Total knee arthroplasty for treatment of post-traumatic arthritis: Systematic review

AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for Englishlanguage clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved articles.We extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and text.RESULTS Sixteen studies, four prospective and ten retrospective,examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion(ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene wear.CONCLUSION Although associated with higher complication rates,TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes.

Volume and fat infiltration of spino-pelvic musculature in adults with spinal deformity

AIM: To investigate fat infiltration and volume of spino-pelvic muscles in adults spinal deformity(ASD) with magnetic resonance imaging(MRI) and 3D reconstructions.METHODS: Nineteen female ASD patients(mean age 60 ± 13) were included prospectively and consecutively and had T1-weighted Turbo Spin Echo sequence MRIs with Dixon method from the proximal tibia up to T12 vertebra. The Dixon method permitted to evaluate the proportion of fat inside each muscle(fat-water ratio). In order to investigate the accuracy of the Dixon method for estimating fat vs water, the same MRI acquisition was performed on phantoms of four vials composed of different proportion of fat vs water. With Muscl'X software, 3D reconstructions of 17 muscles or group of muscles were obtained identifying the muscle's contour on a limited number of axial images [Deformation of parametric specific objects(DPSO) Method]. Musclar volume(Vmuscle), infiltrated fat volume(Vfat) and percentage of fat infiltration [Pfat, calculated as follow: Pfat = 100 ×(Vfat/Vmuscle)] were characterized by extensor or flexor function respectively for the spine, hip and knee and theirs relationship with demographic data were investigated. RESULTS: Phantom acquisition demonstrated a non linear relation between Dixon fat-water ratio and the real fat-water ratio. In order to correct the Dixon fatwater ratio, the non linear relation was approximated with a polynomial function of degree three using the phantom acquisition. On average, Pfat was 13.3% ± 5.3%. Muscles from the spinal extensor group had a Pfat significantly greater than the other muscles groups, and the largest variability(Pfat = 31.9% ± 13.8%, P < 0.001). Muscles from the hip extensor group ranked 2nd in terms of Pfat(14% ± 8%), and were significantly greater than those of the knee extensor(P = 0.030). Muscles from the knee extensor group demonstrated the least Pfat(12% ± 8%). They were also the only group with a significant correlation between Vmuscle and Pfat(r =-0.741, P < 0.001), however this correlation was lacking in the other groups. No correlation was found between the Vmuscle total and age or body mass index. Except for the spine flexors, Pfat was correlated with age. Vmuscle and Vfat distributions demonstrated that muscular degeneration impacted the spinal extensors most.CONCLUSION: Mechanisms of fat infiltration are not similar among the muscle groups. Degeneration impacted the spinal and hip extensors most, key muscles of the sagittal alignment.

Comparative study in vivo of the osseointegration of 3D-printed and plasma-coated titanium implants

BACKGROUND Total hip arthroplasty is a common surgical treatment for elderly patients with osteoporosis,particularly in postmenopausal women.In such cases,highly porous acetabular components are a favorable option in achieving osseointegration.However,further discussion is needed if use of such acetabular components is justified under the condition of normal bone mass.AIM To determine the features of osseointegration of two different types of titanium implants[3-dimensional(3D)-printed and plasma-coated titanium implants]in bone tissue of a distal metaphysis in a rat femur model.METHODS This study was performed on 20 white male laboratory rats weighing 300-350 g aged 6 mo.Rats were divided into two groups of 10 animals,which had two different types of implants were inserted into a hole defect(2×3 mm)in the distal metaphysis of the femur:GroupⅠ:3D-printed titanium implant(highly porous);GroupⅡ:Plasma-coated titanium implant.After 45 and 90 d following surgery,the rats were sacrificed,and their implanted femurs were extracted for histological examination.The relative perimeter(%)of bone trabeculae[bone-implant contact(BIC%)]and bone marrow surrounding the titanium implants was measured.RESULTS Trabecular bone tissue was formed on the 45th day after implantation around the implants regardless of their type.45 d after surgery,group I(3D-printed titanium implant)and groupⅡ(plasma-coated titanium implant)did not differ in BIC%(83.51±8.5 vs 84.12±1.73;P=0.838).After 90 d,the BIC%was higher in group I(87.04±6.99 vs 81.24±7.62;P=0.049),compared to groupⅡ.The relative perimeter of the bone marrow after 45 d did not differ between groups and was 16.49%±8.58%for groupⅠ,and 15.88%±1.73%for groupⅡ.Futhermore,after 90 d,in groupⅠthe relative perimeter of bone marrow was 1.4 times smaller(12.96±6.99 vs 18.76±7.62;P=0.049)compared to the relative perimeter of bone marrow in groupⅡ.CONCLUSION The use of a highly porous titanium implant,manufactured with 3D printing,for acetabular components provides increased osseointegration compared to a plasma-coated titanium implant.

