Volume 135 · Issue 17 · 2022

China and the United States (US) ranked first and third in terms of new liver cancer cases and deaths globally in 2020. Therefore, a comprehensive assessment of trends in the incidence of primary liver cancer with four major etiological factors between China and the US during the past 30 years with age-period-cohort (APC) analyses is warranted.

Data were obtained from the Global Burden of Disease 2019, and period/cohort relative risks were estimated by APC modeling from 1990 to 2019.

In 2019, there were 211,000 new liver cancer cases in China and 28,000 in the US, accounting for 39.4% and 5.2% of global liver cancer cases, respectively. For China, the age-standardized incidence rate (ASIR) consecutively decreased before 2005 but increased slightly since then, whereas the ASIR continuously increased in the US. Among the four etiological factors of liver cancer, the fastest reduction in incidence was observed in hepatitis B virus-related liver cancer among Chinese women, and the fastest increase was in nonalcoholic steatosis hepatitis (NASH)-related liver cancer among American men. The greatest reduction in the incidence of liver cancer was observed at the age of 53 years in Chinese men (-5.2%/year) and 33 years in Chinese women (-6.6%/year), while it peaked at 58 years old in both American men and women (4.5%/year vs. 2.8%/year). Furthermore, the period risks of alcohol- and NASH-related liver cancer among Chinese men have been elevated since 2013. Simultaneously, leveled-off period risks were observed in hepatitis C viral-related liver cancer in both American men and women.

Currently, both viral and lifestyle factors have been and will continue to play an important role in the time trends of liver cancer in both countries. More tailored and efficient preventive strategies should be designed to target both viral and lifestyle factors to prevent and control liver cancer.

To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE).

Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study.

Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9–16.3) months for patients with HPS and 15.1 (95% CI, 7.3–22.9) months for patients without HPS, which is not a significant difference (P = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0–12.8] vs. 8.4 [95% CI, 3.6–13.1] months; P = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003–1.064]; P = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011–3.260]; P = 0.046) were identified to be the independent prognostic factors of OS.

Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.

Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world’s largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO’s goal.

Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B.

In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45–5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = –7.63; 95% CI: –8.25, –7.00), cirrhosis and other chronic liver diseases (EAPC= –4.15; 95% CI: –4.66, –3.65), and liver cancer (EAPC = –5.17; 95% CI: –6.00, –4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019.

Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO’s goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.

Non-transport unintentional injuries (NTUIs) are major public concerns, especially among children and adolescents in low- and middle-income countries. With environmental and cognitive changes, a recent systematic description of global trends and regional differences concerning NTUIs is urgently needed for the global agenda of relevant policy-making and intervention target findings.

We used mortality, population, and socio-demographic-index (SDI) data from Global Burden of Disease 2019 to analyze the trends of NTUIs mortality. We applied the slope index of inequality (SII) and relative index of inequality (RII) to measure the absolute and relative inequality between countries and territories. The concentration curve and concentration index (CI) were also used to measure the inequality. We conducted a sensitivity analysis to make our findings credible.

In 2019, there were 205,000 deaths due to NTUIs among children and adolescents aged 5 to 24 years, which decreased from 375,000 in 1990. In 2019, the age-standardized mortality rate (ASMR) was 8.13 per 100,000, ranging from the lowest in the Netherlands (0.90 per 100,000) to the highest in the Solomon Islands (29.34 per 100,000). The low-middle SDI group had the highest ASMR of NTUIs, while the low SDI group had the slowest decrease. After excluding the death caused by "exposure to forces of nature" and "other unintentional injuries" , drowning accounted for the most deaths in almost every SDI group, gender, and age group, but the major causes of death varied in different subgroups. For example, animal contact was a major cause in low and low-middle SDI groups but less in high SDI groups, while high and high-middle SDI groups had a higher proportion of deaths for foreign body and poisonings. The SII showed a declining trend, but the RII and CI did not, which might indicate that inequality was persistent. Similar results were found in the sensitivity analysis.

Despite the declining trend of the mortality rate and the narrowing gap between countries, there were still a large number of children and adolescents dying from NTUIs, and those experiencing social-economic disadvantages remained at high mortality. Embedding the prevention of NTUIs into sustainable development goals might contribute to the progress of reducing death and inequalities, which ensures that no one is left behind.

Cardiovascular disease (CVD) remains the leading cause of deaths nationwide. However, little is understood about its temporal trend and corresponding influence on longevity improvements. We aimed to describe the updated tendency in CVD mortality and to quantify its impact on life expectancy (LE) increase in China.

All-cause mortality rates were calculated with population sizes from the National Bureau of Statistics and death counts from the National Health Commission. We estimated CVD mortality rates by allocating age- and sex-based mortality envelopes to each CVD subtype based on its proportion derived from the Disease Surveillance Points system. The probability of CVD premature deaths and LE were calculated with life tables and we adopted Arriaga’s method to quantitate age- and cause-specific contributions to LE gains.

During 2013 to 2018, the age-standardized mortality rate of CVD decreased from 289.69 (95% confidence interval [CI]: 289.03, 290.35)/100,000 to 272.37 (95%CI: 271.81, 272.94)/100,000, along with a decline in probability of CVD premature deaths from 9.05% (95%CI: 9.02%, 9.09%) to 8.13% (95%CI: 8.10%, 8.16%). The gap in CVD mortality across sexes expanded with more remarkable declines in females, especially for those aged 15 to 64 years. Among major subtypes, the probability of premature deaths from hemorrhage stroke declined fastest, while improvements of ischemic stroke and ischemic heart disease were limited, and there was an increase in stroke sequelae. LE in China reached 77.04 (95%CI: 76.96, 77.12) years in 2018 with an increase of 1.38 years from 2013. Of the total LE gains, 21.15% (0.29 years) were attributed to reductions of CVD mortality in the overall population, mostly driven by those aged >65 years.

The general process in reducing CVD mortality has contributed to longevity improvements in China. More attention should be paid to prevention and control of atherosclerotic CVD and stroke sequelae, especially for the elderly. Working-age males also deserve additional attention due to inadequate improvements.

Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions.

We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’ demographic profiles and disease characteristics.

In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies.

The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population.

A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min^-1·1.73 m^-2.

After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β -2.53, 95% confidence interval -3.89,-1.17, P_trend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no).

Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.

MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms.

We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 (RUNX3) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC.

MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion.

Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

慢性阻塞性肺病（COPD）的特征是肺气肿和气流受限，是全世界发病率和死亡率的主要原因之一。内镜肺减容术（ELVR）是一种微创技术，适用于严重过度充气和晚期肺气肿患者。迄今为止，研究最多的ELVR形式是瓣膜植入，即在肺气肿肺叶的所有节段中放置瓣膜。然而，在存在叶间侧支通气（CV）的情况下，瓣膜置换不能实现足够的肺容量减少。^[1]此外，由于治疗叶内存在异质性，植入物的完全叶治疗可能导致较少患病节段的过度减少。因此，需要对肺叶最严重的肺气肿部分采取更有针对性的方法。

胰腺癌（PAAD）是全球内分泌癌死亡的主要原因，给公众健康带来负担。新出现的证据表明，PAAD的形成是一个极其复杂的多基因参与和多阶段进化的生物学过程。^[1]因此，表观遗传或基因组不稳定性可能是PAAD患者预后不良的原因。RNA甲基化已成为表观遗传调控的基本过程。最近已显示长非编码RNA(lncRNAs)具有在几个水平(例如转录后、转录和表观遗传)调节基因表达的能力。^[2]因此，我们系统地研究了m7G RNA调节因子在泛癌中的作用和预后表现，尤其是在PAAD中。

后循环卒中的发病率和死亡率很高，占缺血性卒中的20%，大约25%发生在椎动脉和/或基底动脉狭窄的患者中。^[1]另一方面，症状性椎动脉（VA）狭窄患者5年后发生后循环缺血性卒中的风险达到30%。^[2]锁骨下动脉(SA)闭塞，尽管在普通人群中患病率较低，^[3]也是引起后循环脑卒中的重要原因。

致编辑：股总动脉是外科手术最受欢迎的穿刺通路。股深动脉和股浅动脉分叉处的股总动脉远端难以识别，尤其是血管外科医生行顺行股动脉穿刺治疗同侧下肢动脉病变时。许多研究报道了在X射线上解剖定位股骨头的方法。在此，我们介绍一个解剖学标志——Shenton线，它是指正常骨盆正位片上连接股骨颈内外侧缘和耻骨下缘的弧线。

致编辑：支气管哮喘是一种呼吸系统疾病，其病理特征主要包括气道炎症、气道重塑和气道高反应性的改变。哮喘发作时，大量炎症基因被激活，炎症介质表达增加，最终导致气道高反应性和重塑。核因子-κ B（NF-κ B）由Rel家族的转录活性二聚体组成，与哮喘发作时炎症基因的表达密切相关。

致编辑：冠状病毒疾病2019（新冠肺炎）已迅速成为一种巨大的全球感染，并带来了广泛的健康后果，包括由于持续传播而导致的大量死亡。^[1]吴等人^[2]报告称，不同国家的死亡率变化是不同的，这导致新冠肺炎死亡率的共同衡量标准仅限于住院死亡的特定结果，因此可被视为不完整。在中国，由于采取了保持社交距离和佩戴外科口罩等综合对策，COVID-19的状况从爆发到积极预防。同时，基于社区的样本调查应有助于澄清对院外死亡死亡率的疑问。此外，疫情局势对非自然死亡的影响仍不清楚，特别是在自杀方面。这或许可以说明疫情对人们精神状态的不利影响。设计了一项回顾性研究，以分析发生在医院外的所有死亡的特征，以获得更广泛影响的全面概述，并根据研究全因死亡率的需要进一步证明致命关联的特异性。

致编辑：肾细胞癌（RCC）是成人最常见的十大癌症之一。^[1]肾部分切除术（PN）是小型肾细胞癌的标准治疗方法。^[2]近几十年来，微创PN，包括机器人辅助肾部分切除术（RAPN）和腹腔镜肾部分切除术（LPN），由于其侵入性较小，被认为是开放PN的可行替代方案。因此，在微创PN治疗后，在RCC患者中观察到更短的住院时间和良好的临床结果。^[2]术中或术后出血和尿漏（UL）是PN术后最常见的术后并发症，发生率分别为1.2%~9.5%和1.2%~4.5%。^[3]鉴于很难识别复杂的肾脏血管分布和血管边界，微创PN期间最大的挑战之一是最大限度地减少手术区域的失血。^[3]目前，缝合是PN中公认的存档肾实质止血的标准止血方法。^[3]为了改善止血并降低PN后手术并发症的发生率，已经开发和实施了多种止血剂（HAs）。局部可生物降解的HAs，如纤维蛋白密封剂（如TachoSil®[武田制药A/S，林茨，奥地利]，Tisseel®[Baxter Healthcare Corp.，Deerfield，IL，USA]和Evicel®[OMRIX Biopharmaceuticals Ltd，Ramat Gan，Israel])、明胶基质凝血酶密封剂(例如FloSeal®[Baxter Healthcare Corp.，Deerfield，IL，USA])等由于其低毒性和自然降解而成为最佳选择。^[4]

致编辑：对于机械和生物人工心脏瓣膜置换患者，根据指南推荐维生素K拮抗剂（VKA）治疗。有效和安全的华法林治疗需要持续监测凝血酶原时间和国际标准化比值（INR）水平，以调整华法林的剂量。

