[A new understanding of wound repair after surgery for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. Transurethral resection of prostate (TURP), as an important BPH treatment, is also the most effective way to relieve prostatic obstruction. However, postoperative complications, such as lower urinary tract symptoms (LUTS), infection, hematuria and bladder neck contracture, may still occur, which seriously impact the therapeutic effect and patients' quality of life. The wound healing after BPH surgery is closely associated with the occurrence of postoperative complications. Therefore, comprehensively understanding the influencing factors of wound healing and designing tailored interventions will be particularly important for reducing postoperative complications of BPH.

[Jiangsu Province Coronary Artery Bypass Grafting Registry study: a report of 4 661 patients in 13 centers].

Objective: To examine the overall status of the Jiangsu Province Coronary Artery Bypass Grafting Registry database. Methods: The patients date of Jiangsu Province Coronary Artery Bypass Grafting Registry database from October 2017 to December 2019 was collected retrospectively.Risk factors, history, cardiac function (New York Heart Association class), extent of coronary artery lesion, European system for cardiac operative risk evaluation Ⅱ (EuroSCORE Ⅱ), cardiopulmonary bypss, arterial grafts, the numbers and flow of grafts and postoperative major adverse cardiac and cerebrovascular event(MACCE) information were analyzed. The clinical data of patients underwent on-pump CABG(ONCABG) or off-pump CABG (OPCAB) were compared by t test or χ(2) test. Results: Up till December 2019, the database enrolled 7 138 patients, in which 4 661 patients receiving primary isolated CABG. There were 3 486 males and 1 175 females with the age of (64.6±8.1) years (range:31 to 87 years). There were coronary left main disease in 960 patients, triple vessel disease in 3 934 patients, both left main and triple vessel disease in 837 patients, ejection fraction>50% in 3 841 patients, cardiac function class Ⅲ to Ⅳ in 1 664 patients. EuroSCORE Ⅱ was (2.3±0.7)% (range: 0.5% to 35.8%). There were 2 731 patients (58.59%) underwent ONCABG and 1 930 patients (41.41%) underwent OPCAB. There were 4 144 patients (88.91%) for whom the left internal thoracic artery was harvested. Seven centers (2 centers routinely) used left radial artery, 5 centers (3 centers routinely) used the transit time flow meter. The graft was 3.4±0.7 (range:1 to 7), the aortic crossclamp time was (65.0±20.4) minutes (range: 21 to 196 minutes), the cardiopulmonary bypass time was (90.0±24.2) minutes (range: 33 to 227 minutes). In-hospital death ocurred in 84 patients(1.80%), while re-operation in 93 patients (2.00%), myocardial infarction in 71 patients (1.52%), cerebral infarction in 33 patients (0.71%) and dialysis in 56 patients (1.20%). There were 2 936 patients prescribed with secondary prevention drugs(62.99%).Comparing with OPCAB group, ONCABG group had younger age, more female, more diabetes mellitus, more history of myocardial infarction and percutaneous transluminal coronary angioplasty, poorer cardiac function and coronary lesions, higher EuroSCORE Ⅱ, preoperatively (all P<0.05), and was associated with higher MACCE (135/2 731 vs. 71/1 930, χ(2)=4.280, P=0.039), and of more grafts, transfusion and intra-aortic balloon counterpulsation application (all P<0.05). Conclusions: Jiangsu Province Coronary Artery Bypass Grafting Registry database is generally in good operation, and some parameters still need to be improved. Comparing with OPCAB group, ONCABG has more severe preoperative general conditions, while the outcomes is acceptable.

Di-2-ethylhexyl phthalate (DEHP) exposure disturbs lipid metabolism in juvenile yellow catfish Tachysurus fulvidraco.

This study was conducted to determine the mechanism by which di-2-ethylhexyl phthalate (DEHP) exposure influences lipid metabolism of juvenile yellow catfish Tachysurus fulvidraco. Fish were exposed to three DEHP concentrations (0, 0·1 and 0·5 mg l-1 DEHP) for 8 weeks. Fatty acid synthase (FAS) activity significantly decreased with increasing DEHP concentrations, the highest value was in the Tween control group, whereas the lowest activities of carnitine palmitoyltransferase (CPT) and lipoprotein lipase (LPL) were in this group. The messenger (m)RNA levels of 6-phospho-gluconate dehydrogenase (6PGD), FAS and acetyl-CoA carboxylase a (ACCa) significantly increased with increasing DEHP concentration, the highest values were in the 0·5 mg l-1 DEHP group. The mRNA level of peroxisome proliferator-activated receptor γ (PPARγ) was lower in Tween control than in fish exposed to 0·1 and 0·5 mg l-1 DEHP. The highest mRNA level of ACCb was in the 0·1 mg l-1 DEHP group. These results indicate that DEHP exposure can disturb lipid metabolism at the enzymatic and mRNA levels in Pelteobagrus fulvidraco.

[Recurrent bleeding following the renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage: causes and countermeasure].

Objective: To explore the causes and countermeasure in recurrent bleeding following the selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage. Methods: A total of 334 patients of severe renal hemorrhage associated with percutaneous nephrolithotomy (PCNL) from March 2011 to April 2015 were analyzed retrospectively.All the patients underwent super selective angiography and renal artery embolization.The causes of recurrent hemorrhage were analyzed and principles for diagnosis and embolization were studied. Results: The initial embolization was performed in 329 cases hospitalized in the First Affiliated Hospital of Guangzhou Medical University and 318 cases were successfully stopped bleeding with a hemostatic rate of 96.7 %(318/329). Of total 334 consecutive cases, there were 16 cases of recurrent renal hemorrhage, 11 cases were initially embolized in this hospital, and otherwise the other 5 cases were in other hospitals. Causes of recurrent hemorrhage were missed embolization of tiny pseudoaneurysm (n=12), and two cases of 12, the tiny pseudoaneurysm were feeding by accessory renal arteries, undetected arteriovenous fistula(n=2), recanalization of the embolized arteries (n=2). Conclusion: The causes of recurrent bleeding fallowing the initial selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage are varied, and missed embolization of tiny pseudoaneurysm is the major cause of unsuccessful initial renal artery embolization. To strengthen the understanding of tiny pseudoaneurysm is helpful to improve the success rate of hemostasis.

Left ventricular posterior wall thickness is an independent risk factor for paroxysmal atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common significant cardiac arrhythmia in clinical practice, but its risk factors remain to be clarified. We have hypothesized that left ventricular posterior wall thickness is an independent risk factor for paroxysmal atrial fibrillation (PAF). METHODS: A total of 166 consecutive patients with paroxysmal atrial fibrillation were included in this study. Another 166 healthy check-up people, strictly age and sex-matched, were enrolled as controls in the same period. Univariable analysis and multivariable conditional logistic stepwise regression analysis were conducted. Receiver operating characteristic (ROC) curve analysis was performed on those significant indices obtained from the multivariable logistic regression analysis. RESULTS: The multivariable stepwise analysis identified left ventricular posterior wall thickness, left atrial diameter tricuspid insufficiency and residence (countryside) as independent predictors for paroxysmal atrial fibrillation. Receiver operating characteristic curve analysis demonstrated the cutoff values of those risk factors aforementioned. CONCLUSIONS: In this strictly age and sex-matched population-based sample, left ventricular posterior wall thickness, left atrial diameter, tricuspid insufficiency and residence were predictive risks for paroxysmal atrial fibrillation. This study offers novel information therapeutically beyond that provided by traditional clinical atrial fibrillation risk factors.

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

Biosynthetic processing of neu differentiation factor. Glycosylation trafficking, and regulated cleavage from the cell surface.

new differentiation factor (NDF), also known as heregulin, is structurally related to the epidermal growth factor family of growth factors; it stimulates tyrosine phosphorylation of the neu/HER-2 oncogene and causes differentiation of certain human breast cancer cell lines. Alternative splicing of a single gene gives rise to multiple isoforms of NDF/heregulin, as well as the neuronal homologues, designated ARIA (acetylcholine receptor inducing activity) and GGF (glial growth factor); at least 15 structural variants are known. All but two of the NDF/heregulin cDNAs are predicted to encode transmembrane, glycosylated precursors of soluble NDF. In this report we characterized the biosynthetic processing of different NDF isoforms in stably transfected Chinese hamster ovary cells expressing individual NDF isoforms, and in the native cell line Rat 1-EJ, which expresses at least six different NDF isoforms. We found that the precursors for NDF undergo typical glycosylation and trafficking. A portion of the molecules are proteolytically cleaved intracellularly leading to the constitutive secretion of soluble, mature NDF into the culture media. However, a significant portion of the newly synthesized NDF precursor molecules escape intracellular cleavage and are transported to the cell surface of both transfected and native cells, where they reside as full-length, transmembrane proteins. Finally we show that these full-length, transmembrane NDF molecules can undergo phorbol ester regulated cleavage from the membrane, releasing the soluble growth factor into the medium.

The antiproliferative activity of c-myb and c-myc antisense oligonucleotides in smooth muscle cells is caused by a nonantisense mechanism.

Smooth muscle cell (SMC) proliferation is thought to play a major role in vascular restenosis after angioplasty and is a serious complication of the procedure. Developing antisense (AS) oligonucleotides as therapeutics is attractive because of the potentially high specificity of binding to their targets, and several investigators have reported inhibition of SMC proliferation in vitro and in vivo by using AS strategies. We report here the results of our experiments on vascular SMCs using AS oligonucleotides directed toward c-myb and c-myc. We found that significant inhibition of SMC proliferation occurred with these specific AS sequences but that this inhibition was clearly not via a hybridization-dependent AS mechanism. Rather, inhibition was due to the presence of four contiguous guanosine residues in the oligonucleotide sequence. This was demonstrated in vitro in primary cultures of SMCs and in arteries ex vivo. The ex vivo model developed here provides a rapid and effective system in which to screen potential oligonucleotide drugs for restenosis. We have further explored the sequence requirements of this non-AS effect and determined that phosphorothioate oligonucleotides containing at least two sets of three or four consecutive guanosine residues inhibit SMC proliferation in vitro and ex vivo. These results suggest that previous AS data obtained using these and similar, contiguous guanosine-containing AS sequences be reevaluated and that there may be an additional class of nucleic acid compounds that have potential as antirestenosis therapeutics.

The uptake and distribution of phosphorothioate oligonucleotides into vascular smooth muscle cells in vitro and in rabbit arteries.

Oligonucleotides are a class of compounds with potential as therapeutics for a variety of clinical applications. Local delivery of oligonucleotides to the arterial wall is a challenging aspect of the development of these therapeutics for restenosis, and herein we report experiments characterizing the uptake and distribution of phosphorothiate oligonucleotides into vascular smooth muscle cells in primary cultures and in rabbit arteries. Primary cultures of smooth muscle cells incubated with rhodamine-oligonucleotides showed uptake only into cytoplasmic vesicles. No nuclear or cytosolic localization was detected. In normal arteries there was no visible tissue or cellular uptake of oligonucleotides after intralumenal administration. However, in balloon-injured arteries there was significant oligonucleotide uptake into the tissue with apparent cytoplasmic delivery to the medial smooth muscle cells, as evinced by intense staining of their nuclei with labeled oligonucleotides. Measurement of FITC-oligonucleotide in artery extracts showed significantly greater uptake in injured, compared with normal arteries. Light and electron microscopic studies demonstrated a correlation between the degree of damage and the amount of uptake. These results demonstrate that oligonucleotides penetrate easily into the arterial wall of balloon-injured arteries and accumulate in the medial smooth muscle cells-the target cells for antirestenosis therapeutics following balloon angioplasty.

Selective expression of potassium channels during mast cell differentiation.

In rodents, mast cell progenitors differentiate into distinct mucosal and serosal phenotypes which differ markedly in their functional responses to antigenic and peptidergic stimulation. Although the molecular basis of mast cell differentiation or functional specialization is unknown, it is possible that regulation of calcium entry contributes to one or both processes. The prolonged secretory response of mucosal mast cells (MMC) and the antigen-elicited synthesis of interleukin-3 by immature MMC both require a rise of cytoplasmic calcium sustained by Ca2+ influx across the plasma membrane. This Ca2+ entry is highly sensitive to membrane potential, affording a possible site for regulation of mast cell function by receptor-linked ion channels. We found that rat interleukin-3-dependent bone marrow-derived mast cells of the mucosal phenotype expressed two K+ conductances, neither of which is present in the prototype serosal mast cell from rat peritoneum. An inwardly rectifying K+ conductance was constitutively active and a latent outwardly rectifying K+ conductance was elicited rapidly upon ligation of cell surface adenosine or P2 purinergic receptors linked to G proteins of the Gi family. Stimulation of P2 receptors dramatically potentiated antigen-triggered secretion in a pertussis toxin-sensitive manner, suggesting that activation of the outwardly rectifying K+ channel may regulate antigen-dependent functions of MMC.

