Microstructure and Phase Evolution of Ti-Al-C-Nb Composites Prepared by In Situ Selective Laser Forming

In the present work, a novel Ti-Al-C-Nb composite was prepared using in situ selective laser forming (ISLF). The formation mechanism of the Ti-Al-C-Nb bulks, which were synthesized using elemental titanium, aluminum, and carbon (graphite) powders via ISLF techniques, was investigated. The results showed that the Ti₃Al and TiC phases were the dominant synthesis products during the chemical reactions, and these occurred during the ISLF process. The size of the fine nanoscale crystal TiC grains could reach 157 nm at an energy level of 60 J/mm³. The porous structure of the ISLF specimens was disclosed, and an open porosity of 20–44% was determined via the scanning speed and the laser power. Both the high dynamic viscosity and the reactions of the raw powders led to the generation of a considerable number of pores, whereas the specimen processed using 45 W and 100 mm/s possessed the lowest degree of open porosity.     

肝门胆管癌的CT诊断价值探讨

目的探讨肝门胆管癌的CT诊断价值及病理基础。方法本文收集21例均经手术及病理证实的肝门管癌,行CT平扫及增强双期扫描,21例均加做CT延迟扫描。结果①胆管扩张14例;②21例肝门胆管癌动态扫描,呈低密度13例,等密度6例,高密度2例;③延迟扫描,呈相对高密度18例,等密度3例,无低密度,肿瘤边界更明确。结论CT是诊断原发性肝门胆管癌有效、准确的检查方法。     

Dedifferentiated liposarcoma (DDLPS) in the rectum: A case report

Dedifferentiated liposarcoma (DDLPS) is a rare subtype of liposarcoma with a poor prognosis. This current case report describes a rectal DDLPS in a 68-year-old Chinese male that presented with lower abdominal pain and weight loss. Computed tomography and magnetic resonance imaging were undertaken to evaluate the tumour. The patient underwent radical resection of the rectal tumour, sigmoid colostomy and partial ureterectomy. The tumour was positive for mouse double minute 2 by immunohistochemistry. The patient healed well but refused chemotherapy postoperatively for economic reasons. The tumour recurred and metastasized 4 weeks after the operation. After relevant treatment, the patient''s condition deteriorated and he died of shock, metabolic acidosis, hyperlactataemia and acute renal failure. The case report also reviews the literature in terms of the clinical diagnosis, treatment and pathological characteristics of rectal DDLPS with the aim of improving the level of diagnosis and treatment.     

基于Box-Behnken响应面设计优选中药复方便乃通的提取工艺

[目的] 利用Box-Behnken响应面设计法优化中药复方便乃通（BNT）的提取工艺。[方法] 基于单因素实验优选BNT提取工艺的影响因素及其范围,运用Box-Behnken响应面设计法构建三因素三水平实验设计方案,以番泻苷B、番泻苷A及橙皮苷的含量作为响应指标优选最佳提取工艺条件,并进行工艺验证。[结果] 中药复方BNT的最佳提取工艺条件为料液比1∶8,回流时间30 min,提取次数2次。[结论] 利用Box-Behnken响应面设计法优化中药复方BNT提取工艺方法稳定,可为BNT提取工艺提供参考。     

Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease

BACKGROUNDThree-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients.METHODSWe analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label.RESULTSThe decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups.CONCLUSIONSThe combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide.^[1] Three-vessel disease (TVD) is the most severe form of CAD and is characterized by significant stenosis in all three major coronary arteries. The application of myocardial revascularization techniques, including coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), has significantly improved the clinical outcomes of patients with severe CAD. CABG has traditionally been the standard therapy for complex coronary lesions, including TVD.^[2] In recent years, with the advancements in PCI technology and the accumulation of operators’ experience, the incidence of periprocedural and long-term adverse events of PCI has substantially decreased, and PCI has been gradually applied in the treatment of TVD.^[3,4] Current guidelines recommend use of the SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score and diabetes status to guide the revascularization strategy for patients with TVD.^[5,6] Current practice guidelines do not recommend PCI for patients with TVD with a SYNTAX score of ≥ 23. However, using the SYNTAX score to guide clinical decision-making between PCI and CABG remains controversial, and its reasonability has been questioned since a newly published meta-analysis showed no significant association between the SYNTAX score and the comparative effectiveness of PCI and CABG.^[7] Moreover, the SYNTAX score is a quantitative indicator of the anatomical complexity of TVD and does not include clinical variables that may have significant effects on the patient’s prognosis. Whether some patients with specific clinical characteristics can obtain a comparable or even greater survival benefit from PCI than from CABG is unclear. Moreover, risk assessment for patients with TVD after revascularization therapy remain challenging.^[8–10]Machine learning has recently emerged as an important research method and has been successfully applied in many scientific fields, including clinical medicine.^[11–13] The decision tree algorithm, a common approach in machine learning, can handle non-linearity, heterogeneous effects, and high-dimensional features and partition a trial population into subgroups characterized by multiple simultaneous characteristics.^[14] In the present study involving a large cohort of patients with TVD with a SYNTAX score of ≥ 23, we employed a decision tree algorithm to generate specific subgroups, compared the long-term prognosis between patients who underwent PCI or CABG in each subgroup, and conducted a comparative analysis of the long-term prognosis between subgroups generated by machine learning. We evaluated whether machine learning can help in selecting the optimal revascularization method and assessing risk in patients with severe TVD.     

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.