Volume 138 · Issue 12 · 2025

Esophageal squamous cell carcinoma (ESCC) poses a significant global health challenge, necessitating early detection, timely diagnosis, and prompt treatment to improve patient outcomes. Endoscopic examination plays a pivotal role in this regard. However, despite the availability of various endoscopic techniques, certain limitations can result in missed or misdiagnosed ESCCs. Currently, artificial intelligence (AI)-assisted endoscopic diagnosis has made significant strides in addressing these limitations and improving the diagnosis of ESCC and precancerous lesions. In this review, we provide an overview of the current state of AI applications for endoscopic diagnosis of ESCC and precancerous lesions in aspects including lesion characterization, margin delineation, invasion depth estimation, and microvascular subtype classification. Furthermore, we offer insights into the future direction of this field, highlighting potential advancements that can lead to more accurate diagnoses and ultimately better prognoses for patients.

The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.

Anemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin (EPO) production and iron absorption and utilization. Thus, HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism. Here, we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD. Specifically, we highlighted the key features of HIF-PHIs on ACD, such as stimulation of endogenous EPO, handling iron metabolism, inflammation-independent, and prolonging lifespan of red blood cells. In conclusion, the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.

The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD).

We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships.

The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages.

Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit.

No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?

The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections.

This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori. Drug compliance and adverse events (AEs) were also assessed. Pearson’s χ² test or Fisher’s exact test was used to compare eradication rates between groups.

A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT (P = 0.949) or PP analysis (P = 0.921). No significant differences were observed in the incidence of AEs (P = 0.934) or drug compliance (P = 0.849) between groups.

The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs.

ClinicalTrials.gov, NCT05173493.

The epidemiological pattern and disease burden of type 2 diabetes have been shifting in China over the past decades. This analysis described the epidemiological transition of type 2 diabetes in the past three decades and projected the trend in the future three decades in China.

Age-, sex-, and year-specific incidence, prevalence, death, and disability-adjusted life years (DALYs) for people with 15 years or older and diabetes or high fasting glucose in China and related countries from 1990 to 2021 were obtained from the Global Burden of Disease. We obtained the trends of age-, sex-, and year-specific rates and absolute numbers of incidence, prevalence, deaths, and DALYs attributable to type 2 diabetes in China from 1990 to 2021. Using the Lee-Carter model, we projected the incidence, prevalence, death, and DALYs attributable to type 2 diabetes to 2050 stratified by age and sex.

The age-standardized incidence of type 2 diabetes was 341.5 per 100,000 persons (1.6 times in 1990) and the age-standardized prevalence was 9.96% (9960.0 per 100,000 persons, 2.5 times in 1990) in China 2021. In 2021, there were 0.9 million deaths and 26.8 million DALYs due to type 2 diabetes or hyperglycemia, as 2.9 and 2.7 times the data in 1990, respectively. The age-standardized rates of type 2 diabetes and hyperglycemia were projected to raise to 449.5 per 100,000 persons for incidence, 18.17% for prevalence, 244.6 per 100,000 persons for death, and 4720.2 per 100,000 persons for DALYs by 2050. The incidence of type 2 diabetes kept growing among individuals under the age of 20 years in the past three decades (128.7 per 100,000 persons in 1990 and 439.9 per 100,000 persons in 2021) and estimating 1870.8 per 100,000 in 2050.

The incidence, prevalence, and disease burden of type 2 diabetes grew rapidly in China in the past three decades. The prevention of type 2 diabetes in young people and the care for elder adults will be the greatest challenge for the country.

Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization.

Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality.

Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases.

In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.

Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China.

This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion.

The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon.

Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings.

Chinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR2100046322; CDE (www.chinadrugtrials.org.cn) CTR20201568

In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis.

In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL).

In cohort A (abemaciclib: n = 207; placebo: n = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs. placebo (28.27 months vs. 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n = 104; placebo: n = 53), abemaciclib plus fulvestrant improved median PFS vs. placebo (11.41 months vs. 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs. placebo.

Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.

ClinicalTrials.gov (NCT02763566).

致编辑：卒中是中国主要的公共卫生问题之一，卒中复发率、心血管事件率和死亡率都很高，造成了相当大的医疗和经济负担。^[1]新的分子标志物和治疗靶点的鉴定对于更好地细化心血管事件的风险预测和开发缺血性卒中的新治疗策略是必要的。琥珀酸是三羧酸（TCA）循环中间体，因其参与与心血管疾病相关的各种信号通路而受到相当大的关注。^[2,3,4]最近的研究报道，琥珀酸是一种促进动脉粥样硬化病变进展、成纤维细胞活化和凋亡抵抗的新型介质。

致编辑：母体显性甲状腺功能减退（OH）、亚临床甲状腺功能减退（SCH）或甲状腺自身免疫（TAI）可导致不良妊娠结局。在过去的十年中，美国甲状腺协会（ATA）、欧洲甲状腺协会、中国内分泌学会（CSE）和美国妇产科学院（ACOG）发布了几个妊娠期甲状腺疾病管理指南。13年前，妊娠期SCH被定义为血清促甲状腺激素（TSH）水平在2.5 mIU/L至10.0 mIU/L之间，游离甲状腺素（FT4）浓度正常。^[1]6年后，妊娠特异性TSH参考上限提高至4.0 mIU/L。^[2]左旋甲状腺素（LT4）是孕妇补充甲状腺激素最值得推荐的药物。然而，根据不同的指南，孕妇开始补充LT4的条件不同。

致编辑以进行性气流受限和持续呼吸道症状为特征的慢性阻塞性肺疾病（COPD）仍然是全球发病率和死亡率的主要原因。目前的估计表明，全球COPD患病率为4-10%，死亡率约为3%。^[1]肺康复（PR）被广泛认为是COPD最具成本效益的治疗干预措施之一。^[2]最近的一项研究^[3]证明PR在COPD的长期管理中起着关键作用。然而，关于基于远程医疗的肺康复（PTR）干预有效性的有力证据仍然有限。该荟萃分析评估了PTR与常规PR相比在COPD患者中的临床结局。

致编辑：心力衰竭（HF）是一个具有高死亡率的主要健康问题，尽管在主要治疗策略方面取得了进展。尽管有先进的治疗方法，但心脏代谢标志物如胰岛素敏感性和抵抗有助于HF的发生和较差的预后。坚持健康的生活方式行为已被证明可以显著改善心脏代谢标志物并降低心力衰竭的风险。最近的指南建议改变生活方式，如增加体力活动（PA）、健康饮食、减肥和戒烟，作为预防心力衰竭和降低心力衰竭患者死亡率的主要策略。2010年，美国心脏协会（AHA）强化了“生活简单7（LS7）”的概念，重点是预防生活方式和代谢风险因素，以减轻全球心血管疾病（CVD）的负担。^[1]LS7指标已被证明与左心室（LV）结构和功能的变化相关，并将77.1-88.8%归因于HF的发展。2022年，AHA推出了LS7修订版“Life’s essential 8（LE8）”，为七个健康组成部分（PA、血糖、血脂、血压[BP]、吸烟、体重指数[BMI]和饮食）提供了更新的测量方法，并将睡眠健康作为第八个组成部分，以提高心血管健康（CVH）评估的准确性。^[2]使用LE8度量构建的CVH评分范围为0至100，简化了解释并增加了检测个体间差异和个体内CVH纵向变化的灵敏度。在我们之前的研究中，我们发现在开滦研究中，基于LE8指标的较高CVH评分与卒中风险降低67%相关。^[3]为了研究更好地坚持AHA LE8指标是否与HF和HF后死亡率的未来风险改变相关，我们在两个正在进行的中国队列中的约69,000名参与者中进行了一项大规模前瞻性研究。

致编辑：经胎盘地高辛治疗已被证明可有效将胎儿室上性心律失常（SVA）转为窦性心律或实现心室率控制，显著改善胎儿宫内结局。^[1,2,3]然而，来自中国大量患者人群的数据有限。此外，产前地高辛治疗期间相对较高的无应答率和宫内复发率仍然令人担忧。^[4,5]探索地高辛无反应和宫内复发的潜在危险因素的研究有限。因此，本研究旨在分析中国产前地高辛单药治疗胎儿SVA的结局和随访数据，并调查经胎盘地高辛治疗后无反应和宫内复发的相关危险因素。

致编辑：高眼压(OHT)定义为无青光眼性视神经病变的眼内压(IOP)升高。OHT可能进展为原发性开角型青光眼（POAG），导致进行性视神经病变和视力丧失。虽然前列腺素类似物(PGA)等降眼压药物可减轻这种风险，但长期使用会带来经济负担和副作用。先前的研究已经证明了PGAs在降低IOP和改善视网膜血液灌注和黄斑微循环方面的有效性。^[1]然而，OHT与POAG对PGAs的相对反应性仍不清楚。光学相干断层扫描血管造影（OCTA）提供了黄斑血管密度（mVD）的非侵入性评估，mVD是神经节细胞功能和青光眼进展的潜在指标。^[2,3]此外，mVD与黄斑神经节细胞复合体厚度和平均偏差（MD）相关。^[4,5]本研究通过使用OCTA检查黄斑浅表血管参数的变化来评估PGAs治疗OHT和早期POAG的疗效。

致编辑：诊断阿尔茨海默病（AD）仍然具有挑战性，因为临床诊断的准确性通常不如神经病理学确认。由美国国家衰老研究所-阿尔茨海默病协会（NIA-AA）推出的AT（N）系统提供了一个生物标志物框架，以提高AD研究的诊断精度。^[1]最近的技术创新，如单分子阵列（Simoa）等超灵敏检测，已经实现了血液生物标志物的精确评估，为无创诊断提供了潜力。大多数研究集中于认知正常、主观认知下降或轻度认知障碍的个体，检查血浆生物标志物水平在AD进展中的预测作用。^[2]然而，这些生物标志物在AD痴呆中的诊断效用仍未得到充分研究。因此，我们评估了血浆A β 40、A β 42、pTau181、胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）水平在诊断痴呆患者AD中的准确性，扩大了AT（N）系统在基于血液的诊断中的应用。

致编辑：基底细胞癌(BCC)是起源于表皮基底细胞的恶性肿瘤，是皮肤癌中最常见的形式。在中国，由于社会经济进步和人口老龄化，基底细胞癌的发病率有所上升。^[1]虽然早期诊断和治疗通常会产生良好的结果，但0.8-2.0%的患者可能进展为局部晚期基底细胞癌（laBCC），其特征是病变直径≥10 mm。由于发病率、畸形、肿瘤切除不完全和高复发率的风险，传统治疗如手术或放疗可能不适合laBCC。^[2]这些限制强调了对更有效治疗方案的需求。Hedgehog(Hh)信号通路中的突变，特别是在果蝇打补丁（PTCH1）和平滑（SMO），通过导致不受控制的细胞增殖在BCC发育中起至关重要的作用。Sonidegib是一种选择性SMO受体拮抗剂，已证明通过抑制Hh途径和调节免疫反应诱导BCC消退的功效。^[3]它已被批准用于治疗不适合手术或放疗的患者的laBCC。然而，关于sonidegib在中国有效性的真实数据有限，需要进一步研究以评估其在该人群中的有效性和安全性。

致编辑成纤维细胞生长因子受体(FGFR)融合虽然不常见，但代表了癌症治疗的重要靶标，特别是对于主要用化疗治疗的实体恶性肿瘤。胆道癌（BTC）是一个显著的例子。尽管亚叶酸、氟尿嘧啶和奥沙利铂（FOLFOX）是晚期BTC的标准二线治疗，但客观缓解率（ORR）仅为5%。靶向治疗（如pemigatinib）的出现彻底改变了该患者群体的临床反应。然而，与靶向间变性淋巴瘤激酶重排的酪氨酸激酶抑制剂治疗非小细胞肺癌后观察到的>75%ORR相比，这是适度的。融合伴侣、耐药性和靶向毒性已被证明是限制其疗效的重要因素；^[1,2]然而，它们并不能充分解释整个现象。因此，全面了解全FGFR变异概况，以增强研究设计和药物开发，从而改善初始反应的幅度和持续时间。