The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model

OBJECTIVE: To test the hypothesis that an intracavernosal injection with brain-derived neurotrophin factor (BDNF) and vascular endothelial growth factor (VEGF) can facilitate nerve regeneration and recovery of erectile function after cavernosal nerve injury. MATERIALS AND METHODS: The study included 25 Sprague-Dawley rats; four had a sham operation, seven bilateral nerve crushing with no further intervention, and 14 bilateral nerve crushing with either an immediate (seven) or delayed for 1 month (seven) intracavernosal injection with BDNF+VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and neural regeneration by NADPH-diaphorase staining and tyrosine hydroxylase (TH) staining of penile tissue and major pelvic ganglia (MPG). RESULTS: After nerve crushing, the functional evaluation at 3 months showed a lower mean (SD) intracavernosal pressure (ICP) with cavernosal nerve stimulation, at 33.9 (15.3) cmH2O, than in the sham group, at 107.8 (18.1) cmH2O. With an immediate injection with BDNF+VEGF the ICP was significantly higher than in the controls, at 67.8 (38.5) cmH2O. Even delayed injection with BDNF+VEGF improved the ICP, to 78.0 (21.8) cmH2O. Histological analysis of specimens stained for NADPH and TH showed a significant change in the morphology of terminal branches of the cavernosal and dorsal nerves, and the staining quality of the neurones in the MPG. The number of positively stained nerve fibres tended to revert to normal after treatment with BDNF+VEGF. CONCLUSION: An intracavernosal injection with BDNF+VEGF appears to both prevent degeneration and facilitate regeneration of neurones containing neuronal nitric oxide synthase in the MPG, dorsal nerve and intracavernosal tissue. Therefore it might have therapeutic potential for enhancing the recovery of erectile function after radical pelvic surgery.     

Levosimendan in rats decreases acute kidney injury after cardiopulmonary resuscitation by improving mitochondrial dysfunction

BackgroundAcute kidney injury (AKI), the most common complication after cardiac resuscitation, is highly prevalent and harmful. There is increasing evidence that levosimendan can improve cardiac output, increase renal blood flow, and prevent AKI. As a novel calcium sensitizer, levosimendan may exert its protective effect via mitochondria.MethodsRat models of asphyxia-induced cardiac arrest and cardiopulmonary resuscitation (CPR) were set up. Thirty healthy adult male SD rats were randomly divided into CPR group (CPR group, n=10), levosimendan-treated group (levo group, n=10), and sham-operated group (sham group, n=10). Twelve hours after CPR, serum renal function indicators were measured, the kidney injury and mitochondrial morphological changes were observed. Oxygen uptake of the mitochondria, mitochondrial adenosine triphosphate (ATP) and mitochondrial free Ca²⁺ concentration were measured. Oxidative stress-related indicator levels in rat kidney tissues were further detected to analyze the differences in apoptosis rates among these three groups. Mitochondrial optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1), and apoptosis-related proteins were detected using Western blotting.ResultsCompared with the sham group, the CPR group had a significant increase in renal tissue damage. PAS staining and HE stains confirmed that CPR led to renal histopathological damage and destruction of the mitochondrial structure. Levosimendan improved the histopathological and ultrastructural damages of kidneys. Further analysis revealed that mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (CSH-Px) decreased. Free Ca²⁺ concentration and malondialdehyde (MDA) significantly increased (all P<0.05) in the kidney tissues of rats in the CPR group. However, mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, SOD, CAT, and CSH-Px increased, whereas free Ca²⁺ concentration and MDA decreased (all P<0.05) in the levo group. The apoptosis rate increased in the CPR group. There were significantly increased levels of Drp1 protein levels, and significantly decreased Opa1 expression (all P<0.05). However, the levo group showed the opposite effects (all P<0.05).ConclusionsLevosimendan can alleviate AKI following CPR, which may be achieved by improving mitochondrial dysfunction and suppressing the mitochondrial apoptosis pathway.     

Calcineurin-NFAT Signaling and Neurotrophins Control Transformation of Myosin Heavy Chain Isoforms in Rat Soleus Muscle in Response to Aerobic Treadmill Training

