Functional adaptation of cancellous bone in human proximal femur predicted by trabecular surface remodeling simulation toward uniform stress state

Two-dimensional simulation of trabecular surface remodeling was conducted for a human proximal femur to investigate the structural change of cancellous bone toward a uniform stress state. Considering that a local mechanical stimulus plays an important role in cellular activities in bone remodeling, local stress nonuniformity was assumed to drive trabecular structural change to seek a uniform stress state. A large-scale pixel-based finite element model was used to simulate structural changes of individual trabeculae over the entire bone. As a result, the initial structure of trabeculae changed from isotropic to anisotropic due to trabecular microstructural changes caused by surface remodeling according to the mechanical environment in the proximal femur. Under a single-loading condition, it was shown that the apparent structural property evaluated by fabric ellipses corresponded to the apparent stress state in cancellous bone. As is observed in the actual bone, a distributed trabecular structure was obtained under a multiple-loading condition. Through these studies, it was concluded that trabecular surface remodeling toward a local uniform stress state at the trabecular level could naturally bring about functional adaptation phenomenon at the apparent tissue level. The proposed simulation model would be capable of providing insight into the hierarchical mechanism of trabecular surface remodeling at the microstructural level up to the apparent tissue level.     

Bone mineral density in chimpanzees,humans, and Japanese macaques

We performed a comparative study of bone mechanical properties in the radii of chimpanzees (Pan troglodytes), humans (Homo sapiens), and Japanese macaques (Macaca fuscata) using peripheral quantitative computed tomography. We investigated: (1)cortical bone area relative to the total periosteal area (PrA); (2) trabecular bone area relative to PrA; (3) cortical bone density; and (4) trabecular bone density. The cortical bone area index for chimpanzees was almost the same as that of Japanese macaques, whereas the equivalent value in humans was about the two-fifths that of the others. Values for the other three properties were constant among these three catarrhine species. Chimpanzees do not particularly resemble humans, but are more similar to digitigrade macaques in terms of bone properties. The constant trabecular bone area index and trabecular density value in these species may suggest that a certain amount of trabecular bone (20–30% of total bone area at the distal 4% level of the forearm) is necessary to achieve normal bone turnover. The physiological metabolism of bone, including cortical bone density, might be conserved in these catarrhines. Electronic Publication     

The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function

DNA double strand break (DSB) repair pathway choice following ionizing radiation (IR) is currently an appealing research topic, which is still largely unclear. Our recent paper indicated that the complexity of DSBs is a critical factor that enhances DNA end resection. It has been well accepted that the RPA-coated single strand DNA produced by resection is a signaling structure for ATR activation. Therefore, taking advantage of high linear energy transfer (LET) radiation to effectively produce complex DSBs, we investigated how the complexity of DSB influences the function of ATR pathway on the G2/M checkpoint regulation. Human skin fibroblast cells with or without ATM were irradiated with X rays or heavy ion particles, and dual-parameter flow cytometry was used to quantitatively assess the mitotic entry at early period post radiation by detecting the cells positive for phosphor histone H3. In ATM-deficient cells, ATR pathway played a pivotal role and functioned in a dose- and LET-dependent way to regulate the early G2/M arrest even as low as 0.2 Gy for heavy ion radiation, which indicated that ATR pathway could be rapidly activated and functioned in an ATM-independent, but DSB complexity-dependent manner following exposure to IR. Furthermore, ATR pathway also functioned more efficiently in ATM-proficient cells to block G2 to M transition at early period of particle radiation exposure. Accordingly, in contrast to ATM inhibitor, ATR inhibitor had a more effective radiosensitizing effect on survival fraction following heavy ion beams as compared with X ray radiation. Taken together, our results reveal that the complexity of DSBs is a crucial factor for the activation of ATR pathway for G2/M checkpoint regulation, and ATM-dependent end resection is not essential for the activation.     

