Volume 135 · Issue 07 · 2022

抗磷脂综合征(APS)是一种全身性自身免疫性疾病，其特征是由持续性抗磷脂抗体(APL)，即狼疮抗凝剂、抗心磷脂抗体或抗β 2糖蛋白I(抗β 2GPI)抗体引起的血栓形成或产科事件。^[1]APS中的主要靶抗原是β 2GPI，aPL通过其与细胞膜结合，随后激活膜受体和下游信号转导子。这可能会激活自然杀伤(NK)细胞，导致产科并发症。

白癜风是一种普遍的毁容性皮肤病，其特征在于功能性黑素细胞的选择性缺失，影响全球人口的0.5%至1%。^[1]关于其发病机制，已经提出了几种假说，包括自身免疫、氧化应激、遗传和环境因素以及代谢异常。^[2]没有一个单独的因素可以完全解释这种疾病的复杂进展。大多数人类基因组编码不翻译成蛋白质的RNA，称为非编码RNA(ncRNA)。^[3]越来越多的研究表明，ncRNAs作为白癜风的调节因子。我们总结了ncRNAs在白癜风发病机制中的调节，特别是微小RNA（miRNA）、长非编码RNA（lncRNAs）和环状RNA，为开发更有效的白癜风诊断和治疗方法铺平道路[图1].

术后狭窄是小儿先天性食管闭锁修补术后食管狭窄的最常见原因，^[1,2]其次为先天性食管狭窄和化学腐蚀烧伤。^[3]内镜或放射学球囊扩张是治疗食管狭窄的标准方法，但在一些严重增生和严重再狭窄甚至闭塞的复杂病例中，内镜治疗效果有限。1993年，布林宁等人^[4]报道，首次成功运用磁性再通技术治疗儿童难治性食管狭窄，开创了磁性手术治疗小儿食管疾病的历史。该技术充分利用磁性装置和力，可以有效去除吻合口处的瘢痕组织，而不会损伤消化道壁的肌肉层^[5]术后获得理想的治疗效果。近十年来，磁性再通技术在儿童食管狭窄的治疗中得到了进一步的发展，^{[6,7,8,9,10,11,12,13,14,15]}优于内镜下扩张等方法，为儿童顽固性食管狭窄的治疗提供了新的工具。

The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.

H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.

The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID₅₀) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.

The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

The first-line treatment for lung cancer is surgical resection, and one-lung ventilation (OLV) is the most basic anesthetic management method in lung surgery. During OLV, inflammatory cytokines are released in response to the lung tissue damage and promote local and contralateral lung damage through the systemic circulation. We designed a randomized, prospective study to evaluate the effect of the urinary trypsin inhibitor (UTI) ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer.

Adult patients aged 19 to 70 years, who were scheduled for video-assisted thoracic lobectomy surgery to treat lung cancer between May 2020 and August 2020, were enrolled in this randomized, prospective study. UTI (300,000 units) mixed with 100 mL of normal saline in the ulinastatin group and 100 mL of normal saline in the control group was administered over 1 h after inducing anesthesia.

The baseline (T0) interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio was not different between the groups (6941.3 ± 2778.7 vs. 6954.3 ± 2752.4 pg/mL, respectively; P > 0.05). The IFN-γ/IL-4 ratio was significantly higher in ulinastatin group at 30 min after entering the recovery room than control group (20,148.2 ± 5054.3 vs. 6674.0 ± 2963.6, respectively; adjusted P < 0.017). Conclusion: Administering UTI attenuated the anti-inflammatory response, in terms of INF-γ expression and the IFN-γ/IL-4 ratio, after video-assisted thoracic surgery in lung cancer patients.

Clinical Research Information Service of Korea National Institute of Health (CRIS), KCT0005533.

Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations.

This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.

Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively.

Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.

ChiCTR-EOC-17010553.

Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).

Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.

A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR]=1.07, 95% confidence intervals [95% CI]=0.60-1.90, P=0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction=0.0247, HR=0.37, 95% CI=0.14-1.00, P=0.0497).

Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids.

In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids.

Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration >15 years (OR, 2.98; P = 0.046).

Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration >15 years.

Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice.

In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo.

Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.

In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

乳腺癌（BC）是常见诊断的恶性肿瘤之一，在2020年取代肺癌成为全球最主要的诊断癌症。^[1]大约15%至20%的BC患者对人表皮生长因子受体2基因（Her-2)并表现出高度的恶性。然而，定义Her-2积极性仍然存在争议和波动。不确定性的原因包括不同的技术问题和实验室经验、检测和截止点确定的不同准确性、肿瘤异质性、初步临床数据和病理学家之间的差异解释。^[2]使Her-2评估更适合选择患者进行抗Her-2受体治疗，美国临床肿瘤学会（ASCO）/美国病理学家学会（CAP）于2007年首次提出了提高Her-2分析效度的建议，并于2013年和2018年进行了更新。^[3]对于临床医生来说，揭示之间的关系是很重要的Her-2状态，反Her-2治疗和预后，并进一步关注将受益于抗Her-2治疗。

插管后或气管造口术后气管狭窄是获得性良性气道狭窄的最常见原因。由于大容量低压袖带的广泛使用以及对监测袖带压力的必要性的认识，插管后气管狭窄（PITS）的发生率正在降低。然而，气管切开术后气管狭窄（PTTS）的发生率仍然很高，严重影响患者的生活质量。PTTS常由气道软骨损伤、局部缺血性坏死、气管切开部位感染、远端气管切开管与气管壁摩擦等引起。先前的研究报道，手术切除和重建是PTTS治疗的最佳选择；然而，内镜技术的出现使其成为外科治疗的合适替代方案，尤其是对于气管节段长期破坏或有严重合并症的患者。^[1]

致编辑：侵袭性肺毛霉菌病（IPM）是一种罕见但危及生命的机会性真菌病，死亡率高达40%~80%。^[1]尽管IPM约占所有毛霉菌病病例的9.2%，但其死亡率最高（66.6%）。IPM的明确诊断取决于组织病理学发现，与呼吸道标本或肺组织的培养结果无关。

致编辑：高血压是众所周知的心血管疾病，其中肾脏由于其在液体、电解质平衡和血压调节中的作用而成为重要的靶点。^[1]肾小球硬化、肾小管间质纤维化、蛋白尿是高血压肾损伤的主要病理特征。^[2]

致编辑：妊娠急性脂肪肝（AFLP）是一种罕见但潜在致命的妊娠特有疾病，通常发生在妊娠晚期，是危重患者孕产妇死亡的主要原因之一。^[1]Swansea诊断标准自提出以来已在世界范围内广泛用于AFLP的诊断。斯旺西标准包括临床症状和实验室检查、影像学和病理学检查结果。一些研究表明，斯旺西标准评分是评估疾病严重程度的潜在临床工具。^[2]临床症状缺乏特异性，大多数患者无法进行病理检查；因此，最重要的标准是基于实验室检查结果。在这些标准中，实验室检查结果主要反映以下功能障碍：肝脏（总胆红素>14 μ mol/L、天冬氨酸转氨酶[AST]或丙氨酸转氨酶[ALT]>42 U/L、凝血功能障碍[凝血酶原时间>14 s或活化部分凝血活酶时间>34 s]、低血糖<4 mmol/L，血氨升高>47 μ mol/L）、肾脏（血清肌酐>150 μ mol/L）和血液（白细胞计数>11 × 10⁹/L）。如果患者器官的损伤加重，斯旺西标准评分将增加。然而，尚不清楚斯旺西标准评分是否可用于评估AFLP患者的母体和胎儿并发症。

致编辑：急性大叶性肾病(ALN)，也称为急性局灶性细菌性肾炎，是一种严重形式的上尿路感染(UTI)，其特征在于肾脏中存在炎性肿块病变而没有脓肿形成。它被认为是急性肾盂肾炎和肾脓肿之间的中点。^[1]ALN于1979年首次被描述为10名成人和2名儿童的放射学诊断。^[2]

致编辑：微小变化病（MCD）和局灶节段性肾小球硬化（FSGS）是成人和儿童肾病综合征的常见组织学亚型。^[1,2]皮质类固醇是一线治疗，而一些患者出现类固醇依赖性肾病综合征。需要重复使用类固醇治疗，长期伴有与泼尼松单药治疗相关的严重不良反应。^[3]来氟米特是一种竞争性和可逆的二氢乳清酸脱氢酶抑制剂，可抑制增殖T细胞和B细胞中的蛋白酪氨酸激酶，具有抗炎和抗增殖作用。^[4]我们先前报道了来氟米特治疗降低了16例MCD和类固醇依赖性或类固醇耐药肾病综合征成人患者的复发率和维持缓解的泼尼松用量。^[5]我们进行了一项回顾性研究，以调查来氟米特在类固醇依赖性MCD和FSGS中的疗效和安全性。

致编辑：B组链球菌（GBS）定植于7-30%孕妇的阴道和直肠，并导致母婴侵袭性感染。迄今为止，临床GBS菌株的发病机制仍然难以捉摸。

致编辑：东方药理学不可或缺的组成部分“十八种拮抗药物”中指出，马尾藻和甘草不宜同时服用。^[1]研究人员报告说，甘草和马尾藻的共同给药对大鼠的心脏、肝脏和肾脏产生毒性作用。^[2,3]然而，目前使用的是经典配方“海枣玉虎汤”（含有甘草和马尾藻），尽管这种药物的安全性尚未明确定义。因此，有必要对马尾藻和甘草组合进行毒理学研究，以确定其安全性。本研究采用亚急性毒性试验评价毒性。甘草的主要活性成分为甘草素、异甘草素、甘草素、异甘草素和甘草酸（GL）。GL可以转化为甘草次酸(GA)体内研究表明，口服海带-甘草提取物后，大鼠血浆GA浓度升高vs.单独的甘草提取物。^[4]在本研究中，我们建立了超高效液相色谱联用三重四极杆质谱（UPLC-TQ/MS）方法同时测定大鼠血浆中甘草的六种主要成分。

致编辑：大疱性类天疱疮（BP）是一种慢性自身免疫性水疱性疾病，其特征在于与干扰基底表皮角质形成细胞粘附的两种半桥粒蛋白（BP180和BP230）的自身抗体相关。BP的全球发病率为每年2.5至75例/百万。^[1]遗传、环境和随机因素有助于BP的易感性。我们对东北地区的BP进行了回顾性研究，以评估其临床特征。分析了沈阳市第七人民医院2015年1月至2020年1月期间BP患者的数据，其中464例来自东北地区的BP患者。所有患者均符合BP诊断标准。本研究由沈阳市第七人民医院机构审查委员会批准（编号：2015-WQ-01）。

致编辑：帕金森病（PD）是第二种最常见的神经退行性疾病，与显著残疾和对生活质量（QoL）的负面影响相关，影响≥65岁人群的2%至3%。^[1]尽管该障碍由运动特征定义，包括不对称震颤、运动迟缓和强直，但通常可以看到各种非运动特征，包括认知障碍、抑郁、感觉症状、自主神经功能障碍和睡眠障碍。由于复杂性，PD的治疗具有挑战性。目前没有有效的治疗方法来预防或阻止PD的进展。

致编辑：膀胱癌是亚洲人群中最常见的泌尿系统恶性肿瘤。在中国，每年报告80,000例新病例，并且发病率每年都在增加。在这些病例中，75%是非肌层浸润性膀胱癌（NMIBC）。在肌层浸润性膀胱癌（MIBC）和NMIBC患者中，由于肿瘤进展的风险较高，根治性膀胱切除术被认为是主要的治疗方法。此外，膀胱镜检查和传统的经尿道电切术是膀胱癌诊断和分期的主要方法。然而，这些方法相对危险，因为它们的并发症和高围手术期死亡率。^[1]此外，膀胱镜检查最关键的限制是考虑到疾病的多灶性和不明显但显著的病变（如癌），其区分恶性肿瘤和健康尿路上皮的能力低下原位）。