2022年 · 第135卷第05期

The year (2022) marks the 135^thanniversary of the founding of theChinese Medical Journal. Over the past 135 years, the journal has witnessed tremendous changes in the health conditions of the Chinese people, the important role of modern medical technology in improving health, reducing diseases, and extending the life span, and the continuous improvement in medical and healthcare services and social security systems.

Hepatitis B virus (HBV) infection is a global public health problem, causing a high disease burden worldwide.^[1]As a country previously with a high burden of hepatitis, about 70 million people in China are infected with HBV now, and mother-to-child transmission (MTCT) is still a predominant mode of HBV infection in China.^[2]Preventing mother-to-child transmission is the key to eliminating HBV infection, and standardized management of HBV-infected pregnant women and their newborns can effectively cut off the mother-to-child transmission.^[3]Neonatal hepatitis B immune globulin and hepatitis B vaccine can effectively reduce neonatal HBV infection in infants of HBV-positive pregnant women. Peripartum antiviral prophylaxis after 28 pregnant weeks is proved to be highly effective at reducing the risk of HBV (MTCT).^[4]Furthermore, controlling hepatitis B infection in pregnant women not only reduces the risk of transmission within the family and vertical transmission from mother to child,^[5]but also might reduce the risk of adverse pregnancy outcomes.^[6]Therefore, understanding the epidemiological characteristics of HBV infection in pregnant women in China and better regulating the prevention, diagnosis, and treatment of this population is of great significance for realizing the goal of "eliminating viral hepatitis as a major public health threat by 2030" proposed by World Health Organization (WHO).

Ankylosing spondylitis (AS) is a prototype of spondyloarthritis (SpA) with long-term joint inflammation of the spine. SpA manifestations also include psoriasis, uveitis, and inflammatory bowel disease, which suggest these diseases may share some common genetic background.

Air pollution is one of the biggest environmental threats to human health. In 2005, the World Health Organization (WHO) released its first global air quality guidelines (AQGs) for particulate matter (PM), ozone (O₃), nitrogen dioxide (NO₂), and sulfur dioxide.^[1]On September 22, 2021, the WHO updated its AQGs, providing clear evidence of the adverse health effects of air pollution, at even lower concentrations than previously understood.^[2]For instance, the WHO AQGs 2021 recommend annual mean concentrations of PM_2.5not exceeding 5 μg/m³and NO₂not exceeding 10 μg/m³and the peak season mean 8-h O₃concentration not exceeding 60 μg/m.^[2,3]As a comparison, the corresponding WHO AQGs 2005 values were 10 μg/m³for PM_2.5and 40 μg/m³for NO₂, with no recommendation for long-term O₃concentrations.^[1]

With the rapid socioeconomic development, improvements in living standards, and changes in lifestyle, adult diseases, such as cardiovascular diseases, type 2 diabetes mellitus (T2DM), hypertension, obesity, and so on, are increasing dramatically over the past decades, which have caused a huge economic and health burden at both population and individual levels in China.^[1]The increased burden of adult diseases has become the main public health issue, and prevention of adult diseases in China has become a formidable task during recent years. In 2016, China has put forward the concept of whole life-course health and efforts have been made on shifting the focus from treating diseases to prevention. In view of the poor effects of prevention of diseases in adulthood, it is suggested that prevention and management of adult diseases should be extended to early life, which is the critical window for physiological programming and has profound and enduring effects on the whole life-cycle health.^[2,3,4]In 2018, an article named "To Prevent Cardiovascular Disease, Pay Attention to Pregnancy Complications" published in Journal of the American Medical Association (JAMA) also illustrated that pregnancy is a window to future health.^[5]

The cancer burden in the United States of America (USA) has decreased gradually. However, China is experiencing a transition in its cancer profiles, with greater incidence of cancers that were previously more common in the USA. This study compared the latest cancer profiles, trends, and determinants between China and USA.

This was a comparative study using open-source data. Cancer cases and deaths in 2022 were calculated using cancer estimates from GLOBOCAN 2020 and population estimates from the United Nations. Trends in cancer incidence and mortality rates in the USA used data from the Surveillance, Epidemiology, and End Results program and National Center for Health Statistics. Chinese data were obtained from cancer registry reports. Data from the Global Burden of Disease 2019 and a decomposition method were used to express cancer deaths as the product of four determinant factors.