关闭盆底腹膜在腹腔镜直肠癌Miles根治术中的意义

目的:探究关闭盆底腹膜在腹腔镜直肠癌Miles根治术中的意义。方法:选取2012年3月至2014年3月我院治疗的拟行腹腔镜直肠癌Miles根治术患者48例,按随机数字法分为观察组和对照组各24例,观察组在腹腔镜Miles根治术后关闭盆底腹膜,而对照组则不关闭。比较两组手术时间、骶前引流总量、切口感染率及肠梗阻发生率。结果:观察组的手术时间较对照组长(t=5.207,P=0.000),但两组的骶前引流总量、切口感染率和肠梗阻发生率差异无统计学意义(P=0.210、1.000、0.602)。观察组术后分别有3例(12.50%),对照组有2例(8.33%)患者因肿瘤复发而采取放射治疗,其中仅对照组2例患者出现放射性小肠炎。结论:是否关闭盆底腹膜在腹腔镜直肠癌Miles根治术术后疗效差异不大,但关闭盆底腹膜可有效预防术后放射性治疗中放射性小肠炎的发生。     

GCC mRNA和hTERT mRNA在腹腔镜结直肠癌根治术患者外周血中的表达及意义

目的:探讨腹腔镜和开腹手术对结直肠癌根治术患者外周血鸟苷酸环化酶C(GCC)m RNA和人端粒酶逆转录酶(h TERT)m RNA表达的影响及其意义。方法:按照随机数字表法将2009年8月-2014年4月我院收治的结直肠癌患者分为腹腔镜组和开腹手术组,通过逆转录-聚合酶链反应技术(RT-PCR)检测并比较两组患者外周血GCC m RNA和h TERT m RNA的表达情况。结果:与开腹手术组相比较,腹腔镜组患者手术时间长、术中出血量少、术后排气早、住院时间短,差异有统计学意义(P0.01);两组患者手术前GCC m RNA和h TERT m RNA阳性率无显著差异(P0.05);两组患者手术后GCC m RNA和h TERT m RNA阳性率显著升高,差异有统计学意义(P0.05)。结论:腹腔镜和开腹手术均会增加结直肠癌患者血行微转移,但腹腔镜结直肠根治术不会增加术后肿瘤血循环微转移的危险性。     

盐酸右旋美托咪定对脑膜瘤切除术患者围拔管期应激反应的影响

目的：观察不同剂量的盐酸右旋美托咪定对脑膜瘤切除术患者全麻围拔管期应激反应的影响。方法：60 例ASAI～Ⅱ级,年 龄25-65 岁脑膜瘤切除术患者,随机分为四组,NS、D1、D2 和D3 组,NS 组:静脉泵入等量的生理盐水,D1、D2 和D3组静脉泵注 负荷量均为0.6 滋g/kg 的盐酸右旋美托咪定,各组泵注时间均为10 分钟,输注结束后随之给予维持量,D1组：盐酸右旋美托咪定 维持量0.2 滋g·kg-1·hr-1;D2 组：盐酸右旋美托咪定维持量0.4 滋g·kg-1·hr-1;D3组：盐酸右旋美托咪定维持量0.6 滋g·kg-1·hr-1。观察 并记录拔管时的耐管评分、呛咳程度、警觉/ 镇静评分(OAA/S）、拔管时间及拔管即刻和拔管后3 min 的平均动脉压(MAP)、心率 (HR)及恶心、寒战等不良反应。结果：D3 组患者耐管评分高于D1 组、D2 组和NS 组,呛咳程度轻于D1 组、D2 组和NS 组（P<0. 05）;D2、D3 组患者拔管即刻和拔管后3 min 的MDP、HR 均明显低于D1 组（P<0.05）;D1、D2 和D3 组不良反应少于NS 组;四组 拔管时间无明显差异。结论：盐酸右旋美托咪定降低脑膜瘤切除术患者全麻围拔管期的应激反应,增强患者对气管导管的耐受 性。     

Sumoylation regulates EXO1 stability and processing of DNA damage

DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3′-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 expression. Thus, our study identifies a novel layer of regulation of EXO1, making the pathways that regulate its function an ideal target for therapeutic intervention.     

静脉全麻联合超声引导下前锯肌平面+肋间神经阻滞应用于胸腔镜肺楔形切除术效果分析

摘要 目的：探讨静脉全麻联合超声引导下前锯肌平面+肋间神经阻滞应用于胸腔镜肺楔形切除术效果。方法：选择2021年10月至2022年12月来我院诊治的60例行胸腔镜肺楔形切除术患者,根据随机数字表法,将60例患者分为对照组（30例）与观察组（30例）,对照组30例患者行全麻联合胸椎旁阻滞+肋间神经阻滞的麻醉方法,观察组30例患者行全麻联合前锯肌＋肋间神经阻滞的麻醉方法。对比两组患者监测入室时（T0）、插管即刻（T1）、手术切皮时（T2）、拔管即刻（T3 ）时的平均动脉压及心率,对比两组患者术后2 h、4 h、12 h、24 h、48 h的静息、咳嗽状态下的疼痛评分,对比两组患者T0-T3点的应激反应指标,对比两组患者术中血管活性药的使用剂量,对比两组患者围术期的不良反应发生率。结果：与T0点相比,观察组在T1、T2、T3时的平均动脉压、心率均有明显增加（P<0.05）,而在T1点时,两组比较无差异（P>0.05）;T2、T3点时观察组的平均动脉压、心率明显较对照组低（P<0.05）。随着术后时间延长,两组静息、咳嗽状态下的疼痛评分明显降低（P<0.05）,而同时间点组间对比无统计学意义（P>0.05）。与T0点相比,观察组在T1、T2、T3时的肿瘤坏死因子、白介素6、白介素10水平均有明显增加（P<0.05）,而同时间点观察组与对照组对比无统计学意义（P>0.05）。观察组术中血管活性药的使用剂量明显较对照组低（P<0.05）。观察组的不良反应发生率16.77%低于对照组23.33%,但组间对比无统计学意义（P>0.05）。结论：行静脉全麻联合超声引导下前锯肌平面+肋间神经阻滞的胸腔镜肺楔形切除术者血流动力学更加稳定,术中所需血管活性药物用量明显降低。     

Ileo-caecal resection induced pancreatic growth in rats

The effect of ileo-caecal resection on pancreatic growth was studied in rats four weeks after the operation. The results were compared with an identical control group who had undergone laparotomy alone. Pancreatic wet weight in ileo-caecal resectioned rats was 1.4 times greater than that found in control rats. Protein, DNA, RNA contents in the pancreas, pancreatic wet weight per 100 micrograms DNA and RNA/DNA ratio were also found significantly elevated in experimental group as opposed to the control group. Basal plasma levels of cholecystokinin (CCK) and gastrin were measured to delineate the influence of hormonal response on the pancreatic growth in ileo-caecal resected rats and were found not significantly increased after ileo-caecal resection. The data suggest that the enlargement of pancreas in ileo-caecal resected rats may be due to hyperplasia and hypertrophy of pancreatic cells; alternatively, the pancreatic growth may have been influenced by the bile acid deficiency and the reduction or release of an inhibitory factor present in the ileum of rats.     

The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man

Summary. A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 ± 0.4 g/dl (mean ± SD) preoperatively, 3.7 ± 0.7 at day 1 and 3, and 3.9 ± 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 ± 0.4 preoperatively, 3.0 ± 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)^ALB, r = 0.73; CHOL = 16.5(1.610)^ALB (1.001)^ALKPH, r = 0.71; IBC = 68.6(1.391)^ALB, r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) – 6.2(ALB), r = 0.91; ALB = 5.0–0.013(AGE) – {0.5 + 0.003(AGE) _COMPL + 0.012(AGE) _DEATH } _POSTOP , r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness.