It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.
Rats ; Animals ; Rats, Inbred SHR ; Paraventricular Hypothalamic Nucleus/physiology* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Rats, Inbred WKY ; Corticotropin-Releasing Hormone/metabolism* ; Neurons/physiology* ; Hypertension ; Sympathetic Nervous System

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Adolescent ; Adult ; Asian People/genetics* ; Child ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY/genetics* ; Follicle Stimulating Hormone/blood* ; Genitalia, Male/abnormalities* ; Humans ; Hypospadias/genetics* ; Luteinizing Hormone/blood* ; Male ; Membrane Proteins/genetics* ; Mutation/genetics* ; Sequence Alignment ; Steroid Metabolism, Inborn Errors/genetics* ; Testosterone/blood* ; Young Adult

OBJECTIVETo evaluate therapeutic effects of Wallis interspinous dynamic stabilization in treating ASD after lumbar spinal fusion.

METHODSTotally 40 patients (included 16 males and 24 females, aged 25 to 60 years old) with degenerative disc disease were treated with posterior interbody fusion. Among them, 20 cases (treatment group) were treated with posterior interbody fusion combined with Wallis interspinous dynamic stabilization, while other 20 cases (control group) only treated with posterior interbody fusion. JOA score and VAS score were compared after inserted Wallis interspinous dynamic stabilization at 1 month and 3 years, and changes of intervertebral disc height of adjacent segment and cross-sectional area of the canal were tested and compared.

RESULTSAll patients were followed up from 3 to 5 years with an average of 3.6 years. All injuries were healed at stage I and the pain were released after treatment. There were no significant meaning in JOA score and VAS score at 1 month after treatment between two groups (P>0.05), while had meaning at 3 years (P<0.05). There were no statistical significane in intervertebral disc height of adjacent segment and cross-sectional area of the canal at 1 month after treatment (P>0.05), while had statistical meaning at 3 years (P<0.05).

CONCLUSIONThere is no difference in immediate effects between two groups. Both of them can obtain good results for effective decompression. Medial-term effectiveness of treatment group is obviously better than control group, which depends on Wallis interspinous dynamic stabilization to plays good biology effects and effective accelerate adjacent degeneration caused by lumbar fusion.

Adult ; Decompression, Surgical ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Spinal Fusion ; Treatment Outcome

BACKGROUNDResults of perimembranous ventricular septal defects (pmVSD) transcatheter closure have been reported in the literature mostly using a Amplatzer VSD device. However, the data of percutaneous closure of pmVSD with VSD occluder (VSD-O) made in China are still limited. We sought to analyze safety, efficacy, and follow-up results of percutaneous closure of pmVSD with VSD-O made in China.

METHODSBetween February 2005 and June 2009, 78 patients underwent percutaneous closure of pmVSD at our institution. A VSD device made in China was used for all subjects. The safety and the efficacy of the VSD-O were investigated.

RESULTSThe average age at closure was 11 years (range 2.5 to 44 years). The attempt to place device was successful in 74 patients (94.9%). The average device size used was 8 mm (range 5 to 16 mm). No deaths occurred. Total occlusion rate was 62.8% at completion of the procedure, rising up to 87.2% at discharge and 99.0% during follow-up. A total of eight early complications occurred (10.3%), but in all subjects these were transient. The average follow-up period was 40.5 months. The most significant complication was complete atrioventricular block (cAVB) in the early phase (five subjects, 6.4%) and during the follow-up (1 subject, 1.3%), which saw no need for pacemaker implantation in six subjects. Cox proportional hazards regression analysis showed that the age was only the variable significantly associated with the occurrence of this complication during the procedure (P = 0.025; relative risk 0.22). The subjects who experienced this complication were less than five years old.

CONCLUSIONSPercutaneous pmVSD closure used VSD-O made in China is associated with excellent success and closure rates, no mortality, and low morbidity. Longer follow-up data and improvements in device characteristics are needed to reduce the risk of cAVB.