This study elucidated the role of CaN-NFAT signaling and neurotrophins on the transformation of myosin heavy chain isoforms in the rat soleus muscle fiber following aerobic exercise training. To do so, we examined the content and distribution of myosin heavy chain (MyHC) isoforms in the rat soleus muscle fiber, the activity of CaN and expression of NFATc1 in these fibers, and changes in the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neutrophin-3 (NT-3) in the soleus and striatum following high-and medium-intensity aerobic treadmill training. Specific pathogen-free 2 month old male Sprague-Dawley (SD) rats were randomly divided into three groups: Control group (Con, n = 8), moderate-intensity aerobic exercise group (M-Ex, n = 8) and high-intensity aerobic exercise group (H-Ex, n = 8). We used ATPase staining to identify the muscle fiber type I and II, SDS-PAGE to separate and analyze the isoforms MyHCI, MyHCIIA, MyHCIIB and MyHCIIx, and performed western blots to determine the expression of NFATc1, NGF, BDNF and NT-3. CaN activity was measured using a colorimetric assay. In the soleus muscle, 8 weeks of moderate-intensity exercise can induce transformation of MyHC IIA and MyHC IIB to MyHC IIX and MyHC I (p < 0.01), while high-intensity treadmill exercise can induce transform MyHC IIx to MyHC IIB, MyHC IIA and MyHC I (p < 0.01). In comparison to the control group, CaN activity and NFATcl protein level were significantly increased in both the M-Ex and H-Ex groups (p < 0.05, p < 0.01), with a more pronounced upregulation in the M-Ex group (p < 0.05). Eight weeks of moderate- and high-intensity aerobic exercise induced the expression of NGF, BDNF and NT-3 in the soleus muscle and the striatum (p < 0.01), with the most significant increase in the H-Ex group (p < 0.01). In the rat soleus muscle, (1) CaN–NFATcl signaling contributes to the conversion of MyHC I isoform in response to moderate-intensity exercise; (2) Neurotrophins NGF, BDNF and NT-3 might play a role in the conversion of MyHC II isoform in response to high-intensity treadmill exercise.

Key points

• Eight weeks of moderate-intensity treadmill training induces the transformation MyHC IIA and MyHC IIB to MyHC IIX and MyHC I in the soleus muscles, while high-intensity exercise leads to transformation of MyHC IIX to MyHC IIA, MyHC IIB and MyHC I.
• MyHC I conversion in response to moderate-intensity aerobic exercise is mediated by calcineurin-NFATcl signaling.
• Eight weeks of moderate- and high-ntensity aerobic exercise induces the expression of NGF, BDNF and NT-3 in expression noted in rats subjected to high-intensity training. NGF and NT-3 expression in the striatum is lower than in the soleus muscle, while BDNF levels are similar. Neurotrophins may be involved in mediating MyHC II conversion in response to high-intensity aerobic exercise.

Key words: Aerobic treadmill training, the muscle fiber type, neurotrophins, Myosin heavy chain isoforms transformation, Calcineurin/Nuclear factor of activated T cells c1     

Efficiency of using a neurofeedback device in determining ischaemic early electroencephalography indicators in rabbits with acute brain ischaemia

OBJECTIVESContinuous electroencephalography (EEG) monitoring is a useful method in surgical procedures in which brain circulation is at risk. Providing this function using neurofeedback devices reduced to small dimensions may provide ease of use in the early diagnosis of brain ischaemia. The goal of this study was to demonstrate the efficiency of using a neurofeedback device in determining the early EEG indicators of ischaemia in a rabbit model of acute brain ischaemia. Open in a separate windowMETHODSThree randomized groups—carotid ischaemia (CI), global ischaemia (GI) and a sham group—each comprising 8 rabbits, were created. In the CI group, the bilateral main carotid artery was clamped; in the GI group, the bilateral subclavian and main carotid arteries were clamped and brain ischaemia was created for 15 min. Brain reperfusion was then achieved for 30 min. In the sham group, the same surgical preparation was performed but no ischaemia occurred. The brain EEG wave activities of all subjects were recorded during the experiment. At the end of the procedure, all brain tissue was removed and apoptotic indexes were determined by histopathological examination. The statistical significance of the histopathological results and the EEG wave activities among the groups was examined.RESULTSThere was a significant difference between the sham, CI and GI average amplitude ratios, delta (1.02, 0.69, 0.16; P < 0.001) and total wave (0.99, 0.78, 0.49; P < 0.001), respectively. There was no significant difference between the sham and CI groups in delta (sham, CI, 1.01, 0.87; P = 0.1), total wave (sham, CI, 1.22, 0.98; P = 0.2) and amplitude standard deviation rates. However, there was a significant difference in the GI group (P < 0.001). There was a significant difference between all groups in apoptotic index (sham, 17.88; CI, 40.75; GI, 55.88; P < 0.001).CONCLUSIONSSignificant EEG wave changes resulting from experimental brain ischaemia were analysed with the use of a neurofeedback device. The results indicated that the change in the delta and the total wave standard deviations may be an additional indicator in the formation of permanent brain damage.     

骨髓间充质干细胞干预对缺血再灌注致小鼠肾小管上皮细胞损伤的保护作用

目的 观察骨髓间充质干细胞(MSCs)干预对缺血再灌注(I/R)诱导的急性肾损伤小鼠肾小管上皮细胞(RTECs)自身修复的影响.方法 Percoll密度梯度离心结合贴壁培养法分离纯化出C57BL/6小鼠的骨髓间充质干细胞(mMSCs),5-溴脱氧尿嘧啶核苷(BrdU)标记.雄性C57BL/6小鼠45只,分为正常对照组(15只)、I/R组(15只、夹闭双侧肾蒂30 min开放)、I/R+Brdu-mMSCs组(15只、夹闭双侧肾蒂30 min开放的同时尾静脉注射BrdU标记的mMSCs).留取动脉血及肾组织,检测血尿素氮(BUN)及肌酐(Scr)水平,制作肾组织切片行苏木素-伊红(HE)染色,荧光组织化学观察mMSCs在受体小鼠肾组织的分布,免疫组织化学观察RTECs增强细胞核抗原(PCNA)的表达,TUNEL法检测RTECs凋亡,Western blot检测建模后第2天肾小管组织中Caspase-3、bcl-2蛋白的表达.结果 BrdU标记mMSCs的阳性率可达(98.71±0.32)%.I/R+BrdU-mMSCs组小鼠的BUN及Scr水平较I/R组为低,肾小管损伤病理明显减轻,且小鼠的肾脏中可检测到BrdU+细胞的分布.mMSCs干预后,RTECs细胞核PCNA阳性表达明显增多(P＜0.05或P＜0.01),而细胞凋亡的水平却较I/R组明显减少(P＜0.05或P＜0.01).Western blot进一步显示:I/R+BrdU-mMSCs组小鼠的肾组织中Caspase-3蛋白水平明显下降[(1.16±0.33)比(1.64±0.27),P＜0.01],而bcl-2水平却明显增高[(0.94±0.27)比(0.68 ±0.15),P＜0.01].结论 小鼠发生I/R诱导的急性肾损伤后可诱导移植的MSCs向损伤肾组织归巢,锚定在肾脏的MSCs可促进损伤RTECs的再生,抑制其凋亡,从而有助于RTECs的自身修复,延缓肾损害进展.

Abstract：

Objective To observe the effects of mesenchymal stem cells (MSCs) on self-repair of renal tubular epithelial cells ( RTECs) in mice under ischemia/reperfusion ( IR). Methods MSCs in C57BL/6 mice were successfully isolated by Percoll density gradient centrifugation and adherence cultivation, then marked with BrdU. Forty-five healthy male C57BL/6 mice were assigned to control group (n =15 ) , I/R group (n = 15 , clamping bilateral renal pedicles and then reopening after 30 min) , I/R + BrdU-MSCs group (n = 15 , clamping bilateral renal pedicles and then reopening after 30 min, meanwhile, BrdU-marked MSCs were injected through caudal vein into the body of model mice). One, 2,3,7 and 14 days later, the mice were killed (n = 3/each group) , and blood and kidneys were obtained. Serum creatinine (Scr) and urea nitrogen (BUN) were determined, and mice kidneys were stained with Hematoxylin and Eosin ( HE) to observe their pathological changes. The distribution of MSCs in mice was observed by using fluorescence histochemistry. The expression of proliferating cell nuclear antigen ( PCNA) in RTECs was assessed by using immunohistological staining. The apoptosis of RTECs was detected by using TUNEL. The protein levels of Caspase-3 and bcl-2 in renal tubules on the day 2 after establishing the model were detected by using Western blotting. Results The positive BrdU marking ratio was (98. 71 ±0. 32) % in MSCs.As compared with I/R group, the levels of BUN and Scr in I/R + BrdU-MSCs group were significantly reduced, and pathological changes in renal tubules were alleviated significantly. BrdU-marked MSCs desposited in the kidneys of I/R + BrdU-MSCs group. The positive PCNA expression of RTECs was increased significantly after intervention of BrdU-MSCs (P ＜0. 05 or P ＜0. 01) , while the apoptosis relieved significantly. Western blotting analysis revealed: as compared with I/R group, the level of Caspase-3 in I/R + BrdU-MSCs group was decreased notably [(1.16±0.33) vs (1.64±0.27), P＜0.01], while the level of bcl-2 increased significantly [(0.94±0.27) vs (0.68±0.15), P＜0.01). Conclusion Acute renal injury by I/R can induce MSCs homing to injured kidney and anchoring here. The anchored MSCs can contribute to RTECs' self-repair of mice under ischemia/reperfusion, inhibit their apoptosis, which is helpful to the RTECs' self-repair and can delay the progression of renal injury.     

COX4I2 is a novel biomarker of blood supply in adrenal tumors

BackgroundPrevious study has been reported that COX4I2 expression level demonstrated a positive correlation with microvessel density in pheochromocytomas (PCC) samples, suggesting that the expression of COX4I2 maybe related to blood supply level in other adrenal tumors as well. The aim of this study is to clarify the correlation of COX4I2 expression and blood supply in adrenal tumors.MethodsA total of 84 patients were recruited, among which 46 was diagnosed as adrenocortical adenoma (ACA) and 38 was diagnosed as PCC. Contrast-enhanced CT values were used to evaluate the blood supply levels in those patients. The expression of mRNA was examined by quantitative real-time polymerase chain reaction (qPCR) and protein was detected by immunohistochemistry (IHC).ResultsThe COX4I2 expression level in PCC group is significantly higher than that in ACA group (P<0.01). The expression of angiogenesis-related genes EPAS1, VEGFA and KDR mRNA in PCC group is higher than that of ACA group (P<0.05). Correlation analysis shows COX4I2 expression level is correlated with CT values (P<0.001), intraoperative blood loss (P<0.05) and operation time (P<0.05), and the expression of COX4I2 mRNA is correlated with EPAS1, VEGFA and KDR mRNA (P<0.01).ConclusionsThe results displayed a distinct expression level of COX4I2 between ACA and PCC, suggesting that COX4I2 is a novel biomarker of blood supply in adrenal tumors. This research also opens the possibility for further research on COX4I2 as a novel target for anti-tumor angiogenesis.     

Validation of the World Health Organization/International Society of Urological Pathology grading for Chinese patients with clear cell renal cell carcinoma

BackgroundThis study aimed to compare the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system and the Fuhrman grading system and to verify the WHO/ISUP grade as a prognostic parameter of clear cell renal cell carcinoma (ccRCC) in a Chinese population.MethodsThe study consisted of 753 ccRCC patients treated with curative surgery between 2010 and 2018 at Xiangya Hospital Central South University (Changsha, China). All pathologic data were retrospectively reviewed by two pathologists. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were examined as clinical outcomes.ResultsAccording to the WHO/ISUP grading system (ISUP group), nephrectomy type, pT stage and WHO/ISUP grade were independent risk factors for CSS (P<0.0001, P=0.0127 and P<0.0001, respectively) and RFS (P<0.0001, P=0.0077, and P<0.0001, respectively). In the Fuhrman group, nephrectomy type, pT stage and Fuhrman grade were independent risk factors for CSS (P<0.0001, P=0.0004, and P<0.0001, respectively) and RFS (P<0.0001, P=0.0001, and P<0.0001, respectively). The C-index for CSS and RFS using the Fuhrman grading system was 0.6323 and 0.6342, respectively, and that using the WHO/ISUP grading system was 0.6983 and 0.7005, respectively, both higher than the former (P=0.0185, and P=0.0172, respectively). In addition, upgrading from Fuhrman grade 2 to ISUP grade 3 resulted in worse CSS and RFS for ccRCC patients (P=0.0033 and P =0.0003, respectively).ConclusionsWe first verified correlations between the postoperative prognosis and WHO/ISUP grade of ccRCC in a Chinese population and confirmed that the ability to predict clinical outcomes with the WHO/ISUP grading system was superior to that with the Fuhrman grading system.     

雌激素诱导外周血间充质干细胞动员和归巢促进失血性休克大鼠创面愈合的作用

目的:观察雌激素动员外周血间充质干细胞归巢对失血性休克大鼠皮肤创面愈合的影响.方法:制备失血性休克SD大鼠模型,在其背部正中线两侧各制作一个全层皮肤缺损创面(直径2 cm).96只大鼠随机分为4组:假手术对照组(予动、静脉插管但不放血、不补液)、失血性休克组(失血性休克模型大鼠以2:1的乳酸林格液和羟乙基淀粉行常规液体复苏)、雌激素低剂量组(给予失血性休克大鼠雌激素0.2 mg/kg+常规液体复苏)、雌激素高剂量组(给予失血性休克大鼠雌激素0.5 mg/kg+常规液体复苏).观察不同时相点各组动物皮肤创面愈合程度、愈合时间、组织血流量、ATP酶活性以及间充质干细胞动员、归巢情况.结果:与假手术对照组相比,失血性休克大鼠皮肤创面愈合缓慢,在第4天、第8天愈合率分别为(15.40±0 0 1)％、(36.80±1.25)％(P＜0.05),组织血流量及ATP酶活性明显降低(P＜0.01).雌激素能明显促进皮肤创面的愈合,显著改善组织血流量,增强ATP酶活性,增加受损皮肤组织和血液中间充质干细胞的数量.与失血性休克大鼠相比,低剂量雌激素组第4天、第8天皮肤创面愈合率分别为(22.10±0.01)％、(46.40±1.25)％,其外周血及受损皮肤组织中间充质干细胞数量明显增多,同假手术组第4天创面愈合率[(37.10±4.32)％]、第8天创面愈合率[(67.70±1.79)％]相比,愈合仍较为缓慢(P＜0.05);高剂量雌激素具有更好的促创面愈合效果,其第4天、8天创面愈合率分别为(28.40±0.12)％、(57.30±2.01)％(P＜0.05),且间充质干细胞在皮肤创面及外周血中增多更为显著.失血性休克组创面完全愈合时间[(23.98±1.56) d]较假手术对照组[(14.98±1.21)d]显著延长(P＜0.01),高剂量雌激素组(16.87±1.56)d和低剂量雌激素组[(22.67±1.78)d]创面愈合时间明显缩短(P＜0.05),且高剂量雌激素组创面愈合时间最短.结论:雌激素可动员间充质干细胞归巢,促进失血性休克大鼠创面愈合.     

BDNF|TrkB在原发性肝癌中的表达及BDNF对肝癌细胞株Bel-7402的作用

目的探讨脑源性神经营养因子(BDNF)及其受体TrkB在原发性肝癌中的表达及BDNF对肝癌细胞株Bel-7402的作用。方法 (1)检测肝癌组织、癌旁组织及正常肝组织中BDNF和TrkB的表达,分析BDNF和TrkB的表达与临床病理因素之间的关系。(2)检测BDNF,TrkB,Bcl-2在肝癌细胞株Bel-7402及正常肝细胞株L-02的表达及其对Bel-7402细胞增殖、失巢凋亡、黏附、浸润转移能力的影响。结果 (1)肝癌组织中BDNF呈高表达(60.4%,29/48),与Edmondson分级、有无包膜有关(P0.05);TrkB表达率为52.1%(25/48),与Edmondson分级及肿瘤结节数有关(P0.05);BDNF与TrkB在肝癌中的表达呈正相关(r=0.332,P0.05)。BDNF和TrkB在正常肝组织中均无表达。两者在肝癌组织中表达远高于癌旁组织中的表达(P0.01)。肝癌组织中BDNF和TrkB呈高表达者,其2年内复发率增高(P0.05)及生存率下降(P0.01)。(2)外源性BDNF均能增强Bel-7402细胞的增殖、黏附、体外迁移、侵袭能力及抵抗失巢凋亡的能力(P0.01);(3)各浓度的BDNF均可上调Bel-7402细胞Bcl-2 mRNA及其蛋白的表达(P0.05)。结论 (1)BDNF及TrkB在肝癌中高表达,可能与复发、生存率有关;(2)BDNF可调节肝癌细胞的生长、黏附、迁移和侵袭;(3)BDNF可上调Bcl-2的表达,抑制肿瘤细胞的失巢凋亡。     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Three-dimensional measurement and analysis of benign prostatic hyperplasia

BackgroundThe volume and thickness of intravesical prostatic protrusion and other characteristics of benign prostatic hyperplasia have not been investigated. We determine the effects of age and prostate volume on anatomical features of benign prostatic hyperplasia using three-dimensional measurement in this study.MethodsThis retrospective study included a total of 98 patients with benign prostatic hyperplasia. Three-dimensional models of prostate, central gland, peripheral zone, intravesical prostatic protrusion, prostatic urethra and bladder were reconstructed according to pelvic T2-weighted magnetic resonance imaging of these patients. The models were used to measure the intravesical prostatic protrusion volume, intravesical prostatic protrusion thickness, intravesical prostatic protrusion index, intravesical prostatic protrusion, prostate volume, peripheral zone volume, peripheral zone thickness, peripheral zone index, prostatic urethra thickness, the angle and distance of distal prostatic urethra with regard to coronal plane and sagittal plane and so on.ResultsIntravesical prostatic protrusion volume, intravesical prostatic protrusion thickness and peripheral zone volume of prostate volume >80 mL group were significantly higher than these in prostate volume <80 mL group (P<0.001, 0.01, 0.01, respectively). These parameters significantly increased with age (P<0.001, 0.01, 0.05, respectively). Peripheral zone index was significantly lower of prostate volume >80 mL group than these in prostate volume <80 mL group (P<0.05). Peripheral zone index significantly decreased with age (P<0.01). Intravesical prostatic protrusion index had no significant difference in all age groups. Peripheral zone thickness and prostatic urethra thickness had no significant difference in all groups. The distance and angle of distal prostatic urethra prostatic urethra with regard to coronal plane were significantly higher than these with regard to sagittal plane (both P<0.001).ConclusionsThe rearward slope of the prostatic urethra is greater than the left or right offset during the process of benign prostatic hyperplasia. Three-dimensional measurement provides good supports for further clinical and scientific research.     

Efficacy and safety of holmium laser enucleation of the prostate for elderly patients: surgical outcomes and King’s Health Questionnaire

