency of BP also significantly decreased; but the average daily dose of opioids did not change significantly. For the nine symptoms in EORTC QLQ-C30 assessment, the mean scores of pain, fatigue, constipation and insomnia were significantly lower on d 8 and d 15 compared with baseline; the mean scores of the overall health status, nausea/vomiting and the incidence rates of both anxiety and depression also decreased significantly on d 15. Conclusions： To opioid tolerant patients with cancer pain, adjuvant treatment with HANS could improve pain release and patients＇ QOL by decreasing the severity of pain, fatigue, constipation, insomnia and other concomitant symptoms; it could also decrease the incidence rates of anxiety and depression.

Impact of next-generation sequencing on molecular diagnosis of inherited non-syndromic hearing loss

Hearing loss is one of the most common birth defects,with inherited genetic defects play an important role,contributing to about 60%of deafness occurring in infants.However,hearing impairment is genetically heterogeneous,with both common and rare forms occurring due to mutations in estimated 500 genes.Due to the large number and presumably low mutation frequencies of those genes,it would be highly expensive and time-consuming to address this issue by conventional gene-by-gene Sanger sequencing.Next-generation sequencing is a revolutionary technology that allows the simultaneous screening of mutations in a large number of genes.It is cost effective compared to classical strategies of linkage analysis and direct sequencing when the number or size of genes is large,and thus has become a highly efficient strategy for identifying novel causative genes and mutations involved in heritable disease.In this review, we describe major NGS methodologies currently used for genetic disorders and highlight applications of these technologies in studies of molecular diagnosis and the discovery of genes implicated in non-syndromic hearing loss.

An efficient strategy for establishing a model of sensorineural deafness in rats

Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.

Arthroscopic Debridement and Synovium Resection for Inflammatory Hip Arthritis

Objective To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis.Methods A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflammatory arthritis.There were 17 cases of ankylosing spondylitis,11 cases of rheumatoid arthritis,and 8 cases of psoriatic arthritis.The joints were irrigated and the inflamed tissues were debrided with anthroscopy.The patients were followed up with Harris hip score,Oxford hip score,Visual Analog Scale(VAS),and magnetic resonance imaging(MRI).Statistical analysis was performed using Student t test.Results All of the 36 cases were followed up for 46-103 months,averaging 67.2±8.4 months.Harris and Oxford scores increased from 66.9±12.1 and 69.4±16.4 before operation to 78.4±19.3 and 80.2±18.8 after operation,respectively(P<0.05).VAS score decreased from pre-operative 8.5±2.5 to post-operative 7.2±2.5(P<0.05).All the patients showed improved joint range of motion.MRI revealed alleviation of hip synovitis.The results were classified as excellent in 8 patients,good in 17 patients,fair in 8 patient,and poor in 3 according to Harris hip score.Twenty-seven patients were satisfied with the operative outcomes as they regained normal daily activities.Conclusions Arthroscopy-assisted joint debridement and synovium resection is an effective procedure for hip lesion in inflammatory arthritis.The inflammatory lesion might be thereby controlled and the symptoms be relieved.

Application of Gas Chromatography-mass Spectrometry in Analyzing Pharmacokinetics and Distribution of Deltamethrin in Miniature Pig Tissues

Objective To characterize the pharmacokinetics and distribution profiles of deltamethrin in miniature pig tissues by gas chromatography-mass spectrometry （GC-MS）. Methods Pharmacokinetics and distribution of deltamethrin in blood and tissues of 30 miniature pigs were studied by GC-MS after oral administration of deltamethrin （5 mg/kg bw）. Data were processed by 3P97 software. Results The serum deltamethrin level was significantly lower in tissues than in blood of miniature pigs.The AUC0-72 h, Cmax, of deltamethrin were 555.330±316.987 ng h/mL and 17.861±11.129 ng/mL, respectively. The Tmax, of deltamethrin was 6.004±3.131 h.Conclusion The metabolism of deltamethrin in miniature pigs is fit for a one-compartment model with a weighting function of I/C^2. Deltamethrin is rapidly hydrolyzed and accumulated in miniature pig tissues.

