2022年 · 第135卷第17期

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.

Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and airflow limitation and is one of the leading causes of morbidity and mortality worldwide. Endoscopic lung volume reduction (ELVR) is a minimally invasive technique for patients with severe hyperinflation and advanced emphysema. To date, the most investigated form of ELVR is valve implantation, which is to place valves in all the segments of an emphysematous lobe. However, valve replacements do not achieve adequate lung volume reduction in the presence of interlobar collateral ventilation (CV).^[1]In addition, with the heterogeneity existing within the treatment lobe, complete lobar treatment from implants may result in excessive reduction of the less diseased segments. Thus, a more targeted approach of the most severe emphysematous parts of the lobe is warranted.

Pancreatic adenocarcinoma (PAAD) is the primary cause of mortality from endocrine cancer globally, bringing a burden to public health. Emerging evidence has suggested that the formation of PAAD is an extremely complicated biological process with multi-gene participation and multi-stage evolution.^[1]Therefore, epigenetic or genomic instability may be responsible for the poor prognosis of PAAD patients. RNA methylation has emerged as a fundamental process in epigenetic regulation. Long non-coding RNAs (lncRNAs) have recently been shown to have the capacity to modulate the gene expression at several levels, such as post-transcriptional, transcriptional, and epigenetic.^[2]Therefore, we systematically investigated contributions and prognostic performances of m7G RNA regulators in pan-cancer, especially in PAAD.

With high rates of morbidity and mortality, posterior circulation stroke accounts for 20% of ischemic strokes, and approximately 25% occurs in patients with stenosis in the vertebral and/or basilar arteries.^[1]On the other hand, the risk of posterior circulation ischemic stroke reaches 30% in patients with symptomatic vertebral artery (VA) stenosis after 5 years.^[2]Subclavian artery (SA) occlusion, although with a low prevalence in the general population,^[3]is also an important cause of posterior circulation stroke.

To the Editor:The common femoral artery is the most popular puncture access route for surgical intervention. The distal end of the common femoral artery where the deep femoral artery and the superficial femoral artery bifurcate is difficult to identify, especially when vascular surgeons perform antegrade femoral artery puncture to treat ipsilateral lower extremity artery disease. Many studies have reported methods to anatomically localize the femoral head on the X-ray. Here, we introduce an anatomic landmark, Shenton’s line, which refers to the arc line connecting the internal lateral margin of the femur neck and the inferior margin of the pubic bone in a normal anteroposterior radiograph of the pelvis.

To the Editor:Bronchial asthma is a respiratory disease with pathological features that mainly comprise changes in airway inflammation, airway remodeling, and airway hyperresponsiveness. During an asthma attack, a large number of inflammatory genes are activated, and the expression of inflammatory mediators increases, eventually leading to airway hyperresponsiveness and remodeling. Nuclear factor-κB (NF-κB) is composed of transcriptionally active dimers of the Rel family, which is closely related to the expression of inflammatory genes during an asthma attack.

To the Editor:Coronavirus disease 2019 (COVID-19) has rapidly become a great global infection and brought about a wide range of health consequences, including a high number of deaths due to continuous spread.^[1]Wuet al^[2]reported that the changes in mortality were heterogeneous across different countries, and this resultantly restricts the common measure of COVID-19 mortality to the particular outcome of in-hospital death and can therefore be regarded as incomplete. In China, the status of COVID-19 has varied from outbreak to proactive prevention due to comprehensive countermeasures such as maintaining social distance and wearing surgical masks. Meanwhile, investigation with community-based samples should contribute to clarifying the doubt about mortality in out-hospital deaths. Moreover, the impact of the pandemic situation on unnatural death remains unclear, particularly about suicide. This may illustrate the adverse effect of the epidemic on people’s state of mind. A retrospective study was designed to analyze the characteristics of all deaths that occurred outside hospitals to obtain a full overview of the broader impact, as well as to lend further plausibility to the specificity of fatal associations according to the need to study all-cause mortality.

To the Editor:Renal cell carcinoma (RCC) is one of the top ten most common cancers in adults.^[1]Partial nephrectomy (PN) is the standard treatment for small RCC.^[2]In recent decades, minimally invasive PN, including robotic-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN), has been considered as a viable alternative for open PN due to its less invasive approach. As a result, shorter hospital stay and favorable clinical outcomes are observed in RCC patients after minimally invasive PN treatment.^[2]Intraoperative or post-operative hemorrhage and urinary leakage (UL) are the most common post-operative complications after PN, with the incidence rates of 1.2% to 9.5% and 1.2% to 4.5%, respectively.^[3]Given that it is difficult to identify the complex renal vascularity and vascular border, one of the biggest challenges during minimally invasive PN is to minimize blood loss in the operating field.^[3]At present, suture is recognized as the standard hemostatic method in PN for archiving renal parenchymal hemostasis.^[3]To improve hemostasis and reduce the incidence of surgical complications after PN, a wide variety of hemostatic agents (HAs) have been developed and implemented. Topical biodegradable HAs, such as fibrin sealants (eg, TachoSil® [Takeda Pharma A/S, Linz, Austria], Tisseel® [Baxter Healthcare Corp., Deerfield, IL, USA], and Evicel® [OMRIX Biopharmaceuticals Ltd, Ramat Gan, Israel]), gelatin matrix thrombin sealants (eg, FloSeal® [Baxter Healthcare Corp., Deerfield, IL, USA]), etc, are the best choice owing to their low toxicity and natural degradation.^[4]

