Myeloproliferative neoplasms

The myeloproliferative neoplasms (MPN) are a group of clonal myeloid proliferations characterised by varying combinations of increased circulating red cells, granulocytes and platelets caused by excess proliferation of haemopoietic precursors in bone marrow with retained cellular maturation. These disorders typically pursue an indolent course requiring management of the consequences of the increased circulating elements (predominantly effects of thrombosis of haemorrhage in different body organs). Patients have complex symptoms, including fatigue, which are not yet fully explained. The MPN carry varying risks of progression to an acute phase characterised by increasing bone marrow and circulating blasts cells, and/or to fibrosis characterised by falling peripheral cell counts and increasing splenomegaly. Megakaryocyte morphology in BMT samples provides essential clues for diagnosis and subtyping in MPN; high quality and consistent reticulin staining for accurate assessment is also key.     

转化生长因子β1缓释微球对体外P3/4HB无纺支架细胞生长的影响

目的:研究转化生长因子β2(TGF-β1)壳聚糖缓释微球对体外3-羟基丁酸酯-co-4-羟基丁酸酯(P3/4HB)无纺支架培养肌成纤维细胞的作用.方法:静电纺丝法制备P3/4HB无纺支架,接种大鼠肌成纤维细胞.在实验组培养基中分别加入TGF-β1.缓释微球和TGF-β1,体外培养1周后行扫描电镜观察,检测羟脯氨酸和DNA含量;并用ELISA法动态检测TGF-β1缓释微球缓释效果.结果:TGF-β1可从缓释微球中缓慢释放,1周内微球释放率为40.6%.与对照组比较,实验组细胞生长紧密,羟脯氨酸及DNA含量增高.结论:TGF-β1壳聚糖缓释微球可在体外稳定释放,并具有生物学活性;其运用于P3/4HB无纺支架,可促进细胞增殖和胶原合成,为研究为制备携带壳聚糖TGF-β1缓释微球的组织工程复合支架打下了良好的基础.     

Utilizing the McGill Thyroid Nodule Score to compare between hemithyroidectomy cases who required completion thyroidectomy and cases of hemithyroidectomy alone

ObjectivesThis study aims to evaluate whether the McGill Thyroid Nodule Score (MTNS) accurately helps to decide the extent of surgery (hemithyroidectomy versus total thyroidectomy) based on the malignancy risk and to assess whether its use lowers the rate of completion thyroidectomy in cases of indeterminate thyroid nodules.MethodsWe performed a retrospective cohort study comparing MTNS results of patients undergoing hemithyroidectomy in King Abdulaziz Medical City, NGHA, Jeddah from the period of January 2013 to December 2017. We divided the cases into hemithyroidectomy who required completion and hemithyroidectomy who did not need completion surgery. The pre-operative indeterminate FNA biopsy subgroup comprised of Bethesda type III (atypia of undetermined significance/follicular lesion of undetermined significance) and Bethesda type IV (follicular neoplasm/suspicious for a follicular neoplasm/Hurthle cell neoplasm). Post-operative histopathology was divided into benign or malignant groups.ResultsOf the 501 patient charts reviewed, 111 (22.2%) had an indeterminate FNA biopsy. 97 (87.4%) patients were females and 14 (12.6%) were males. In the hemithyroidectomy group, the pre-operative mean of the MTNS was 6.65, while in the completion thyroidectomy the mean was 11.47. The median MTNS was 7 (32% risk of malignancy) for the hemithyroidectomy group and 11 (63% risk of malignancy) for the completion thyroidectomy group (p < 0.001).ConclusionsBased on the MTNS the risk of malignancy in cases of hemithyroidectomy who required completion surgery was significantly higher than those who underwent hemithyroidectomy only. The MTNS can be of value to thyroid surgeon in the pre-operative decision-making when dealing with an indeterminate thyroid nodule on FNA biopsy.     

Risk Factors for Dysphagia after Anterior Cervical Discectomy and Fusion with the Zero‐P implant system: A Study with Minimum of 2 Years Follow‐up

ObjectiveTo evaluate the risk factors for dysphagia after anterior cervical discectomy and fusion (ACDF) with the Zero‐P Implant System by multidimensional analysis and investigated the predictive values of these risk factors for dysphagia.MethodsA retrospective analysis of 260 patients who underwent ACDF with the Zero‐P Implant System and had at least 2 year of follow‐up were performed. All patients were divided into a non‐dysphagia group and a dysphagia group. Sex, age, body mass index (BMI), intraoperative time, estimated blood loss, diabetes mellitus, hypertension, smoking, alcohol consumption, prevertebral soft‐tissue thickness, the levels of surgery, O‐C₂ angle, C_2–7 angle, T₁ slope and segmental angle were analyzed. The Modified Japanese Orthopaedic Association (JOA) scoring system was used to determine functional status. NDI was used to evaluate neck pain and disability. The Bazaz grading system was chosen to evaluate dysphagia after surgery. Postoperative cerebrospinal fluid (CSF) leakage, infection, and dysphagia were recorded in both groups. An independent t‐test was used to compare quantitative variables, a chi‐square test was used to compare qualitative data between the two groups. To eliminate the influence of confounding factors, logistic regression was performed for multifactor regression of factors. The results were regarded as significant when the P‐values were less than 0.05 in this study.ResultsIn total, the non‐dysphagia group comprised 70 patients and the dysphagia group comprised 190 patients, with an average age of 58.33 ± 4.68 years (ranging, 42–82 years). These patients were followed up for 28.5 ± 3.5 months (range, 24–32 months). For clinical outcomes, both groups demonstrated significant improvement in the NDI and JOA scores (P < 0.001). According to the Bazaz dysphagia grading system, mild, moderate, and severe dysphagia were found in 50, 17, and 3 patients, respectively. In total, 37.1% (n = 26) had resolved by 3 month, 38.6% (n = 27) by 6 months, and 17.1% (n = 12) by 12 months. Chi‐square test results indicated that number of operated levels, operation time dT1 slope, dO‐C₂ angle, dC_2–7 angle, segmental angle and dPSTT were associated with a high incidence of dysphagia. Multivariate logistic regression analysis showed that number of operated levels, operation time, dC_2–7 angle and dPSTT were significantly associated with postoperative dysphagia.ConclusionsMore operated levels, more operation time, more dC_2–7 angle and dPSTT were the risk factors for postoperative dysphagia. In additional, sufficient preoperative preparation, evaluation combined with proficient and precise surgical treatment were suggested to reduce the incidence of postoperative dysphagia when ACDF was performed.     

