2024年 · 第137卷第03期

香港医学杂志（HKMJ）是中国香港特别行政区的旗舰全科医学期刊，具有国际视野。我们致力于发表和推广高质量的研究。我们的编辑委员会在总编辑黄志光教授的带领下，很高兴能与中华医学杂志（CMJ），以及CMJ的编辑，以提高我们各自期刊的知名度，并营造一个合作环境，为我们的读者带来想法和知识。

不确定胆道狭窄(IBS)是指组织学诊断不确定的胆道狭窄^[1]可分为非肿瘤性狭窄或肿瘤性狭窄。前者主要由各种炎性胆胰疾病、先天性畸形或术后胆管损伤所致，后者则存在于胆管癌、胰腺癌浸润、胆管内腺瘤等肿瘤性病变中。大多数非肿瘤性狭窄可通过内镜或内科保守治疗缓解，仅少数需要手术干预。然而，根据疾病的进展，应应用根治性手术或姑息性胆道引流治疗肿瘤性狭窄。因此，在临床工作中获得IBS的准确诊断至关重要。

Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations, while reliable biomarkers to detect or monitor are still under investigation. Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers, including proteins, ribonucleic acids (RNAs), and deoxyribonucleic acids (DNAs), for early detection of pathological changes in susceptible patients, rapid diagnosis at the bedside after onset, and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.

根据2017年全球疾病负担研究，中国有1.32亿慢性肾脏病（CKD）患者，^[1]且中国CKD患者高血压患病率（67.3%）显著高于普通人群（23.2%）。^[2,3]CKD既是高血压的原因，也是高血压的后果，这两种情况形成恶性循环，导致CKD患者高血压的高患病率。不受控制的高血压会加速肾功能恶化，从而显著增加发生终末期肾病（ESRD）以及心脑血管疾病的风险，导致患者预后不良。

Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.

The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.

In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.

In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.

We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.

We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.

REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.

The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.

The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, −1.0 to −0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019.

Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’ clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.

We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.

We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils (P = 0.010), total IgE (P = 0.006), high-sensitivity C-reactive protein (P <0.001), erythrocyte sedimentation rate (P <0.001), complement C4 (P <0.001), IgG (P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA (P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).

Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.

ClinicalTrials. gov, NCT01670695.

A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.

In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.

From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA (n = 384) or rt-PA (n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups.

rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.

www.ClinicalTrials.gov (No. NCT02835534).

The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown.

We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t-test, Mann–Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer–Lemeshow test for 11 prediction models.

We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m², the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (% TWL) was (29.1 ± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al’s regression model, and Panunzi et al’s regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74–0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73–0.89]), and Panunzi et al’s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78–0.92]) showed good discernibility. In the Hosmer–Lemeshow goodness-of-fit test, except for DiaRem (P <0.01), DiaBetter (P <0.01), Hayes et al (P = 0.03), Park et al (P = 0.02), and Ramos-Levi et al’s (P <0.01) models, all models had a satifactory fit results (P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively.

The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.

Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.

Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth (t = 9.917, P <0.001), thickness (t = 4.037, P <0.001), occupation (t= 2.169, P <0.050), orientation of collagen (t = 3.669, P <0.001), and the DEJ contour ratio (t = 5.105, P <0.001).

Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.

Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.

Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.

This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

致编辑：食管癌是中国最常见的癌症类型之一，预计2022年新增病例346,633例，死亡病例323,600例，正成为日益严重的临床和公共卫生问题。^[1]自我管理策略的成功推广表明，生活方式的改变在癌症发展的一级预防中是有价值的。采取健康的生活方式已成为高风险地区初级预防和降低风险的新颖策略。先前的流行病学研究已经确定了食管癌的几个与生活方式相关的危险因素，包括吸烟和饮食。^[2]每个因素通常都可以解释适度比例的癌症风险。然而，当组合时，这些已知的风险因素可能显著影响食管癌的风险。然而，食管癌的一些危险因素是不可改变的，包括年龄、低社会经济地位和家族史。这些不可改变的风险因素是否以及如何通过干预可改变的风险因素来影响一级癌症预防仍不清楚。

致编辑：虽然20-60%的慢性鼻窦炎伴鼻息肉(CRSwNP)患者患有共病哮喘（称为难治性哮喘），但在25-48%的患有共病哮喘的CRSwNP患者中哮喘未被诊断。^[1]此外，持续性气流受限（PAL）的患病率在伴有哮喘的CRSwNP患者中很高。然而，指示CRSwNP患者共病哮喘和反映共病哮喘患者PAL的因素尚未完全阐明。在CRSwNP患者中发现了小气道功能障碍（SAD），即使没有哮喘；并且共病哮喘患者SAD的严重程度与哮喘病史的持续时间相关。^[2]因此，本研究旨在评估临床特征，特别是小气道参数作为CRSwNP患者共病哮喘的指标和CRSwNP共病哮喘患者PAL的指标。此外，为了确定CRSwNP哮喘患者的特征，我们还比较了伴有或不伴有CRSwNP的哮喘患者之间SAD和PAL的患病率。