Adolescent ; Adult ; Cardiac Catheterization ; adverse effects ; methods ; Child ; Child, Preschool ; China ; Female ; Heart Septal Defects, Ventricular ; therapy ; Humans ; Infant ; Male ; Prospective Studies ; Treatment Outcome ; Young Adult

Objective To analyze the incidence of coronary artery disease (CAD) and outcome of patients with left ventricular noncompaction (LVNC). Methods Fifty-one patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January 2006 to August 2010 were retrospectively reviewed. Coronary angiography or MDCT was performed for detecting coronary artery disease. Predictors of the cardiac events were analyzed by Cox regression analysis. Results There were 31 LVNC patients without CAD and 20 LVNC patients with CAD including single vessel coronary disease in 9 cases, double vessel coronary disease in 3 cases, three vessel coronary disease in 5 cases and left main coronary disease in 3 cases. Coronary artery bypass graft and percutaneous coronary intervention (PCI) were performed in 4 patients. Compared to LVNC patients without CAD, mean age ( P = 0. 008 ), incidence of hypertension (65.0% vs. 19. 4% , P = 0. 001 ), diabetes mellitus (40. 0% vs. 12. 9% , P = 0. 026) and hyperlipidemia ( 55.0% vs. 25. 8%, P = 0. 035 ) were significantly higher while NT-proBNP level was significantly lower( P = 0. 049 ) in LVNC patients with CAD. Incidence of major cardiac events was similar in LVNC patients with or without CAD. LogNT-proBNP is the independent prognostic factor for adverse cardiac events in patients with LVNC( HR 3.993,95% CI 1. 140-13. 988 ,P =0. 030). Conclusions Coronary artery disease is common in patients with LVNC and associated with traditional risk factors for CAD. Poor prognosis is associated with increased NT-proBNP but not with CAD in this patient cohort.

Objective To characterize the clinical and cardiac MRI features of dilated cardiomypathy ( DCM) and left ventricular noncompaction (LVNC). Methods Compared the clinical and MRI features between 25 patients with LVNC and 21 patients with DCM. The MRI derived diastolic left ventricular wall thickness and the number and degree of noncompaction (NC) were evaluated using the 17-segment model. Results Chest distress, shortness of breath and abnormal ECG were presented in all DCM patients, abnormal ECG was evidenced in 22 LVNC patients and 21 out of 25 LVNC patients presented similar clinical symptoms as DCM patients while the rest 4 LVNC patients were asymptomatic. Left atrial and ventricular dimensions were significantly smaller in LVNC patients compared to DCM patients. The degree of left ventricular (LV) spherical remodeling was significantly greater in patients with DCM (sphericity index, SI = 0. 81 ± 0. 06) than in patients with LVNC ( SI = 0. 74 ± 0. 11, P < 0. 05). The LV ejection fraction ( LVEF) was significantly higher in patients with LVNC (32. 7% ± 14. 2% ) than that in patients with DCM (15. 0% ±5. 1% ). The number of NC segments in LVNC patients (9 ± 1) was significantly higher than the number of hypertrabeculation segment in DCM patients (5 ±2). The left ventricular apex (the 17th segment) was unexceptionally involved in all LVNC patients, while hypertrabeculation was absent in the 17th segment of DCM patients. The NC was more common in the apical and mid segments (16th, 12th and 11th segments) than in basal and mid septal segments (2nd, 3rd, 8th and 9th segments) in both LVNC and DCM patients. The thickness of compacted myocardium of the segments associated with noncompaction appeared thin in two groups. The wall thickness of noncompaction myocardium segments was thicker in LVNC patients than in DCM patients. The end-diastolic NC/C ratio was, on average, higher in patients with LVNC (3. 3 ± 0. 6) than in patients with DCM (1.9 ± 0. 3 ) . Conclusions The clinical manifestation is similar while there are significant differences in the morphology and function of left atria and left ventricle between the LVNC and DCM patients. The different distribution and degree of NC were helpful to differentiate LVNC from DCM.

Objective To analyze the stem cell re-distribution after intra-coronary infusion (ICI)into arrested and beating hearts in a swine myocardial infarction ( MI ) model using magnetic resonance imaging (MRI). Methods Bone marrow-derived mesenchymal stem cells were obtained from male swine and labeled with iron oxide during culture. One week after MI in female swine, the survivors were randomly divided into 4 groups. Cardiopulmonary bypass was set up to arrest the heart, and then SPIO labeled male stem cells ( 1 × 108 ) were infused through coronary of beating heart ( n = 6) and the arrested heart ( n = 6).Saline was injected in either the beating or arresting heart as respective controls. Three days later, cell distribution was assessed by T2* change with magnetic resonance imaging and Y-chromosome (SRY) was detected with quantitative polymerase chain reaction. Results The reduction of T2* values was significantly different in the hearts, spleens, livers and lung between the transplantation groups and the control groups. Only few transplanted cells were localized in the heart and T2 * values were similar between beating and arrest heart groups [ ( -7.81 ±2.03) ms vs. ( -6.56 ± 1.72)ms, P＞0.05], while T2* value reduction was more significant in the spleen and liver in arrest heart group than in beating heart group [spleen: (-16.72 ±2.83)ms vs. ( -22.18 ±3.98)ms, P＜0.01, liver: ( -2.40±0.44)ms vs.( -5.32 ± 3.40 ) ms, P ＜ 0. 05 ] . T2 * value was similar in kidney among the four groups. qRT-PCR detected SRY gene was similar in the heart, less in the spleen and liver while more in the lung in beating heart group compared to arrested heart group. In vitro Prussian blue stained positively transplanted cells were found in the above organs in transplantation group. Conclusions The majority of stem cells transplanted by ICI would be entrapped by the extracardial organs. Stem cell transplantation via ICI into the arrested heart does not favor more cells retention in the injured myocardium. Further investigation is needed to optimize the approach of stem cell delivery.

OBJECTIVETo evaluate the safety of living related donors in short term after transplantation.

METHODSTwo hundred and fifty-one cases of living related donor kidney transplantation from May 2000 to July 2007 were analysed retrospectively. There were 117 male and 134 female aged from 22 to 72 years old, with a mean of 46.6 years old. The indexes were compared including serum creatinine (SCr), creatinine clearance (CCr), glomerular filtration rate (GFR) and quality of life before and after donation. Surgical complications were followed-up.

RESULTSDonors' SCr was (75.9 +/- 17.2) micromol/L before donation, (107.4 +/- 21.2) micromol/L on 7 d after donation, (130.4 +/- 58.2) micromol/L at the 1(st) month and (116.1 +/- 24.1) micromol/L at the 3(rd) month. There were significant difference between any 2 time points (P < 0.01). CCr was (94.4 +/- 17.5) ml/min before donation and (63.5 +/- 17.8) ml/min on 10 d after donation (P < 0.01). In 62 donors, total GFR was (82.4 +/- 21.8) ml/min before donation. On 10 d after donation, GFR of remaining kidney was (57.4 +/- 14.1) ml/min which was 34.7% higher than GFR of this kidney before donation (42.6 +/- 11.8) ml/min. There was no significant difference in quality of life before living related donors and non-donor populations (P = 0.116). Surgical complications included splenic rupture in 1 case, descending colon rupture in 1 case and wound infection in 5 cases.

CONCLUSIONLiving donor kidney transplantation is safe for donors, although part of indexes would vary within normal range during the early time after donation.

Adult ; Aged ; Female ; Humans ; Kidney Transplantation ; adverse effects ; Living Donors ; Male ; Middle Aged ; Nephrectomy ; adverse effects ; Postoperative Period ; Retrospective Studies ; Safety ; Young Adult

OBJECTIVESTo analyze the prognostic factors for elderly patients with pancreaticoduodenectomy for periampullary tumor.

METHODSA retrospective analysis of the prognostic factors for the mortality rate was made in 127 elderly patients within 30 days of pancreaticoduodenectomy for periampullary tumor from January 1985 to November 2006 Chi-squared test, Fisher's exact test, t-test were used.

RESULTSThe prognostic factors for the first-month mortality rate in elderly patients with pancreaticoduodenectomy included time length of the operation, operative hemorrhage, postoperative hemorrhage, pulmonary infection, and postoperative TP.

CONCLUSIONSAn overall consideration should be paid to the factors that affect the prognosis of elderly patients with pancreaticoduodenectomy for periampullary tumor during the perioperative period. The security of the patients can be promoted by controlling these prognostic factors.

Aged ; Ampulla of Vater ; Common Bile Duct Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Pancreaticoduodenectomy ; mortality ; Prognosis ; Retrospective Studies ; Survival Analysis

Adult ; Aneurysm, False ; etiology ; therapy ; Embolization, Therapeutic ; Humans ; Intracranial Arterial Diseases ; etiology ; therapy ; Male ; Wounds and Injuries ; therapy