舒莱在肾移植免疫诱导治疗中有效性和安全性研究

目的 探讨在肾移植免疫诱导治疗中巴利昔单抗(舒莱)的有效性和安全性.方法随机选取69例肾移植受者,在常规三联免疫抑制方案的基础上,分别接受舒莱或ATG诱导治疗,对比观察两组的人/肾存活率、排斥反应以及包括感染在内的药物相关副作用的差异.结果接受舒莱的患者组药物相关副作用显著低于接受ATG的患者组(P＜0.05),两组患者的人/肾存活率、急性排斥反应和肺部感染的发生率均无显著差异(P＞0.05).移植物功能(移植后血肌酐水平及下降速度)在移植早期舒莱组优于ATG组,而长期随访结果显示两组之间无显著差异.结论 肾移植受者接受巴利昔单抗(舒莱)免疫诱导治疗是安全和有效的,与ATG诱导治疗方法比较具有更少的副作用.     

树突状细胞激活的肿瘤浸润淋巴细胞抗小鼠乳腺癌研究

目的 探讨C127细胞全细胞性抗原致敏的DC激活的TIL体外抗小鼠乳腺癌活性,并将C127细胞全细胞性抗原致敏的DC激活的TIL(C127-DC-TIL)过继免疫荷瘤小鼠,研究其对C127荷瘤小鼠免疫功能的影响及抑瘤作用.方法 从小鼠四肢长骨骨髓中获取DC,应用粒,巨噬细胞集落刺激因子(GM-CSF)、白介素-4(IL-4)和肿瘤全细胞性抗原致敏DC,然后用DC激活TIL,观察TIL在体外对C127细胞、MA782细胞和B16细胞的杀伤活性;检测应用C127-DC-TIL后荷瘤小鼠的脾淋巴细胞的NK、LAK、CTL活性、血清TNF活性、抑瘤作用以及瘤体病理改变,并与对照组相比较.结果 ①C127-DC-TIL具有很强的对C127细胞杀伤活性[杀伤率为(70.21±2.86)%],明显高于其对MA782和B16细胞的杀伤活性[杀伤率分别为(51.31±3.25)%,(31.41±2.65)%],也明显高于未经DC激活的TIL、C127-DC-脾淋巴细胞和未经DC激活的脾淋巴细胞对C127细胞杀伤活性[杀伤率分别为(48.30±2.97)%,(47.76±3.43)%和(17.23±2.56)%]和对MA782细胞杀伤活性[杀伤率分别为(38.52±2.87)%,(36.62±2.75)%和(18.07±2.40)%]以及对B16细胞杀伤活性[杀伤率分别为(25.38±2.63)%,(24.82±2.81)%和(17.34±2.81)%],同时B16细胞全细胞性抗原致敏的DC激活的TIL(B16-DC-TIL,TIL来源于C127瘤体)也可诱导相对较低的对B16细胞的特异性细胞杀伤活性.②C127-DC-TIL可明显诱导提高荷瘤小鼠脾淋巴细胞NK、LAK和CTL活性[活性分别为(32.21±1.24)%、(30.35±1.72)%和(37.43±1.54)%],并可检测到血清TNF水平明显上升[血清TNF水平为(38.41±1.77)U/ml],它们均达正常对照组水平,与未经DC激活的TIL组、C127-DC-脾淋巴细胞组、未经DC激活的脾淋巴细胞组、生理盐水组分别对应比较,差异均有显著性(P＜0.01).该组瘤体内淋巴细胞浸润程度也高于对照组,其瘤体生长明显受到抑制.结论 ①C127-DC-TIL可产生很强的体外针对C127细胞的特异性杀伤活性.②C127-DC-TIL具有很强的特异性抗小鼠乳腺癌作用.     

Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models—Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)^−/−, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)^−/−, and Pax7-Arl3^−/−—by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3^−/− mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3^−/− and Pax7-Arl3^−/− mice or primary isolated Myf5-Arl3^−/− and Pax7-Ift88^−/− myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.

