多西他赛联合卡培他滨方案在新辅助化疗三阴乳腺癌与非三阴乳腺癌中的近期疗效观察

目的探讨三阴乳腺癌(triple-negative breast cancer,TNBC)与非三阴乳腺癌患者应用多西他赛联合卡培他滨(DX)方案行新辅助化疗的临床疗效及不良反应。方法选择2008年7月—2013年8月收治的102例乳腺癌患者,其中TNBC 27例,非TNBC75例,均应用DX方案新辅助化疗。观察临床疗效和毒副反应发生情况。结果TNBC患者总有效率与非TNBC患者比较差异无统计学意义(P>0.05)。TNBC患者病理完全缓解率、临床完全缓解率高于非TNBC患者(P<0.01,P<0.05)。毒副反应主要表现为胃肠道反应、骨髓抑制及手足综合征等,TNBC与非TNBC患者毒副反应发生率比较差异无统计学意义(P>0.05)。结论 TNBC患者较非TNBC患者对DX方案新辅助化疗更敏感,且未增加毒副反应发生率。     

Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.     

VVS患者心率变异性、CK、CK-MB变化及治疗前后变化的意义

目的：探讨血管迷走性晕厥(VVS)患者的心率变异性指标、血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)的变化及其临床意义。方法：选取我院心血管内科收治的VVS患者67例作为VVS组、领选取70例同龄健康体检对象作为对照组;对比两组的心率、超声心动图参数、心率变异性指标及血清CK、CK-MB水平,并对比67例患者在接受射频导管消融术治疗前后的上述指标变化情况。结果：VVS组患者的最大心率与对照组差异无统计学意义;VVS组患者的最慢心率、平均心率均低于对照组;VVS组的心率总体标准差、差值标准差、差值均方根均高于对照组;VVS组患者的左心房前后径、左心室舒张末内径、左心室射血分数与对照组差异无统计学意义;VVS组患者的血清CK、CK-MB均低于对照组;经射频导管消融术治疗后,VVS组患者的平均心率较治疗前提高;VVS组的心率总体标准差、差值标准差、差值均方根均较治疗前降低;经射频导管消融术治疗后,VVS组血清CK、CK-MB均较治疗前提高。结论：VVS患者的心率变异性更加明显、血清CK、CK-MB水平降低,采用射频导管消融术治疗能显著改善患者的心率变异性。     

SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons

AimsPotassium (K⁺) channels have been demonstrated to play a prominent involvement in nociceptive processing. Kir7.1, the newest members of the Kir channel family, has not been extensively studied in the CNS, and its function remains largely unknown. The present study investigated the role of spinal Kir7.1 in the development of pathological pain.Methods and ResultsNeuropathic pain was induced by spared nerve injury (SNI). The mechanical sensitivity was assessed by von Frey test. Immunofluorescence staining assay revealed that Kir7.1 was predominantly expressed in spinal neurons but not astrocytes or microglia in normal rats. Western blot results showed that SNI markedly decreased the total and membrane expression of Kir7.1 in the spinal dorsal horn accompanied by mechanical hypersensitivity. Blocking Kir7.1 with the specific antagonist ML418 or knockdown kir7.1 by siRNA led to mechanical allodynia. Co‐IP results showed that the spinal kir7.1 channels were decorated by SUMO‐1 but not SUMO‐2/3, and Kir7.1 SUMOylation was upregulated following SNI. Moreover, inhibited SUMOylation by GA (E1 inhibitor) or 2‐D08 (UBC9 inhibitor) can increase the spinal surface Kir7.1 expression.ConclusionSUMOylation of the Kir7.1 in the spinal cord might contribute to the development of SNI‐induced mechanical allodynia by decreasing the Kir7.1 surface expression in rats.     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

The effectiveness of Salvianolate injection for in-stent restenosis after percutaneous coronary intervention: A protocol for systematic review and meta-analysis

Background:In-stent restenosis (ISR) caused by vascular remodeling after percutaneous coronary intervention limits the long-term efficacy of this method. Salvianolate injection is now widely used in the clinical treatment of ISR. However, there is no systematic review or meta-analysis to evaluate the effects of Salvianolate injection on ISR.Methods:We will search articles in 8 electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Database, and the Chinese Scientific Journal Database for randomized controlled trials of ISR treated by Salvianolate injection from their inception to February 27, 2022. The primary outcome measure will be the restenosis rate. The data meeting the inclusion criteria were analyzed by RevMan V.5.4 software. Two authors evaluated the study using the Cochrane collaborative risk bias tool. We will use a scoring method to assess the overall evidence supporting the main results.Results:This study will analyze the clinical effectiveness of Salvianolate injection in the treatment of ISR.Conclusion:The findings of this systematic review will provide evidence to evaluate the effectiveness of Salvianolate injection for the treatment of ISR.INPLASY registration number:INPLASY202220117.     

Combined prognostic value of preoperative serum thyrotrophin and thyroid hormone concentration in papillary thyroid cancer

BackgroundA growing number of studies have found a close association between thyroid hormones and thyrotrophin (TSH), and they also have prognostic significance in some cancer types; this study aimed to investigate the prognostic value of free triiodothyronine (fT3), free thyroxine (fT4), fT3/fT4, TSH, and their combination in patients with papillary thyroid carcinoma (PTC).MethodsThis study retrospectively analyzed the relevant data of 726 newly diagnosed PTC patients. Both univariate and multivariate analyses were used to predict the recurrence rate, and a risk score was established. In addition, with the use of a random survival forest, a random forest (RF) score was constructed. After calculating the area under the curve (AUC), the diagnostic efficacy of risk score, RF score, and four indicators was compared.ResultsfT3, fT4, fT3/fT4, and TSH were strongly associated with some invasive clinicopathological features and postoperative recurrence. Patients with high expression of fT4 and TSH have a high risk of recurrence. By contrast, patients with high expression of fT3 and fT3/fT4 have a low risk of recurrence. At the same time, the combined use of various indicators is more helpful for establishing an accurate diagnosis. By comparison, we found that the RF score was better than the risk score in terms of predicting the recurrence of PTC.ConclusionThe diagnostic accuracy of a combination of fT3, fT4, fT3/fT4, and TSH can help improve our clinical estimate of the risk of recurrent PTC, thus allowing the development of a more effective treatment plan for patients.     

Preparation and photodynamic antibacterial/anticancer effects of ultralong-lifetime room-temperature phosphorescent N-doped carbon dots

Room-temperature phosphorescent (RTP) N-doped carbon-dots (CNDs) featuring eco-friendliness, low cost and high biocompatibility, are ideal photodynamic antibacterial and anticancer nanomaterials. However, the existing CNDs are limited by low singlet oxygen (¹O₂) quantum yield, which has become a bottleneck in the development of CNDs. One basic reason is the short T₁-state exciton lifetime of CNDs. Herein, triethylenetetramine hexaacetic acid was used to synthesize CNDs via a one-step hydrothermal method. CNDs are characterized with low toxicity, high biocompatibility and ultralong-lifetime RTP (URTP). In addition to the URTP (average lifetime 414 ms) under solid conditions, CNDs even had URTP (average lifetime 320 ms) in a water environment. The ultralong T₁ exciton lifetime largely extends the collision time between T₁ state excitons and O₂ and prolongs the energy transfer time, not only improving the quantum yield (0.63) of singlet oxygen (¹O₂) in solution, but also facilitating the photodynamic antibacterial and anticancer effects.

The URTP CNDs largely extends the collision time between T₁ state exciton and O₂, which improve quantum yield of singlet oxygen (¹O₂) in solutions, facilitating the photodynamic antibacterial and anticancer effects.     

成年功能性构音障碍患者辅音错误类型及方式分析

目的 探讨成年功能性构音障碍患者辅音发音错误的特点,为制定语音训练方案提供依据.方法以42例成年功能性构音障碍患者为研究对象,借助计算机语音工作站对患者进行语音评估,对其辅音的发音错误类型及方式进行分析.结果42例成年功能性构音障碍患者主要的辅音发音错误类型为置换、扭曲,其次为脱落.按发音部位,错误辅音依次为舌尖后音(39例,92.86%)、舌尖前音(31例,73.81%)、舌面音(22例,52.38%)、舌根音(19例,45.24%)、舌尖中音(18例,42.86%)、唇齿音(6例,14.29%)及双唇音(6例,14.29%);辅音错误频率由高至低依次为/sh/、/zh/、/ch/、/r/、/z/、/c/、/s/、/q/、/x/、/j/、/g/、/k/、/h/、/t/、/l/、/d/、/f/、/p/.辅音错误方式有:舌前音化(22例,52.38%)、非送气化(12例,28.57%)、侧化构音(12例,28.57%)、辅音脱落(9例21.42%)、舌后音化(8例,19.05%)、舌面音化(4例,9.52%)、双唇音化(4例,9.52%)、唇齿音化(3例,7.14%).结论成年功能性构音障碍患者的辅音发音错误类型主要是置换和扭曲;错误辅音主要为舌尖后音、舌尖前音、舌面音、舌根音、舌尖中音;辅音发音错误方式主要为舌前音化、非送气化、侧化构音、辅音脱落.