In 2022, there will be approximately 4,820,000 and 2,370,000 new cancer cases, and 3,210,000 and 640,000 cancer deaths in China and the USA, respectively. The most common cancers are lung cancer in China and breast cancer in the USA, and lung cancer is the leading cause of cancer death in both. Age-standardized incidence and mortality rates for lung cancer and colorectal cancer in the USA have decreased significantly recently, but rates of liver cancer have increased slightly. Rates of stomach, liver, and esophageal cancer decreased gradually in China, but rates have increased for colorectal cancer in the whole population, prostate cancer in men, and other seven cancer types in women. Increases in adult population size and population aging were major determinants for incremental cancer deaths, and case-fatality rates contributed to reduced cancer deaths in both countries.

The decreasing cancer burden in liver, stomach, and esophagus, and increasing burden in lung, colorectum, breast, and prostate, mean that cancer profiles in China and the USA are converging. Population aging is a growing determinant of incremental cancer burden. Progress in cancer prevention and care in the USA, and measures to actively respond to population aging, may help China to reduce the cancer burden.

Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.

We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. ¹¹C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.

The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.

Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.

This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high-risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.

A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.

In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.

To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.

PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.

As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.

Restoring proper lower limb alignment on the coronal plane after total knee arthroplasty (TKA) can decrease stress in the bone cement-implant interface, polyethylene wear, and implant loosening. Weight-bearing long-leg radiographs (LLRs) are used to assess the mechanical axis in the coronal plane, identify anatomic variations in the femur and tibia, and plan the degree of bone resection preoperatively. However, rotation or flexion of the lower limb may affect the accuracy of the measurement of alignment parameters from LLRs. Furthermore, known rotation-dependent linear changes can be used to relate the degree of lower limb rotation to the alignment parameters of the femur and tibia and the hip-knee-ankle (HKA) angle.^[1]

To the Editor:Chronic airflow obstruction (CAO) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and occurs due to airway and/or alveolar abnormalities typically associated with exposure to noxious particles or gases.^[1]The major risk factor for CAO is cigarette smoking, but exposure to solid fuel likely influences CAO development. Studies have found that solid fuel exposure is associated with a high prevalence of CAO, particularly among women.^[2]Comparing COPD caused by either solid fuel or tobacco smoke exposure is very significant because about 3 billion people are exposed to solid fuel smoke, and 1.01 billion people smoke tobacco, globally. This study aimed to investigate and compare the clinical and functional characteristics of CAO patients exposed to solid fuel and tobacco smoke using propensity score matching (PSM) in western China.

To the Editor:Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.^[1]A previous study based on the China Neonatal Genomes Project investigated the genetic causes of early infant deaths and found that >25% of deceased neonates with genetic diagnoses can be cured if diagnosed in time.^[2]Therefore, it is crucial to target and diagnose neonates with genetic diseases as early as possible. According to our experience, the typical phenotypes, such as special facial features or multiple congenital anomalies (MCAs), indicate a high risk of genetic disease and lead physicians to perform genetic testing in neonates as early as possible. However, in practice, infants without typical phenotypes typically undergo a long and costly diagnostic process before genetic diagnoses are confirmed. Moreover, a recent survey by the American College of Medical Genetics and Genomics (ACMG) and other national professional organizations indicated that there are insufficient numbers of qualified geneticists to fulfil genetic service needs.^[3]The ACMG published the general clinical features for genetic testing indications. For example, patients with phenotypes or family history data that strongly implicate a genetic cause may undergo genetic testing.^[1]However, the study indicated that many genetic conditions arisede novoor are inherited with no family history.^[1]A previous study attempted to apply the non-phenotype-driven panel approach in neonates admitted to the neonate intensive care unit (NICU).^[4]However, at present, the diagnostic yield is only 3.45% (1/29).^[4]In addition, the economic and ethical issues associated with genomic screening remain challenging. Therefore, the available indications for genetic testing may improve the management of genetic diseases.

To the Editor:Liver fibrosis was characterized by the activation of hepatic stellate cells (HSCs) and extracellular matrix deposition. The pathogenesis of liver fibrosis involved many aspects. Studies have found that endoplasmic reticulum stress (ERS) in HSCs could lead to HSC activation and aggravate liver fibrosis.^[1]Although liver fibrosis has been extensively studied, effective anti-fibrotic drugs are lacking at present. Tetrahydropalmatine (THP) was the active ingredient of Chinese herbsCorydalis yanhusuo. Previous studies have found the hepatoprotective effect of THP. Our study aimed to investigate the effects of THP on liver fibrosis and the underlying mechanisms.