Volume 135 · Issue 11 · 2022

Congenital heart disease (CHD) is one of the most common congenital malformations, with a prevalence of approximately 1% in live births.^[1,2]Among them, 1/4 to 1/3 are major CHD, including critical CHD (CCHD) and serious CHD, which require surgical or catheter intervention before 1 year of age.^[3]Major CHD, if left untreated, may cause serious outcomes, such as heart failure, cardiogenic shock, acidosis, and hypoxic-ischemic brain damage, and is one of the leading causes of infant death and childhood disability.^[4]The missed diagnosis rate of CCHD in four nurseries ranges from 13% to 48% in developed countries,^[4,5]but in China, is >71% before serious symptoms occur after birth.^[6]Therefore, screening for CHD is useful for early detection, diagnosis, and treatment and helps to improve prognosis and reduces the medical, economic, and mental burden to both the family and the society.^[5,7]

Liver disease is a collective term for hepatic damage caused by heterogeneous etiologies and poses a heavy health burden worldwide. Modern medical imaging, such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography, plays an essential role in the diagnosis and management of liver diseases. Imaging-based deep learning (DL) is one of the most actively investigated techniques in recent decade. It enables high-dimensional features extraction through the layered structures and can be used in a variety of clinical scenarios, especially with the convolutional neural network in computer vision.

China faces a substantial burdensome pandemic of obesity. Recent data from the Chinese Centre for Disease Control and Prevention suggested that over an estimated 8.1% of Chinese adults (85 million Chinese adults) had obesity in 2018, which was three times the level in 2004.^[1]

Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.

Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.

With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.

Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019.

This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex.

From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of -1.35 (95% uncertainty interval [UI]: -1.67, -1.02) and -0.37 (95% UI: -0.43, -0.31), -2.01 (95% UI: -2.07, -1.94) and -2.32 (95% UI: -2.37, -2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669-462,767) and 493,765 (95% UI: 416,705-578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019.

The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.

Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.

Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.

A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 (RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process.

RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China.

Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality.

During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08-1.51) for low appendicular muscle mass index, 1.38 (1.16-1.62) for low total muscle mass index, 1.68 (1.41-2.00) for low grip strength, and 1.41 (1.20-1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories.

Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.

Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.

This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.

In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals (P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals (P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria.

This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

To the Editor: There have been growing concerns about the gut bacterial dysbiosis associated with HIV infection, addressing a critical role of gut bacteria in persistent chronic inflammation and severe intestinal dysfunction among the human immunodeficiency virus (HIV) infected population. However, little is known about the gut fungal dysbiosis caused by HIV-infection. Therefore, we launched a case-control study aiming to explore the gut dysbiosis of bacteria and fungi in HIV infection, which may reveal a more comprehensive feature of HIV infection-related gut dysbiosis of bacteria and fungi that possibly play a role in the chronic systemic immune activation observed in HIV infection.

To the Editor: Laboratory diagnostic methods of bullous pemphigoid (BP) include direct immunofluorescence (DIF) microscopy, BP180 NC16A enzyme-linked immunosorbent assays (ELISA), and indirect immunofluorescence using salt-split skin (ssIIF) in our daily clinical practice. Immunofluorescence (IF) studies are important parts of the laboratory workup for BP. DIF is regarded as the gold standard for BP diagnosis; however, it is not specific and can also be found in other acquired autoimmune subepidermal blistering dermatosis. ssIIF was found to have a specificity of 100% for BP diagnosis and in some guidelines, it is recommended to perform ssIIF in every patient with clinically suspected BP.^[1]To date, it is still not defined whether ssIIF can be used as a routine diagnosis method of BP. The BP180 NC16A ELISA is a practical and reliable diagnostic test for BP; however, the false-positive results of BP180 NCA6A ELISA were recently reported in a wide range of dermatoses, which might cause its uncertainty in the diagnosis of BP. Thus, we conducted a single center retrospective study to compare diagnostic values of these tests for BP from Hospital for Skin Diseases, Chinese Academy of Medical Sciences between January 2014 and January 2019. It was approved by the local medical ethical committee (No. 2017-KY-022) and consent was obtained from patients prior to serum collection.