To the Editor: For patients with mechanical and bioprosthetic heart valve replacement, vitamin K antagonist (VKA) therapy is recommended according to guidelines. Effective and safe therapy with warfarin requires continuous monitoring of prothrombin time and international normalized ratio (INR) levels to adjust the dose of warfarin.

To the Editor:Cancer and cardiovascular (CV) disease are associated with the largest morbidity and mortality in the world, and they are related to each other through some common risk factors.^[1]The incidence of cardiac toxicity during anticancer treatment will continue to increase as the survival time of cancer patients is prolonged, the population ages, the incidence of chronic underlying diseases related to CV diseases increases, and a large number of new drugs are introduced.^[1]Cardio-oncology is a new interdisciplinary research field focusing on the screening, prevention, detection, monitoring, and treatment of CV toxicity related to anticancer treatment, and the development of rational management strategies for cancer patients is within its research scope.^[1]

To the Editor:Type 2 diabetes (T2D) and cholelithiasis are both common diseases with a high prevalence. In China, the prevalence of T2D is 0.9%^[1]and that of adult cholelithiasis is 6.83%.^[2]Obesity, insulin resistance, and abnormal metabolism are risk factors for T2D; epidemiologic studies have suggested that they are also risk factors of cholelithiasis.^[3,4]Several studies indicated that patients with diabetes are at an increased risk of developing cholelithiasis.^[5]In recent years, increasing evidence has demonstrated an imbalance in the gut microbiota in both diabetes and cholelithiasis. In patients with T2D, the generaBifidobacterium, Bacteroides,andRoseburiaare decreased, whereasRuminococcus, Fusobacterium,andBlautiaare significantly increased. In patients with gallstone, intestinal bacteria (Bacteroides, Eubacterium,andEscherichia coli) involved in the oxidation and epimerization of bile acids can disrupt enterohepatic circulation and lead to cholelithiasis.^[6,7]

To the Editor: Uremic pruritus is a common and distressing complication that affects >65% of patients undergoing maintenance hemodialysis (MHD). The intensity of uremic pruritus is associated with depression, impaired sleep, reduced quality of life, and increased mortality in MHD patients; however, the pathogenesis of uremic pruritus is poorly understood and no effective treatments currently exist.^[1]In cutaneous inflammatory diseases such as atopic dermatitis and psoriasis, platelets are involved in the immune responses in the skin and interact with leukocytes and endothelium to regulate inflammation, promote allergic sensitization, and provoke pruritus.^[2]Currently, the role of platelets in the pathogenesis of pruritic skin disease is unclear. Therefore, this study aimed to explore the relationships between the severity of uremic pruritus and platelet parameters, including platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR), and plateletcrit (PCT).

To the Editor:Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis deeply perturbs immune homeostasis, and impairs innate and adaptive immunity by directly altering the lifespan, production, and function of the effector cells responsible for homeostasis.^[1]A previous study by Demaretet al^[2]reported that the phase of sepsis-induced immunosuppression is characterized by a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, lactoferrin content, and an increased number of circulating immature granulocytes, and these aspects were associated with an increased risk of death after septic shock. However, little is known about the key genes and pathways of neutrophils during the sepsis-induced immunosuppression phase. Therefore, this calls for the use of bioinformatics analysis to identify differentially expressed genes (DEGs) and signaling pathways during sepsis-induced immunosuppression, with the overarching goal of elucidating the role of neutrophils in sepsis-induced immunosuppression.

To the Editor: Remimazolam besylate is a novel, ultra-short-acting benzodiazepine with a rapid and a predictable onset and offset profile, no accumulation and extended effect, and independence of organ elimination.^[1,2]There have been several reports showing the application of remimazolam besylate for sedation in short-term procedures and general anesthesia, however, no study has reported its use in the intensive care unit (ICU).^[3,4]The aim of this study is to investigate the infusion doses of remimazolam besylate that provide a light to moderate level of sedation in mechanically ventilated patients after noncardiac surgeries in ICUs.

Following the original article’s publication,^[1]the authors informed us of the following errors:^[1]The Figure 1 was submitted incorrectly, while correct Figure 1 should be submitted as following: