2024年 · 第137卷第21期

The term "acute-on-chronic liver failure" (ACLF) was initially proposed nearly 30 years ago.^[1]ACLF is distinct from decompensated cirrhosis and acute liver failure, representing an independent clinical syndrome resulting from an acute insult on the background of chronic liver disease.^[2,3]

The global outbreak of coronavirus disease 2019 (COVID-19) began toward the end of 2019 and persists as of 2024.^[1]Patients infected with COVID-19 may show multiple organ involvement, and body systems can be affected with varying degrees of severity. After acute infection, many patients have physical and psychological symptoms that involve multiple systems and persist for a long time.^[2]Pulmonary rehabilitation is a crucial issue in the management of COVID-19. Early recommendations for respiratory rehabilitation in adults with COVID-19^[3]were based on the studies and knowledge of severe acute respiratory syndrome and Middle East respiratory syndrome, combined with knowledge of COVID-19 accrued during the initial stage of the pandemic. However, the recommendations lacked clinical evidence. Therefore, an updated, evidence-based guideline is needed, given the further investigation of COVID-19 that has occurred during the past 3 years.

Recent advancements in the field of medical artificial intelligence (AI) have led to the widespread adoption of foundational and large language models. This review paper explores their applications within medical AI, introducing a novel classification framework that categorizes them as disease-specific, general-domain, and multi-modal models. The paper also addresses key challenges such as data acquisition and augmentation, including issues related to data volume, annotation, multi-modal fusion, and privacy concerns. Additionally, it discusses the evaluation, validation, limitations, and regulation of medical AI models, emphasizing their transformative potential in healthcare. The importance of continuous improvement, data security, standardized evaluations, and collaborative approaches is highlighted to ensure the responsible and effective integration of AI into clinical applications.

B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

Moyamoya disease (MMD) is a cerebrovascular disorder characterized by a steno-occlusive internal carotid artery and compensatory vascular network formation. Although the precise pathogenic mechanism remains elusive, genetic association studies have identified RNF213 as the principal susceptibility gene for MMD, with the single nucleotide polymorphism p.R4810K recognized as the founder variant predominantly in the Asian populations. Distinct genotype-phenotype correlations are observable in RNF213-related MMD. The clinical manifestations linked to p.R4810K bear commonalities within Asian cohort, including familial predisposition, earlier age of onset, ischemic episodes, and involvement of the posterior cerebral artery (PCA). However, despite these shared phenotypic characteristics, there is significant heterogeneity in RNF213-related MMD presentations. This diversity manifests as variations across ethnic groups, inconsistent clinical symptoms and prognosis, and occurrence of other vasculopathies involving RNF213. This heterogeneity, in conjunction with the observed low disease penetrance of RNF213 mutations, suggests that the presence of these mutations may not be sufficient to cause MMD, underscoring the potential influence of other genetic or environmental factors. Although the current research might not have fully identified these additional contributors, experimental evidence points toward the involvement of RNF213 in angiogenesis, lipid metabolism, and the immune response. Future research is required to unveil the molecular mechanisms and identify the factors that synergize with RNF213 in the pathogenesis of MMD.

Cerebral small vessel disease (CSVD) is a significant cause of stroke and dementia. CSVD causes up to 30% of ischemic strokes and 80% of spontaneous intraparenchymal hemorrhages.^[1]Compared with data from developed countries, Asian populations exhibit a heavier burden of strokes caused by CSVD.^[2]The clinical manifestations of CSVD can vary. We propose the concept of acute CSVD (aCSVD) describing the phenotypes with sudden-onset stroke symptoms. This aims to draw equal attention to both ischemic and hemorrhagic aCSVD and to promote a better understanding of the discrepancies and connections between aCSVD and nonacute or covert CSVD. We focus on the heterogeneous mechanisms and discuss the therapeutic challenges and potential strategies.

Sensory abnormalities represent a prevalent chief complaint within clinical neurology, which is an essential but neglected domain in neurology. This subset of individuals presents substantial challenges for clinical diagnosis and treatment. Hence, there is an urgent need to focus on the clinical diagnosis and treatment of patients experiencing sensory abnormalities.

Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.

Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.

In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.

TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

Lung cancer is the most common cancer and a leading cause of cancer-related deaths globally. The aim of this study was to evaluate the incidence and mortality of lung cancer worldwide in 2022 and to project the number of new cases and deaths due to lung cancer in China and the United States in 2050.

In this study, data from the GLOBCAN 2022 database were used to analyze lung cancer incidence and mortality. The current status of lung cancer incidence and deaths was described by country/region, sex, age, and the human development index (HDI), and future lung cancer incidence and deaths in China and the United States were projected for 2050.

Globally, an estimated 2,480,675 new lung cancer cases and 1,817,469 lung cancer-related deaths occurred in 2022, with age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) of 23.6/100,000 and 16.8/100,000, respectively. In China, the ASIR and ASMR for male lung cancer patients were approximately 1.7 times and 2.7 times greater than those for female lung cancer patients, respectively. The ASIR and ASMR in high-HDI countries were approximately 8.5 times and 6.5 times those in low-HDI countries, respectively. It is estimated that in 2050, there will be approximately 1120 thousand new cases and 960 thousand deaths among Chinese men, 680 thousand new cases and 450 thousand deaths among Chinese women, approximately 170 thousand new cases and 110 thousand deaths among American men, and 160 thousand new cases and 90 thousand deaths among American women.

There are significant differences in the incidence and mortality of lung cancer among different regions and sexes. Therefore, sex factors need to be considered in the prevention, screening, and treatment strategies of lung cancer, and the implementation of tertiary prevention measures for lung cancer, especially primary and secondary prevention, needs to be actively promoted.

Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.

Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.

The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.

With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

One of the significant challenges for cell therapies, such as chimeric antigen receptor (CAR)-T cell therapy, is the poor infiltration of immune cells into tumor tissues. CAR-monocytes/macrophages (CAR-M) are promising therapies because of their enrichment in the tumor microenvironment. Thus, we constructed a novel CAR-M to facilitate the infiltration of T cells and other immune cells.

The suicide gene inducible caspase-9 (iCasp9) and anti-erb-b2 receptor tyrosine kinase 2 (HER2) CAR elements were transfected into THP1 (an immortalized human monocyte cell line) by lentivirus. The suicide efficiency and specific anti-tumor efficacy were assessed using flow cytometry, inCucyte, and tumor-bearing BALB/c-nude mouse models. The activation of related signaling pathways in CAR-THP1 activation was explored by transcriptome sequencing. Finally, the synergistic therapeutic efficacy of CAR-THP1 combined with RAK cell treatment was demonstrated in tumor-bearing NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen mouse models.

We developed a novel CAR-THP1, which incorporated iCasp9, CD3ζ, and CD147 intracellular segments, based on the first-generation HER2-CAR backbone. By constructing and comparing a series of CARs with different permutations, CAR-CD3ζ-CD147-iCasp9-THP1 was selected as the optimal combination. CAR-CD3ζ-CD147-iCasp9-THP1 initiated suicide quickly and efficiently under the control of iCasp9 gene, which enabled us to achieve controlled proliferation of CAR-THP1. CAR-THP1 also exhibited robust specific anti-tumor efficacy independently of T cells in vitro and in vivo. Through transcriptional sequencing, we found that CAR-THP1 tended to differentiate into the M1 phenotype and bridged innate and adaptive immunity. A combination of CAR-THP1 and Retronectin actived killer cells (RAKs) showed better therapeutic efficiency, as the metalloproteinases (MMPs) secreted by CAR-THP1 facilitated the degradation of the dense tumor matrix. This further assisted intratumoral infiltration of T cells and augmented the anti-tumor immune response.

CAR-THP1 might be effective against HER2-positive tumor cells and has great potential for combination therapy with other immune cells.

Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 (Ndrg2) in R-I/R injury.

We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient (Ndrg2^-/-) mice and wild type (Ndrg2^+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2^+/+ and Ndrg2^-/- mice after R-I/R injury or HK-2 cells in OGD-R injury.

Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2^-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2^+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway.

Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

For patients with locally advanced gastric cancer (LAGC), the effectiveness of perioperative chemotherapy can be significantly improved by adding programmed cell death protein 1 (PD-1) inhibitors during the neoadjuvant phase. However, a substantial percentage of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) <1 or microsatellite stable (MSS) status may still not experience benefits. The antiangiogenic agent apatinib can promote vascular normalization, which is indicated by the ratio of neural/glial antigen 2 (NG2)-labeled pericytes to platelet endothelial cell adhesion molecule (CD31)-labeled endothelial cells,^[1]and work synergistically with PD-1 inhibitors to improve the efficacy of both chemotherapy and immunotherapy. However, the predictive value of the baseline NG2⁺/CD31⁺ratio for immunotherapy has not yet been established. Based on the positive outcomes from our pilot study [Supplementary Table 1, http://links.lww. com/CM9/C151], a phase II trial, which aimed to enhance treatment efficacy without increasing the risk of toxicity compared with previous studies involving FLOT chemotherapy alone, was conducted using the combination of triple perioperative FLOT chemotherapy with sintilimab and apatinib in patients with cT3/4 LAGC. Furthermore, we also examined the potential of the baseline NG2⁺/CD31⁺ratio as a predictive marker for this intensified treatment regimen.

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease that affects peripheral and axial joints, entheses, skin, and nails. It seriously reduces the quality of life and psychosocial function. Although tumor necrosis factor inhibitors (TNFi) significantly improve patient outcomes in PsA, there is still a significant unmet need.

To the Editor: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide during the coronavirus disease 2019 (COVID-19) pandemic. Experts agree that the Omicron variant is less pathogenic and has a shorter incubation period, making it more likely to cause upper respiratory tract infections. After comprehensive consideration, the National Health Commission of China had renamed the term for COVID-19 from "novel coronavirus pneumonia" to "novel coronavirus infection" on December 26, 2022, and downgraded management from Class A to Class B on January 8, 2023.^[1]Although this adjustment is the most significant strategic change in the epidemic prevention and control policy in the last three years, SARS-CoV-2 has not completely disappeared, and some countries are experiencing multiple waves of increased infections. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority.

To the Editor: Systemic light chain (AL) amyloidosis, a rare and deadly disease affecting approximately 10 individuals per million each year worldwide, is marked by misfolded, aggregated immunoglobulin light chains produced by dangerous plasma cell or B cell clones. Diagnosis of AL amyloidosis often faces obstacles due to non-specific symptoms. Owing to a deeper understanding and therapeutic advancements of AL amyloidosis, patients’ overall survival (OS) has significantly improved globally.^[1,2]However, data of China’s situation remain limited, especially since the novel therapeutic agents were included in the national medical insurance reimbursement list (NMIRL) in late 2017, systemic light chain is listed in the first national list of rare diseases released, and the neoplasm multidisciplinary teams (MDTs) was established by the National Health Commission of China in 2018. Therefore, a multicenter, retrospective, real-world study (AMY4002) was conducted in Western China to report the clinical baselines, treatment patterns, and outcomes of Chinese AL amyloidosis patients before and after 2018.

To the Editor:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs mostly occur in the stomach or small intestine among patients around 40-60 years of age, and are insensitive to chemotherapy or radiotherapy. Approximately 10% and 85% of adult and pediatric patients, respectively, with GISTs do not harbor a mutation in eitherKITorPDGFRA, thereby being defined asKIT/PDGFRAwild type.^[1]According to succinate dehydrogenase subunit B (SDHB) immunohistochemical (IHC) staining,KIT/PDGFRAwild-type-GISTs (WT-GISTs) can be divided into two groups: succinate dehydrogenase (SDH)-deficient GIST, characterized by the absence of SDHB expression and mutations of SDH subunits (SDHX, i.e.SDHA,SDHB,SDHC,andSDHD), especiallySDHAand epimutation ofSDHCmethylation; and SDH non-deficient GIST, characterized by the absence ofSDHXmutation and mutations of other genes, mostly involved in the RAS-signaling pathway [Supplementary Figure 1, http://links.lww.com/CM9/C138].

To the Editor: Primary liver cancer is one of the most common malignant tumors in China. In 2020, 410,038 new cases of liver cancer and 391,152 deaths due to liver cancer were reported in China, which places liver cancer as the second most common cancer-related cause of death in China; of these cancers, hepatocellular carcinoma (HCC) accounts for 85-90%.^[1]HCC poses a significant threat to the lives and health of Chinese people.

To the Editor:The emergence of Omicron has gained global attention since November 2021. Of the Omicron strains, Omicron XBB.1.5 is the most recently identified. It carries deletions and more than 30 mutations, which have modified the biological features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) for enhanced transmissibility and immune escape capacity.^[1]People living with human immunodeficiency virus (PLWH) are featured with acquired cluster of differentiation (CD)4⁺T cell deficiency and at a higher risk of progression to severe coronavirus disease 2019 (COVID-19).^[2]Vaccines are the most protective tools against SARS-CoV-2 infection.^[3]Nevertheless, the extent to which booster vaccination induces neutralizing antibody (NAb) production against Omicron XBB.1.5 in PLWH is not well defined.

To the Editor: The incidence of melanoma, a highly aggressive malignancy, is associated with the level of social development, with a higher incidence being documented in developed than in developing countries.^[1]With a large population, China has experienced substantial economic growth and urbanization over the past 30 years, with increasing severity of population aging.

To the Editor: Esophageal stenosis can be either benign or malignant. Benign stenosis usually results from esophageal reflux, radiation therapy, corrosive ingestion, or surgical anastomosis following endoscopic submucosal dissection (ESD) or endoscopic mucosal resection for early esophageal tumors. Malignant stenosis is caused by advanced cancer. Esophageal stenosis often leads to dysphagia, malnutrition, aspiration, and respiratory failure, making conservative treatment challenging. Stent insertion is a primary option for relieving dysphagia, managing stenosis-related complications, and improving patient quality of life.

To the Editor: Sympathetic paraganglioma in the pericardium is rare, which can be life-threatening. It presents with symptoms, such as refractory hypertension, palpitations, and other hormone-related manifestations. This study presented a unique case of type 3 paraganglioma originating from the mediastinum, accompanied by multimodality imaging findings, including computed tomography (CT) scan,¹⁸F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG PET/CT),⁶⁸Ga-DOTA-1-Nal3-octreotide positron emission tomography/CT (⁶⁸Ga-DOTANOC PET/CT), and¹⁸F-fluorodihydroxyphenylalanine positron emission tomography/CT (¹⁸F-FDOPA PET/CT).

To the Editor: Gouty arthritis, an autoinflammatory disease, exhibits a rapid onset of clinical symptoms but often resolve spontaneously within 7-10 days. In the acute gouty inflammatory responses, monosodium urate (MSU) crystal is recognized as damage-associated molecular patterns by Toll-like receptors (TLRs) on macrophage membranes. Subsequently, the TLR-NF-kappa-B inhibitor alpha (IκBα)/nuclear factor kappa B (NF-κB) pathway is activated, producing many inflammatory factors, neutrophil chemokines, and cathepsin and participating in the assembly of nucleotide-binding oligomerization domain receptor protein 3 (NLRP3) inflammasomes.^[1]The NLRP3 inflammasome consists of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1. Synergism between the NLRP3 inflammasome and the NF-κB pathway plays a crucial role in gouty inflammation by activating the maturation of interleukin (IL)-1β and IL-18, inducing pyroptosis and releasing large amounts of proinflammatory mediators. Studies have shown that increased anti-inflammatory mediators, such as transforming growth factor β1 (TGF-β1) and IL-10, are involved in acute inflammatory spontaneous remission.^[2]Decoy receptor 3 (DcR3) serves as an essential regulator of inflammation and the immune response. DCR3 exerts anti-inflammatory effects by blocking the human tumor necrosis factor-related ligand 1A (TL1A)/death receptor 3 (DR3) axis by competing with DR3 to bind to TL1A. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of several autoinflammatory disorders.^[3]However, it is unclear whether the TL1A/DR3/DcR3 axis is involved in the occurrence, progression, and spontaneous remission of gouty arthritis. Here, we measured the expression levels of DcR3, TL1A, and DR3 in patients with acute gout (AG) or intercritical gout (IG). Subsequently we used THP-1 cells transfected with DcR3-specific small interfering RNA (si-DcR3) or a DcR3 overexpression plasmid (pcDNA-DcR3) to determine the function of DcR3 in MSU-induced gouty inflammation.

The authors declare that in the article published in vol. 136, issue 22 of theChinese Medical Journal,^[1]an error was identified in the "Validation by real-time quantitative PCR (qPCR)" section. The primer sequences forVeillonella parvulawere incorrectly pasted as the 16S rRNA primer sequences. The corrected primer sequences should be as follows: