Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

New phenanthrene and 9, 10-dihydrophenanthrene derivatives from the stems of Dendrobium officinale with their cytotoxic activities.

Two new phenanthrene and 9, 10-dihydrophenanthrene derivatives (1-2) with six known congeners (3-8) were isolated from the extraction of stems of Dendrobium officinale. Compounds 1 and 2 were based on carbon skeleton in which phenanthrene and 9, 10-dihydrophenanthrene moiety were linked with a phenylpropane unit through a dioxane bridge, respectively. Their structures were determined by comprehensive NMR spectroscopic data, the absolute configuration of new compounds were determined by comparing their experimental and calculated ECD for the first time. All the compounds were investigated contains two cancer cell lines (HI-60, THP-1). All the isolates showed cytotoxicity, especially compound 4 showed markedly cytotoxic activities against HI-60 and THP-1 cell lines with IC50 values of 11.96 and 8.92 µM.

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells.

OBJECTIVE: This study aimed to investigate the damage mechanism of nanosized hydroxyapatite (nano-HAp) on mouse aortic smooth muscle cells (MOVASs) and the injury-inhibiting effects of diethyl citrate (Et2Cit) and sodium citrate (Na3Cit) to develop new drugs that can simultaneously induce anticoagulation and inhibit vascular calcification. METHODS: The change in cell viability was evaluated using a cell proliferation assay kit, and the amount of lactate dehydrogenase (LDH) released was measured using an LDH kit. Intracellular reactive oxygen species (ROS) and mitochondrial damage were detected by DCFH-DA staining and JC-1 staining. Cell apoptosis and necrosis were detected by Annexin V staining. Intracellular calcium concentration and lysosomal integrity were measured using Fluo-4/AM and acridine orange, respectively. RESULTS: Nano-HAp decreased cell viability and damaged the cell membrane, resulting in the release of a large amount of LDH. Nano-HAp entered the cells and damaged the mitochondria, and then induced cell apoptosis by producing a large amount of ROS. In addition, nano-HAp increased the intracellular Ca2+ concentration, leading to lysosomal rupture and cell necrosis. On addition of the anticoagulant Et2Cit or Na3Cit, cell viability and mitochondrial membrane potential increased, whereas the amount of LDH released, ROS, and apoptosis rate decreased. Et2 Cit and Na3Cit could also chelate with Ca+ to inhibit the intracellular Ca2+ elevations induced by nano-HAp, prevent lysosomal rupture, and reduce cell necrosis. High concentrations of Et2Cit and Na3Cit exhibited strong inhibitory effects. The inhibitory capacity of Na3Cit was stronger than that of Et2Cit at similar concentrations. CONCLUSION: Both Et2Cit and Na3Cit significantly reduced the cytotoxicity of nano-HAp on MOVASs and inhibited the apoptosis and necrosis induced by nano-HAp crystals. The chelating function of citrate resulted in both anticoagulation and binding to HAp. Et2Cit and Na3Cit may play a role as anticoagulants in reducing injury to the vascular wall caused by nano-HAp.

Expression of kallikrein-related peptidase 7 is decreased in prostate cancer.

Recent evidence suggests that the human kallikrein 7 (KLK7) is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57%) benign cases showed positive staining for KLK7 and 23 of 116 (19.83%) malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001). The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

The advantages of unilateral pedal lymphography in the diagnosis of chyluria.

OBJECTIVES: To evaluate the efficacy and safety of pedal lymphography (PLG) in the localization diagnosis of chyluria. METHODS: Cystoscopy was performed in 153 patients and PLG in 121 cases. Unilateral or staged bilateral ligation and stripping of renal lymphatic vessel were performed according to the results of cystoscopy and/or PLG. RESULTS: Unilateral and bilateral urinary excretion of chyle was detected in 123 and 1 case by cystoscopy, respectively. In 121 cases receiving PLG, 100 cases of unilateral fistulous connection between the renal pelvis and the lymphatic system, 18 cases of bilateral fistulas and 1 case of lymphatic bladder fistula were demonstrated. PLG has a higher diagnostic rate for the detection of bilateral lymphatic renal pelvis fistulas than cystoscopy (p<0.05). 28 cases received renal pedicle lymphatic disconnection only according to the results of cystoscopy, and 3 of them failed (10.1%). While 121 cases had the same operation according to the results of PLG, only 1 case failed the operation (0.8%). CONCLUSIONS: PLG was efficient and safe for the localization diagnosis of chyluria, with a higher detection rate of bilateral fistulas than cystoscopy. PLG might benefit the selection of appropriate therapy and improve the surgical effect.

