重组人表皮生长因子凝胶联合CO2点阵激光治疗增生性瘢痕的效果观察

目的观察重组人表皮生长因子凝胶联合CO₂点阵激光治疗烧伤及创伤后增生性瘢痕的临床效果。 方法选择2020年12月至2021年10月安徽医科大学第一附属医院烧伤与创面修复外科收治的20例增生性瘢痕患者，按照随机数字表法将患者分为联合治疗组及单纯激光治疗组，每组10例。术前均对2组患者术区进行拍照存像、消毒、擦干，局部均匀涂抹5%复方利多卡因乳膏后以无菌薄膜封闭保护60 min，擦去乳膏后再次消毒术区。术中使用CO₂点阵激光治疗仪对患者瘢痕部位进行扫描，根据患者增生性瘢痕厚度选定合适的机器参数，维持机器频率300 Hz及密度5%，在20～30 J调整能量参数的大小，时间间隔1 s，保证点阵矩形完全覆盖增生瘢痕，允许2次激光形成的热损伤矩阵之间存在25%面积的重叠。术后即刻冷敷创面60 min，冷敷结束至术后1周，单纯激光治疗组不外用任何药物，联合治疗组术区加用重组人表皮生长因子凝胶外用，3次/d。术后3 d治疗部位不碰水，若出现感染情况，可以加用抗生素软膏，点状损伤创面外痂皮未掉落完全时禁止擦洗创面，禁止直接剥除痂皮，禁止术区涂抹化妆品等，避免接受阳光直射。于第1次激光治疗后2个月进行第2次激光治疗，以2次CO₂点阵激光治疗为1个疗程，1个疗程治疗后间隔2个月待术区稳定后行疗效判断，计算2组患者治疗的总有效率；根据温哥华瘢痕量表(VSS)与患者与观察者瘢痕评估量表(POSAS)对患者治疗前、第1次激光治疗后2个月、第2次激光治疗后2个月瘢痕的各项指标进行评分。数据比较采用重复测量方差分析和χ²检验。 结果(1)治疗1个疗程后2个月，单纯激光治疗组与联合治疗组患者治疗的总有效率分别为80%(8/10)、90%(9/10)，2组间比较差异无统计学意义(χ²＝2.40，P＝0.49)。(2)对2组VSS评分的各项指标进行比较，其中疼痛、瘙痒、柔软度及厚度评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中色泽评分分别为(1.9±0.7)、(1.9±0.1)、(1.8±1.0)分，联合治疗组分别为(2.9±0.7)、(2.8±0.6)、(1.9±0.7)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.143，P<0.05)；2组组间不同时相点比较，差异有统计学意义(F＝6.753，P＝0.018)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中血管分布评分分别为(1.8±1.0)、(1.7±0.7)、(1.5±1.0)分，联合治疗组分别为(2.6±0.5)、(2.5±0.5)、(1.7±0.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝17.603，P<0.05)，2组组间不同时相点比较，差异无统计学意义(F＝ 2.538，P＝0.129)。(3)对2组POSAS评分的各项指标进行比较，其中厚度、粗糙度、柔软度和表面积评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中色泽评分分别为(4.9±2.6)、(4.1±0.8)、(3.5±2.0)分，联合治疗组分别为(7.6±1.1)、(6.8±1.4)、(5.4±1.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.509，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 8.973，P＝0.008)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中血管分布评分分别为(4.4±2.1)、(3.9±0.9)、(3.5±1.6)分，联合治疗组分别为(6.3±1.1)、(5.7±2.0)、(4.5±1.6)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 20.118，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 5.744，P＝0.028)。 结论重组人表皮生长因子凝胶联合CO₂点阵激光及单独使用CO₂点阵激光治疗增生性瘢痕均效果明确，但联合使用重组人表皮生长因子凝胶能有效促进创面愈合、改善瘢痕组织血管分布和减少局部色素沉着。     

Arterial spin labeling MR image denoising and reconstruction using unsupervised deep learning

Arterial spin labeling (ASL) imaging is a powerful magnetic resonance imaging technique that allows to quantitatively measure blood perfusion non-invasively, which has great potential for assessing tissue viability in various clinical settings. However, the clinical applications of ASL are currently limited by its low signal-to-noise ratio (SNR), limited spatial resolution, and long imaging time. In this work, we propose an unsupervised deep learning-based image denoising and reconstruction framework to improve the SNR and accelerate the imaging speed of high resolution ASL imaging. The unique feature of the proposed framework is that it does not require any prior training pairs but only the subject's own anatomical prior, such as T1-weighted images, as network input. The neural network was trained from scratch in the denoising or reconstruction process, with noisy images or sparely sampled k-space data as training labels. Performance of the proposed method was evaluated using in vivo experiment data obtained from 3 healthy subjects on a 3T MR scanner, using ASL images acquired with 44-min acquisition time as the ground truth. Both qualitative and quantitative analyses demonstrate the superior performance of the proposed txtc framework over the reference methods. In summary, our proposed unsupervised deep learning-based denoising and reconstruction framework can improve the image quality and accelerate the imaging speed of ASL imaging.     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

Diagnosis of pituitary abscess and treatment via transsphenoidal surgery: experience from 15 cases

ObjectivePituitary abscess is an often misdiagnosed, rare clinical disorder. To improve diagnostic accuracy and the efficacy of surgical and antibiotic therapy for patients with pituitary abscess, herein, we retrospectively reviewed 15 patients who presented with pituitary abscesses from 2005 to 2022.DesignRetrospective study.PatientsFifteen patients underwent transsphenoidal surgery and received antibiotic treatment.MeasurementsComplete details regarding medical history, clinical manifestations, laboratory examinations, imaging studies, and treatment strategies were obtained for all patients.ResultsMost patients presented with hypopituitarism and headaches, while some presented with fever, visual disturbances, and diabetes insipidus (DI). Abscesses showed significant annular enhancement post gadolinium injection. In most patients, pituitary abscess can be cured via microscopic or endoscopic drainage of the abscess followed by antibiotic treatment. Complete cure of pituitary abscess was observed in nine patients, with six cases of prolonged hypopituitarism and only one case of recurrence. Long-term hormone replacement therapy was effective in the postoperative management of hypopituitarism.ConclusionsThe typical manifestations of pituitary abscess include hypopituitarism and headaches; the presence of an enhanced ring at the edge of the mass on contrast-enhanced magnetic resonance images (MRI) is highly suggestive of pituitary abscess. We recommend antibiotic treatment for 4–6 weeks postoperatively, based on the results of bacterial cultures or metagenomic next-generation sequencing (mNGS).     

Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

ω-3多不饱和脂肪酸对慢性移植物抗宿主病狼疮小鼠的免疫调控作用

目的探讨ω-3多不饱和脂肪酸(ω-3 poly unsaturated fatty acids,ω-3 PUFAs)对慢性移植物抗宿主病(chronic graft versus host disease,cGVH)狼疮模型小鼠的免疫调节功能影响。方法单次腹腔注射bm12小鼠淋巴细胞建立cGVH小鼠模型,造模当天分别给予90%ω-3 PUFAs和97%EPA灌胃治疗,持续14 d。通过流式细胞术检测小鼠脾脏淋巴细胞中各免疫指标,ELISA检测小鼠血清中总IgG水平。结果与正常对照组相比,cGVH组明显下调Treg亚群,明显上调T_FH细胞、生发中心B细胞和浆细胞亚群;与模型对照组相比,90%ω-3和97%EPA均明显上调Treg亚群,并明显下调T_FH细胞、生发中心B细胞和浆细胞亚群;且97%EPA组小鼠血清中总IgG水平明显下降。结论在cGVH狼疮小鼠模型中,ω-3 PUFAs通过增加Treg细胞,减少T_FH细胞、生发中心B细胞和浆细胞,抑制IgG的分泌,从而发挥免疫抑制作用,且其免疫抑制作用可能与ω-3 PUFAs含量相关。