Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while β-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of β-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of β-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of β-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.     

澳大利亚护理硕士专业学位人才培养现状及启示

通过比较我国与澳大利亚护理硕士专业学位研究生人才培养项目在办学规模、师资情况、教育模式、课程设置、临床实践与评估、毕业要求方面的现状,提出了立足我国实际的教学改革建议,为完善具有中国特色的护理硕士专业学位研究生教育培养体系,培养健康中国建设所需要的高级护理人才提供参考。     

LAT1表达水平与非肌层浸润性膀胱癌患者术后复发风险的相关性研究

目的：探讨L型氨基酸转运蛋白1(L-type amino acid transporter 1,LAT)表达水平与非肌层浸润性膀胱癌患者术后复发风险的相关性。方法：选取2021年2月至2022年2月于重庆医科大学附属永川医院接受手术治疗的非肌层浸润性膀胱癌患者108例作为研究对象,采用反转录酶聚合酶链反应测定膀胱癌组织(取自肿瘤所在部位区域)和癌旁组织(取自邻近正常区域组织)LAT1表达含量,对比膀胱癌组织和癌旁组织LAT1表达水平。同时根据膀胱癌组织LAT1表达含量的二分位数将所有患者分为高表达组和低表达组,对比2组临床病理参数。随访观察12个月观察2组术后复发情况,采用Kaplan-Meier曲线分析对比2组术后复发风险,使用多变量Cox比例风险回归模型确定术后复发的影响因素。结果：膀胱癌组织LAT1表达水平(1.80±0.35)较配对的癌旁组织LAT1表达水平(1.05±0.17)高(P<0.05);LAT1高表达组吸烟史、临床分期T₁占比较LAT1低表达组高(P<0.05);108例膀胱肿瘤患者术后的平均随访时间为(10.84±1.94)个月,...     

Simplified Chinese Version of the Spinal Instability Neoplastic Score in Evaluating Patients with Metastatic Spinal Tumor: A Cross‐Cultural Adaptation and Validation

ObjectiveTo translate the original English version of the Spinal Instability Neoplastic Score (SINS) into simplified Chinese, adapt it cross‐culturally, validate its psychometric properties in measuring spinal instability in patients with metastatic spinal tumors in the Chinese mainland, examine the reliability and validity to demonstrate its accuracy and applicability in clinical practice.MethodsPatients diagnosed with metastatic spinal disease between January 2016 and January 2020 were recruited. The number of participants was advised to be at least 50 for appropriate analysis of reliability, construct validity, as well as ceiling or floor effects, and recruitment of 100 patients was advised for internal consistency analysis. The study was conducted in two phases: first, the SINS was translated into simplified Chinese; second, the factor structure, internal consistency, test–retest reliability, validity, and floor and ceiling effects of the SC‐SINS were assessed. The internationally recognized cross‐cultural adaptation guidelines were followed. Internal consistency was evaluated with Cronbach''s alpha. Test–retest reliability was examined among the patients with a 4‐week interval. The validity of the Chinese version of SINS (SC‐SINS) was assessed by examining its relationship with Kostuik classification. Principal component analysis was conducted to confirm the factor structure of each subscale.ResultsA total of 160 participants (88 males and 72 females) were enrolled. No major difficulties occurred in the forward and backward translations of SINS. The internal consistency of SC‐SINS was excellent (Cronbach''s α =0.857, ranging from 0.68 to 0.85). Test–retest reliability was also excellent with a value of 0.89, ranging from 0.86 to 0.95. Validity analyses indicated that the SC‐SINS was positively and significantly correlated with Kostuik classification. The correlation between “Posterolateral Involvement of Spinal Elements” and “1‐2 Partial Damage” was the highest with a correlation value of 0.792. The correlation between “Pain” and “1–2 Partial Damage” was the lowest with a value of 0.341. All items showed principal component coefficients greater than 0.4. The values of Factor 1 ranged from 0.523 to 0.681; Factor 2 ranged from 0.591 to 0.731; Factor 3 ranged from 0.613 to 0.754; Factor 4 ranged from 0.461 to 0.711; Factor 5 ranged from 0.513 to 0.701; and Factor 6 ranged from 0.501 to 0.668. In addition, neither floor nor ceiling effects were seen in the SC‐SINS.ConclusionThe SC‐SINS demonstrated high internal consistency and test–retest reliability, which has been proven valid and reliable to measure spinal stability in patients from the Chinese mainland with metastatic spinal tumor.     

The novel infra‐pectineal buttress plates used for internal fixation of elderly quadrilateral surface involved acetabular fractures

ObjectivesIn geriatric acetabular fractures, the quadrilateral surface (QLS) was frequently involved in acetabular fracture patterns and accompanied by medial displacement. It was important to buttress the medial displaced QLS and reconstruct the congruity of the affected acetabulum. To evaluate the clinical effectiveness of the novel infra‐pectineal quadrilateral surface buttress plates for the treatment of geriatric acetabular fractures.MethodsTwenty‐three geriatric patients who were treated for acetabular fractures involving QLS with the novel infra‐pectineal buttress plates (NIBP) through a single supra‐ilioinguinal approach between January 2015 and June 2019 were retrospectively analyzed; all patients received at least 1 year''s follow‐up. All patients were aged ≥60 years old and including 18 males and five females. Radiologic and clinical outcomes of patients involved in the study were collated and analyzed according to the Matta scoring system and the Merle D''Aubigné–Postel scoring system. The functional recovery scoring was compared using q‐test.ResultsAll 23 consecutive patients had relatively satisfactory clinical treatment effectiveness. Average ages, length of incision, operation time, and intraoperative blood loss were 69.8 ± 6.1 years, 12.1 ± 2.6 cm, 166.5 ± 43.5 min, and 500 (500,700) ml, respectively. According to the Matta scoring system, 14 cases of reduction were graded as excellent, five as good, and four as fair. At the last follow‐up, the clinical outcome evaluation was excellent in 13 cases, good in seven cases, and poor in three cases with the use of the Merle D''Aubigné–Postel scoring system. The difference of modified Merle D''Aubigne‐Postel score at 3 months, 6 months and last follow up was statistically significant (F = 21.56, p < 0.05). Postoperative lateral femoral cutaneous nerve injury occurred in three patients and heterotopic ossification occurred in one patient.ConclusionsFor the treatment of geriatric acetabular fractures, the NIBP could provide stable and effective fixation to the QLS involved acetabular fractures, and related satisfactory clinical results with few complications were noted.     

The Butterfly Fragment in Wedge‐Shaped Femoral Shaft Fracture: Comparison of Two Different Surgical Methods

ObjectiveOur study compared the results of wedge‐shaped femoral shaft fracture following intramedullary (IM) nailing with or without fixation of the third fragment.MethodsWe retrospectively reviewed patients presenting with femoral shaft fracture with AO/OTA type 32‐B from 2011 to 2016. Patients were divided into two groups: closed reduction without touching the third fragment and open reduction with fixation of the third fragment. The fragment ratio, fragment length, nail size, dynamization or not, mRUST scores, union rate, and union time were compared between the two groups. Risk factors of non‐union were also investigated, including sex, age, fracture pattern, fracture location, dynamization, nail size, fragment ratio, fragment size, and postoperative fragment displacement.ResultsA total of 80 patients met inclusion criteria, 20 patients with wedge‐shaped shaft femoral fracture were managed with IM nailing and open reduction with fixation of the third fragment. Sixty patients were treated with IM nail without touching the third fragment. The union rate for the fixation and non‐fixation groups were 60.0% and 81.7%, respectively. The mean union time for the fixation group was 19 months vs 14 months for the non‐fixation group. Multi‐regression analysis showed larger nail size (odds ratio: 2.26) and fixation of the third fragment (odds ratio: 0.18) influenced fracture healing.ConclusionsFixation of the third fragment in wedge‐shaped shaft femoral fracture results in a longer union time and lower union rate. In the management of femoral fracture with a third fragment, a larger nail size is recommended and fixation should be performed in a closed manner. Fixation of the fragment may achieve better fracture reduction. However, disruption of the vasculature and surrounding structures may further result in nonunion of the fracture site.     

解毒生肌膏调控GSK-3β/β-catenin减轻炎症反应促糖尿病SD大鼠慢性创面修复的影响

目的 从GSK-3β/β-catenin角度探讨炎症反应对糖尿病SD大鼠慢性创面修复的影响。方法 使用高脂饲料喂养联合腹腔注射链脲霉素（Streptozocin,STZ）及手术制备全层皮肤缺损的方法建立糖尿病SD大鼠创面模型,成模后随机分为模型组（n=15）,磺胺嘧啶银组（n=15）及解毒生肌膏组（n=15）,并设立正常创面组（n=15）。磺胺嘧啶银组创面和解毒生肌膏组创面予以磺胺嘧啶银软膏和解毒生肌膏外敷,每日1次,模型组与正常创面组不予干预。给药后第3天、7天和14天肉眼观察各组大鼠的创面愈合情况,计算创面愈合率;HE观察组织基本形态;Masson检测胶原生成情况;超微电镜观察内质网结构差异;免疫组织化学法检测肿瘤坏死因子-α（Tumor necrosis factor-α,TNF-α）和白细胞介素-6（Interleukin-6,IL-6）表达;蛋白质免疫印迹法检测糖原合成酶激酶-3β（glycogen synthase kinase-3β,GSK-3β）蛋白和β-连环蛋白（β-catenin）蛋白表达。结果 给药后3天解毒生肌膏组创面愈合率高于模型组（P<0.05）;给药后14天解毒生肌膏组创面愈合率高于磺胺嘧啶银组（P<0.05）。HE结果 给药后3、7天解毒生肌膏组创面较其他组肿胀程度较小,毛细血管数量丰富;14天,解毒生肌膏组和正常创面组出现皮肤附属器新生,组织结构完整度好。Masson结果 解毒生肌膏组较其他各组胶原纤维分布均匀,排列结构较为整齐,新生胶原纤维更为粗壮,分布均匀,排列整齐。电镜结果：解毒生肌膏组内质网丰富,数量较多,形态结构趋于正常。免疫组织化学法结果：与模型组相比,各组TNF-α、IL-6表达水平明显降低;解毒生肌膏组TNF-α表达水平低于正常创面组;解毒生肌膏组TNF-α、IL-6表达低于磺胺嘧啶银组。Western blot法结果显示：与正常创面组相比,各组β-catenin表达量均上调（P<0.05）,解毒生肌膏组上调表达量最少;与正常创面组相比,各组GSK-3β蛋白表达含量明显下调（P<0.05）;给药后7天,磺胺嘧啶银组和解毒生肌膏组GSK-3β蛋白表达含量上调（P<0.05）,但仍低于正常创面组。结论 解毒生肌膏作用糖尿病大鼠创面修复机制通过调控GSK-3β和β-catenin表达,使炎症因子IL-6和TNF-α表达下调,最终达到糖尿病大鼠慢性创面愈合。     

Onyx embolization of a spinal epidural hemorrhage caused by thoracic spinal epidural arteriovenous fistula: A case report and literature review

Spinal epidural hemorrhages (SEDH) caused by spinal epidural arteriovenous fistulas (SEAVFs) are rare; thus, their specific pathogenesis has not been explained. Furthermore, the standard treatment for SEAVFs has not yet been defined. Here we report the case of a 36-year-old Chinese man who experienced acute onset chest pain and tightness. His symptoms rapidly aggravated until the lower limbs were unable to support him. Spinal magnetic resonance angiography (MRA) revealed a localized SEAVF and a secondary spinal cord lesion at the T4 level. Digital subtraction angiography (DSA) confirmed the presence of the SEDH/SEAVF at the T3–4 level with the left radicular artery feeding the fistula. Based on DSA and MRA findings, SEDH, local spinal cord infarction, and spinal venous reflux disorder were conditionally diagnosed. Using the arterial route, Onyx-34 was injected into the fistula to embolize the feeding arteries and the venous system. Angiography was performed after the microcatheter was withdrawn, and no residual fistula or anterior spinal artery was observed. The six-week follow-up MRI showed acceptable healing of the SEAVF, and the patient improved neurologically. This case suggests that endovascular treatment with Onyx-34 embolization should be considered a promising treatment strategy for this type of complicated SEAVF.     

留守因素、家庭关系对留守中学生人格的影响

目的 了解留守因素、家庭关系对留守中学生人格的影响。方法 于2019-2022年采用《艾森克人格问卷》少年版和《家庭亲密度与适应性量表》对眉山市某县级中学1 424名中学生进行调查。结果 纳入的受访者中,616名为留守中学生(占43.26%)。除了人格的精神质维度外,留守与非留守中学生在人格的其余维度及家庭关系的亲密度、适应性两个维度得分比较,差异有统计学意义(P<0.05)。结构方程模型分析显示,在留守初中生中,母亲外出时个体年龄对家庭亲密度有正向影响,路径系数为0.169;家庭亲密度对精神质与神经质有正向影响,路径系数分别为0.310、0.296;父亲在外时间长短对神经质有负向影响,路径系数为-0.146(P<0.05)。在留守高中生中,父亲外出时个体年龄对人格中的内外向有负向影响,路径系数为-0.111;母亲外出时个体年龄对精神质有负向影响,路径系数为-0.125;父亲在外时间长短对家庭亲密度、家庭适应性有负向影响,路径系数分别为-0.146、-0.163;家庭亲密度对精神质、神经质有正向影响,路径系数分别为0.253、0.266;家庭适应性对内外向有负向影响,路径系数为-0.241(P<0.05)。结论 留守经历会影响中学生的人格和家庭关系,但留守初中生和高中生在留守因素、家庭关系对人格特征的影响有所不同。     

Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate

BackgroundBipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients.MethodsSixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale.ResultsBD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS.ConclusionsThe study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.