Volume 133 · Issue 14 · 2020

The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.

All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.

At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.

Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.

ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132

Benign epilepsy with centrotemporal spikes (BECTS) is the most common type of childhood idiopathic focal epilepsy. BECTS is associated with pervasive cognitive deficits and behavior problems. While seizures can be easily controlled, it is crucial to select anti-epileptic drugs that do not impair cognition, do not cause psychosocial effects, and improve the quality of life. Previous studies showed effects of oxcarbazepine (OXC) monotherapy on the cognitive and psychosocial profiles of patients with BECTS. Here, we studied the effects of OXC monotherapy on the neuropsychologic profiles and quality of life in patients with BECTS in China.

Thirty-one patients aged 6 to 12 years newly diagnosed with BECTS were recruited. A psychometric assessment was performed before and during the follow-up of OXC monotherapy with Cognitive Computerized Task Battery, Depression Self-Rating Scale for children, Screen for Child Anxiety Related Emotional Disorders, and Quality of Life in Epilepsy-31 (QOLIE-31). The results of the assessments were compared to explore the effect of OXC monotherapy in patients with BECTS.

Thirty children with BECTS completed the study. Five of ten cognitive test scores improved after treatment via OXC monotherapy, including visual tracing (F = 14.480, P < 0.001), paired associated learning (language) (F = 6.292, P < 0.001), paired associated learning (number) (F= 9.721, P < 0.05), word semantic (F = 6.003, P < 0.05), and simple subtraction (F = 6.229, P < 0.05). Of the neuropsychology data concerning the quality of life, statistically significant improvements were observed in emotion (F = 4.946, P < 0.05), QOLIE-social (F = 5.912, P < 0.05), and QOLIE-total (F= 14.161, P < 0.001).

OXC is safe and does not impair neuropsychologic functions, with no obvious mood burden on children with BECTS. Most importantly, OXC has positive impacts on children’s perception of quality of life, especially in terms of happiness and life satisfaction.

Early neurologic deterioration (END) may occur in patients with anterior circulation ischemic stroke (ACIS) after receiving endovascular treatment (EVT). Hemodynamic insufficiency, re-occlusion, and post-re-canalization hyper-perfusion are likely to play a critical role in END. We hypothesized that hemodynamic changes can predict END in patients with ACIS post-successful EVT using trans-cranial Doppler (TCD).

We utilized a prospectively maintained database of ACIS patients treated with EVT between September 2016 and June 2018 in the Xuanwu Hospital, Capital Medical University. TCD parameters including peak systolic velocity (PSV), bilateral mean flow velocity (MFV), and pulse index (PI) were determined via the middle cerebral arteries within 72 h post-EVT. A logistic regression model was applied to detect independent predictors for END.

Totally, 112 EVT patients were included in this study and 80/112 patients experienced successful re-canalization with <50% residual stenosis, while 17/80 (21.3%) patients suffered END, for which vasogenic cerebral edema (11/17) was considered as a leading role and followed by symptomatic intra-cranial hemorrhage (4/17) and ischemia progression (2/17). For the 80 patients, the PSV (median: 127 cm/s vs. 116 cm/s, P = 0.039), the ratio of ipsilateral-MFV/contra-lateral-MFV (iMFV/cMFV) (median: 1.29 vs. 1.02, P = 0.036) and iMFV/mean blood pressure (MBP) (median: 0.97 vs. 0.79, P = 0.008) in END patients were higher than those of non-END. Using the receiver-operating characteristic curve to obtain cut-off values for PSV, PI, iMFV/cMFV, and iMFV/MBP for END, we found that PI ≥0.85 (odds ratio: 11.03, 95% confidence interval: 1.92-63.46, P = 0.007) and iMFV/MBP ≥0.84 (odds ratio: 9.20, 95% confidence interval: 2.07-40.84, P = 0.004) were independent predictors of END in a multivariate logistic regression model, with a sensitivity of 82.4% and 76.5% and a specificity of 42.9% and 66.7%, respectively, and had the positive predictive values of 29.0% and 38.2%, and negative predictive values of 90.0% and 91.3%, with an area under the receiver-operating characteristic curve of 0.57 and 0.71, respectively.

TCD examination of EVT patients may be used as a real-time tool to detect END predictors, such as the higher PI and iMFV/MBP, allowing for better post-thrombectomy management in ACIS patients.

Angiopoietin-2 (Ang-2) is a type of endothelial growth factor involved in angiogenesis and vascular remodeling. Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease (CAD). This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.

A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study. Coronary flow reserve (CFR) was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography. The patients were divided into the following two sub-groups according to CFR: the impaired CFR group with CFR values <2.5 and the preserved CFR group with CFR values ≥2.5. Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay. Independent predictors for impaired CFR were identified by binary logistic regression analysis. The receiver-operating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.

We found that age, percentage of female sex, N-terminal pro-B-type natriuretic peptide levels, Ang-2 levels (763.3 ± 264.9 vs. 579.7 ± 169.3 pg/mL, P < 0.001), and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR. Serum Ang-2 levels were negatively correlated with CFR (r = -0.386, P < 0.001). Binary logistic regression analysis showed that Ang-2 (odds ratio: 1.004, 95% confidence interval [CI]: 1.001-1.006, P = 0.003) and age (odds ratio: 1.088, 95% CI: 1.023-1.156, P = 0.007) were independently associated with impaired CFR. Furthermore, Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve (P < 0.001). The area under the curve was 0.712 (95% CI: 0.612-0.813).

High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.

Certain hemophilia patients are unable to cooperate with or afford magnetic resonance imaging (MRI) examinations. The purpose of our study was to explore the value of multislice spiral computed tomography (MSCT) in evaluating hemophilic arthropathy (HA).

Thirty-eight patients with 73 joints of HA were consecutively selected from January 2016 to May 2018 for this prospective study. All 73 joints were examined by X-ray, CT, and MRI within 2 days. The MRI scores of the joints were determined by the International Prophylaxis Study Group (IPSG) standard. The CT findings were quantified according to the IPSG standard, except for cartilage injury, which was quantified by joint space narrowing using the X-ray Pettersson score. The CT and MRI scores were compared by the paired Wilcoxon signed-rank test. The correlations between the CT score of joint space narrowing and MRI score of cartilage injury and the total CT and MRI scores were analyzed by Spearman rank correlation. The kappa test was used to compare the consistency of CT and MRI scores.

MRI was superior to CT based on the scores for small amount of effusion (P < 0.05), synovial hypertrophy and hemosiderin deposition in the mild groups (P < 0.05). The CT and MRI scores were not significantly different for moderate and massive effusion, synovial hypertrophy, and hemosiderin deposition in the moderate and severe groups, bone erosion or cystic changes (P > 0.05), and there was a high degree of consistency between the two scores (kappa > 0.81). The consistency between the Pettersson scores of joint space narrowing on CT and the IPSG scores of cartilage injury on MRI was high (kappa = 0. 774, P < 0.05).

The image scores of MSCT are generally consistent with MRI except for mild synovitis, which can be used as an alternative for the evaluation of HA.

Recently, adjustable-loop devices (ALDs) have been widely used, and their reliability has always been the focus of attention. This study compared loop length changes under pull stress caused by flexion and extension of the cadaver knee between ALDs and fixed-loop devices (FLDs) in terms of femoral fixation after anterior cruciate ligament (ACL) reconstruction.

ACL reconstruction in cadaveric knee joints was performed under arthroscopy with femoral suspension devices and tibial fixation by tying sutures on staples. The knee joint was repeatedly flexed and extended 30 times after fixation. According to the femoral fixation device used (Endobutton or Ultrabutton), the knee joints were divided into two groups: the ALD group (12 specimens) and the FLD group (ten specimens). The length of the loop before and after fixation was measured, and the loop length of the ALD group was re-measured 1 day after reconstruction.

There was no significant difference in the length of the loop between the two groups (t = 0.579, P = 0.569). One day later, the loop length of the ALDs retracted by 0.29 ± 0.33 (0-1.1) mm, and there was no retraction in three specimens.

There was no significant difference in the loop length under flexion and extension stress after ACL reconstruction between ALDs and FLDs.

The catheter-tissue contact force (CF) is one of the significant determinants of lesion size and thus has a considerable impact on the effectiveness of ablation procedures. This study aimed to evaluate the impact of CF on the lesion size during right ventricular outflow tract (RVOT) ablation in a swine model.

Twelve Guangxi Bama miniature male pigs weighing 40 to 50 kg were studied. After general anesthesia, a ThermoCool SmartTouch contact-sensing ablation catheter was introduced to the RVOT via the femoral vein under the guidance of the CARTO 3 system. The local ventricular voltage amplitude and impedance were measured using different CF levels. We randomly divided the animals into the following four groups according to the different CF levels: group A (3-9 g); group B (10-19 g); group C (20-29 g); and group D (30-39 g). Radiofrequency ablations were performed at three points in the free wall and septum of the RVOT in power control mode at 30 W for 30 s while maintaining the saline irrigation rate at 17 mL/min. At the end of the procedures, the maximum depth, surface diameter, and lesion volume were measured and recorded. A linear regression analysis was performed to determine the relationship between continuous variables.

A total of 72 ablation lesions were created in the RVOT of the 12 Bama pigs. The maximum depth, surface diameter, and volume of the lesions measured were well correlated with the CF (free wall: β = 0.105, β = 0.162, β = 3.355, respectively, P < 0.001; septum: β = 0.093, β = 0.150, β = 3.712, respectively, P < 0.001). The regional ventricular bipolar voltage amplitude, unipolar voltage amplitude, and impedance were weakly positively associated with the CF (β = 0.065, β = 0.125, and β = 1.054, respectively, P < 0.001). There was a significant difference in the incidence of steam pops among groups A, B, C, and D (free wall: F = 7.3, P = 0.032; septum: F = 10.5, P = 0.009); and steam pops occurred only when the CF exceeded 20 g. Trans-mural lesions were observed when the CF exceeded 10 g in the free wall, while the lesions in the septum were non-trans-mural even though the CF reached 30 g.

CF seems to be a leading predictive factor for the size of formed lesions in RVOT ablation. Maintaining the CF value between 3 and 10 g may be reasonable and effective for creating the necessary lesion size and reducing the risk of complications, such as steam pops and perforations.

Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.

We generated Zbtb46^fl/fl and Zbtb46^fl/flMx1-Cre mice. The deletion of Zbtb46 in Zbtb46^fl/flMx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46^fl/fl and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.

The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46^fl/fl littermates (Zbtb46^fl/flvs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46^fl/flMx1-Cre mice was similar to those from Zbtb46^fl/fl control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation.

Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

羊水栓塞（AFE）是一种罕见但可能致命的疾病，其特征是突然发作、不可预测和高死亡率。母胎医学学会（SMFM）于2016年发布了第9号临床指南《羊水栓塞：诊断和管理》。^[1]基于该指南和其他相关研究，中华医学会中华妇产科学会产科学组于2018年12月制定了AFE诊断和治疗共识，旨在规范其诊断和管理，改善孕产妇和围产儿结局。^[2]

高血压是心血管疾病的重要原因。如果控制不力，高血压会导致心脏病和中风，它们共同构成了全球过早死亡和残疾的主要原因。根据中国一项全国性横断面调查，2015年≥18岁成年人高血压患病率为23.2%。^[1]

致编辑：患者女，43岁，因阵发性咳嗽6个月于2013年7月入住我科。她在其他医院被诊断为右下肺腺癌（cT2aN3M1b，IV期，间变性淋巴瘤激酶[ALK]+）伴骨转移，前来参加克唑替尼III期试验（编号NCT01639001）。

致编辑：一名先前健康的33岁中国男性最初因发热、上腹痛、呕吐和腹泻到当地医院就诊，持续5天。当地医疗中心的实验室检查结果显示肝肾功能受损。患者因疑似细菌感染和无尿而接受治疗。在患病第8天，患者变得困惑和迷失方向。他被转移到我们的急诊室。初步调查显示转氨酶严重升高和中度凝血病[表1].甲型、乙型、丙型和戊型肝炎的病毒血清学检查均为阴性。胸部X光检查正常。大脑和腹部的计算机断层扫描显示肝肿大和少量腹水。在患病第10天，他出现癫痫持续状态，并进行插管以保护气道。亲属否认有酗酒、非法药物使用和口唇病变的病史。患者在患病第10天入住重症监护室接受进一步治疗。

致编辑：卵裂早期的胚胎发育是一个复杂且精心策划的生物过程。期间体外受精-胚胎移植（IVF-ET），胚胎按形态学标准常规分层，受精后第3天早晨移植。胚胎发育的这一阶段主要受母体因素调控，因为胚胎基因组尚未完全激活。^[1]第3天是胚胎完成胚胎基因组激活（EGA）的关键时期。具有较高发育潜力的胚胎启动EGA用于随后的发育和植入，而无活力的胚胎经历停滞。^[2]然而，很难精确地选择具有EGA的胚胎。因此，IVF-ET中的着床率保持在20%至30%。^[3]在IVF-ET治疗期间，我们发现超过一半的第3天胚胎在08:00-09:00至16:00的7至8小时的扩展培养（EC）期间继续发育，并且当这些胚胎被转移时，活产率增加。然后，这种策略被用来提高IVF-ET期间的活产率。

致编辑：心肌电重构和结构重构与心房颤动(AF)的发病机制密切相关，心房颤动主要由Ca紊乱引起²⁺心房的稳态。最近的证据表明，肌醇1，4，5-三磷酸受体改变₃R)活动可影响窦房结的传导速度和节律。Ca的破坏²⁺IP介导的体内平衡₃Rs与房颤中观察到的特殊病理生理学密切相关，包括心房重构、炎症和氧化应激（OS）。

致编辑：人类病原体经过长时间进化成为嗜温菌，以适应人体典型的37℃温度。酵母和酵母样真菌在这个温度下也生长得很好，而丝状真菌生长的最佳温度是25~28℃。中国海南岛属热带海洋性季风气候，四季分明。此地多年平均气温为24.4℃，年气温变化较小；降水量约1718.6毫米，相对湿度82%。这些独特的天气特征为病原体提供了有利的生长环境。恶性血液病患者免疫力差，易受病原体感染。这导致恶性血液病患者的高医院感染率和频繁使用抗生素。不同地区和医院的流行病学调查可以为血液科医生治疗恶性血液病患者感染的临床用药提供更多指导。

致编辑：慢性肾脏疾病（CKD）正迅速成为主要的公共疾病负担，影响约11%至13%的普通人群。^[1]其相关治疗通过限制患者的日常活动严重影响患者的身体、心理和社会福祉。研究表明，在改善CKD患者的身体活动、增强心肺功能和提高生活质量（QoL）方面，运动可能对他们有多种益处。^[2]此外，一些关于运动对CKD患者生活质量有效性的结果不一致。几项研究表明，运动显著改善了CKD患者的QoL，而其他研究未能检测到显著差异，尽管有证据表明透析前CKD患者的运动后QoL评分高于基线。即使在表明锻炼对生活质量有效的研究中，改善的组成部分也各不相同。因此，进行了一项荟萃分析，以评估运动对透析前CKD患者QoL的影响。

致编辑：定量磁共振成像（MRI）通过测定蛋白聚糖、胶原纤维和含水量的变化，客观评价膝骨关节炎（KOA）患者软骨的退变情况，从而便于临床早期诊断和治疗。^[1]西安大略和麦克马斯特大学（WOMAC）骨关节炎指数评分用于评估KOA患者的症状。^[2]目前，很少有研究评估定量MRI发现和临床症状之间的相关性（例如，由Zarins进行的研究等人^[3]).本研究探讨了T1rho和T2标测序列定量MRI与KOA患者WOMAC骨关节炎指数评分的关系。

致编辑：髌骨袖状骨折被认为是儿科人群中一种独特类型的髌骨损伤。它是一种特殊类型的撕脱骨折，其中撕脱碎片由来自髌骨的小骨碎片组成，伴有大部分关节软骨。^[1]它约占儿童髌骨骨折的一半。^[2]然而，这种损伤在双侧发生是极其罕见的，并且关于这种损伤在其慢性期的治疗和预后的报道很少。在此，我们报告一例13岁健康男孩的慢性双侧髌骨袖状骨折，他在跑步比赛中受伤。据作者所知，这是目前英国文献中首例慢性双侧髌骨袖状骨折。

致编辑：患者男，52岁，发热，右大腿疼痛溃疡10天。患者急性淋巴细胞白血病2年。2个月前，患者出现咳嗽、咳痰。血液和肺组织培养结果为阴性，但血清1，3-β-D-葡聚糖测定为阳性。胸部计算机断层扫描（CT）显示右肺有新的渗出。诊断为肺部真菌感染。十天前，患者开始发烧，同时注意到右大腿上有一个小红斑，并伴有剧烈疼痛。病灶迅速扩大，中央变成溃疡。查体示右大腿溃疡2cm × 4cm，周围有红斑、硬结，溃疡上可见坏死焦痂，无脓性分泌物渗出[图1A].组织病理学显示表皮增生和真皮血管周围淋巴细胞、中性粒细胞和浆细胞浸润。真皮内可见血管血栓形成[图1B].苏木精和高碘酸-Schiff染色均显示血栓形成中相似的直角宽无隔膜菌丝[图1B和C].病灶的直接显微镜检查和福尔马林固定的石蜡包埋组织中毛霉菌病的聚合酶链反应（PCR）试验均为阴性。根据病史、临床检查和组织病理学，患者被诊断为播散性毛霉菌病。静脉注射脂质体两性霉素B 50 mg/d和泊沙康唑800 mg/d进行治疗。四周后，胸部CT扫描显示有很大改善，皮肤溃疡愈合并结痂[图1D].

致编辑：人体皮肤不仅是防止外来物质侵入的物理屏障，也是对病原微生物、外源性大分子物质、同种异体移植物等产生免疫反应的生物屏障。^[1]对于外源性皮肤移植物，免疫系统识别的靶标是外源性细胞衍生的主要组织相容性复合物(MHC)1类分子以及肽-MHC 1类复合物。^[2]所有已知被皮肤排斥的外源性物质都是有机的；目前尚不清楚人类皮肤是否对无机物有排斥作用。作者在自己的经历中注意到了一种现象，即驻留在他脚皮肤下的金属颗粒被皮肤排出。值得注意的是，在去除金属之前，皮肤是完整的。因此，作者进一步研究了这一过程。

在题为“卵泡抑素样1通过转化生长因子β 1/丝裂原活化蛋白激酶信号通路促进博莱霉素诱导的肺纤维化”的文章中，第16期，第131卷中华医学杂志,^[1]的上面板图4C错误地包含相同的图像（FSTL1/DMSO和TGF-β 1/U0126的图像），更新和正确图4具体如下：