Activation of mast cell K+ channels through multiple G protein-linked receptors.

The rat basophilic leukemia (RBL) mast cell line possesses cell surface receptors for adenosine whose ligation markedly potentiates antigen-driven Ca2+ influx and secretion. Here we show that engagement of these receptors and of separate P2 purinergic receptors rapidly activates an outwardly rectifying K+ conductance [GK(OR)] in RBL cells. Activation of GK(OR) by the ligands 5'-(N-ethylcarboxamido)adenosine (NECA), ADP, and ATP was prevented by cytoplasmic guanosine 5'-[beta-thio]diphosphate as well as by pretreatment of the cells with pertussis toxin, implicating mediation by a G protein. Multiple cycles of induction and decay of GK(OR) were produced upon application and removal of ligand. Induction of GK(OR) by either ligand was much faster than the induction caused by guanosine 5'-[gamma-thio]triphosphate (t1/2 < 10 sec vs. 210 sec.). In control cells the maximal whole-cell conductance elicited by ADP (2.25 +/- 0.30 nS) or ATP (2.50 +/- 0.33 nS) was about twice as large as that induced by NECA (1.03 +/- 0.11 nS), and similar to that previously reported for the guanosine 5'-[gamma-thio]triphosphate-elicited GK(OR) in RBL cells (2.58 +/- 1.59 nS). Treatment of RBL cells with dexamethasone upregulated Ca2+ responses to NECA, and it also nearly doubled the maximal conductance elicited by NECA without appreciable effect on responses to ADP or ATP. The failure of water-soluble second messengers to activate GK(OR) and the inability of 11 mM EGTA (< 10 nM Ca2+) to prevent activation by ADP suggest that the relevant pathway is membrane-delimited. Two ion-channel blockers inhibited antigen-stimulated secretion with IC50 values similar to those at which they blocked GK(OR), suggesting that activity of the outwardly rectifying K+ channel may be important for stimulus-response coupling in these cells. Potentiation of the secretory response by NECA may reflect, in part, the activation of GK(OR), which serves to repolarize the membrane more effectively than does the constitutive mechanism, thereby enhancing antigen-driven Ca2+ influx. This channel and its functionally associated receptors may allow neighboring cells of the host to modulate the response of mast cells to exogenous antigen.

[Antifertility effects of RU-486 in combination with anordrin in rats].

RU-486 and anordrin suspended or dissolved in tea seed oil, alone or in combination, were given orally to rats on d 6-8 or d 11-13 of pregnancy, respectively. Complete interruption of early pregnancy was obtained after RU-486 at 8 mg/kg alone or 2.5 mg/kg combined with anordrin 2 mg/kg when given on d 6-8 of pregnancy. A complete mid-trimester abortion was obtained after RU-486 10 mg/kg alone or 4 mg/kg combined with anordrin 3 mg/kg when given on d 11-13 of pregnancy. Results obtained from the endometrial transformation test, the uteri cytoplasmic progesterone receptor estimation in immature rabbits, the deciduoma-inhibited test in pseudopregnant rats and the serum progesterone level in pregnant rats showed that RU-486 in combination with anordrin did not possess progestational, but rather marked antiprogestational activities. Since anordrin is relatively easy to obtain in China, RU-486 combined with anordrin may be ready to be used clinically as an effective oral antifertility agent.

Spermicidal effect in vitro by the active principle of garlic.

The in vitro spermicidal effect of Allitridum, an active principle of garlic, was investigated. The data showed that sperm motility was inhibited with various concentrations of Allitridum at different intervals ranging from 20 seconds-200 minutes as compared to control. An obvious immobilization of spermatozoa occurred at 7.5 mg/ml of Allitridum. The effects on sperm motility appeared to be dose-dependent.

PIP: The in vitro spermicidal effect of Allitridum, an active principle of garlic, was investigated. The data showed that sperm motility was inhibited with various concentrations of Allitridum at different intervals ranging from 20 seconds-200 minutes as compared to control. An obvious immobilization of spermatozoa occurred at 7.5 mg/ml of Allitridum. The effects on sperm motility appeared to be dose-dependent. Male rats and hamsters were used for the study as well as human spermatozoa.