致编辑：癌症和心血管（CV）疾病与世界上最大的发病率和死亡率相关，它们通过一些共同的风险因素相互关联。^[1]抗癌治疗过程中心脏毒性的发生率将随着癌症患者生存期延长、人口老龄化、与CV疾病相关的慢性基础疾病发病率增加以及新药的大量引入而不断增加。^[1]心脏肿瘤学是一个新的跨学科研究领域，专注于与抗癌治疗相关的心血管毒性的筛查、预防、检测、监测和治疗，为癌症患者制定合理的管理策略属于其研究范围。^[1]

致编辑：2型糖尿病（T2D）和胆石症都是患病率较高的常见病。在中国，T2D患病率为0.9%^[1]成人胆石症发病率为6.83%。^[2]肥胖、胰岛素抵抗和代谢异常是T2D的危险因素；流行病学研究表明，它们也是胆石症的危险因素。^[3,4]几项研究表明，糖尿病患者患胆石症的风险增加。^[5]近年来，越来越多的证据表明糖尿病和胆石症的肠道微生物群失衡。在T2D患者中，属双歧杆菌、拟杆菌、和罗斯布里亚减少了，而瘤胃球菌、梭杆菌、和布劳蒂亚都显著增加。在胆结石患者中，肠道细菌（拟杆菌、真杆菌、和大肠杆菌）参与胆汁酸的氧化和差向异构化，可破坏肠肝循环，导致胆石症。^[6,7]

致编辑：尿毒症性瘙痒是一种常见且令人痛苦的并发症，影响>65%接受维持性血液透析（MHD）的患者。尿毒症瘙痒的强度与MHD患者的抑郁、睡眠障碍、生活质量下降和死亡率增加相关；然而，尿毒症瘙痒症的发病机制知之甚少，目前没有有效的治疗方法。^[1]在皮肤炎性疾病如特应性皮炎和银屑病中，血小板参与皮肤中的免疫应答，并与白细胞和内皮相互作用以调节炎症、促进过敏致敏并引发瘙痒。^[2]目前，血小板在瘙痒性皮肤病发病机制中的作用尚不清楚。因此，本研究旨在探讨尿毒症瘙痒的严重程度与血小板参数之间的关系，包括血小板计数（PC）、平均血小板体积（MPV）、血小板分布宽度（PDW）、血小板—大细胞比值（P-LCR）和血小板比（PCT）。

致编辑：脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍。脓毒症严重扰乱免疫稳态，并通过直接改变负责稳态的效应细胞的寿命、产生和功能来损害先天和适应性免疫。^[1]Demaret之前的一项研究等人^[2]据报道，脓毒症诱导的免疫抑制阶段的特征是中性粒细胞趋化性（功能性和趋化因子受体表达）、氧化爆发、乳铁蛋白含量和循环未成熟粒细胞数量增加的显著改变，这些方面与脓毒症休克后死亡风险增加相关。然而，对脓毒症诱导的免疫抑制期中性粒细胞的关键基因和途径知之甚少。因此，这需要使用生物信息学分析来鉴定脓毒症诱导的免疫抑制期间的差异表达基因（DEGs）和信号通路，首要目标是阐明中性粒细胞在脓毒症诱导的免疫抑制中的作用。

致编辑：苯磺酸瑞马唑仑是一种新型、超短效苯二氮卓类药物，起效和抵消特征迅速且可预测，无蓄积和延长效应，且不依赖于器官消除。^[1,2]有几份报告显示苯磺酸瑞马唑仑在短期手术和全身麻醉中的镇静应用，然而，没有研究报告其在重症监护室（ICU）中的应用。^[3,4]本研究的目的是调查在ICU非心脏手术后机械通气患者中提供轻度至中度镇静的苯磺酸瑞马唑仑输注剂量。

在最初的文章发表之后，^[1]作者告知我们以下错误：^[1]图1提交不正确，而正确的图1应按如下方式提交：