Volume 135 · Issue 20 · 2022

人类胃肠道包含数万亿的共生微生物，包括细菌、病毒和真菌，形成一个生态群落，通常称为肠道微生物组。作为肠道中第二个最主要的分类王国（占总微生物组DNA的5.8%），肠道病毒因其在塑造肠道微生物组的整体组成和维持人类健康中的作用而日益得到认可。^[1,2]宏基因组测序的最新进展在破译肠道病毒组的特征和功能方面带来了突破。^[3]值得注意的是，有几个因素限制了该技术在病毒组研究中的应用。例如，从人样品中分离的病毒DNA的量通常不足以进行宏基因组测序。为了解决这个问题，扩增技术如聚合酶链式反应和多重置换扩增被广泛用于在测序之前增加提取的病毒DNA的量，这反过来可能引入扩增偏倚、嵌合读数和随机突变。^[4]同时，鉴于大多数研究分析了低深度（从0.0003 GB到7.7 GB）的宏基因组读数，^[5,6]目前缺乏高质量组装的病毒基因组，以及未能鉴定样品中低丰度的病毒。此外，经常使用产生短读段的Illumina测序。然而，据报道，短测序读数不足以准确组装病毒基因组，因为它们含有高变序列和重复区。^[7]

Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy.

Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification.

A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1.

The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients.

The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared.

For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE (n = 204) and OE groups (n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs. 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs. 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs. 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs. 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs. 3.9% [2/51], P= 0.031) subgroups.

MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.

Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer.

A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology.

Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs. 16.3% [14/86], P = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014).

The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.

Keratinocytes play an important role in wound healing; however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions.

We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody^TM Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes.

In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons’ diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum.

This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways.

Acute kidney injury (AKI) is a common complication in patients, especially elderly patients, who undergo cardiac surgery with cardiopulmonary bypass. Studies have indicated a protective role of autophagy in AKI. However, the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood. In this study, we aimed to test the hypothesis that exosomal microRNAs (miRNAs) regulate autophagy in tubular epithelial cells after AKI.

Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery, and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing. The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses. Renal tubular epithelial cell line (HK-2 cells) was cultured and hypoxia/reoxygenation (H/R) model was established, which is an in vitro renal ischemia/reperfusion (I/R) model. We used Western blot analysis, cell viability assay, transfection, luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy.

miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery. Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins, including Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3II), and prolonged the autophagic response in HK-2 cells after H/R treatment. These effects were achieved mainly via increases in the exosomal miR-590-3p levels, and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction.

Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner, which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.

A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA.

Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan-Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF.

A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8-62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7-60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ± 15.9 mL/h vs. 169.0 ± 15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study.

When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice.

Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR-IPR-17012629)

前列腺苗勒管囊肿常见于年轻男性，是相对罕见的临床并发症。中等大小的囊肿表现为尿路梗阻、尿路刺激、随后的尿频、尿急和排尿困难。较大的囊肿可压迫精囊或射精管，引起顽固性血精或梗阻性无精子症。苗勒管囊肿恶变更为罕见。在以前的研究中仅报告了10例苗勒管恶性肿瘤。^{[1,2,3,4,5,6,7,8,9]}我们报告了我中心收治的一例患者，并根据文献资料讨论了该病的临床病理特征、诊断、治疗和预后。此外，我们对病理组织进行了全外显子组测序和分析，筛选了苗勒管囊肿透明细胞癌的突变基因，并初步探讨了其发病机制。

超级微创手术（SMIS）是2016年提出的一个新概念，定义为“在保持人体器官解剖结构完整性的同时治愈疾病”。^[1]其理念已被世界内镜组织和中国消化内镜学会接受。SMIS的明显优势是在不损害器官结构和功能的情况下治愈疾病。对于癌症患者，可以保证正常的生存时间和术后生活质量（QoL）。^[1]然而，SMIS和食管切除术治疗浅表性食管鳞状细胞癌（SESCC）的高质量比较研究缺乏。因此，本研究主要旨在直接比较SMIS和食管切除术的结果，特别是在生活质量和生活方式方面。

血小板减少症是妊娠期常见的合并症。血小板（PLT）计数<100 × 10⁹/L作为血小板减少症的诊断。血小板减少症在临床环境中的主要不良反应是不同严重程度的出血。^[1]妊娠期血小板减少症的病因与其他疾病不同。妊娠期血小板减少症占孕妇血小板减少症病例的75%以上，发生在5%至8%的妊娠中。血小板减少症的其他原因包括溶血、肝酶升高、低血小板计数综合征、自身免疫性血小板减少性紫癜和其他潜在的血液疾病。^[2,3]大多数患有血小板减少症的女性不需要任何特殊治疗。^[2]对于临产时PLT计数仍较低的孕妇，预防性PLT输血用于预防产后出血。目前产科患者PLT输血指南通常基于以下标准：PLT计数维持>80 × 10⁹/L用于硬膜外麻醉下剖宫产且>50 × 10的患者⁹/L用于无麻醉自然分娩的妇女。^[4]