BackgroundHolmium laser enucleation of the prostate (HoLEP) has been a widely utilized minimally invasive surgical procedure for benign prostate hyperplasia. The current study aimed to compare surgical outcomes and King’s Health Questionnaire (KHQ) assessment scores following HoLEP between younger men and those aged ≥75 years.MethodsThis prospective single-center study compared perioperative complications, postoperative urinary conditions, and KHQ scores (nine categories) between men aged ≥75 years (group A) and men aged <75 years (group B) before and 1, 3, and 6 months after surgery.ResultsA total of 100 patients were included for analysis (group A, n=38 and group B, n=62). No differences in patient backgrounds, perioperative complications, such as perioperative decrease in hemoglobin, postoperative fever, postoperative indwelling catheterization duration, or postoperative hospitalization duration, and KHQ were observed between both groups. Both groups showed significantly better International Prostate Symptom Scores, quality of life, maximum urinary flow rate, and postvoid residual volume 1, 3, and 6 months after HoLEP compared to their respective preoperative levels (P<0.01). Regarding KHQ categories, both groups showed significantly better general health perceptions, impact on life, emotions, and sleep/energy 1 month after HoLEP; role limitations, physical limitations, and social limitations 3 months after HoLEP; and personal relationships and incontinence severity measures 6 months after HoLEP compared to their respective preoperative levels (P<0.05).ConclusionsHoLEP could be safe and effective even for men aged ≥75 years, comparing complications, urinary condition, and KHQ scores.     

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia

BackgroundTo study the effects of L-carnitine (LC) combined with pancreatic kininogenase on thioredoxin 2 (Trx 2), thioredoxin reductase 1 (TrxR 1), and sperm quality in patients with oligoasthenospermia.MethodsA total of 300 male infertility patients with oligoasthenospermia who were treated in the andrology clinic of our hospital from December 2019 to December 2020 were randomly divided into an LC group and combined treatment group, and 50 males with normal semen were selected as a control group. The computer-assisted semen analysis system (CASA) was used to detect the total number, vitality, and forward motility of the sperm before and after treatment, and sperm morphology was detected by the Diff-Quik method of the sperm staining kit. Sperm chromatin dispersion (SCD) method was used to detect sperm DNA fragments, and Western-blot was used to detect the protein expression of Trx 2 and TrxR 1.ResultsThere were no significant differences in sperm density, motility rate, forward motile sperm rate, and DNA fragmentation rate in oligoasthenospermia patients before treatment (P>0.05). However, after 1 month of treatment, the sperm density, motility rate, and forward motile sperm rate were all higher than before treatment (P<0.05), while the DNA fragmentation rate was lower than before treatment. At the same time, each index of semen in the combination group was higher than that in the LC group (P<0.05), and the total effective rate in the combination group was significantly higher than in the LC group (P<0.01). The expression of Trx2 protein in oligoasthenospermia patients was significantly increased (P<0.05), while the expression of TrxR1 protein was significantly decreased (P<0.05). After 3 months of treatment, the expression of Trx2 protein was significantly decreased (P<0.05), while the expression of TrxR1 protein was significantly increased (P<0.05).ConclusionsThe results suggest Trx 2 and TrxR 1 may be candidate protein markers for oligoasthenospermia. LC combined with pancreatic kininogenase in the treatment of male oligoasthenospermia can effectively promote sperm maturation, enhance sperm motility, and improve semen quality, which has high application value.     

Benefits of robotically-assisted surgery for complex mitral valve repair

OBJECTIVESTo determine whether robotic mitral valve repair can be applied to more complex lesions compared with minimally invasive direct mitral valve repair through a right thoracotomy. Open in a separate windowMETHODSWe enrolled 335 patients over a 9-year period; 95% of the robotic surgeries were performed after experience performing direct mitral valve repair.RESULTSThe mean age in the robotic versus thoracotomy repair groups was 61 ± 14 vs 55 ± 11 years, respectively (P < 0.001); 97% vs 100% of the patients, respectively, had degenerative aetiologies. Repair complexity was simple in 106 (63%) vs 140 (84%), complex in 34 (20%) vs 20 (12%) and most complex in 29 (17%) vs 6 (4%) patients undergoing robotic versus thoracotomy repair, respectively. The average complexity score with robotic repair was significantly higher versus thoracotomy repair (P < 0.001). The robotic group underwent more chordal replacement using polytetrafluoroethylene and less resections. All patients underwent ring annuloplasty. Cross-clamp time did not differ between the groups, and no strokes or deaths occurred. More patients undergoing robotic repair underwent concomitant procedures versus the thoracotomy group (30% vs 14%, respectively; P < 0.001). The overall repair rate was 100%, with no early mortality or strokes in either group. Postoperative mean residual mitral regurgitation was 0.3 in both groups, and the mean pressure gradient through the mitral valve was 2.4 vs 2.7 mmHg (robotic versus thoracotomy repair, respectively; P = 0.031).CONCLUSIONSRobotic surgery can be applied to repair more complex mitral lesions, with excellent early outcomes.     

Impact of protruded median lobe on perioperative,urinary continence and oncological outcomes of Retzius-sparing robot-assisted radical prostatectomy

BackgroundTo investigate the effect of protruded median lobe (PML) on the perioperative, oncological, and urinary continence (UC) outcomes among patients underwent Retzius-sparing robot-assisted radical prostatectomy (RS-RARP).Methods231 consecutive patients who had undergone RS-RARP were collected and analyzed. Patients were divided into three groups based on the PML degree: PML<5 mm (n=99); 5≤ PML <10 mm (n=91); PML ≥10 mm (n=41). The perioperative outcomes, short-term oncological, and UC outcomes were compared among the three groups. Those outcomes were also compared in patients with significant PML (>10 mm) who underwent the traditional or Retzius-sparing RARP.ResultsThe median PML was significantly associated age (P<0.001) and prostate volume (P<0.001). Perioperative characteristics including console time, estimated blood loss (EBL), intraoperative transfusion rate, and complications were not statistically different among the three groups (P=0.647, 0.574, 0.231, 0.661, respectively). The rate of positive surgical margin (PSM) were not significantly different in the three groups (P=0.065). No significant difference regarding UC and biochemical recurrence (BCR) at 12-month follow-up was observed in the three groups (P>0.05). Comparison between the two approaches in men with significant PML showed better recovery of UC (HR =1.83, 95% CI: 1.117–3.01, log-rank P=0.002) and similar BCR (log-rank P=0.072) after RS-RARP.ConclusionsRS-RARP is an oncologically and functionally equivalent approach for patients with PML. Compared with the traditional approach, RS-RARP offers benefits regarding UC for cases with significant PML.     

The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion

Purpose:In this experimental study, activated protein C (APC), which has anticoagulant, antithrombotic, profibrinolytic, anti-inflammatory and antiapoptotic properties, was used to prevent coagulopathy in a disseminated intravascular coagulation (DIC) model formatted with lipopolysaccharide (LPS) infusion.Methods:Twenty-five Wistar albino rats weighting 280 – 320 g each were used. They were randomly divided into three groups: sham, control and study groups. To sham group (n = 5), only normal saline was infused. To control (n = 10) and study groups (n = 10), 30 mg/kg LPS was infused for 4 h from femoral vein. After LPS infusion, 100 µg/kg recombinant APC was given during 4 h in study group. Eight hours later, blood samples were taken from abdominal aorta and the animals sacrificed. From these samples, platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were studied.Results:Platelet counts and fibrinogen levels were significantly lower in control and study groups than sham group (p < 0.05). The PT, aPTT and D-dimer levels were significantly higher in control and study groups than in sham group (p < 0.05). When comparing control and study groups, platelet counts were not statistically different (p = 0.36). However, the difference of the fibrinogen levels was significant between these groups (p = 0.0001). While PT and aPTT were longer in the study group compared to the control group (p < 0.05), D-dimer levels were lower in the study group than in control (p = 0.0001).Conclusion:Use of APC can prevent hypercoagulation and consumption coagulopathy in the DIC as a result of correcting hematological parameters other than prolongation of coagulation time.Key words: Disseminated Intravascular Coagulation, Lipopolysaccharide Receptors, Fibrinogen, Rats     

The effects of autologous bone marrow mesenchymal stem cell arterial perfusion on vascular repair and angiogenesis in osteonecrosis of the femoral head in dogs

Purpose

The purpose of this study was to observe the effects of marrow mesenchymal stem cell (MSCs) arterial perfusion on vascular repair and angiogenesis in osteonecrosis of the femoral head (ONFH).

Methods

Twelve healthy male adult Beagle dogs were randomly divided into two groups: group A (the control group) and group B (the MSCs arterial perfusion group). ONFH animal models were established by hip dislocation and liquid nitrogen. At the same time, MSCs were obtained, cultured and proliferated. After three weeks, arterial perfusion was performed in all animals. Group B was given 1 ml MSCs (5 × 10⁶–1 × 10⁷/ml), while 0.9 % normal saline was used in group A. After four weeks or eight weeks, the dogs were put to death. The changes of main arteries, the expression of vascular endothelial growth factor (VEGF), VEGF mRNA and microvessel density (MVD) of ONFH were observed. All the data were analysed by SPSS13.0.

Results

In digital subtraction angiography (DSA), after four or eight weeks of treatment, the quantity and diameter of the main arteries of the femoral head in group B were improved, compared to group A (P < 0.05,P < 0.01). Concerning histology and immunohistochemistry, after four or eight weeks of treatment, the expression of VEGF and MVD were significantly higher than that of group A (P < 0.05, P < 0.01). For real-time quantitative polymerase chain reaction (RT-PCR), after four or eight weeks of treatment, the expression of VEGF mRNA in group B was significantly higher than that of group A (P < 0.05, P < 0.01), and after eight weeks of treatment, the expression of VEGF mRNA were significantly higher than that of four-weeks treatment in group A (P <0.01).

Conclusions

MSCs arterial perfusion can promote vascular repair and angiogenesis and then improve blood supply and repair of femoral head.     

Efficacy of anastrozole in the treatment of hypogonadal,subfertile men with body mass index ≥25 kg/m2

BackgroundAnastrozole is a non-steroidal fourth generation aromatase inhibitor that stops the conversion of testosterone to estradiol and has been used as empiric medical therapy for the treatment of male infertility in men with an abnormal testosterone-to-estradiol ratio <10 in order to increase endogenous testosterone levels. This study sought to evaluate the efficacy of anastrozole in the treatment of hypogonadal, subfertile men with body mass index greater than 25 mg/kg² with respect to hormonal profile, semen parameters and overall fertility status.MethodsRetrospective chart review was performed of hypogonadal, subfertile men with body mass index ≥25 kg/m² who were treated with anastrozole (1 mg daily). Hormonal measurements and semen analysis prior to and after treatment was analyzed in 30 men. Total motile count was calculated from semen analysis. Clinical pregnancy rates were recorded.ResultsMen treated with anastrozole had increases in follicle stimulating hormone (4.8 versus 7.6 IU/L, P<0.0001), luteinizing hormone (3.4 versus 5.4 IU/L, P<0.0001), testosterone (270.6 versus 412 ng/dL, P<0.0001) and testosterone-to-estradiol ratio (9 versus 26.5, P<0.0001) and decrease in estradiol level (32 versus 15.9 pg/mL, P<0.01) after 5 months of therapy. Increases in sperm concentration (7.8 versus 14.2 million/mL, P<0.001), total motile count (12.6 versus 17.7 million, P<0.01) and strict morphology (3.0% versus 3.5%, P<0.05) was appreciated. Clinical pregnancy rate for our cohort was 46.6% (14 of 30), with 71.4% (10 of 14) conceiving through in vitro fertilization, 14.2% (2 of 14) through intrauterine insemination and 14.2% (2 of 14) through natural intercourse.ConclusionsAnastrozole improves hormonal profiles and semen parameters in hypogonadal, subfertile men with body mass index over 25 kg/m² and may aid in achieving pregnancy especially in conjunction with assisted reproductive techniques.     

Use of the turnover epineurial sheath tube for repair of peripheral nerve gaps

Autologous nerve grafting is the conventional technique for bridging nerve gaps, despite its various disadvantages. In this study, the authors investigated the effects of the turnover epineurial sheath tube (TEST) as an alternative to nerve grafting for the repair of nerve gaps, using a rat sciatic nerve model in four groups: Group 1 (n = 5): sham control; Group 2 (n = 10): segmental nerve resection + no repair; Group 3 (n = 10): segmental nerve resection + nerve grafting; Group 4 (n = 15): segmental nerve resection + TEST. Functional recovery was evaluated by walking-track analysis. The sciatic nerves and gastrocnemius muscles were harvested for histologic and quantitative histomorphometric evaluation at 12 weeks. Sciatic functional indices and histomorphometric analyses revealed statistically significant differences between the sham control and the three experimental groups (p < 0.001). The difference between the TEST group and the nerve graft group was not significant; however functional recovery was significantly improved in these two groups, compared to the non-repaired group (p < 0.05). The authors suggest that the TEST provides a suitable conduit between two stumps, eliminates donor-site morbidity, reduces the number of suture sites, fibrosis, and operating time, and might be an alternative to nerve grafting for nerve gap repair.     

Stretched penile length and its associations with testosterone and infertility

BackgroundMale infertility can be associated with secondary sexual characteristics, hypogonadism, and several findings in the examination of external genitalia. We sought to identify if stretched penile length (SPL) is associated with infertility or baseline testosterone.MethodsWe performed a retrospective review of all males age 18–59 presenting to a Men’s health clinic from 2014 to 2017. SPL of patients with infertility were compared to patients with any other complaint. Patients with Peyronie’s disease, prior penile surgery, prostatectomy, on testosterone replacement, clomiphene or β-hCG were excluded from our study. Baseline characteristics were compared between the two groups (infertile vs. other). Linear regression was used to assess the association between infertility and testosterone with SPL after adjusting for patient age, BMI, and race. Scatterplot was used for correlation between testosterone and SPL.ResultsSix hundred and sixty-four men were included in our study (161 infertile, 503 other). The unadjusted mean SPL in the infertile group was 12.3 cm compared to 13.4 cm in the other group (P<0.001). The significance remained when adjusted for age, BMI, testosterone and race (12.4 vs. 13.3, P<0.001). Mean total testosterone in the infertile group was not significantly different than the other group (414 vs. 422, P=0.68). Infertile men were younger than the other group (33.2 vs. 42.1 years, P<0.001). BMI did not significantly differ (28.9 vs. 28.9 kg/m², P=0.57). There was a weak positive correlation between testosterone and penile size in both the infertile group (r=0.20, P=0.01) and the other group (r=0.24, P<0.001).ConclusionsThough SPL differed amongst our groups, adult testosterone levels did not. If developmental levels of testosterone exposure accounted for some of the differences in SPL between our two groups, these variations did not persist into adulthood. It remains unknown if reduced length is a result of genetic or congenital factors associated with infertility. Further investigation is needed to better understand the association of shorter SPL with male infertility.