Volume 135 · Issue 04 · 2022

乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）的慢性感染在全球范围内造成严重的公共卫生负担。在过去的三十年里，中国在慢性乙型肝炎（CHB）和丙型肝炎（CHC）的预防、诊断和治疗方面做出了巨大努力并取得了显著进展。^[1]

Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).

A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.

In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).

This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

欧洲呼吸学会/美国胸科学会临床实践指南（仅推荐性）建议使用非侵入性呼吸支持疗法（NRST）作为避免低氧性急性呼吸衰竭（ARF）插管的预防策略。^[1]反对使用NRST的理论担忧基本上与病毒在医护人员（HCW）中传播的风险以及在失败的情况下延迟插管的风险的安全原因有关。

Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.

This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis.

Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR= 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.

In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.

Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment.

Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups.

This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group (P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant.

Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

GALLIUM is a global phase III study that demonstrated significant improvements in progression-free survival (PFS) for obinutuzumab plus chemotherapy (G-chemo) vs. rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). This study aimed to report the results of a subgroup of patients in China.

Patients were randomized to G-chemo or R-chemo. Responders received maintenance therapy for 2 years or until disease progression. The primary endpoint was investigator (INV)-assessed PFS. Secondary endpoints included the overall response rate (ORR) and complete response rate (CRR) at the end of induction chemotherapy, overall survival (OS), and safety.

Overall, 58 patients with FL were randomized to the G-chemo (n = 25) and R-chemo arms (n = 33). The INV-assessed PFS rate at 3 years was 81.8% in the G-chemo arm, vs. 70.2% in the R-chemo arm (hazard ratio 0.35; 95% confidence interval: 0.09-1.34; P = 0.1120). The INV-assessed CRRs (without positron emission tomography [PET]) in these arms were 24.0% and 21.2%, respectively, whereas the ORRs were 80.0% and 90.9%, respectively. INV-assessed CRR-PET was 52.6% in the G-chemo, vs. 60.9% in the R-chemo. Median OS was not reached in either arm. Grade 3 to 5 adverse events were more frequent in the R-chemo arm (97.0% vs. 88.0%).

The results of this subgroup analysis were consistent with those of the global population, and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.

ClinicalTrials.gov, No. NCT01332968.

Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients.

We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed.

One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ²= 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ²= 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ² = 11.686, P= 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t=-0.638, P= 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups.

IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).

TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown- TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.

TPCN2 might be a potential protective factor against SLE.

Previous studies have shown that bufalin exerts antitumor effects through various mechanisms. This study aimed to determine the antineoplastic mechanism of bufalin, an extract of traditional Chinese medicine toad venom, in ovarian cancer.

The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2^′-deoxyuridine (EdU), and colony formation assays were used to investigate the antiproliferative effect of bufalin on the ovarian cancer cell line SK-OV-3. Molecular docking was used to investigate the combination of bufalin and epidermal growth factor receptor (EGFR) protein. Western blotting was performed to detect the expression of EGFR protein and its downstream targets.

Bufalin inhibited the proliferation of SK-OV-3 cells in a dose- and time-dependent manner. Bufalin was confirmed to combine with EGFR protein using molecular docking and downregulate expression of EGFR. Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK).

Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway.

慢性阻塞性肺疾病急性加重（AECOPD）的适当管理非常重要，因为这种加重会对患者的健康状况、疾病进展和死亡率产生负面影响。恶化发作主要由病毒和细菌感染引发，一项研究显示55%的AECOPD住院患者有细菌感染。^[1]一些分析表明，抗生素治疗可以降低短期死亡的风险，改善预后。然而，并非所有AECOPD患者都受益于抗生素治疗。血液嗜酸性粒细胞计数已被用作嗜酸性粒细胞相关气道炎症和脓毒症的生物标志物。然而，外周血嗜酸性粒细胞计数与细菌病原体之间的联系尚未见报道。我们的目的是分析嗜酸性粒细胞计数、细菌病原体、临床治疗和患者预后之间的关系，为AECOPD的管理提供有用和全面的参考。

免疫球蛋白（Ig）G4相关疾病（IgG4-RD）是一种免疫介导的纤维炎性疾病，其特征是血清IgG4水平升高和多器官受累。IgG4-RD的特征性组织学发现是致密的淋巴浆细胞浸润、纤维化和浸润受影响组织的大量IgG4阳性浆细胞。^[1]先前的研究已经证明了与人口统计学、临床特征、实验室检查结果和治疗药物相对应的各种复发预测因素。然而，没有研究揭示病理学上耀斑的危险因素。本研究旨在确定病理特征是否与治疗结果相关。