致编辑：胃神经内分泌肿瘤（gNENs）是源自胃中不同神经内分泌细胞的高度异质性肿瘤。最近的流行病学证据表明，gNENs占所有胃恶性肿瘤的0.3%至1.8%。^[1]然而，关于中国患者gNENs的研究数据很少，但中国医生需要提高对这种疾病的认识。

致编辑：多发性骨髓瘤（MM）是第二常见的血液恶性肿瘤，由浆细胞的克隆性增殖引起，其特征包括贫血、骨痛、肾功能不全和高钙血症。骨髓瘤细胞与骨髓（BM）微环境的粘附导致MM主要受累于髓内，然而，有时浆细胞可以播散并浸润到髓外（EM）部位，称为髓外疾病（EMD）。MM中EMD的患病率在初始诊断时为6%至8%，在疾病进展/复发期间可高达10%至30%。^[1]几十年来，据报道EMD的发病率不断增加，这可能是由于成像的进步以及生存期延长导致的继发性EMD的增加。EMD是一种高度侵袭性的疾病实体，即使在新型药物的时代，对治疗的反应也很差；因此，探讨髓外骨髓瘤（EMM）的发病机制和特点具有重要意义。^[2]

致编辑：内镜袖状胃成形术（ESG）是最近开发的一种无切口经口胃镜减肥手术，可以通过内镜全层缝合将胃腔缩小成类似于外科袖状胃切除术的管状结构。临床实践证明其安全性、耐用性、微创性、长期减肥效果接近减肥手术。^[1]

致编辑：脑脊液（CSF）渗漏增加了颅骨手术后术后并发症的风险，其进展并不总是可预测的。目前，外科医生使用各种方法来实现CSF的水密闭合，包括合成密封剂、胶原或明胶基海绵，^[1]和纤维蛋白密封剂(FS)。^[2,3]Bioseal（猪纤维蛋白密封剂试剂盒，广州生物密封生物技术有限公司，中国广州）是一种病毒灭活的猪血浆衍生FS，已被批准作为控制手术出血的支持治疗。^[4]在两种不同临床环境（神经外科和血管外科）中进行的两项4期试验（ClinicalTrials.gov，编号NCT02094885和NCT02034799）证明Bioseal作为辅助止血剂是安全有效的。这项多中心、前瞻性、随机、对照、单盲临床试验旨在评估Bioseal作为硬膜缝合术辅助手段在接受脑神经外科手术的受试者中实现术中防水闭合的安全性和有效性。

致编辑：联合核团刺激可能对控制神经系统疾病症状和改善生活质量具有协同作用。^[1]然而，增加导线可能会增加成本和并发症。^[2]因此，我们的研究旨在调查单弯曲电极导线的安全性和可行性，该电极导线可以同时到达丘脑底核（STN）和桥脚核（PPN）。

致编辑：原发性醛固酮增多症以高血压为特征，伴有或不伴有低钾血症，是内分泌性高血压最常见的形式，多由双侧肾上腺增生或产生醛固酮的肾上腺皮质腺瘤（APAA）引起。然而，它也可以由产生醛固酮的肾上腺皮质癌（APAC）诱导，这是罕见的。由于APAC的罕见性和恶性，APAC的临床特征以及APAC与APAA的差异仍不清楚，APAC的术前诊断是有价值的。因此，我们旨在通过从APAC患者病例报告和APAA临床文献中提取数据并制定APAC的术前诊断标准来比较APAA和APAC的临床特征。

致编辑：类风湿性关节炎(RA)是一种慢性炎性疾病，其特征在于心血管疾病(CVD)风险过高，估计比一般人群高至少50%。^[1]CVD已被认为是确定的RA患者死亡的主要原因，但最近的数据证实了这种趋势在疾病的早期阶段也是如此。^[2]几个因素被认为是这种额外风险的决定因素，但最统一的理论将这种现象归因于慢性高度炎症和“经典”心血管风险因素（包括糖尿病）患病率升高之间的相互作用。

致编辑：许多体检测试用于诊断股骨髋臼撞击（FAI）。屈曲、外展和外旋（FABER）试验与屈曲、内收和内旋（FADIR）试验对FAI诊断的敏感性和特异性有很大差异。因此，基于临床实践，我们提出了增加体检测试的可能性，以提高传统体检的准确性。