Exercise is considered as the primary intervention to improve muscle strength and to counteract muscle atrophy. While physical exercise training is considered a suitable intervention to improve muscle strength and endurance in healthy individuals, some people are resistant to the beneficial effects of exercise (1–3). It has been debated whether exercise is beneficial or harmful for patients with myopathic disorders (4) and type 2 diabetes (5). This so-called “exercise resistance” is considered congenital, and one recently identified causative factor involved in exercise resistance is hepatokine selenoprotein P (2, 6).Primary cilia have a mechanosensory function in bone cells (7), renal cells (8), and airway smooth muscle cells exert a role in sensing oscillatory fluid flow and transducing extracellular mechano-chemical signals into intracellular biochemical responses (9). Intriguingly, low muscle tone is a clinical feature often present in congenital ciliopathies with unclear underlying mechanisms (10). Arf-like Protein 3 (ARL3) is a highly conserved ciliary protein across ciliated organisms. ARL3, a regulator of intraflagellar transport in primary cilia, has been reported involving with various ciliary signaling functions (11, 12) and maintaining cell division polarity (13). Arl3 mutations cause Joubert syndrome (14, 15). Arl3^−/− knockout does not affect cilia structure but compromises ciliary function (16).Cells utilize primary cilia to convert environmental cues, mechanical or chemical, into various cellular signaling essential for development (17–21). During skeletal muscle development, Hedgehog (Hh) signaling helps to initiate the myogenic program (22). In myoblast cells, Fu et al. (23) showed that primary cilia are assembled during the initial stages of myogenic differentiation but disappear as cells progress through myogenesis. The ablation of primary cilia suppresses Hh signaling and myogenic differentiation while enhancing proliferation. However, there are still significant gaps in our understanding of how exercise and mechanical signals activate the Hh signaling pathway. In the present study, we hypothesize that primary cilia in satellite cells (SCs) transduce mechanical stimulation through activation of Hh signaling and promote muscle hypertrophy induced by exercise.Hypertrophy of skeletal muscle is a complex biological process that involves multiple cell types, including SCs, fibro-adipogenic precursors, endothelial cells, fibroblasts, pericytes, and immune cells. Removing cilia from fibro-adipogenic precursors can reduce intramuscular adipogenesis and increase myofibril size during muscle healing (24). SCs play an essential role in muscle hypertrophy and exercise adaptation (25, 26), especially in young mice (27). Mechanical signals can interrupt SC suppression in a skeletal muscle loss model induced by ovariectomy. Diminished SC number and elevated adipogenic gene expression in muscle caused by ovariectomy are averted by mechanical stimulation (28). Experiments in vitro indicate that mechanical stimulation enhances the fusion of SCs (29). SCs are a heterogeneous population of stem cells and committed progenitors (30). Paired box protein Pax-7 (Pax7) is a traditional marker of SCs and acts at different levels in a nonhierarchical regulatory network controlling SC-mediated muscle hypertrophy (31). A major target gene of Pax7 is Myogenic factor 5 (Myf5), and loss of Pax7 significantly decreases Myf5 expression in myoblasts (32). However, Myf5 is present in Pax3/Pax7 double mutants, indicating Myf5 activation occurs independently of Pax3/Pax7 (33). Furthermore, 10% of Pax7-expressing satellite cells have never expressed Myf5 (30). Parise et al. (34) observed an approximately sixfold increase in the number of Myf5-expressing cells by 48 h following exercise, which remained elevated until at least 96 h after exercise. We established three mouse models of Myf5-Arl3^−/−, Pax7-Intraflagellar transport protein 88 homolog (Ift88^−/−), and Pax7-Arl3^−/− to investigate the SC during mechanical stimulation and exercise. In the present study, we provide exciting evidence that SC cilia act as the key mechanical sensor for exercise-induced hypertrophy.     

The effects of hydroxyapatite implantation with the autogenous sclera cap: A cohort study

We performed a novel hydroxyapatite (HA) prosthesis implantation method in which an HA implant was implanted into the scleral shell with an autogenous scleral cap.Twenty-six patients who had undergone the novel HA prosthesis implantation method and 32 patients who had undergone traditional HA prosthesis implantation were retrospectively reviewed. The postoperative activity of the artificial eye was measured by the Hirschberg test combined with arc perimetry. The visual analog score (VAS) was used to evaluate 2-month postoperative pain and 2-month postoperative discomfort. HA implant vascularization was measured with enhanced magnetic resonance imaging (MRI) 2 and 6 months after the operation. The enhancement volume (V_E) and the volume of the HA implant (V_HA) were measured. All cases were followed up for 2 years. Measurement data were processed using SAS 6.12.There was a statistically significant difference (P = .016) between the percentages of excellent grade in the two groups. Two months after implantation, the median pain scores of the study and control groups were 2 and 2.5, respectively, and there was a statistically significant difference (W = 585.0, P = .004); there was a statistically significant difference (W = 535.5, P = .000) between the median discomfort scores of the study group (score = 1) and control group (score = 2); the mean VE/VHA values of the study and control groups were 0.3075 and 0.1535, respectively, and there was a statistically significant difference (t = −8.196, P = .000). Six months after implantation, the V_E/V_HA values of the study and control groups were 0.9686 and 0.5934, respectively, and there was a statistically significant difference (W = 549.0, P = .000). Within 2 years of postoperative follow-up, there were no serious complications in the study group.In the study group, in which the hydroxyapatite implant was implanted into a preserved scleral shell with unaltered muscles and covered with an autogenous scleral cap, postoperative activity and the fibrovascularization of the HA implant were significantly increased, and postoperative pain and discomfort were significantly reduced.     

Successful limb salvage in progressive proximal tibia osteosarcoma following denosumab chemotherapy: A case report

Rationale:Osteosarcoma (OS) is a primary malignant bone tumor that originates in the mesenchymal tissue. It is the most common type of pleomorphic tumor occurring in children and adolescents. Currently, there is no established systematic treatment for OS that progresses during standard preoperative chemotherapy.Patient concerns and diagnoses:We describe a 14-year-old male patient with a 4-month history of pain in the upper right leg. Based on the results of percutaneous biopsy, a diagnosis of OS was made. After admission, the patient was treated with first-line chemotherapy agents. After a single course of treatment, the tumor progressed locally and no limb salvage was feasible.Interventions and outcomes:Intervention with denosumab combined with chemotherapy led to a significant reduction in tumor volume and ossification of soft tissue, which successfully resulted in limb salvage rather than amputation. The patient showed no evidence of recurrent or distant metastasis at 6-month follow-up.Lessons:Treatment with receptor activator of nuclear factor-ĸB ligand inhibitor denosumab combined with standard chemotherapy is effective for advanced OS progressing after chemotherapy. We recommend denosumab therapy for successful limb salvage in patients with high-grade OS associated with osteolytic bone destruction and refractory to preoperative neoadjuvant chemotherapy.     

复旦中文版神经肌肉疾病运动功能评估量表在儿童和青少年中的信度和效度研究

目的：验证复旦中文版神经肌肉疾病（NMD）运动功能评估量表（MFM）在中国儿童和青少年NMD中的信度和效度。 方法：2013年6月至2017年7月在复旦大学附属儿科医院（我院）神经科经基因检测或肌肉活检明确诊断为各类NMD、＞2岁且在我院康复科接受过复旦中文版MFM 20和MFM 32评估的患儿,排除1年内接受过手术、具有严重认知障碍和测试前3 d内从事过严重影响体力的活动患儿。2名物理治疗师同时进行MFM 20和MFM 32测试,检验不同测试者间的信度;同一评价者在第1次评价后间隔3~7d进行第2次评价,检测重测信度;以6 min步行距离（6MWT）和4项功能性计时测试为效度指标;通过分析MFM分值与之的相关性确定关联效度。通过分析纳入对象中杜氏进行性肌营养不良（DMD）患儿的MFM分值与北极星移动量表（NSAA）分值之间的相关性确定关联效度。 结果：372例患儿符合本文纳入排除标准,平均（6.5±2.7）岁,<7岁222例,男性338例,其中DMD 263例,重测信度（2~7岁16例,>7岁38例）和测试者间信度（2~7岁16例,＞7岁29例）检测结果显示,MFM 32和MFM 20的总分和各分区分值ICC=0.89~0.97。基于372例患儿,MFM 32和MFM 20的总分和D1区分值与6MWT和功能性计时测试结果具有中等和较强的相关性（r=0.48~0.73）,与D2和D3分区的分值相关性为中等和较弱。在263例DMD患儿中,MFM 32和MFM 20的总分和D1区分值与NSAA分值的相关性为强和极强相关性。 结论：复旦中文版MFM量表在儿童和青少年NMD患儿中具有很好的信度和效度,可以有效地测定NMD患儿的运动功能状态。     

Study on Remote Field Eddy Current Testing Technology for Crack-like Defects in Long Truss Structure of Aircraft

Detection of hidden defects of aircraft long truss structures (aluminum alloy) is a challenging problem. The shape of the aircraft truss structure is complex, and the crack defects are buried in a large depth. Without the restriction of skin effect, remote field eddy current (RFEC) has great advantages in detecting buried depth defects. In this paper, in order to detect the hidden defects of the aluminum alloy aircraft long truss structure, the remote field eddy current probe is improved from two aspects of magnetic field enhancement and near-field signal suppression using the finite element method. The results show that indirect coupling energy is greatly enhanced when the connected magnetic circuit is added to the excitation coil. By adding a composite shielding structure outside the excitation coil and the detection coil, respectively, the direct coupling energy is effectively restrained. As a result, the size of the probe is reduced. By optimizing the coil spacing and probe placement position, the detection sensitivity of the probe is improved. The simulation is verified by experiments, and the experimental results are consistent with the simulation conclusions.     

Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accord...     

COVID-19 Symptoms and Deaths among Healthcare Workers,United States

We evaluated whether demographics and COVID-19 symptoms predicted COVID-19 deaths among healthcare workers (HCWs) in the United States by comparing COVID-19 deaths in HCWs with 3 control groups (HCW nondeaths, non-HCW deaths, and non-HCW nondeaths) using a case–control design. We obtained patient-level data of 33 variables reported during January 1, 2020–October 12, 2021, in all US states. We used logistic regression analysis while controlling for confounders. We found that persons who were >50 years of age, male, Black, or Asian experienced significantly more deaths than matched controls. In addition, HCWs who died had higher risks for the most severe clinical indicators. We also found that the most indicative symptoms were preexisting medical conditions, shortness of breath, fever, cough, and gastrointestinal symptoms. In summary, minority, male, and older HCWs had greater risk for COVID-19 death. Severe clinical indicators and specific symptoms may predict COVID-19–related deaths among HCWs.     

纹状体梗死患者黑质弥散变化的弥散张量研究

目的 观察纹状体梗死后黑质的弥散变化,探讨纹状体梗死后黑质的继发性损害及其意义.方法 收集首次发病、单侧纹状体梗死、非纹状体梗死、病程在3个月以上的患者各20例分别作试验组和临床对照组,募集健康志愿者20名作对照研究.研究对象均进行1次弥散张量成像(DTI),试验组与临床对照组进行改良Rankin量表(mRS)、Barthol指数(BI)的评分,评估患者脑梗死的预后以及日常生活能力,同时对部分有类似帕金森病症状的患者采用统一帕金森病综合评分量表(Unified Parkinson's Disease Rating Scale,UPDRS)的第Ⅲ分量表评价其严重程度.结果 DTI的参数分析显示:分别与临床对照及健康对照比较,试验组梗死灶同侧黑质的平均弥散量(mean diffusion,MD)值分别升高30.86%(t=40.07,P=0.000)及31.42%(t=42.64,P=0.000),临床对照组梗死灶同侧黑质的MD值与健康对照组比较差异无统计学意义.与没有帕金森病样症状的患者比较,试验组患者中4例出现帕金森病样症状患者梗死灶同侧黑质的MD值升高22%(t=18.03,P=0.01),同时患侧黑质的MD值的上升与其帕金森病样症状的严重程度呈正相关(r=0.97,P=0.03).结论 纹状体梗死可以导致同侧黑质的继发性损害,而且这种继发性损害可能是部分帕金森综合征的发病原因.