Fast-Acquiring High-Quality Prony Series Parameters of Asphalt Concrete through Viscoelastic Continuous Spectral Models

Prony series representations have been extensively applied to characterizing the time-domain linear viscoelastic (LVE) material functions for asphalt concrete. However, existing methods that can generate high-quality Prony series parameters (i.e., discrete spectra) mostly involve complicated programming algorithms, which poses a challenge for quick access of Prony series parameters. Also, very limited research has been devoted to establishing methods for simultaneously determining both retardation and relaxation spectra. To resolve these issues, this study presented a practical approach to fast acquiring high-quality Prony series parameters for both relaxation modulus and creep compliance of asphalt concrete by using the complex modulus test data. The approach adopts the analytical representations of the continuous relaxation and retardation spectra from the Havriliak-Negami (HN) and 2S2P1D complex modulus models to directly determine the discrete spectra, and the elastic constants, E_e and D_g, for both LVE modulus and compliance functions are further calculated by fitting the corresponding generalized Maxwell model representations to smoothed data from the storage modulus representations of the HN and 2S2P1D complex modulus models. In this way, all the procedures in the proposed method can be easily implemented in Microsoft Excel. The results showed that the HN and 2S2P1D models yielded slightly different continuous spectral patterns at shorter relaxation times and longer retardation times. However, at the region covered by the test data, the continuous spectra of the two complex modulus models were very close to each other. Thus, the two models can generate comparable Prony series parameters within the time or frequency range covered by the test data. Considering that the quality of the resulting Prony series parameters are closely related to the master curve models used for presmoothing, the HN and 2S2P1D models were compared with the conventional Sigmoidal model. Additionally, the Black diagram was recommended for examining the quality of the complex modulus test data before constructing the master curves.     

P38 MAPK激活在高血糖致大鼠微血管通透性增高过程中的作用

目的研究P38 MAPK信号传导通路在糖尿病大鼠微血管内皮细胞通透性增高中的作用机制。方法SD雄性大鼠,腹腔注射链脲佐菌素(STZ 55 mg/kg)制备糖尿病模型。分正常组、糖尿病组、溶剂对照组、MKK6b(A)组和MKK6b(E)组。溶剂组:给予相同容量的柠檬酸缓冲液;MKK6b(A)组:在糖尿病模型基础上,实验前24 h尾静脉注射MKK6b(A)2.5 mL/kg;MKK6b(E)组:在实验前24 h给正常大鼠尾静脉注射MKK6b(E)2.5 mL/kg。用荧光强度检测微血管通透性;用荧光染色法观察微血管内皮细胞骨架蛋白的形态。结果糖尿病大鼠的微血管通透性明显高于正常组;注射MKK6b(E)可以增高大鼠微血管的通透性,而注射MKK6b(A)后微静脉的高通透性则被抑制。结论P38 MAPK信号转导系统参与介导了糖尿病微血管通透性增高的反应过程。     

Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5–100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25–10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.     

感觉神经肽P物质在糖尿病大鼠皮肤损伤修复中的应用

目的 观察外源性感觉神经肽P物质(SP)在糖尿病大鼠皮肤伤口愈合中的作用.方法 链脲佐菌素(STZ)致糖尿病大鼠48只,行鼠背部脊柱两侧皮肤切割伤口后,随机分为实验组与对照组,每组24只.实验组伤后在伤口四周注射10-7mol/L的SP,每日2次,每个伤口 200μl/次,连续注射4天;对照组注射等量SP溶剂生理盐水.伤后4、7、10、14、17、21天用透明膜描记法记录伤口愈合面积,伤后4、7、10天取材检测肉芽组织羟脯氨酸总量和Ⅰ型、Ⅲ型胶原含量.结果 实验组在伤后4、7、10、14天伤口愈合面积明显高于对照组(P<0.01),愈合时间比对照组缩短1周;伤后4、7、10天肉芽组织中羟脯氨酸含量、Ⅰ型、Ⅲ型胶原含量明显高于对照组(P<0.01).结论 应用外源性SP明显促进糖尿病大鼠皮肤创伤愈合.     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.