致编辑：慢性阻塞性肺疾病（COPD）是一种严重危害人类健康的疾病。2018年，王等人^[1]报道称，中国约有1亿COPD患者，40岁以上人群患病率为13.7%。在COPD患者中常见（30-57%）的疾病严重程度、恶化频率和合并症是影响COPD经济和社会后果的三个最关键因素。^[2]因病情恶化而住院是医疗保健费用的主要来源。为了减轻COPD的临床和经济负担，需要干预措施来减缓病程、避免恶化和减少合并症，例如改善COPD预后和治疗效果的方法。高通量组学技术的进步彻底改变了疾病研究。我们收集了COPD研究领域组学方法的数据。基因组学、转录组学、单细胞转录组分析、蛋白质组学、代谢组学、微生物组学、放射组学和药物基因组学研究来自PubMed数据库。我们的发现通过使用具有预测潜力的组学数据揭示了与COPD预后和治疗疗效相关的因素【补充图1，http：//links.lww.com/CM9/B913】。组学可能构成监测COPD预后的有力工具，为未来个体化治疗提供希望。

致编辑：在全膝关节置换术（TKA）中，显著的纤溶亢进总是伴随着手术创伤和止血带的使用，导致相当大的隐性失血、炎症和疼痛，从而阻碍恢复过程。近几十年来，增强术后恢复（ERAS）促进了患者血液管理的发展。并且已经研究了许多血液保存方法，包括氨甲环酸(TXA)，一种纤溶酶和纤溶酶原的赖氨酸类似物竞争性抑制剂。^[1,2,3]然而，一些问题仍有争议，如TKA中的最佳TXA方案。另一方面，TXA在关节成形术中的使用被认为是适应症外的，尽管目前的指南或共识建议其在关节成形术中的常规使用。此外，说明书中规定的TXA的最大日剂量为2g。我们之前的单中心研究表明，与60 mg/kg加5次术后给药方案相比，高初始剂量（60 mg/kg）加3次术后给药（1 g为3 h、12 h和24 h）应对TKA的血液节约产生上限效应。^[4]这些结果令人鼓舞，但尚不清楚总剂量（约6 g）是否优于法定剂量（2 g）。

致编辑：去甲肾上腺素（NE）属于儿茶酚胺家族，当宿主处于应激状态时，交感神经系统和肾上腺髓质会越来越多地产生。已经证明NE具有显著的抗炎作用。此外，越来越多的证据表明应激激素直接参与细菌和宿主之间的相互作用。多种细菌可以通过高浓度的NE表现出生长、毒力和生物膜的变化。因此，本文旨在总结NE对宿主免疫和细菌感染的影响及其分子机制的主要研究进展[图1].

致编辑：心脏淀粉样变性（CA）是一种浸润性心肌病，其特征是错误折叠的不溶性淀粉样原纤维的细胞外沉积。^[1]心电图（ECG）是一种重要的诊断检查，其特征是CA中的低QRS电压，在20-74%的患者中观察到。^[2]西普里亚尼等人^[3]报道称，低QRS电压可以独立预测心血管死亡。但是CA中低QRS电压的潜在机制仍不清楚。

致编辑：乳腺癌是一种常见的恶性肿瘤，在全球范围内是癌症相关死亡的第二大原因。^[1]乳腺是一些内分泌激素的靶器官，调节乳腺的生长发育。除了雌激素和黄体酮，催乳素、雄激素和乳腺癌之间的关系最近越来越受到关注。

致编辑：精索静脉曲张（VC）是一种血管疾病，被认为是男性不育的主要原因。^[1]普通男性人群VC的发病率为4.4-22.6%，其中原发性不育症的发病率为35-40%，而继发性不育症的发病率高达80%。^[2]VC引起男性不育的确切病理生理机制及调控分子尚不清楚。明确明确的VC病分子标志物有助于早期预防和及时治疗。本研究旨在筛选在VC引起的男性不育中起作用的候选调节分子。

致编辑：神经精神系统性红斑狼疮（NPSLE）是系统性红斑狼疮（SLE）的一组严重并发症，预后差，死亡率高。^[1]因此，识别NPSLE的危险因素对于改善患者的预后尤为重要。磁共振成像（MRI）是目前诊断NPSLE患者的首选成像检查。然而，几乎一半的NPSLE患者在常规MRI上没有显示异常。^[2]因此，神经精神症状（指与SLE直接相关的多种神经精神表现）与MRI表现的相关性亟待研究。在本研究中，我们调查了NPSLE的临床特征、预后和预后因素，并分析了神经精神症状与MRI特征的相关性。

致编辑：甲状旁腺肿瘤是一种内分泌肿瘤，可导致钙、磷代谢紊乱，累及多个器官系统。在过去，甲状旁腺肿瘤的遗传学已经很好地建立，并且基因的重要作用，例如男人1,CDC73，和CCND1在甲状旁腺肿瘤发生过程中已被鉴定和证实[表1].然而，随着进一步的研究和测序技术的广泛使用，“旧”基因的“新”角色和新的致病机制被发现。