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis

AIM To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODS Magnetic resonance(MR) images were acquired from5 subjects scheduled for total knee arthroplasty(TKA)(mean age 70 years) and 20 young healthy control subjects without knee pain(mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained.Following TKA each condyle was divided into 4 parts(distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens(bone and cartilage blocks) were examined. For each joint,the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system.In magnetic resonance imaging(MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTS Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis(OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461;medial posterior condyle(MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550],suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage.Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA(P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients. CONCLUSION Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.

软骨母细胞瘤:射频消融术在部分病例中替代外科手术切除

目的证明射频（RF）消融可以安全有效地治疗有选择的软骨母细胞瘤（selected cases of chondroblastoma）。方法本研究得到机构伦理委员会批准，并符合HIPPA的要求。由于为回顾性研究，故未签署知情同意书。回顾性分析了1995年7月-2007年7月2个医学中心行射频消融治疗后经活检证实为软骨母细胞瘤的病例。在CT引导下进行单极RF消融，同时获得病变影像学资料。记录术前和术后1d症状。由病历记录获取长期随访情况。结果13例男性和4例女性经RF治疗（平均年龄17-3岁）。

Conversion total hip arthroplasty: Primary or revision total hip arthroplasty

Total hip arthroplasty(THA) is an increasingly common procedure among elderly individuals.Although conversion THA is currently bundled in a diagnosis related group(DRG) with primary THA,there is a lack of literature supporting this classification and it has yet to be identified whether conversion THA better resembles primary or revision THA.This editorial analyzed the intraoperative and postoperative factors and functional outcomes following conversion THA,primary THA,and revision THA to understand whether the characteristics of conversion THA resemble one procedure or the other,or are possibly somewhere in between.The analysis revealed that conversion THA requires more resources both intraoperatively and postoperatively than primary THA.Furthermore,patients undergoing conversion THA present with poorer functional outcomes in the long run.Patients undergoing conversion THA better resemble revision THA patients than primary THA patients.As such,patients undergoing conversion THA should not be likened to patients undergoing primary THA when determining risk stratification and reimbursement rates.Conversion THA procedures should be planned accordingly with proper anticipation of the greater needs both in the operating room,and for in-patient and followup care.We suggest that conversion THA be reclassified in the same DRG with revision THA as opposed to primary THA as a step towards better allocation of healthcare resources for conversion hip arthroplasties.

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits:A biomechanical study

BACKGROUND Today,biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty.Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant,and their ability to withstand functional loads.AIM To compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODS The study was performed in 50 female California rabbits divided into nonovariectomized(non-OVX)and ovariectomized groups(OVX)at 6 mo of age.Rabbits were sacrificed 8 wk after the implantation of four biomaterials[TTM,CONCELOC,Zimmer Biomet's Trabecular Metal(TANTALUM),and ATLANT]in a 5-mm diameter defect created in the left femur.A biomechanical evaluation of the femur was carried out by testing implant breakout force.The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTS The breakout force needed for implant detachment was significantly higher in the non-OVX group,compared with the OVX group for all implants(TANTALUM,194.7±6.1 N vs 181.3±2.8 N;P=0.005;CONCELOC,190.8±3.6 N vs 180.9±6.6 N;P=0.019;TTM,186.3±1.8 N vs 172.0 N±11.0 N;P=0.043;and ATLANT,104.9±7.0 N vs 78.9 N±4.5 N;P=0.001).In the OVX group,The breakout forces in TANTALUM,TTM,and CONCELOC did not differ significantly(P=0.066).The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC,and by 2.2 compared with TTM(P=0.001).In the non-OVX group,the breakout force for ATLANT was significantly different from all other implants,with a reduction in fixation strength by a factor of 1.9(P=0.001).CONCLUSION TANTALUM,TTM,and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone.ATLANT had significantly decreased osseointegration(P=0.001)in healthy and in osteoporotic bone.

Postural spinal balance defined by net intersegmental moments: Results of a biomechanical approach and experimental errors measurement

