高分辨率CT在非结核分枝杆菌肺病诊治中的价值

搜集广州市胸科医院2015年3月至2017年9月经菌种鉴定为非结核分枝杆菌(NTM)肺病、并行胸部高分辨率CT(HRCT)检查的99例患者,回顾性分析肺内病灶部位、数量、形态、大小、密度、边界、分布及淋巴结的CT征象;评估99例NTM肺病患者治疗前后HRCT的表现。HRCT检查表现为斑点片状渗出、实变93例,支气管扩张78例,空洞60例,纤维条索状影59例,结节状影58例,树芽征55例,磨玻璃样影46例,淋巴结肿大45例,胸膜增厚18例,胸腔积液9例,病变通常以多种形态混杂存在。91例NTM肺病患者经克拉霉素、利福平、乙胺丁醇及阿米卡星治疗6~18个月后CT复查,显示病灶均减少;8例患者经HRCT精准定位后行患侧肺叶切除术,术后肺部病灶明显减少,但均出现术侧胸膜肥厚粘连。胸部HRCT对NTM肺病的诊断及治疗具有重要的应用价值。     

A mathematical simulation of the tip-apex distance and the calcar-referenced tip-apex distance for intertrochanteric fractures reduced with lag screws

BackgroundAs a predictor of the risk of lag screw cutout, it was recommended that keeping tip-apex distance (TAD) < 25 mm and placing the screw centrally or inferiorly, but positioning the lag screw too inferiorly in the head would produce TAD > 25 mm. We aim to simulate various positions of the lag screw in the femoral head and identify whether 25 mm is a suitable cut-off value that favours all sizes of femoral heads with intertrochanteric fractures of the hip.MethodsUsing a general mathematical software, the positions of the screw tip points were simulated. The virtual anterior–posterior and lateral views were then visualised, and the locus of the screw tips was projected into a Cartesian coordinate system according to the TAD and calcar-referenced tip-apex distance (CalTAD) formulas. Each original virtual anterior–posterior and lateral image was zoomed and compiled to match a calculated average image. The screw tip points were recorded, traced and compiled into volumes which could be used to visualise the screw's movements and positioning within the femoral head. The extracted volumes were calculated when 10 mm < TAD < 25 mm and 10 mm < CalTAD < 25 mm, and the region where these two volumes overlapped was also calculated. Suitable positions for the screw tip were then assessed.ResultsFor the TAD calculation, the shape of the traced screw tip points had a pancake-like appearance, while the CalTAD plot produced a teardrop-shaped region. The volume ratios of TAD, CalTAD and overlapping region relative to the femoral head volume were respectively 3.51 ± 1.30%, 5.19 ± 1.62% and 2.64 ± 1.32%. The volumes of the traced TAD, CalTAD and overlapping regions increased slower than the volume of an idealised sphere.ConclusionPositioning the lag screw should address geometrical effects of both tip-apex distance and femoral head size, with an emphasis on measuring the position of the screw tip for the suitable zone by volume ratio. The previous 25 mm TAD cut-off value should be adjusted according to the individual femoral head size.     

MRI contrast agents: Basic chemistry and safety

Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals used widely in MRI examinations. Gadolinium‐based MRI contrast agents (GBCAs) are by far the most commonly used. To date, nine GBCAs have been commercialized for clinical use, primarily indicated in the central nervous system, vasculature, and whole body. GBCAs primarily lower the T₁ in vivo to create higher signal in T₁‐weighted MRI scans where GBCAs are concentrated. GBCAs are unique among pharmaceuticals, being water proton relaxation catalysts whose effectiveness is characterized by a rate constant known as relaxivity. The relaxivity of each GBCAs depends on a variety of factors that are discussed in terms of both the existing agents and future molecular imaging agents under study by current researchers. Current GBCAs can be divided into four different structural types (macrocyclic, linear, ionic, and nonionic) based on the chemistry of the chelating ligands whose primary purpose is to protect the body from dissociation of the relatively toxic Gd³⁺ ion from the ligand. This article discusses how the chemical structure influences inherent and in vivo stability toward dissociation, and how it affects important formulation properties. Although GBCAs have a lower rate of serious adverse events than iodinated contrast agents, they still present some risk. J. Magn. Reson. Imaging 2012;36:1060–1071. © 2012 Wiley Periodicals, Inc.     

T cells expressing CD26-specific chimeric antigen receptors exhibit extensive self-antigen-driven fratricide

Abstract

Background: Immunotherapy utilizing T cells genetically modified to express chimeric antigen receptors (CARs) is rapidly emerging as a promising novel treatment for hematological and nonhematological malignancies. In order to target the TKI-insensitive leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) by CAR T cells, we chose CD26 as a cell surface tumor-associated antigen due to preferentially expression on LSCs. Additionally, CD26 has also been suggested to be a multipurpose therapeutic target for other cancer. Therefore, developing the CD26-targeting CAR T cells may be a promising therapy for not only LSCs but also other CD26+ cancer cells.

Methods: We designed the second-generation CD26-targeting CAR utilizing 4-1BB (CD137) as costimulatory domain, and transduced T cells with CD26-CAR containing lentiviral. Then we evaluated the transduction efficiency and expansion ability, and demonstrated the existence of self-antigen-driven fratricide by cytokine assay and cytotoxicity assay.

Results: Anti-CD26-4-1BB-CAR T cells exhibited poor viability, multiple cytokine secretion, down-regulation of CD26 and direct cytotoxicity against themselves, indicating self-antigen-driven fratricide.

Conclusion: Eradicating CML-LSCs via anti-CD26-4-1BB-CAR T cells is not applicable, and optimized design or alternative target is needed.     

MicroRNA-323 regulates ischemia/reperfusion injury-induced neuronal cell death by targeting BRI3

Purpose: MicroRNA-323 (miR-323) has been reported to be upregulated in Ischemia/Reperfusion (I/R) injury-treated neuronal cell. However, the effect and underlying mechanism of miR-323 in I/R-induced neuronal cell death remains poorly understood. The current study was aim to investigate the role and molecular basis of miR-323 in I/R-induced neuronal cell. Methods: An oxygen-glucose deprivation (OGD) model of hippocampal neuron I/R was produced in vitro. Cell apoptosis, cell survival, and the expression of miR-323 were determined after 6 h, 12 h and 24 h after OGD treatment. The up- or down-regulation of miR-323 was performed by miR-323 mimics or anti-miR-323, respectively. Results: OGD induced apoptosis and suppressed survival in rat hippocampal neurons. And the expression levels of miR-323 were increased after OGD treatment. Furthermore, the up-regulation of miR-323 promoted apoptosis and suppressed survival, whereas the inhibition of miR-323 suppressed apoptosis and enhanced survival in OGD-treated neurons. Moreover, miR-323 could directly bind to BRI3 3’-UTR. Notably, the knockdown of BRI3 by BRI3 siRNA apparently abrogated cell survival and induced cell apoptosis in rat neurons. Conclusion: This study indicated that miR-323 might regulate ischemia/reperfusion-induced rat neuronal cell death via targeting BRI3.     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

Salivary gland transplantation for dry eye disease: Indications,techniques, and outcomes

The transplantation of salivary glands to the eye serves as a substitute for restoring tear volume in patients with severe dry eye disease. The lacrimal gland and salivary glands share similar acinar-ductal organization with some differences in the nature of secretions. This review summarizes the comparative anatomy of salivary and lacrimal glands, various salivary gland transplantation techniques, their indications, outcomes and complications along with future perspectives. Autologous microvascular submandibular gland transplantation (SMGT) into the temporal fossa with duct placement into the conjunctival fornix improves tear volume considerably but provides a hyposmolar tear film, which can induce corneal edema (in 3.5-40% of eyes). The transplanted submandibular graft improves tear volume and stability but visual acuity and conjunctival inflammation remain unchanged. The transplanted submandibular gland maintains stable function in the long-term and can have hypersecretion in 24–60% secondary to persistent autonomic innervation. Partial SMGT, gland reduction surgery, topical atropine gel or Botulinum Toxin A injection are options for treatment of postoperative epiphora. Minor salivary gland transplantation (MSGT) into the upper and/or lower conjunctival fornix results in an average improvement of 2–4 mm in Schirmer values compared to 16 to > 30 mm observed in eyes after SMGT. Reflex epiphora is rarely a problem in MSGT. Both MSGT or SMGT can improve the ocular surface and quality of life of patients with severe, debilitating dry eye disease. However, postoperative visual acuity and outcomes of corneal transplantation are still inconsistent. More studies and additional technical improvements are needed to further improve the results of these procedures.