INHIBITORY EFFECT OF ANGIOTENSIN II TYPE 1 RECEPTOR-ASSOCIATED PROTEIN ON VASCULAR SMOOTH MUSCLE CELL GROWTH AND NEOINTIMAL FORMATION

Objective To investigate the mechanism of a novel angiotensin Ⅱ type 1 receptor-associated protein (ATRAP) interfering with angiotensin II type 1 (AT1) receptor-mediated vascular smooth muscle cell (VSMC) growth and neointimal formation. Methods VSMCs isolated from thoracic aorta of adult Sprague-Dawley (SD) rats were used in this study. ATRAP cDNA was subcloned into pcDNA3 vector and then transfected into VSMCs. DNA synthesis and extracellular signal-regulated kinase (ERK) and phospho-ERK expressions in VSMCs were assayed by measurement of 3H thymidine incorporation and Western blotting, respectively. Morphological changes were observed in the balloon injured artery with or without transfection of ATRAP cDNA using 12-week-old male SD rats. Results ATRAP overexpression in VSMCs inhibited angiotensin II(Ang II)-induced 3H thymidine incorporation 48 hours after Ang II stimulation (P<0.05). In VSMC, Ang II stimulation increased the phosphorylation of ERK, which reached the peak around 60 minutes. The activation of phospho-ERK was significantly decreased by ATRAP (P<0.05). Neointimal formation was markedly inhibited by ATRAP overexpression in injuried arteries. Conclusions The AT1 receptor-derived activation of ERK plays an essential role in Ang II-induced VSMC growth. The growth inhibitory effects of ATRAP might be due to interfering with AT1 receptor-mediated activation of ERK in VSMC growth and neointimal formation.

Inhibition of Radiation-Induced Lung Adenocarcinoma Cell Metastasis by Adenovirus of PIAS3 Overexpression Driven by Radiation-Inducible Promoter (<i>Ad-pig3RRP-PIAS3</i>)

Radiotherapy is one of important approaches for pulmonary adenocarcinoma. However, many studies have shown that radiation can also enhance the ability of tumor cells metastasis, although the lung adenocarcinoma could be killed. The increased metastasis induced by radiation is associated with the activation of STAT3?in lung adenocarcinoma cells. Based on the importance role of?STAT3?in cell proliferation and survival, we can construct an adenovirus vector of?PIAS3 overexpress driven by radiation-induced promoter to inhibit the activation of STAT3 specifically. In this way, when?STAT3 was activated by radiation, the expression of?PIAS3 will be increased at the same time;this lead to the inhibition of invasion and metastasis caused by?STAT3 in lung adenocarcinoma cells. These researches are expected to develop a novel target and method for radiotherapy and molecular therapy of lung adenocarcinoma.

Role of VEGF-A/C and CCR-7 in the enhanced metastasis of A549 cells induced by 2 and 4 Gy X-rays in vitro and in vivo

Radiotherapy is a common strategy in treating lung cancer.Accumulating evidence suggested that radiotherapy has the potential to promote the metastasis and invasion of carcinoma cells.In this study,we aimed to testify the role of vascular endothelial growth factor(VEGF)and C-C chemokine receptor-7(CCR-7)in the metastasis of human adenocarcinoma A549 cells in vivo and in vitro.Nude mice were injected with A549 cells irradiated by 0,2 and 4 Gy X-rays,respectively.Quantitative detections of VEGF-A/C and CCR-7 mRNA from lung sample were performed by real-time RT-PCR.Small interfering RNA(siRNA)transfection technology was further used to testify the role of the genes in the metastasis of A549 cells.VEGF and CCR-7mRNA could only be detected 10 weeks post injection in vivo when visible tumor foci scattered in lung.In addition,VEGF-A/C mRNA expressed significantly higher in mice injected with A549 cells irradiated by 2 and 4 X-rays than those with 0 Gy X-rays irradiation.On the other hand,A549 cells with or without X-rays irradiation transfected with VEGF siRAN and CCR-7 siRNA showed a dramatic decrease of invasiveness compared to normal A549 cells with or without irradiation.The migration indexes were?0.7,?0.48,?0.34 and?0.32 for A549 cells with CCR-7 siRNA,VEGF siRNA,X-rays combined CCR-7 siRNA and X-rays combined VEGF-siRNA respectively.These results demonstrated that X-rays could promote the metastasis of A549 cells,and VEGF-A/C and CCR-7 mRNA were closely related to the metastasis of A549 cells in vivo and in vitro.

The impact of X-rays on the expressions of miR-130a/miR-25 and its potential role in the enhanced metastasis of A549 cell lines in vitro induced by X-rays

We aimed to investigate the impact of X-rays on miR-130a and miR-25 expressions of A549 cell lines and to understand the mechanism of miR-130a and miR-25 on the regulation of invasion and metastasis of A549 cell lines. Human adenocarcinoma cells of the line A549 were cultured and radiated by X-rays at the absorbed doses of 2 and 4, respectively by linear accelerator. Transwell invasion and migration assay were employed to exam the metastasis ability of A549 cells post X-rays irradiation. Both the miRNA and mRNA were extracted from A549 cells at different time points post radiation. The expressions of miR-130a and miR-25, as well as the expressions of VEGF and CCR-7 mRNAs, were detected in A549 cells with 2 and 4 Gy X-rays radiation, respectively by real time PCR. Results were statistically analyzed by SAS 8.2 software, which showed that the invasiveness of A549 cells post 2 and 4 Gy X-rays increased significantly compared with that of untreated A549 cells (the migration cell numbers are 20, 48 and 62 in Group 0, 2 and 4 Gy X-rays, respectively). Furthermore, the expressions of miR-130a and miR-25 also increased significantly at the time-points of 1, 2, 4, and 8 h post radiation, and began to decrease to the control level at 12 h post radiation. VEGF and CCR-7 mRNAs were detected to be up-regulated 18 h post radiation and remained at a high level till 72 h post radiation. The expression of VEGF mRNA has a close correlation with that of CCR-7 mRNA, and the expression of miR-130a also has a correlation with that of VEGF and CCR-7mRNAs. It is concluded that the metastasis of A549 cells in vitro could be promoted by X-rays, and miR-130a might play a role in the metastasis of A549 cells via regulating the expressions of VEGF and CCR-7 mRNAs.

Short-term Rosuvastatin Treatment for the Prevention of Contrast-induced Acute Kidney Injury in Patients Receiving Moderate or High Volumes of Contrast Media： A Sub-analysis of the TRACK-D Study

Background:Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI).However,the consistency of these effects on patients administered different volumes of contrast media is unknown.Methods:In the TRACK-D trial,2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care.This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV],200-300 ml,n =712) or (high contrast volume [HCV],≥300 ml,n =220).The primary outcome was the incidence of CIAKI.The secondary outcome was a composite of death,dialysis/hemofiltration or worsened heart failure at 30 days.Results:Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1％ vs.4.4％,P =0.050) in the overall cohort and in patients with MCV (1.7％ vs.4.5％,P =0.029),whereas no benefit was observed in patients with HCV (3.4％ vs.3.9％,P =0.834).The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7％ vs.5.3％,P =0.049) in the overall cohort,but it was similar between the patients with MCV (2.0％ vs.4.2％,P =0.081) or HCV (5.1％ vs.8.8％,P =0.273).Conclusions:Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.

Insult of gastroesophageal reflux on airway： clinical significance of pharyngeal nozzle

At the very time of global paying the highest attention to the worst insults of smoking as well as haze on the airway, everybody knows both are exogenous and noticeable. However, people mostly, including many medical personnel, do not know how badly the gastroesophageal reflux （GER） insults on our own airway. Symptoms of GER are commonly seen as heartburn and regurgitation, which can be mostly tolerated. However, when the up going gastric content reversely passes the esophagus and then the distal pharynx, where it appears a beak like stricture, serving as a nozzle, so as to produce numerous micro-particles and reach the oro-nasal cavity and also the airway causing allergic rhinitis and asthmatic attacks, even pulmonary parenchyma lesions. It will reduce life quality or even jeopardize life. The point that the endogenous insult appears in the respiratory system, but originates from the digestive tract is not well known and often undiagnosed and not correctly treated. The GER induced airway challenge is a treatable and preventive entity, as soon as a diagnosis is made, a good relief could be expected by means of life style adjustment, medicine, or fixation of the patulous cardia through radiofrequency or fundoplication. The author Dr. Zhonggao Wang had suffered it for long and symptoms disappeared for 8 years after anti-reflux surgery. Here is a presentation of Dr. Zhonggao Wang and his team＇s work and would call attention to the public so as to recognize this relatively unknown entity -- a treatable condition occurring from human itself, but not from outside surroundings as smoking or haze does.

Outcome of Stretta radiofrequency and fundoplication for GERD- related severe asthmatic symptoms

This study aimed to investigate the outcome of treatment with Stretta radiofrequency （SRF） or laparoscopic Nissen fundoplication （LNF）. A total of 137 gastroesophageal reflux disease （GERD） patients with severe asthmatic symptoms who responded inadequately to medical treatment for asthma were investigated. The patients were followed up 1 year and 5 years after SRF （n = 82） or LNF （n = 55） treatment. A questionnaire covering 29 related symptoms and medication use was employed. Digestive, respiratory, and ear-nose-throat （ENT） symptom scores significantly decreased after antireflux treatment. Symptom scores respectively changed from 17.2 ± 10.1, 31.9 ± 6.6, and 21.1± 11.8 to 5.0 ±6.2, 11.5 ±10.2, and 6.3± 6.8 at 1 year and to 5.6 ± 6.5, 13.1± 10.1, and 7.8 ± 7.2 at 5 years （P 〈 0.001）. The outcome of LNF was significantly better than that of SRF in terms of digestive （P 〈 0.001, P = 0.001）, respiratory （P = 0.006, P = 0.001）, and ENT symptoms （P = 0.006, P = 0.003） at both 1 year and 5 years. SRF and LNF were both effective against the digestive symptoms of GERD as well as GERD-related severe asthmatic and ENT symptoms, with better outcomes exhibited by the LNF group. Severe asthmatic symptoms and GERD were closely associated, and this finding warrants further study.

Wall Imaging for Unilateral Intracranial Vertebral Artery Hypoplasia with Three-dimensional High-isotropic Resolution Magnetic Resonance Images

Background：There are few studies for evaluating wall characteristics of intracranial vertebral artery hypoplasia （VAH）.The aim of this study was to determine wall characteristics of VAH with three-dimensional volumetric isotropic turbo spin echo acquisition （3D VISTA） images and differentiate between acquired atherosclerotic stenosis and VAH.Methods：Thirty patients with suspicious VAH by luminograms were retrospectively enrolled between January 2014 and February 2015.The patients were classified as ＂acquired atherosclerotic stenosis＂ or ＂VAH＂ based on 3D VISTA images.The wall characteristics of VAH were assessed to determine the presence of atherosclerotic lesions,and the patients were classified into two subgroups （VAH with atherosclerosis and VAH with normal wall）.Wall characteristics of basilar arteries and vertebral arteries were also assessed.The clinical and wall characteristics were compared between the two groups.Results：Five of 30 patients with suspicious VAH were finally diagnosed as acquired atherosclerotic stenosis by 3D VISTA images.25 patients were finally diagnosed as VAH including 16 （64.00%） patients with atherosclerosis and 9 （36.00%） patients with normal wall.In the 16 patients with atherosclerosis,plaque was found in 9 patients,slight wall thickening in 6 patients,and thrombus and wall thickening in 1 patient.Compared with VAH patients with normal wall,VAH patients with atherosclerosis showed atherosclerotic basilar arteries and dominant vertebral arteries more frequently （P =0.000）.Conclusions：Three-dimensional VISTA images enable differentiation between the acquired atherosclerotic stenosis and VAH.VAH was also prone to atherosclerotic processes.