AIM: To describe initial results and experimental error measurement of a protocol analyzing Human posture through sagittal intersegmental moments. METHODS: Postural analysis has been recently improved by development of three-dimensional radiographic imaging systems. However, in various situations such as global sagittal anterior malalignment interpretation of radiographs may not represent the real alignment of the subject. The aim of this study was to present initial results of a 3D biomechanical protocol. This protocol isobtained in a free standing position and characterizes postural balance by measurement of sagittal intersegmental net moments. After elaboration of a specific marker-set, 4 successive recordings were done on two volunteers by three different operators during three sessions in order to evaluate the experimental error measurement. A supplementary acquisition in a "radiographic" posture was also obtained. Once the data acquired, joint center, length, anatomical frame and the center of mass of each body segment was calculated and a mass affected. Sagittal net intersegmental moments were computed in an ascending manner from ground reaction forces at the ankles, knees, hips and the lumbosacral and thoraco-lumbar spinal junctions. Cervicothoracic net intersegmental moment was calculated in a descending manner.RESULTS: Based on average recordings, clinical interpretation of net intersegmental moments(in N.m) showed a dorsal flexion on the ankles(8.6 N.m), a flexion on the knees(7.5 N.m) and an extension on the hips(8.5 N.m). On the spinal junctions, it was flexion moments: 0.34 N.m on the cervico-thoracic; 6.7 N.m on the thoraco-lumbar and 0.65 N.m on the lumbo-sacral. Evaluation of experimental error measurement showed a small inter-trial error(intrinsic variability), with higher inter-session and inter-therapist errors but without important variation between them. For one volunteer the "radiographic" posture was associated to significant changes compared to the free standing position. CONCLUSION: These initial results confirm the technical feasibility of the protocol. The low intrinsic error and the small differences between inter-session and intertherapist errors seem to traduce postural variability over time, more than a failure of the protocol. Characterization of sagittal intersegmental net moments can have clinical applications such as evaluation of an unfused segment after a spinal arthrodesis.

复合型口服避孕药在系统性红斑狼疮妇女中的应用

Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. METHODS: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 μ g plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. RESULTS: The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12- month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P = 0.95; upper limit of the one sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person year for subjects receiving oral contraceptives and 1.44 flares per personyear for subjects receiving placebo (relative risk, 0.98; P = 0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). CONCLUSIONS: Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2-/-Lung Fibroblasts

The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor （MIF） in lung fibroblasts derived from COX-2 / but not wild-type （WT） or COX-1-/- mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2 /- fibroblasts seemingly from the pre- formed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2-/- was ＂prostaglandin-independent.＂ GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2 ! cells. Furthermore, COX-2-/- fibroblasts also exhibit a significant increase in transcriptional activity of various regu- lators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser （IntroGen） analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX- p53 axis in inflammation and cancer at the genomic and proteomie levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

关节置换术后手术部位感染细菌的抗生素敏感性研究

背景：目前，对于治疗疑似全髋或全膝关节置换术后假体周围感染的抗生素使用原则还没有共识。本研究旨在建立这样一个用药原则。方法：对146例患者进行回顾性研究。在这些患者进行全髋或全膝关节置换术后的翻修术时，共194个标本得到了细菌培养阳性结果。患者的一般信息、并存疾病情况、细菌种类、抗生素敏感性资料以及翻修术后细菌培养出现阳性结果所需要的天数均被记录。结果：共110髋、84膝得到的标本培养结果为阳性。其中70％为慢性感染，17％为急性术后局部感染，13％为急性血源性感染。翻修术后出现阳性培养结果的平均时间为3天。革兰氏阳性菌感染占绝大多数。在这些细菌中，88％对庆大霉素敏感，96％对万古霉素敏感，61％对头孢唑林敏感。多数的耐药菌来自于先前有过抗生素治疗失败史的患者。术后急性感染的菌株比慢性感染或血源性感染的菌株更易发生耐药。血源性感染患者分离得到的菌株对庆大霉素和头孢唑林都有高度的敏感性。结论：对疑似假体周围感染的经验性抗生素用药应该在对感染进行分类和确定革兰氏染色结果的指导下进行。我们认为，在得到培养结果之前，急性血源性感染应该一开始就使用头孢唑林和庆大霉素的联合治疗。所有术后慢性或急性革兰氏阳性菌感染或不能明确革兰氏染色结果的细菌感染都应该用万古霉素。革兰氏阴性菌感染应该用第三代或第四代头孢霉素。革兰氏阳性菌和阴性菌的混合感染应该联合使用万古霉素和第三代或第四代头孢霉素。另外，我们认为如果在术后第4天还没有得到细菌培养或是其他确诊的阳性结果就应该结束经验性抗生素治疗。可信水平：诊断性研究，Ⅳ级。进一步可信度参见作者介绍。

A SPECIFIC PROTEIN FOUND IN HUMAN SENESCENT FIBROBLASTS

The limited potential for proliferation of human fibroblasts in culture represents cell level senescence. Aging is a programed process under generic control, and at certain stage of the life-span of animal cells, some genes start to express. Studying the biomarkers of senescent cells is important to understanding the basic mechanism of aging which may be relevant to the normal cell growth control and tumor biology. A protein with 72 000 Dalton molecular weight was detected by the hybridoma method in our laborotary. The protein shows specificity to senescent or presenescent cells of several cell lines, including WI-38, K.D., U2OS, etc.

