Volume 136 · Issue 14 · 2023

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research. They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.

A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities.

We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer.

During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93–1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03–1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12–1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk.

These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.

Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients.

A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO.

Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection (P = 0.003). Age ≤60 years (P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L (P <0.001), well-differentiated tumor (P = 0.008), no liver involvement (P <0.001), and T1-2 stage disease (P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group (P <0.05).

Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.

This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1: 1: 1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.

A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).

The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

ClinicalTrials.gov, No. NCT05014334

Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness.

From 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts.

LASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients (P < 0.001).

The nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.

Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients.

An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018–2022 period. The primary outcome was major postoperative complications (Clavien–Dindo class III–V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level.

The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018–2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5–18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24–12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6–22.1%]; aOR, 7.89 [95% CI, 5.76–10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching.

Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications.

NCT05677815 at https://clinicaltrials.gov/.

Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism.

Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2′-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo. The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay.

In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N⁶-methyladenosine (m⁶A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m⁶A site on the 3′-untransated regions (3′-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells.

HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.

根据最新中国癌症流行病学报告,^[1]国家癌症中心（NCC）公布，肺癌是我国发病率最高的恶性肿瘤（57.26/10万）。我们开发了肺结节评估：亚洲临床实践共识指南,^[2]和中国肺结节诊治专家共识.^[3]为了提高肺癌的早期诊断和改善预后，我们还开发了中国肺癌筛查与管理专家共识.^[4]然而，在临床实践中仍然存在挑战，因此，中国抗肺癌联盟（CAALC）邀请临床、信息技术（IT）和卫生经济学专家对这些问题进行讨论，并起草了这份文件，中国肺癌筛查标准及规范化管理.^[5]

As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.

Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.

In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70–0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80–1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03–1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25–0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67–0.92, P = 0.002).

The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.

致编辑：肺泡蛋白沉积症（PAP）是一种以肺泡腔内肺表面活性物质异常和过度积聚为特征的罕见疾病。PAP病例通常分为三种病因形式：先天性、继发性和特发性PAP。全肺灌洗（WLL）已被广泛用于治疗PAP。^[1]根据文献，PAP与肺癌相关的病例报告很少。此外，据我们所知，很少有PAP伴肺癌接受确定性胸部放射治疗（TRT）的病例报道。在此，我们报告了一例与有限期小细胞肺癌（LS-SCLC）相关的PAP病例，该病例采用化疗和序贯TRT联合治疗。出乎意料的是，患者的PAP临床和影像学异常在TRT后完全缓解。

高血压，也称为高血压，是一种严重的疾病，可能导致严重的健康问题，如心脏病发作和中风。据世界卫生组织（WHO）称，^[1]据估计，2021年全球有12.8亿30-79岁的成年人患有高血压，其中三分之二生活在中低收入国家。许多关于高血压诊断、评估和治疗的国家和国际临床实践指南（CPG）已经出版，以促进其控制。其中，与“狭义”类型的指南相比，综合性高血压指南为更多目标用户，尤其是初级保健从业者提供了更广泛的方向。高血压指南的可信度是利益相关者非常关心的问题。许多研究人员使用研究与评估指南评估（AGREE）工具和医疗保健实践指南报告项目（RIGHT）清单来评估高血压指南的质量。然而，由于指南方法学的发展和高血压新证据的不断发表，早期的结果可能不再反映高血压指南的现状。本研究的目的是评估过去6年出版的综合高血压指南的方法学和报告质量，发现主要问题，并根据现状，具体针对中国的情况，评估新的高血压指南的必要性。

致编辑：尽管进行了最佳的二级预防治疗，但经皮冠状动脉介入治疗（PCI）后仍有很大比例的冠状动脉疾病（CAD）患者处于心血管事件复发的高风险中。炎症是残余心血管风险的众所周知的组成部分，并有助于动脉粥样硬化的进展，导致动脉粥样硬化斑块的不稳定和破裂。^[1]作为介导动脉粥样硬化进展的活化炎症通路中的下游蛋白，高敏C反应蛋白（hsCRP）被广泛用作心血管疾病一级和二级预防中炎症状态的生物标志物和不良结局的预测因子。肥胖被认为是日益增长的全球负担，也是心血管疾病的显著危险因素。几项研究先前提出并检验了体重指数（身体质量指数）可以改变hsCRP和心血管风险之间的关联的假设。^[2,3]然而，在CAD患者中这种关系尚不清楚。因此，我们旨在基于一个大型前瞻性队列研究BMI、hsCRP和PCI后长期结局的相互关系。

致编辑：胆汁反流（BR）又称十二指肠胃反流，是指胆汁、胰液、十二指肠液等十二指肠内容物反流至胃内。未经胃手术而发生的BR称为原发性胆汁反流（PBR）。^[1]一项回顾性研究显示，慢性胃炎患者PBR的患病率高达20.5%。^[2]BR可有助于上消化道疾病的发展，^[3,4,5]但目前尚不清楚相应的风险因素。我们旨在确定PBR的相关危险因素。

致编辑：多发性骨髓瘤(MM)是一种以异质性特征为特征的浆细胞疾病。^[1]准确的风险分层可以预测骨髓瘤患者的不同预后，并获得风险适应治疗以延长其寿命。近日，欧洲骨髓瘤网络（EMN）进行了一项涉及7000多名骨髓瘤患者的大型回顾性分析，开发了一种新的风险模型，定义为国际分期系统第二修订版（R2-ISS），在入组临床试验的患者中风险分布极佳。^[2]R2-ISS分层基于不同预后因素的加权风险评分：ISS II 1.0分，ISS III 1.5分，del（17p）1.0分，乳酸脱氢酶（LDH）升高1.0分，t（4；14）1.0分，2021年第一季度+0.5分。根据累积总分，患者进一步分为四个风险组：R2-ISS I（0分）、II（0.5-1.0分）、III（1.5-2.5分）和IV（3.0-5.0分）。然而，关于R2-ISS在现实世界中的适用性和预测性能的证据是有限的。因此，本研究旨在确定R2-ISS是否对在中国接受真实世界治疗模式的MM患者有效。

致编辑：全膝关节置换术（TKA）已经成为终末期关节疾病的既定治疗方法。在中国，2011年至2019年间，TKA病例数量增加了5.9倍。各种感染都是TKA的灾难性并发症。最近的报告强调了手术部位感染（SSIs）的低估患病率，并预计2020年至2030年间髋关节和膝关节置换术后复杂SSIs将增加14%。^[1]然而，描述中国人群SSIs的报道很少。这项初步的回顾性研究旨在了解中国SSI的发生、危险因素和微生物学模式。

致编辑：肾母细胞瘤，或称肾母细胞瘤，是最常诊断的儿童肾癌，占1-7岁儿童所有肾肿瘤的>90%，该病可能与遗传因素有关。^[1]作为一个新兴的研究热点，表转录组与人类疾病（包括癌症）的不同RNA修饰有关。^[2]甲基转移酶样1（梅特尔1），一种关键的RNA N7-甲基鸟苷（m7G）甲基转移酶，可以通过与WD重复结构域4（WDR4).根据不同的位置，tRNA m7G修饰具有各种功能。特别地，位于反密码子区的tRNA修饰在翻译和生长中起关键作用，而反密码子区之外的那些修饰负责调节tRNA折叠、稳定性和蛋白质合成。m7G修饰在进化上是保守的，并且在哺乳动物中具有更复杂和重要的生理功能。^[3]越来越多的证据有力地支持梅特尔1m7G甲基转移酶与肿瘤的发生和不良预后密切相关。^[2]从机理上讲，已经确定了一种潜在的分子机制梅特尔1-介导的m7G修饰导致恶性转化和肿瘤发生。奥雷利亚纳等人^[2]发现tRNAs的m7G修饰在某些癌症中上调，这一过程是由METTL1/WDR4复杂的。m7G修饰的tRNA可以解码相应的致癌和细胞周期调节信使RNA（mRNA），这些信使RNA富含m7G-tRNA依赖性密码子，而不会发生核糖体碰撞，从而促进这些mRNA的翻译和细胞的潜在恶性转化。

致编辑：高级碳水化合物计数（CC）是1型糖尿病（T1DM）患者推荐的饮食策略和必要的营养知识。^[1]有证据支持晚期CC对血糖控制、生活质量和食物灵活性的积极影响。^[2]然而，对于T1DM患者甚至医疗保健专业人员来说，晚期CC的教育和意识远非理想。^[3]因此，量化T1DM患者对此类营养知识理解的测量对于定制护理至关重要。

致编辑：多囊卵巢综合征（PCOS）是育龄妇女常见的内分泌疾病。PCOS的特征是排卵不频繁或不排卵、高雄激素水平和高胰岛素血症。雄激素过多是本病的主要病理生理机制。二甲双胍可降低胰岛素和雄激素水平，升高雌二醇水平，诱导排卵。^[1]吡格列酮可增加外周组织对胰岛素的敏感性，改善胰岛素抵抗，降低雄激素水平，恢复月经周期，促进排卵。^[2]尽管进行了广泛的研究，但介导二甲双胍或吡格列酮治疗PCOS有益作用的分子机制仍不清楚。个体患者对药物的反应也存在差异。据报道，遗传因素可能导致这种变异性。^[3]有机阳离子转运蛋白1编码单核苷酸多态性的影响（OCT1）对二甲双胍的摄取和疗效的影响先前已被广泛研究。^[4,5]此外，在脂肪细胞分化的早期阶段需要lipin-1来诱导成脂基因转录程序，包括关键调节因子过氧化物酶体增殖物激活受体γ（PPAR γ).^[6]迄今为止，LPIN1据报道，多态性与2型糖尿病和代谢综合征相关。^[7]因此，在这项研究中，我们旨在确定遗传多态性对OCT1和LPIN130例PCOS患者对吡格列酮—二甲双胍片的反应。

致编辑：大约1500万早产儿，即在<全球每年都有37周胎龄(GA)出生，其中0.4%是极早产儿(EPI)，即在<28周GA。^[1]新生儿护理的迭代显著延长了早产儿的生存能力。然而，生存能力的提高伴随着不可逆损伤的风险增加，例如支气管肺发育不良和脑室内出血。因此，更生理模拟子宫内需要地位来保护EPI在过渡期内未成熟的器官，并确保它们以与在子宫中相同的方式发育。