Outcome of nephrostomy balloon dilation for vesicourethral anastomotic strictures following radical prostatectomy: a retrospective study.

To evaluate the efficacy of nephrostomy balloon dilation (NBD) for patients who developed vesicourethral anastomotic stricture (VAS) following radical prostatectomy. NBD was performed in patients who developed VAS following radical prostatectomy. Quality of life (QoL), International Prostate Symptom Score (IPSS) and maximal urinary flow rate (Qmax) were evaluated. Four hundred and sixty-three prostate cancer patients underwent radical retropubic prostatectomy (RRP), and 86 underwent laparoscopic radical prostatectomy (LRP). Most patients (90.3%) had T2 or T3 prostate cancer and a pathological Gleason score of ≤ 7. Forty-five (8.2%) and four (4.7%) patients developed VAS due to radical or LRP, respectively. Forty (89%) patients underwent NBD, including three cases of repeat dilation. The median Qmax was 4 ml s-1 (interquartile range (IQR), 2.3-5.6) before dilation and improved to 16 ml s-1 (IQR, 15-19) and 19 ml s-1 (IQR, 18-21) at the 1- and 12-month follow-up, respectively (P < 0.01). Fifteen (37.5%) patients had urinary incontinence prior to dilation, whereas only three (7.5%) patients had incontinence 12 months following dilation (P < 0.01). The median IPSS score improved from 19 (IQR, 17-24) before dilation to 7 (IQR, 6-8) at 12 months following dilation, and the QoL score improved from 5 (IQR, 4-6) before dilation to 2 (IQR, 2-3) at 12 months following dilation (P < 0.01 in both). VAS occurs in a small but significant proportion of patients following radical prostatectomy. NBD offers an effective remedy for VAS.

[Experience in reducing intraoperative blood loss in radical retropubic prostatectomy].

OBJECTIVE: To search for an effective method of reducing intraoperative blood loss in radical retropubic prostatectomy (RRP). METHODS: We performed RRP for 100 patients with prostate cancer, 50 (group A) with the Walsh or Poor method for handling the dorsal venous complex (DVC), and the other 50 (group B) through the following three additional procedures for hemostasis: first placing a #7 prophylactic suture in the distal position of DVC, then ligating the vascular bundle of the prostatic apex with continuous 4-0 Vicryl sutures, and lastly placing a 4-0 absorbable suture followed by freeing the neurovascular bundle (NVB) or freeing NVB before suturing the remained levator ani myofascia and the deep layer of Denovilliers' fascia above the rectal serosa with 4-0 Vicryl. We assessed the effects of the three hemostatic methods in RRP by comparing the volumes of intraoperative blood loss and transfusion, operation time and perioperative levels of hemoglobin. RESULTS: There were no significant differences between groups A and B in age, PSA, Gleason score, clinical stage, prostate volume, operation time and perioperative hemoglobin levels (P>0.05). The volumes of intraoperative blood loss and transfusion were markedly higher in group A ([1103.00 +/- 528.03] ml and [482.00 +/- 364.60] ml) than in B ([528.00 +/- 258.96] ml and [140.00 +/- 266.28] ml) (P<0.05). CONCLUSION: Intraoperative blood loss in RRP could be significantly decreased by placing a prophylactic hemostatic suture in the distal position of DVC, continuous suture of the vascular bundle of the prostatic apex after cutting off the urethra, and placing a fine absorbable suture above NVB or continuous suture of the remained levator ani mony fascia and the deep layer of Denovilliers'fascia above the rectal serosa with absorbable sutures after freeing NVB.

Ureteroscopic lithotripsy using holmium laser for 187 patients with proximal ureteral stones.

BACKGROUND: Improving the success rate of ureteroscopic lithotripsy for proximal ureteral stones is the hot issue in this field. Here we reported our experience on the treatment of proximal ureteral stones. METHODS: From 2005 to 2010, 187 consecutive patients with proximal ureteral stones who underwent ureteroscopic lithotripsy were enrolled. The initial 52 patients treated by semi-rigid ureteroscope alone were classified as group 1. The subsequent 135 patients treated by semi-rigid ureteroscope with the aid of stone basket and flexible ureteroscope were classified as group 2. RESULTS: In group 1, the overall stone-free rate was 67.3%. By a single procedure of ureteroscopic lithotripsy using a semi-rigid instrument, patients with ureteral stones below the 4th lumbar vertebra level achieved 91.7% stone-free rate, which was only 50% in patients with stones above the 4th lumbar vertebra level. Conversion to open surgery occurred in two patients since ureteral perforation was observed. In group 2, the stone-free rate achieved 93.2% with the aid of an N-Trap basket, which was significantly higher than that of patients without the aid of the basket (51.6%). Flexible ureteroscope was subsequently used in patients with fragment migration, thus making the overall success rate in group 2 increases to 97.0%. CONCLUSIONS: Ureteroscopic lithotripsy is a safe and efficacious treatment for proximal ureteral stones. A single procedure of ureteroscopic lithotripsy using semi-rigid ureteroscope could achieve a satisfactory stone-free rate in patients with proximal ureteral stones below the 4th lumbar vertebra level. However, patients with ureteral stones above the 4th lumbar vertebra level experienced higher stone-migration rate, which would decrease the success rate. Fortunately, the stone-free state could possibly be achieved with the aid of an N-trap basket and flexible ureteroscope.

[Retropubic radical prostatectomy: 10 years' experience with 100 cases].

OBJECTIVE: To summarize the experience and lessons from 100 cases retropubic radical prostatectomy performed in the past 10 years. METHODS: From July 1999 to July 2009, we performed 100 cases of retropubic radical prostatectomy, of which 84 were followed up for 3 - 120 months. We analyzed their preoperative age, PSA level, amount of intraoperative blood transfusion, operation time, urinary continence, penile erectile function, stricture of the anastomotic stoma and Qmax. RESULTS: The mean age, PSA level, amount of intraoperative blood transfusion, operation time were 66.8 yr, 20.1 ng/ml, 585.7 ml and 198.9 min; the recovery rates of bladder control at 3, 6 and 12 months postoperatively were 65.5%, 81.7% and 92.4%, respectively. At 12 months after surgery, penile erection was restored in 19 cases (42.2%), anastomotic stoma stricture developed in 5 (5.9%), Qmax averaged 20.5 ml/min, biochemical recurrence was found in 13, and 1 died from prostate cancer. CONCLUSION: Retropubic radical prostatectomy is a desirable procedure for the treatment of local prostate cancer, in which ligation of the puboprostatic ligament and prostatic venous plexus before cutting off the ligament helps improve urinary continence, protection of the neurovascular bundle and collateral pudendal artery contributes to the recovery of penile erectile function, and proper connection of urethral and bladder mucosa can reduce anastomotic stoma stricture. Postoperative external-beam radiotherapy for those with T3a or local lymph node metastasis could decrease biochemical recurrence.

Selective α1-adrenoceptor antagonist (controlled release tablets) in preoperative management of pheochromocytoma.

The objective of this article is to evaluate the efficacy of Doxazosin Mesylate Controlled Release Tablets for preoperative treatment of patients with pheochromocytoma. Between 2003 and 2008, 67 patients with confirmed diagnoses of pheochromocytoma were enrolled in this study. According to the drug used in preoperative management, patients were divided into two groups: Doxazosin Mesylate pretreatment group (n=36) and Phenoxybenzamine pretreatment group (n=31). Surgery was performed only in patients who met the optimal preoperative condition. The hematocrit decreased significantly (P<0.001) after antiadrenergic therapy in patients pretreated with phenoxybenzamine or doxazosin. There was no significant difference between the fluid intakes during operation in both groups. The systolic arterial pressures both before and after induction of anesthesia were all significantly higher in the doxazosin patients than in the phenoxybenzamine group (P<0.05). After tumor removed, the lowest systolic arterial pressure was significantly higher in doxazosin group than in phenoxybenzamine group (P<0.05). The fluctuation of systolic arterial pressure during operation was more stable in doxazosin group than in phenoxybenzamine group (P<0.05). Doxazosin mesylate controlled release tablet was as effective as phenoxybenzamine in preoperative volume expansion. Although phenoxybenzamine provided better arterial pressure control, patients pretreated with DOX experienced more stable perioperative hemodynamic changes, shorter preoperative management periods and more simple medication.

[The clinical observation of bipolar transurethral plasma kinetic resection of prostate for high risk benign prostate hyperplasia].

OBJECTIVE: To evaluate therapeutic effect and reliability of bipolar transurethral plasma kinetic prostatectomy (TUPKP) for high risk level benign prostatic hyperplasia (BPH). METHODS: A total of 230 cases of high risk of BPH were treated with TUPKP. Among them, 132 cases with the residual urine of 40 to 420 ml had accepted long term but inefficient medical therapy, 98 cases were suffered with repeating acute urinary retention. One hundred and seventy-three cases with the functional capacity>4 MET were performed the standard transurethral resection of the prostate (TURP), the other 57 cases with the functional capacity<4 MET were accepted the minimally invasive TURP. Among them 12 cases complicated with bladder stones accepted Ho: YAG lithotripsy priory. The international prostate symptom score (IPSS), The maximal urinary flow rate (Qmax) and residual urine of the 2 groups before and after operation were analyzed. RESULTS: There was no transurethral resection syndrome occurred in both groups. After 3 to 12 months of follow-up postoperatively, the IPSS of the two groups were reduced from (21.9+/-5.7) and (23.7+/-5.0) to (4.4+/-2.3) and (5.5+/-2.4), residual urine were reduced from (61.8+/-18.4) ml and (103.9+/-77.3) ml to (13.0+/-6.2) ml and (15.8+/-6.1) ml, respectively. The Qmax was increased from (5.7+/-3.0) ml/s and (4.8+/-2.8) ml/s to (20.9+/-6.3) ml/s and (16.8+/-3.9) ml/s, there existed significant differences (P<0.01). However the IPSS, Qmax and residual urine of the standard group had progressed more obviously than the minimally invasive TURP group (P<0.05). CONCLUSIONS: It is safe and effective to use TUPKP for treating high risk patients of BPH with classic TURP and minimally invasive TURP according to different functional capacity. When the functional capacity is more than 4 MET, the standard procedures is preferred.

[Surgical treatment of 486 cases of adrenal gland diseases: a retrospective study].

OBJECTIVE: To evaluate the roles of laparoscopic adrenalectomy (LA) and open adrenalectomy (GA) for treatment of adrenal gland diseases. METHODS: The data of 486 patients with adrenal gland diseases was analyzed retrospectively during 5 years. A total of 478 patients received surgical treatments including 318 GAs and 160 LAs. The operation time, bleeding volume during operation, intestine function recovery time, pain postoperatively, hospital stay time postoperatively and postoperative complications in group GA and group LA respectively were compared. RESULTS: All cases in group GA were successful. A total of 154 cases in group LA were successful, and 6 cases were converted to open surgery. In group LA, there were 9 cases whose tumor diameter exceeded 6 cm. There were 3 malignant cases in group LA, and no recurrence and metastasis were observed during 3-20 months follow-up. The average operation time was (112 +/- 16) mmn and (69 +/- 10) min in group GA and LA respectively. The average bleeding volume during operation was (286 +/- 23) ml, (56 +/- 10) ml in group GA and LA respectively. The average intestine function recovery time was (66 +/- 7) h, (24 +/- 7) h in group GA and LA respectively. The average frequency of treatment of pain was 1.9 +/- 0.4 and 0.5 +/- 0.1 in group GA and LA respectively. The average hospital stay time postoperatively was (10.3 +/- 1.1) d and (7.2 +/- 0.7) d in group GA and LA respectively. The rate of postoperative complications was 40.3% and 7.5% in group GA and LA respectively. All differences were significant (P = 0.023, 0.007, 0.039, 0.003, 0.029 and 0.001). CONCLUSIONS: LA has the added benefit of shorter convalescent times, improving patients satisfaction and less associated complications, as it has proved to be as effective as OA.