远外侧入路（FLA）及其改良入路是手术切除位于枕骨大孔腹侧或腹外侧病变的基本手术入路。^[1,2,3,4,5]FLA的关键步骤是暴露椎动脉（VA），尤其是V3节段。^[1,5,6]当进行FLA时，大多数神经外科医生选择首先暴露枕下三角（由头直肌后大肌、上斜肌和下斜肌形成）作为关键的解剖标志，然后暴露V3节段。^[1,2,5,6,7]然而，一方面，这种肌肉解剖标志——枕下三角在不同患者中的深度、形态和位置各不相同，这增加了术中VA损伤的风险。^[3]另一方面，由于上覆肌肉层的阻塞和血管的分布，该手术可能导致暴露困难，这可能会相当延长开颅时间。VA的病程可以变化，例如在枕下三角的唇部之间向后循环和向后凸出，如果人们期望它在枕下三角的深度被发现，它可能会受损。^[3]因此，神经外科医生具有VA损伤的可能性和相当长的时间来成功暴露VA。

致编辑：类风湿性关节炎（RA）是一种慢性自身免疫性疾病，不仅以关节症状为特征，还以关节外和全身表现为特征。^[1]传统上，RA的评估集中在炎症的实验室测量和临床医生生成的评估。然而，一些指南推荐患者报告的结果（PROs）来评估疾病进展。PROs还有助于减少医生的评估和患者自己对疾病状态的判断之间的差异，并且在过去十年中已经确定了它们对疾病管理和医患沟通的重要性。^[2]然而，尚不确定这种认识是否促进了PRO措施在中国人群RA相关研究和临床实践中的使用和报告。因此，本研究系统地回顾了最近研究中收集的PRO测量，并总结了中国RA人群的PRO结果。

致编辑：骨关节炎(OA)是一种与高发病率和高残疾相关的疾病。肥胖，通常测量为体重指数(BMI)≥30 kg/m²，是OA及其相关并发症发病的众所周知的危险因素。^[1]有趣的是，这两种疾病可能具有共同的潜在机制，这些机制有助于发病机制，如遗传变化，并且这些机制尚未被充分探索。基因表达谱是一种强有力的工具，用于系统地鉴定与复杂的多因素疾病（如OA）相关的遗传变异的分子特征。此外，已经显示了基因表达在理解肥胖和OA发病机制中的意义。^[2]这项研究假设hub基因可以解释肥胖和OA之间的关系。因此，确定这些基因的参与可以提供对肥胖对OA的详细调节机制的见解。

致编辑：SRY相关的高迁移率群盒蛋白-2（SOX2）最显著地在眼睛，基板，前脑和下丘脑-垂体中表达，并参与早期胚胎发育。^[1]功能丧失突变或缺失SOX2可能导致单侧或双侧无眼症/小眼症（A/M）以及其他相关疾病，如无眼症/食管-生殖器综合征。越来越多的研究发现，SOX2突变可导致不同的眼外症状，包括生长迟缓、感音神经性听力损失、精神发育迟滞、无青春期体征和男性泌尿生殖道畸形（小阴茎、隐睾和尿道下裂）。事实上，案例SOX2致病突变但无或轻微眼部症状的报道较少。多项研究发现，SOX2杂合突变导致男性或女性完全性腺功能减退的典型体征，而无主要眼部畸形，如孤立性低促性腺激素性性腺功能减退（HH），但未鉴定出其他HH致病基因。^[2,3]因此，我们的研究首次报道了三名中国患者的病例SOX2由于小阴茎和/或隐睾合并颅面畸形或智力残疾而转诊的突变。

致编辑：接触热诱发电位（CHEPs）已成为小纤维神经病变的重要电生理诊断方法，^[1]其特征在于由于各种病因而累及有髓的A δ和无髓的C纤维。^[1,2]CHEP受性别、年龄、身高等影响。^[1,2]尚未研究第二至第四（2D：4D）数字比对CHEP参数的影响。手指比率定义为食指长度除以无名指长度，男性小于女性。^[3]我们的目的是了解数字比是否对CHEPs有任何影响，并加强对CHEPs的理解和改进方法。