Genomic,Lipidomic,and Metabolomic Analysis of Cyclooxygenase-null Cells:Eicosanoid Storm,Cross Talk,and Compensation by COX-1

The constitutively-expressed cyclooxygenase 1（COX-1） and the inducible COX-2 are both involved in the conversion of arachidonic acid（AA） to prostaglandins（PGs）.However,the functional roles of COX-1 at the cellular level remain unclear.We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type（WT） mice and COX-2^（-/-） or COX-1^（-/-） mice may help address the functional roles of COX-1 in inflammation and other cellular functions.Compared to WT,the number of specifically-induced transcripts were altered descendingly as follows：COX-2^（-/-） 〉 COX-1^（-/-） 〉 WT ＋ IL-1β.COX-1^（-/-） or COX-2^（-/-） cells shared about 50%of the induced transcripts with WT cells treated with IL-1β,respectively.An interactive ＂anti-inflammatory,proinflammatory,and redox-activated＂ signature in the protein-protein interactome map was observed in COX-2^（-/-） cells.The augmented COX-1mRNA（in COX-2^（-/-） cells） was associated with the upregulation of mRNAs for glutathione S-transferase（GST）,superoxide dismutase（SOD）,NAD（P）H dehydrogenase quinone 1（NQO1）,aryl hydrocarbon receptor（AhR）,peroxiredoxin,phospholipase,prostacyclin synthase,and prostaglandin E synthase,resulting in a significant increase in the levels of PGE2,PGD2,leukotriene B4（LTB4）,PGF（1α）,thromboxane B2（TXB2）,and PGF（2α）.The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities.Compared to WT,the upregulated COX-1 mRNA in COX-2^（-/-） cells generated an ＂eicosanoid storm＂.The genomic characteristics of COX-2^（-/-） is similar to that of proinflammatory cells as observed in IL-1β induced WT cells.COX-1^（-/-） and COX-2^（-/-） cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

局部麻醉药对人类神经元的细胞毒性

背景局部麻醉药（LAs）除了能抑制外周神经兴奋性传递作用，对中枢神经系统、心血管系统、神经肌肉接头及细胞代谢还具有毒性作用。手术后多种神经并发症都可归因于LAs的细胞毒性作用，但其作用机制尚不清楚。临床上使用的局部麻醉药浓度远远大于其抑制离子通道作用的EC50，离子通道阻滞这一单一因素不足以解释LAs诱导细胞死亡的所有原因，因为其他因素也可能参与其中。本研究比较了6种常用局部麻醉药的细胞毒性，并探讨其毒性作用的可能机制。方法将人类SH—SY5Y神经母细胞分别浸泡在6种局部麻醉药中（布比卡因、罗哌卡因、甲哌卡因、利多卡因、普鲁卡因和氯普鲁卡因），通过MTT[3-（4，5-二甲基噻唑-2）-2，5-二苯基四氮唑澳盐]光度计法定量，LIVE／DEAD（钙黄绿素／AM和溴乙啶二聚体-1）荧光成像检测方法定性测量它们的差异。此外采用荧光半胱天冬酶抑制剂（FLICA^TM）测定半胱天冬酶-3／-7的活性测定凋亡活性，同时还研究了局部麻醉药对极化和碳酰胆碱诱导细胞内钙反应的作用。结果（1）用局部麻醉药处理细胞10分钟后，6种局部麻醉药均呈浓度依赖地降低了细胞活性。杀伤力为普鲁卡因≤甲哌卡因〈利多卡因〈氯普鲁卡因〈罗哌卡因〈布比卡因（根据所得LD50，即致50％细胞死亡的浓度）。在所有局部麻醉药中，只有布比卡因和利多卡因随着浓度的增加而能够杀灭所有细胞。（2）布比卡因和利多卡因均激活了半胱天冬酶-3／-7，所需浓度利多卡因高于布比卡因，但布比卡因激活半胱天冬酶的速度较利多卡因迟缓。高浓度利多卡因能立即诱发半胱天冬酶活化，但浓度低于10mM时不产生该作用。（3）普鲁卡因和氯普鲁卡因浓度依赖性地抑制去极化或受体激活诱发的胞浆Ca^2＋反应，并与以往研究中发现的布比卡因、罗哌卡因、甲哌卡因和利多卡因的作用方式相类似。没有一种局部麻醉药能够显著增加基础状态和Ca^2＋诱发的胞浆Ca^2＋浓度变化。结论局部麻醉药导致细胞迅速死亡，主要原因是细胞坏死。利多卡因和布比卡因可以通过延长作用时间或增加浓度来触发细胞凋亡，这些作用可能与手术后神经损伤有关。虽然利多卡因不是本研究模型中毒性最强的局部麻醉药，但是它诱发一过性神经性症状的概率最高，而毒性最高的布比卡因却极少造成一过性神经性症状。这提示不同的局部麻醉药可能通过不同机制，以及作用于神经元以外的其他靶点而产生细胞毒性神经损伤。