[Surgical treatment of tricuspid valve disease due to permanent pacemaker lead].

Objective: To summarize the etiology and surgical treatment experience of tricuspid valve disease due to permanent pacemaker lead. Methods: The medical records of 22 patients who underwent tricuspid valve operation for tricuspid valve disease due to permanent cardiac pacemaker lead from January 2008 to December 2017 were retrospectively reviewed. There were 12 males and 10 females, with a mean age of (62.6±12.1) years old (45-82 years old). All patients underwent tricuspid valve surgery via open thoracotomy under general anesthesia, including 8 patients through median thoracotomy approach, 4 patients through right mini-thoracotomy approach, and 10 patients with endoscopy-assisted and totally endoscopic technique. Moreover, 8 patients underwent tricuspid valve replacement, and 14 patients received tricuspid valve repair. Results: During the operation, 10 cases of severe tricuspid regurgitation were detected due to valve and subvalvular structures dysfunction involved in the pacing electrode, 7 cases showed tricuspid annulus dilation, and pacing electrode-related infective endocarditis were involved in the tricuspid valve of 5 cases. Compared with conventional median thoracotomy surgery, the amount of postoperative drainage fluid and hospitalization time after minimally invasive surgery (including right mini-thoracotomy and endoscopic surgery) were significantly reduced [281(120, 489) ml vs 368(180, 560) ml, P=0.02; 9.2(4.8, 14.5) d vs 11.2(6.3, 16.9) d, P=0.03]. Postoperative echocardiographic data showed that the size of the right atrium and ventricle in these patients was significantly reduced compared with preoperative data, and their cardiac function were normal. There was no difference of pacing electrode parameters between pre-and postoperative period. All 22 patients were cured and discharged, with no valve-and pacemaker-related complications. Conclusions: Patients with tricuspid valve disease due to permanent cardiac pacemaker lead should actively undergo surgery including tricuspid replacement or repair according to different etiologies, which exhibit satisfactory outcomes. Minimally invasive endoscopic tricuspid surgery is a new technique for the treatment of isolated tricuspid valve disease, with less surgical trauma and faster recovery.

[Clinical application of one-stage operation of epicardial permanent pacemaker implantation and cardiac surgery].

Objective: To summarize the results and clinical application experience of one-stage operation of epicardial permanent pacemaker implantation and cardiac surgery. Methods: From November 2014 to July 2016, 15 patients (9 males and 6 females) with ages ranging from 50 to 73 (63.5±6.2) years requiring cardiac surgery with bradycardia underwent one-stage operation of epicardial permanent pacemaker implantation and cardiac surgery. All operations were performed under general anesthesia with chest median incision approach. Among them, single chamber pacemaker (n=10) and dual chamber pacemaker (n=5) permanent epicardial pacing leads were implanted. Simultaneous procedures included valve replacement in 7 cases, valve replacement combined with atrial fibrillation ablation in 3 cases, coronary artery bypass grafting in 2 cases, aortic root replacement in 2 cases, and valve replacement combined with coronary artery bypass surgery in 1 case. Their parameters of pacemaker including sensitivity, pacing threshold, pacing impedance were measured during surgery and closely followed up at 1 week and 3, 6 months after surgery. Results: All 15 patients with epicardial permanent pacemaker implantation in the same period of cardiac surgery were successfully cured and discharged, without any surgical complications. A total of 20 epicardial electrodes were implanted for them including 5 right atrial electrodes and 15 right ventricular electrodes. The postoperative follow-up period ranged from 3 to 22 months. No electrode fracture and surgical wound infection occurred in those patients, and their impedance, sensing and stimulation thresholds were all in normal ranges during follow-up. Conclusions: For patients with bradycardia who required cardiac surgery, one-stage operation of epicardial permanent pacemaker implantation and cardiac surgery is safe and effective, and the results in the short-term and medium-term are satisfactory, avoiding the risk of staged surgery.

[Long-term outcome of surgical revascularization in patients with ischemic heart disease and left ventricular dysfunction].

