2024年 · 第137卷第08期

The Institute of Basic Medical Sciences (IBMS) is a global leader in biomedical research and advanced medical education. This year (2023) marks the 65^thanniversary of its foundation at the Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine (SBM) of the Peking Union Medical College (PUMC). In the beginning, the IBMS and SBM incorporated the premedical departments of the PUMC, which was established by the Rockefeller Foundation in 1917. Since then, these departments have been committed to undertaking first-rate medical science research in China.

Gastric cancer is one of the most common malignant tumors in the digestive system in China. Few comprehensive practice guidelines for early gastric cancer in China are currently available. Therefore, we created the Chinese national clinical practice guideline for the prevention, diagnosis, and treatment of early gastric cancer.

This clinical practice guideline (CPG) was developed in accordance with the World Health Organization’s recommended process and with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) in assessing evidence quality. We used the Evidence to Decision framework to formulate clinical recommendations to minimize bias and increase transparency in the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guidelines to ensure completeness and transparency of the CPG.

This CPG contains 40 recommendations regarding the prevention, screening, diagnosis, treatment, and follow-up of early gastric cancer based on available clinical studies and guidelines. We provide recommendations for the timing of Helicobacter pylori eradication, screening populations for early gastric cancer, indications for endoscopic resection and surgical gastrectomy, follow-up interval after treatment, and other recommendations.

This CPG can lead to optimum care for patients and populations by providing up-to-date medical information. We intend this CPG for widespread adoption to increase the standard of prevention, screening, diagnosis, treatment, and follow-up of early gastric cancer; thereby, contributing to improving national health care and patient quality of life.

Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

Caloric restriction (CR) is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases, including cardiovascular conditions. Sirtuins, a family of nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylases, have emerged as key regulators of cellular metabolism, stress responses, and the aging process, serving as energy status sensors in response to CR. However, the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear. This review not only provided an overview of recent research investigating the interplay between Sirtuins and CR, specifically focusing on their potential implications for cardiovascular health, but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via Sirtuins. CR has also been shown to have considerable impact on specific metabolic organs, leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system. The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection. Understanding the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. ¹⁸F-prostate specific membrane antigen positron emission tomography/computerized tomography (¹⁸F-PSMA PET/CT) has several advantages over ⁶⁸Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of ¹⁸F-PSMA PET/CT for lymph node staging in medium/high-risk PCa.

We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, ¹⁸F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of ¹⁸F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses.

A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89).

¹⁸F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for ⁶⁸Ga-PSMA PET/CT.

International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

Inherited cardiovascular diseases (CVDs) threaten human health and pose an enormous economic burden worldwide. Genetic alteration is a major risk factor for many CVDs. These disorders are usually controlled by a pair of alleles, affecting offspring according to the Mendelian principle, regardless of isolated primary damage or secondary injury from other syndromes or deficiency. To date, there are hundreds of inherited CVDs. With advances in next-generation sequencing (NGS) technologies, rapid and accurate molecular diagnosis of patients with inherited CVDs is clinically practical. Besides, great improvements have been made in recent years, and targeted therapy and assist devices have been used in clinical practice. Yet there is still no totally efficient strategy for dealing with inherited CVDs. Accordingly, there is an urgent need to develop better therapeutic strategies for treating inherited CVDs.^[1]

Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE.

We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, the Republic of Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.

Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to-4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.

Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.

https://clinicaltrials.gov; NCT02388737.

The serum vitamin D level varies widely by population, and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus (T2DM). However, the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear. The study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition.

In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cohort, 1862 participants free of T2DM at baseline were included. A weighted genetic risk score was calculated with 28 variants associated with T2DM. Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM.

After a 5-year follow-up, 132 cases of T2DM were documented. We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment (χ² = 0.571, P_{for trend} = 0.426). Compared to those in the lowest quartile of 25(OH)D, the odds ratios (ORs) (95% confidence interval [CI]) for participants with increased quartiles were 1.29 (0.74-2.25), 1.35 (0.77-2.36), and 1.27 (0.72-2.24), respectively. We observed a positive association of glycated hemoglobin (HbA1c) with 25(OH)D at baseline (β = 1.752, P = 0.001) and after follow-up (β = 1.385, P = 0.003), and a negative association of ln conversion homeostasis model assessment (HOMA)-β with 25(OH)D at baseline (β = -0.982, P = 0.021). There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM (χ² = 2.710, P_{for interaction} = 0.100). The lowest OR (95% CI) of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D (0.17 [0.05–0.62]).

Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.

This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.

A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis.

The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve.

Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.

3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001).

In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

Heart transplantation is an effective treatment for end-stage heart failure; however, problems such as the severe shortage of donor hearts, rejection, the toxic effects of immunosuppressants, and serious postoperative complications remain.^[1]Heart xenotransplantation is one of the most promising alternatives to address the shortage of allogeneic donor hearts. However, the recipient survival rate and quality of life are affected by major obstacles, including immune rejection, complement and coagulation dysfunction, and infection.^[2,3]Owing to the continuous improvement of gene editing strategies for donor pigs and anti-immune rejection strategies for non-human primate recipients, heart xenotransplantation research and clinical applications have made important breakthroughs. However, using multiple types and high doses of immunosuppressive drugs increases the incidence of postoperative infections in the recipient, also affecting the survival rate.^[4]On January 7, 2022, surgeons at the University of Maryland Medical Center transplanted a genetically modified pig heart into a human body. The recipient survived only for 60 days, demonstrating that more preclinical studies are still needed to address the issue of long-term graft survival.^[5]In this study, we performed six-gene edited pig-rhesus heterotopic heart transplantations. The recipient survival times were significantly extended, and the comprehensive treatment plan after xenograft transplantation, including anti-inflammation, anticoagulation, anti-immune rejection, and anti-infection therapies, was further improved. Here, we summarized our experience and experimental results in detail to guide further study on heart xenotransplantation.

To the Editor: Spontaneous preterm labor (PTL) causes infant morbidity and mortality. Regular uterine contractions were the common characteristics in spontaneous labor at term or PTL. Thus, effective decrease or suppression of myometrial contraction could prevent preterm delivery. We discovered that microRNA-206 (miR-206) was a myometrium contraction-associated miRNA based on the transcriptome data of human laboring myometrium and indicated that miR-206 suppressed myometrial contractility by targeting junction protein alpha 1 (GJA1) in the myometrium and would be a new potential therapeutic for preterm birth. Administration of miR-206 in RU486-induced PTL decreased myometrial contractility, prolonged pregnancy, reversed PTL to term labor, and improved perinatal outcomes.

To the Editor:Atherosclerosis is the main pathological feature of ischemic stroke, which remains a major cause of disability and death worldwide.^[1]Vulnerable plaque, was characterized by ulceration, platelet activation, and thrombosis, potentially leading to emboli detachment and stroke.^[2]Vascular smooth muscle cells (VSMCs), a major cellular component within lesions, can display pleiotropic phenotypes, including osteogenic or inflammatory phenotypes, which may be harmful in maintaining advanced atherosclerotic plaque stability.^[3]The modulation of the function of VSMCs, including proliferation, migration, and synthesizing the extracellular matrix (ECM) and matrix metalloproteinase (MMP), is thought to markedly affect plaque formation and vulnerability.^[4]Therefore, it is of considerable significance to drive harmful VSMCs toward VSMCs having beneficial properties to strengthen plaque stability and retard plaque development.

To the Editor:Acne vulgaris is a prevalent skin disorder affecting both physical and psychosocial health.^[1]Although photodynamic therapy (PDT) exists for moderate-to-severe acne, due to its adverse reactions, we are still looking forward to a novel therapeutic option with fewer side effects. Recently, radiofrequency has been used to treat moderate acne.^[2]