致编辑：食管鳞状细胞癌（ESCC）是最具侵袭性的癌症类型之一，给人类健康带来沉重负担。ESCC的早期诊断和预后监测对治疗具有重要意义。尽管最近ESCC的治疗方案取得了进展，但ESCC的预后仍然很差。^[1]因此，为ESCC患者寻找新的分子治疗靶点和预后监测生物标志物具有重要意义。在这项研究中，我们旨在探索ESCC新的预后生物标志物。

致编辑：食管闭锁（EA）是最常见的先天性食管异常。在70%至90%的出生时患有EA的患者中，同时发生气管食管瘘（TEF）。自沃格特以来^[1]在1929年对异常类型进行识别和分类后，提出了许多其他分类系统，包括Ladd、Gross、Swenson和Kluth分类系统。^[2]然而，1953年提出的EA/TEF解剖模式的粗略分类是最广泛接受和使用的分类系统之一^[3]并被引用于小儿外科.^[4]虽然近几十年来手术和影像学技术有了很大的发展，但我们回顾了中国连续434例EA/TEF病例。通过仔细检查这些患者的影像学研究和病理解剖结构，我们发现了插图中需要修改的某些“缺陷”和细节。

致编辑：肾脏是一个高耗能器官，如果能量供应障碍，就容易受损。一磷酸腺苷（AMP）活化蛋白激酶（AMPK）是一种丝氨酸/苏氨酸激酶，在代谢、自噬、炎症和线粒体稳态中起关键作用。AMPK作为能量传感器参与肾脏的生理和病理过程。

致编辑：憩室病在世界范围内很常见，随着年龄的增长，该病的发病率增加。复杂性憩室炎是严重的，包括脓肿、瘘管、梗阻和腹膜炎。最终，对有症状并发症的患者建议进行手术治疗。其中，憩室炎引起的结肠瘘是罕见的发现，尤其是乙状结肠瘘是一种极其罕见的并发症。本报告描述一例憩室炎引起的乙状结肠-乙状结肠瘘。该病例的结果可能有助于医生认识到，治疗并发瘘管的憩室炎需要多学科管理和手术。

致编辑：全主动脉弓置换术（TAR）是一种与显著围手术期风险相关的外科手术，导致较高的死亡率和神经系统并发症。升主动脉或半弓置换术与不太复杂的手术相关，可用于有效切除近端内膜撕裂，并有可能提高这些患者的生存率。^[1]结合开胸手术和支架置入的混合主动脉修复术已有效用于主动脉弓动脉瘤患者。^[2]虽然经常采用混合技术，但只有有限数量的研究和少量病例调查了该手术在治疗I型主动脉夹层中的应用。^[1,2]本研究旨在通过分析大样本量来评估混合技术在该队列中的早期和中期安全性和有效性。

致编辑：截至2020年8月9日，严重急性呼吸系统综合症冠状病毒2（新型冠状病毒）在全球已感染19,432,244人，导致721,594人死亡。为及时识别感染者，已对武汉、北京和新疆等已知有冠状病毒疾病19（COVID-19）病例的地区的高感染风险人群进行了核酸检测筛查。感染患者的快速识别和隔离措施的实施对于预防新型冠状病毒的传播具有重要作用。然而，存在一些与这种病毒的大规模筛查相关的问题。标本采集和检测的设备和试剂消耗高，导致筛查成本升高。而且，随着样本采集量的增加，医疗机构的检测能力已经达到饱和点，阻碍了大规模筛查的速度和范围。因此，在许多地区提出了RNA提取后(在从多个患者提取的核酸的混合物中检测)或RNA提取前(在核酸提取前从不同患者获得的咽拭子转移缓冲液的混合物中检测)的混合检测。^[1]然而，在核酸提取之前合并拭子转移缓冲液和在核酸提取之后合并RNA都不可避免地导致样品的稀释和检测灵敏度的降低。但如何有效提高筛选效率，将稀释引起的灵敏度下降控制在适当范围内，目前还缺乏研究。在这项研究中，我们通过优化当前的混合采集技术，并在一次有希望的中试后，设计了一种新的10合1测试（将来自10个人的10份咽拭子样本置于一个定制的病毒采集管[CMT]中进行核酸提取和测试）。