BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left

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Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

Objective To analyze the clinical characteristics for hypertensive attack during operation and clinical experience of preoperative evaluation and preparation in patients with pheochromocytoma and paraganglioma(PHEO/PGL).Methods A total 219 PHEO/PGL cases from September 2016 to September 2018 were retrospectively reviewed.It included 99 males and 120 females,aged 13 to 76 (average 47) years old.The mean diameter of tumor was 5.3 cm (1.5-18.0 cm).140 cases were unilateral PHEO,6 cases were bilateral PHEO,68 cases were PGL(jugular,mediaphragm,heart,retroperitoneum,pelvic and bladder) and 5 cases were PHEO combined with PGL.Preoperative highest systolic blood pressure (SBP)was 240 mmHg(1 mmHg-0.133 kPa) and highest diastolic blood pressure (DBP) was 160 mmHg.20 cases were occult PHEO without hypertension.217 cases accepted preoperative preparation of alpha-blocker [phenoxy-benzamine,dosage ranging from 5 mg Q12h to 40 mg Q8h,maximum dosage not exceeding 1 mg/(kg· 24 h)].2 cases did not accept preoperative preparation.All cases accepted open or endoscope surgery.The patients were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery.Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack.Results Histopathological results showed that all cases were PHEO or PGL,while 205 cases were benign,14 cases were malignant.Hypertensive attack were recorded in 112 cases(51％).The diameter of tumors in the hypertensive attack group were larger than that in the non-hypertensive attack group[(6.70 ± 2.95)cm vs.(3.95 ± 1.70) cm,P =0.005].There was no significant difference between the two groups among age [(51.0 ± 10.8) years vs.(38.5 ± 17.6) years,P =0.105],preoperative catecholamine level [norepinephrine (111.20 ± 41.49) μg/24 h vs.(419.15 ± 154.81) μg/24 h,P =0.075],time of use of alpha blockers [(53.0 ± 7.5) d vs.(38.0 ± 6.4) d,P =0.139],daily dosage of alpha blocker [(40.0 ±7.2)mg vs.(27.1 ± 1.8) mg,P =0.111] and blood pressure at diagnosis[(173.75 ± 26.69) mmHg vs.(155.0 ± 20.75) mmHg,P =0.139].Among 219 cases,2 case had emergency hemostasis after operation,1 case had catecholamine cardiomyopathy after operation for occult pheochromocytoma,and no perioperative death occurred.Conclusions Patients with large tumor tend to have hypertensive attack during operation so that should be better prepared.

Objective: To investigate the radiological and histopathological features of giant cell tumor of bone treated with RANKL inhibitor denosumab. Methods: Eleven cases were retrieved from the surgical pathology records between March 2015 and June 2017 in Beijing Jishuitan Hospital. Formalin fixed, paraffin embedded specimens were collected and the histological features were evaluated. The imaging features including X ray, magnetic resonance imaging, and computed tomography were also reviewed. Results: These 11 cases of giant cell tumor of bone were derived from five female and six male patients, with age ranged from 20 to 62 years (mean age, 35 years). The tumors were located in the sacrum (6 cases), femur (2 cases), radius (1 case), tibia (1 case) and patella (1 case), respectively. Histologically, all cases showed depletion of giant cells, proliferation of mononuclear cells and different degrees of ossification 3 to 6 months after denosumab therapy. Radiography showed marked osteosclerosis and sclerotic rim formation. Three cases of the sacrum recurred after 5, 6 and 11 months of surgery, and the remaining cases showed no recurrence within follow-up of 1 to 14 months. Conclusions Denosumab treated giant cell tumors morphologically differ from untreated tumors. Careful attention to a history of denosumab administration is crucial to avoid misdiagnosis and to allow proper differentiation from other tumors and tumor-like lesions.

OBJECTIVE:To investigate clinical efficacy and safety of different dosages of bromocriptine in the treatment pro-lactinoma,and its effects on serum prolactin(PRL)and tumor volume. METHODS:A total of 60 patients with prolactinoma were selected from our hospital during Jan.-Dec. 2015 as research objects,and then divided into group A and B according to random number table,with 30 cases in each group. Both groups were given Bromocriptine mesilate tablets orally during meal. Group A was given medicine with initial dose of 2.5 mg/d,increasing to 3.75 mg/d 3 d later,increasing by 2.5 mg every week after 2-3 d,and then recovering to 3.75 mg/d till serum PRL level had been controlled. Group B was given medicine with initial dose of 1.25 mg/d, increasing to 2.5 mg/d 3 d later,increasing by 1.25-2.5 mg every week after 2-3 d,and then recovering to 2.5 mg/d till serum PRL level recovered to normal. Both groups were treated for consecutive 3 months. Clinical efficacies as well as serum level of PRL and tumor size were observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:The total response rate of group A (83.33％) was higher than that of group B (66.67％),without statistical significance (P>0.05). Before treatment,there was no statistical significance in serum level of PRL and tumor size between 2 groups (P>0.05). After 1,2 months of treatment,serum levels of PRL in 2 groups were decreased significantly,and the group A was significantly lower than the group B,with statistical significance(P<0.05). After 3 months of treatment,serum levels of PRL in 2 groups were decreased significantly compared to be-fore treatment,but there was no statistical significance between 2 groups(P>0.05). After treatment,tumor size of 2 groups were decreased significantly,and large adenoma and giant adenoma size in group A were significantly smaller than group B,with statisti-cal significance(P<0.05). There was no statistical significance in microadenoma size between group A and B(P>0.05). The inci-dence of ADR in group A(12 cases,40.00％)was significantly higher than group B(5 cases,16.67％),with statistical signifi-cance(P<0.05). CONCLUSIONS:Increasing dosages of bromocriptine no significant influence on therapeutic effect of prolactino-ma,but it can shorten the time of serum PRL level back to normal,and reduce the tumor size. The incidence of adverse reactions in-crease with the dosage.

Objective To determine the ED50 of dexmedetomidine for suppressing cardiovascular responses to placement of laryngeal mask airway (LMA) in patients undergoing gynecological laparoscopic surgery with induction of propofol. Methods ASA I or II Patients aged 18 to 55 undergoing elective gynecological laparoscopic surgery were enrolled. After an bolus dose of dexmedetomidine over 10 min , anaesthesia was induced with target-controled propofol, and then bolus of vecuronium of 0.1 mg/kg was injected when the BIS was between 45 and 55. LM palcement was performed 3 minutes after vecuronium injection. The modified Dixon ’ s up-and-down method was used to determine the bolus dose of dexmedetomidine , starting from 1.0 μg/kg (step size:0.1 μg/kg). Cardiovascular response was defined as an increase in SBP and/or HR by 15% of baseline within 2 min after placement of LMA. The test ended after at least 7 crossovers ( successive ‘response’ or ‘non-response’) were obtained. Probit analysis was used to calculate ED50, ED95 and 95% confidence interval (CI). Results The ED50 and ED95 (95% confidence interval) of dexmedetomidine for suppressing cardiovascular responses to placement of LMA was 0.65 μg/kg (0.44-0.80) μg/kg and 0.94 μg/kg (0.79-2.47) μg/kg. Conclusion Under induction of target-controled propofol , the ED50 of dexmedetomidine is 0.65 μg/kg for suppressing cardiovascular responses to placement of LMA in female patients.

Objective To study the effect of APETx2 on the expression of ASIC3 APETx2 in a rat model of acute gastric mucosal lesion(AGML). Methods Twenty-four Wistar rats were randomly assigned to three groups in equal number : normal control group, water immersion restraint stress (WIRS) group, APETx2 treatment group. AGML was induced by WIRS for 6 hours, and APETx2 (25 μg/kg) was injected intraperitoneally before the onset of stress. Intragastric pH and gastric histopathological changes were measured and the expression of ASIC3 mRNA in DRG neurons projecting to rat stomach was examined by real-time PCR. Immunohistochemistry was performed to detect the localization of ASIC3. Results Compared with the normal control group, the WIRS group showed obvious gastric injury with lower values of intragastric pH and extensive expression of ASIC3 in the DRG neurons (P < 0.05). The treatment with APETx2 before the onset of WIRS significantly alleviated the gastric mucosal injury, decreased gastric acidity and reduced ASIC3 expression in DRG neurons (P < 0.05). Conclusions ASIC3 expression in DRG neurons projecting to rat stomach is strongly associated with gastric mucosal lesion and acidosis in the WIRS model. APETx2 can improve gastric acidosis and prevent the occurrence of these lesions.

Animals ; Cell Line ; Cytological Techniques ; methods ; Embryonic Stem Cells ; cytology ; Interleukin Receptor Common gamma Subunit ; genetics ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation

Objective To observe the protective effect of sufentanil pretreatment on the rats with acute gastric mucosa lesion (AGML) induced by water immersion and restrain stress (WIRS) and its effect on TRPV1 mRNA expression in the hypothalamus and gastric mucosa. Methods Thirty male Wistar rats were randomly designed into 3 groups, including the normal control group (Group NC, n = 10), the group treated with WRIS for 6 h (Group WIRS, n = 10) and the group pretreated with sufentanil (Group SF, n = 10). The model of AGML was established by the classic WIRS method , and observed for the general extent of gastric mucosal injury at WIRS for 6 hr, and calculated gastric mucosal injury ulcer index (UI) and the PH value of gastric juice; The quantification of TRPV1 mRNA expression in hypothalamus and gastric mucosa was performed using quantitative real-time PCR; In addition, the activity of super oxide dismutase (SOD) and the level of malondialdehyde (MDA) in serum were detected. Results Compared with group NC, gastric mucosal in Group WIRS was injured more seriously , and the UI and the activity of MDA were also obviously increased , but the change of SOD activity was not apparent; The TRPV1 expression in gastric mucosal decreased apparently. Sufentanil pretreatment could effectively relieve gastric mucosal injury induced by WIRS , and make the UI and the activity of MDA decreased , and up-regulate TRPV1 mRNA expression in the hypothalamus and gastric mucosa. Conclusions Sufentanil pretreatment can effectively relieve AGML induced by WIRS , which may be related to the control of oxidative stress response , the reduced gastric acid secretion , and the upregulation of the TRPV1 mRNA expression in the central and periphera nerve.