[Prevention of incontinence after radical prostatectomy].

OBJECTIVE: To discuss the effect of urine control after radical retropubic prostatectomy by preserve the membranous part of sphincter urethrae and the neurovascular bundle, or to rebuild the bladder neck. METHODS: The radical retropubic prostatectomy was performed on a total of 32 cases of prostate cancer. We preserve the membranous part of sphincter urethrae and the neurovascular bundle lateral to the prostate. We evaginate the posterior wall of the bladder adequately and make an additional folding stitch to rebuild the bladder neck. RESULTS: The follow up is of 6-72 months. All patients could void without difficulty, no tumor recurrence and only 2 cases occurred slight incontinence. Other 30 cases regained the ability of controlling their urinations within 6 months. CONCLUSIONS: The incontinence after radical retropubic prostatectomy could be reduced by the method of preserving the membranous part of sphincter urethrae and preserving the neurovascular bundle lateral to the prostate in operation. It could also be avoided by evaginate the posterior wall of the bladder adequately and make an additional folding stitch to the bladder neck.

[Primary pigmented nodular adrenocortical disease report of 5 cases].

OBJECTIVE: To study the pathology, diagnostic and therapeutic method of primary pigmented nodular adrenocortical disease (PPNAD). METHODS: The data of 5 cases of PPNAD were analyzed retrospectively. Among the 5 cases, 2 were male and 3 were female. The range of age was from 12 to 53 years. All the 5 cases had symptoms of Cushing syndrome. The diagnose depended on the results of endocrine exams, ultrasound, CT, MR and pathological reports. All patients received operation of unilateral adrenalectomy. The therapeutic effects were determined by post-operative results, which concluded clinical symptoms and endocrine exams. RESULTS: The follow-up time was from 4 months to 3 years. All patients' symptoms of Cushing syndrome were relieved in 6 months after operation. The endocrine exam was normal in one case and obvious improved in the other four cases. Up to now, one patient drop out of the follow-up, the other 4 cases had no evidence of recurrence. CONCLUSION: PPNAD is a rare type of Cushing syndrome. Diagnose depends on endocrine exams and pathological results. Operation is the effective method for the disease.

[The analysis of the factors for postoperative blood pressure recovery of aldosterone producing adenoma patients].

OBJECTIVE: To investigate the factors regarding the recovery of postoperative blood pressure of aldosterone producing adenoma (APA) patients. METHODS: Sixty-eight patients with APA were recruited and their data including retinal blood vessel by Doppler sonography, urinary trace albumin, pathological changes of renal biopsy and the adrenal tissues around the adenoma were analyzed in order to determine the correlation between these data and postoperative durative hypertension. RESULTS: Postoperative durative hypertension occurred in 14 cases (41.2%) with increased resistance of unilateral or bilateral central artery of retina, in 16 cases (66.7%) with increased level of urinary trace albumin. Fifteen cases underwent renal biopsy and all of them showed different pathological alterations, 11 cases (73.3%) of which presented with postoperative durative hypertension. The pathological changes of the adrenal tissues around the adenoma is either atrophy or non-atrophy (normal or hyperplasia), 8 cases (40%) and 10 cases (22.2%) of which showed postoperative durative hypertension, respectively. CONCLUSION: The renal pathological changes and increased resistance of retinal blood vessel are the main reasons leading to postoperative hypertension in patients with APA.