Volume 137 · Issue 08 · 2024

基础医学科学研究所（IBMS）是生物医学研究和高级医学教育的全球领导者。今年（2023年）是65周年^th中国医学科学院（CAMS）和北京协和医学院（PUMC）基础医学院（SBM）成立周年。最初，IBMS和SBM合并了由洛克菲勒基金会于1917年建立的PUMC的医学预科部门。此后，这些科室一直致力于承担国内一流的医学科学研究。

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.

遗传性心血管疾病（CVDs）威胁着人类健康，并在世界范围内造成巨大的经济负担。基因改变是许多心血管疾病的主要危险因素。这些疾病通常由一对等位基因控制，根据孟德尔原理影响后代，无论孤立的原发性损伤或其他综合征或缺乏的继发性损伤。迄今为止，有数百种遗传性心血管疾病。随着下一代测序(NGS)技术的进步，遗传性CVDs患者的快速和准确的分子诊断在临床上是实用的。此外，近年来有了很大的改进，靶向治疗和辅助设备已用于临床实践。然而，仍然没有完全有效的策略来处理遗传性心血管疾病。因此，迫切需要开发更好的治疗策略来治疗遗传性CVD。^[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, South 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.

心脏移植是终末期心力衰竭的有效治疗方法；但供心严重不足、排斥反应、免疫抑制剂毒性作用、术后并发症严重等问题依然存在。^[1]心脏异种移植是解决同种异体供体心脏短缺的最有前途的替代方案之一。然而，受体存活率和生活质量受到主要障碍的影响，包括免疫排斥、补体和凝血功能障碍以及感染。^[2,3]由于供体猪的基因编辑策略和非人灵长类受体的抗免疫排斥策略的不断改进，异种心脏移植研究和临床应用取得了重要突破。然而，使用多种类型和大剂量的免疫抑制药物增加了受体术后感染的发生率，也影响了生存率。^[4]2022年1月7日，马里兰大学医学中心的外科医生将一颗转基因猪心脏移植到人体中。受体仅存活60天，表明仍需要更多的临床前研究来解决长期移植物存活的问题。^[5]在这项研究中，我们进行了六基因编辑的猪-恒河猴异位心脏移植。受者生存时间明显延长，异种移植后的综合治疗方案，包括抗炎、抗凝、抗免疫排斥、抗感染等治疗进一步完善。在此，我们详细总结了我们的经验和实验结果，以指导心脏异种移植的进一步研究。

致编辑：自发性早产（PTL）导致婴儿发病率和死亡率。规律的子宫收缩是足月或PTL自然分娩的共同特征。因此，有效减少或抑制子宫肌层收缩可以预防早产。基于人类分娩子宫肌层的转录组数据，我们发现microRNA-206（miR-206）是一种与子宫肌层收缩相关的miRNA，并表明miR-206通过靶向子宫肌层中的连接蛋白α 1（GJA1）来抑制子宫肌层收缩性，将是一种新的早产潜在治疗药物。在RU486诱导的PTL中施用miR-206降低了子宫肌层收缩性，延长了妊娠，将PTL逆转为足月分娩，并改善了围产期结局。

致编辑：动脉粥样硬化是缺血性卒中的主要病理特征，缺血性卒中仍然是世界范围内致残和死亡的主要原因。^[1]易损斑块的特征是溃疡、血小板活化和血栓形成，可能导致栓子脱落和中风。^[2]血管平滑肌细胞(VSMC)是病变内的主要细胞成分，可以显示多效性表型，包括成骨或炎性表型，这在维持晚期动脉粥样硬化斑块稳定性方面可能是有害的。^[3]VSMCs功能的调节，包括增殖、迁移和合成细胞外基质（ECM）和基质金属蛋白酶（MMP），被认为显著影响斑块形成和易损性。^[4]因此，将有害的VSMC向具有有益特性的VSMC驱动以增强斑块稳定性和延缓斑块发展具有重要意义。

致编辑：寻常痤疮是一种影响身体和心理健康的普遍皮肤病。^[1]虽然针对中重度痤疮存在光动力疗法（PDT），但由于其不良反应，我们仍然期待一种副作用更少的新型治疗选择。最近，射频已被用于治疗中度痤疮。^[2]