OBJECTIVE: To analyze the long-term results and risk factors of surgical revascularization in patients with ischemic heart disease (IHD) and left ventricular dysfunction (LVD). METHODS: From January 2003 to July 2013, 2 132 patients underwent coronary artery bypass grafting (CABG) in our institution. Among them, 318 patients with LVD[left ventricular ejection fraction (LVEF) ≤50%]were included in the final study. There were 26 6 male and 52 female patients with age from 36 to 83 (63±9) years old. 76 patients underwent off-pump CABG (OPCAB) and 242 patients underwent conventional CABG (CCABG). Risk factors, perioperative results and follow-up data were collected and analyzed with cox hazard ratio model. RESULTS: Among 318 patients, 6 cases died of the operation with a hospital mortality of 1.9%. With follow-up time from 1 to 128(45.5±32.4)months, 25 patients were lost of follow-up, causing a follow-up rate of 92.0%. Among the 287 cases with long-term follow-up results, all-cause death, cardiogenic death and re-hospitalization due to heart failure were 14.6% (42/287), 5.9%(17/287), 14.6% (42/287), respectively. Re-revascularization rate, recurrent angina and myocardial infarction rate and cerebral incidence were 3.5%(10/287), 13.6% (39/287), 1.7%(5/287), respectively. The five-year survival rate was 85.6%. With all-cause death as the endpoint, preoperative LVEF (HR=0.943, 95%CI: 0.893-0.995, P=0.031) and perioperative implantation of IABP (HR=2.509, 95%CI: 1.051-5.992, P=0.038) emerged as the risk factors that affected the long term survival. The five-year survival rate of patients with severe LVD (LVEF≤35%) was significantly lower than that of patients with mild to moderate LVD (35%

Heterogeneity of CFTR modulator-induced sweat chloride concentrations in people with cystic fibrosis.

BACKGROUND: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator. METHODS: PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies. RESULTS: Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %). CONCLUSIONS: Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population.

Willingness of people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor (ETI) to participate in randomized modulator and inhaled antimicrobial clinical trials.

OBJECTIVE: To assess the feasibility of enrolling people with CF (pwCF) taking the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) in clinical trials of a new modulator. METHODS: PwCF receiving ETI at CHEC-SC study (NCT03350828) enrollment were surveyed for interest in 2-week to 6-month placebo- (PC) and active-comparator (AC) modulator studies. Those taking inhaled antimicrobials (inhABX) were surveyed for interest in PC inhABX studies. RESULTS: Of 1791 respondents, 75% [95% CI 73, 77] would enroll in a 2-week PC modulator study versus 51% [49, 54] for a 6-month study; 82% [81, 84] and 63% [61, 65] would enroll in 2-week and 6 month AC studies; 77% [74, 80] of 551 taking inhABX would enroll in a 2-week PC inhABX study versus 59% [55, 63] for a 6-month study. Previous clinical trial experience increased willingness. CONCLUSIONS: Study designs will affect feasibility of future clinical trials of new modulators and inhABX in people receiving ETI.

Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamma 2.

CD40 is a 50-kD glycoprotein that plays an important role in B cell survival, memory, and immunoglobulin isotype switch. Engagement of the CD40 antigen by monoclonal antibodies (mAbs) results in increased protein tyrosine kinase (PTK) activity, which plays an important role in mediating the biologic effects of CD40. We demonstrate, using an in situ phosphorylation technique, that CD40 cross-linking by the anti-CD40 mAb 626.1 resulted within 1 min in increased phosphorylation of the src type kinase, lyn, in Daudi B cell lines and remained sustained for up to 20 min. The activity of lyn kinase, as measured by immune complex kinase assay, was also increased after CD40 engagement, with similar kinetics. In contrast, the phosphorylation and activity of fyn, fgr, and lck kinases demonstrated minimal changes following stimulation of Daudi cells with mAb 626.1 over this same time period. CD40 engagement also resulted in phosphorylation of phospholipase C gamma 2 of phosphatidylinositol (PLC gamma 2) and phosphatidylinositol (PI)-3-kinase. Phosphorylation of PI-3-kinase was shown to be associated with an increase in its enzymatic activity. These results suggest that lyn plays an important role in CD40-mediated PTK activation and identify PLC gamma 2 and PI-3-kinase targets for CD40-mediated phosphorylation, suggesting a role for these two enzymes in CD40 signal transduction.

International approaches for delivery of positive newborn bloodspot screening results for CF.

BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) is a well-established public health strategy with international standards. A European survey demonstrated considerable variability in approach to delivering a positive NBS result. We used a mixed methods approach to explore healthcare systems and beliefs around this process. METHODS: We used semi-structured interviews and online questionnaires with a purposive, international sample of health professionals involved in communicating positive NBS results to parents. Data were analysed using thematic analysis and Qualtrics Survey Software. RESULTS: In total, 63 healthcare professionals were approached; 25 interviews were conducted with delegates at the 2017 ECFS conference, 4 online questionnaires were subsequently completed by participants in the EU, 1 from Australia and 33 from the US. Methods used to communicate positive NBS results to families varied considerably. This influenced the quality and quantity of information provided which had the potential to heighten anxiety and affect timely diagnostic testing. Participants identified positive practices including systems to improve the timeliness of screening and processing of results, as well as areas for improvement. Respondents stated that knowledge of CF and familiarity with the family were both important when deciding who should communicate positive NBS results. CONCLUSIONS: Guidance and practice regarding communication of positive NBS results for CF to families varies considerably internationally. Further research is needed to ensure information received is accurate, up-to-date and from the most appropriate person. Also, that all children are followed up in a timely manner to minimise potential negative outcomes for the child and family.

Up-regulation of miR-517-5p inhibits ERK/MMP-2 pathway: potential role in preeclampsia.

OBJECTIVE: To investigate the potential role of miRNA-517-5p in preeclampsia and its underlying mechanism. MATERIALS AND METHODS: Placenta samples were obtained from 20 women with preeclampsia and 20 women with normal pregnancies. Expression level of miR-517-5p in placenta samples and JAR cells was detected. MiRNA-517-5p mimics or inhibitor was transfected in JAR cells, followed by detection of proliferative and invasive abilities of JAR cells. In addition, the expressions of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK) and matrix metalloproteinase-2 (MMP-2) in JAR cells were evaluated by Western blot. Meanwhile, the mRNA level of MMP-2 was evaluated by Real-time polymerase chain reaction (PCR). The luciferase assay was applied to identify the target gene of miRNA-517-5p. RESULTS: Increased level of miR-517-5p was detected in placenta samples of preeclampsia patients compared with normal pregnancies. MiRNA-517-5p could regulate proliferative and invasive abilities of JAR cells. Furthermore, miRNA-517-5p could regulate ERK/MMP-2 pathway in JAR cells, which would contribute to the pathophysiology of preeclampsia. The luciferase assay showed MMP-2 was the target gene of miR-517-5p. Further studies showed that MMP-2 was dysregulated in preeclampsia. CONCLUSIONS: MiR-517-5p is highly expressed in placenta samples of preeclampsia pregnancies, which could promote proliferative and invasive abilities of JAR cells by inhibiting ERK/MMP-2 pathway.

[Isolated vertigo as the first symptom of posterior circulation infarction:reporot of 11 cases].

Objective:To analyze the clinical characteristics of patients with cerebellar and brainstem infarction who initially presented with isolated vertigo to avoid misdiagnosing of this disease.Method:Eleven patients with cerebellar and brainstem infarction who initially presented with isolated vertigo treated in our clinic between January 2014 and September 2017 were reviewed and the clinical characteristics and imaging presentation of the patients were evaluated.Result:Vertigo as the first attack was in 5 cases, recurrent attacks was in 6 cases,10 cases were with vascular risk factors except for 1 case, initially diagnosed as vestibular neuritis was 4 cases, Meniere's disease was 1 case, posterior circulartion ischemia was 1 case,and unknown causes was 5 cases; delayed neurological symptoms and signs occurring was 4 cases, but not in other cases; finally determined by brain MRI as acute cerebellar infarction was 5 cases, brainstem infarction was 5 cases, and concurrent cerebellar and brainstem infarction was 1 case. All patients had good prognosis.Conclusion:Isolated vertigo due to posterior circulation infarction is easy to be misdiagnosed as peripheral vertigo.Patients presenting with isolated vertigo, when with vascular risk factors, should receive MRI and DWI examinations. Properly diagnosis and treatment may lead a good prognosis.

Role of protein tyrosine kinases and phosphatases in isotype switching: crosslinking CD45 to CD40 inhibits IgE isotype switching in human B cells.

Protein tyrosine kinases and protein tyrosine phosphatases play an important role in the transduction of signals via antigen receptors in T and B cells, and in CD40-dependent B-cell activation. To examine the role of tyrosine kinases and phosphatases in B-cell isotype switching, we examined the effects of the engagement of the transmembrane phosphatase CD45 on the synthesis of IgE induced by IL-4 and anti-CD40 monoclonal antibody (mAb). Crosslinking CD45 to CD40 using biotinylated mAbs and avidin strongly inhibited CD40-mediated IgE synthesis in IL-4-treated human B cells. CD40/CD45 crosslinking did not affect epsilon germline transcription in B cells stimulated with IL-4, but strongly inhibited induction of S mu/S epsilon switch recombination as detected by a nested primer polymerase chain reaction assay. The B-cell src-type tyrosine kinase lyn, which is activated following CD40 engagement, is a potential target for the effects of CD45 observed in our experiments, because CD45/CD40 crosslinking resulted in the inhibition of CD40-mediated lyn phosphorylation and activation. These results suggest an important role for protein tyrosine kinases and phosphatases in CD40-mediated induction of isotype switching to IgE.

[Renal angiomyolipoma--a clinicopathologic study of 16 cases].

A clinicopathologic study on 16 cases of renal angiomyolipoma is presented. Eleven were women and 5 men. The age ranged from 23 to 80 years with an average of 44.4. The course was from three days to one year. Abdominal mass, pain and hematuria were the main symptoms. Some individual cases were associated with tuberous sclerosis. Spontaneous rupture of the kidney was the principal complication often resulting in shock. The tumor was amenable to resection with a cure rate of 100% without recurrence, metastasis or infiltration of the large renal veins. The prognosis was good. B-type ultrasound and CT scan were helpful in the clinical diagnosis. Of 16 cases, 15 tumors occurred in unilateral kidney, in which the mass was usually located in one pole of the organ. The other tumor involved bilateral kidneys. The tumor was easily misdiagnosed as renal carcinoma by gross examination because of its being relatively large, yellow on the cut surface with hemorrhage and necrosis and often infiltrating tissues surrounding the kidney. Histologically, the tumor consisted of mature blood vessels, smooth muscles and adipose tissues. Sometimes, misdiagnosis of the renal angiomyolipoma with malignant change or angiomyoliposarcoma was made because of the active growth of the smooth muscle and adipose cells. In this paper, special emphasis is put in the discussion of the pathologic features and and causes leading to the misdiagnosis. Basing on long-term follow-up, it is suggested that angiomyolipoma of the kidney be a benign tumor of the hamartomatous nature.

[Epithelioid sarcoma--immunohistochemical and ultrastructural study].

Five cases of epithelioid sarcoma are reported, of which four were studied by immunohistochemistry and one by electron microscopy. Immunohistochemically, the results of cytokeratin showed that these four cases were positive to different degrees by polyclonal cytokeratin and three out of four revealed positive results with low molecular weight cytokeratin monoclonal antibody. Two cases were positive with carcinoembryonic antigen and the other two were negative. The immunohistochemical stain was helpful for differential diagnosis from other sarcomas, such as malignant fibrous histiocytoma and rhabdomyosarcoma. By electron microscopy, tumor cells could be divided into light and dark cells which possessed more or less cell organelles, intermediate microfilaments in the cytoplasm and numerous pinocytic vesicles lying along the cell membrane. The occasional presence of poorly developed desmosomes or the absence of tonofibril bundles and glandular structures can rule out the diagnosis of carcinoma. One of these cases was originally diagnosed as metastatic carcinoma to the skin by light microscopy, which was refuted by electron microscopy, and the keratin positive reaction by immunohistochemistry was helpful for the diagnosis of epithelioid sarcoma. Therefore, the authors suggest that immunohistochemical and electron microscopic studies be used for diagnosing difficult cases of epithelioid sarcoma. From our observation, we consider that the cells of epithelioid sarcoma may derive from undifferentiated mesenchymal cells possessing the potentials of differentiating into synovioblasts, histiocytes or fibroblasts.

[Dynamics of growth and total tanshinones accumulation in crown gall cultures of salvia miltiorrhiza].

AIM: To determine the dynamics of growth and total tanshinones accumulation in crown gall cultures of Salvia miltiorrhiza in MS and 67-V liquid media. METHODS: Fresh, dry weight and total tanshinones yields in the cultures and in the medium were determined every 5 days in crown gall suspension cultures. RESULTS: In MS medium, the logarithmic growth phase of crown gall cultures in S. miltiorrhiza was from the 5th to 30th days, and the stationary growth phase was from the 30th to 35th days. From the 25th to 30th days, physiological activity of crown gall cultures was higher and their growth was better. However, in 67-V medium, the logarithmic growth phase of crown gall cultures was from the 10th to 25th days, and the stationary growth phase was from the 25th to 35th days. Total tanshinones were largely accumulated in the cultures and in the medium after 25 days. The total tanshinones yield (60 mg.L-1) was reached at the 35th day. CONCLUSION: Knowing the regularity of the growth and total tanshinones accumulation in crown gall cultures of S. miltiorrhiza will be helpful to take proper regulative measures in order to obtain the maximum total tanshinones yield.

Anatomic distribution of autonomic neural tissue in the developing dog heart: I. Sympathetic innervation.

We used immunocytochemical localization of tyrosine hydroxylase to trace the ontogenesis and anatomic distribution of sympathetic innervation in fetal, neonatal, and mature canine hearts. Sparse tyrosine hydroxylase-positive neural tissue first appeared in the atrium, including sinoatrial and atrioventricular nodes, and the ventricular epicardium at midgestation and progressively increased in extent to reach the adult pattern by 2 months following birth. Sympathetic innervation of the atrioventricular bundle occurred relatively later, with no nerve processes in the neonate but a mature pattern by 2 months. At each developmental stage the atria contained more tyrosine hydroxylase-positive neural tissue than the ventricles. Thus, sympathetic nerve processes appear in the developing canine heart earlier than was previously recognized. The time course of sympathetic innervation as defined by this anatomic study is in accord with electrophysiologic studies indicating progressive neonatal development of sympathetic effect which achieves maturity by 2 months of age.