To The Editor:Acne vulgaris is a chronic inflammatory skin disease involving the sebaceous glands. It has an incidence of approximately 9.4%, often occurring in adolescents.^[1]The disease itself and the scars left after treatment can cause psychological stress in adolescents and seriously affect patients’ quality of life.^[2]At present, skin care products, either alone or in combination with medical drugs, have become important means for treating acne. This single-center, single-blind (clinician-blind), masculine-paralleled, randomized study (Registration number: ChiCTR2100051398) evaluated the efficacy and safety of a cream containing octyl salicylic acid, salicylic acid, linoleic acid, nicotinamide, and piroctone olamine (Duo+, La Roche-Posay, Paris, France) alone and in combination with benzoyl peroxide (BPO, Galderma, Paris, France) for the treatment of mild-to-moderate acne. The research was approved by the Ethics Committee of Shanghai Skin Disease Hospital, China (No. 2020-13 ke). All participants provided written informed consent.

To the Editor: Gastric cancer is one of the most commonly diagnosed cancers in the world. For patients with a pathological tumor-node-metastasis stage of II or III, postoperative adjuvant chemotherapy is generally required to reduce recurrence risk by controlling residual tumor cells following curative resection.^[1]Although taxanes have recently shown promising activity in gastric cancer,^[2,3]non-responders may incur costs and experience adverse reactions without clinical benefit, and efforts to select effective regimens for individuals are very important. The application ofin vitrochemosensitivity assays as predictive markers in personalized cancer treatment has been investigated in several studies.^[4]However, the heterogeneity of the gastric cancer response to taxane-based chemotherapy and the correlation betweenin vitrochemosensitivity and clinical outcomes remain unclear.

To the Editor:The randomized evaluation of coronavirus 2019 (COVID-19) therapy (RECOVERY)^[1]clinical trial showed that glucocorticoids can affect the prognosis of severe COVID-19 patients, but they have no benefit for mild disease. Other clinical trials, such as COVID-19-associated acute respiratory distress syndrome (ARDS) treated with dexamethasone (CoDEX) and efficacy study of dexamethasone to treat the ARDS (DEXA-ARDS), have also proven the effectiveness of glucocorticoids. On the basis of these trials, glucocorticoids have been recommended for the treatment of COVID-19, although their mechanism of action is unclear. Diffuse alveolar damage (DAD) is not the only pathological change of ARDS caused by COVID-19. In some cases, organizing pneumonia (OP) or acute fibrinous and organizing pneumonia (AFOP) is the main manifestation.^[2]Acute patterns of AFOP with AFOP as the main pathological feature often leads to respiratory failure and rapidly progresses to death, whereas subacute patterns of AFOP has a good prognosis. There are two types of COVID-19-related ARDS: type 1 is atypical ARDS, with low elasticity (type L), increased compliance, and imbalance of ventilation/perfusion ratio; and type 2 is classic ARDS, with high elasticity (type H), reduced compliance, and increased right to left diversion, which is mainly related to disease progression (but not absolutely). Some patients with type H ARDS presented with AFOP. Glucocorticoids have little effect on typical DAD, but have a definite therapeutic effect on secondary OP and subacute patterns of AFOP caused by infection (including viral infection). On the basis of current literature, the effectiveness of glucocorticoids for treatment of COVID-19 may be attributable to the pathological changes of OP or AFOP. A meta-analysis of clinical trials of critically ill patients with COVID-19 showed that the administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.^[3]Therefore, it is important to identify patients who are suitable candidates for glucocorticoid therapy. Computed tomography manifestations that indicate the effectiveness of glucocorticoid therapy are: (1) consolidation dominated by bilateral, peripheral, and lower lung distribution (in line with the characteristics of OP);^[4](2) consolidation around the bronchi that may be accompanied by patchy ground-glass opacity in the subpleural area of the lower lobe (in line with the characteristics of OP);^[4]and (3) focal or diffuse lung parenchymal abnormalities, similar to those of OP (in line with the characteristics of subacute AFOP).^[5]Identification of suitable patients for glucocorticoid therapy may improve treatment accuracy and prognosis of severe COVID-19 and reduce the adverse effects of glucocorticoids. In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone (≥1 mg kg^-1·d^-1, ≥3 d) can lead to a further decreased mortality as compared with dexamethasone (≥6mg/d, ≥7 d).^[6]