2025年 · 第138卷第22期

Prurigo nodularis (PN) is a chronic pruritic inflammatory skin disease characterized by hyperkeratotic papules and nodules symmetrically distributed on the back and extensor surfaces of the extremities, accompanied by severe pruritus. PN has a serious impact on quality of life.^[1,2,3]PN is a complex and difficult-to-treat condition. There is a lack of unified understanding of its diagnosis and treatment specifications, and the means approved for treating PN are limited; thus, clinicians mostly use empirical therapies.

Approximately 90% of individuals infected withMycobacterium tuberculosis(MTB) do not progress to active tuberculosis (ATB) but remain in an asymptomatic latent tuberculosis infection (LTBI) state. Rheumatic diseases (RDs) are characterized by immune dysfunction and are commonly managed with glucocorticoids, immunosuppressants, and biologics. Both the disease itself and its treatment make patients with RD a high-risk population for tuberculosis (TB) infection and disease progression. Conservative estimates suggest that the prevalence of ATB is approximately 2-5 times higher than that observed in the general population. Both RD and ATB can lead to multi-organ and multi-system damage. Patients with RD and concurrent ATB often present with complex clinical manifestations, making diagnosis and treatment challenging and resulting in high mortality rates.

How to choose the drugs of adjuvant therapy for non-small-cell lung cancer (NSCLC) patients harboring driver gene mutation?

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.

Over the past decade, high-throughput RNA sequencing (RNA-seq) has vastly expanded our understanding of transcriptome dynamics in human physiology and disease. As a powerful tool for investigating systematic changes in RNA biology, RNA-seq has facilitated the discovery of novel functional RNA species. Mature RNA transcripts, which transmit genetic information from DNA to proteins, undergo intricate transcriptional and post-transcriptional regulation. This process allows a single gene to produce multiple RNA transcripts, each performing specific functions depending on the physiological or pathological context. Specific RNA transcripts (SRTs) are uniquely expressed in particular tissues or tumors and are closely associated with tissue-specific functions or disease states, particularly cancer. This review explores the generation of SRTs through key mechanisms, such as alternative splicing (AS), transcriptional regulation, polyadenylation (polyA), and the influence of transposable elements (TEs). We also examine their critical roles in normal tissue development and diseases, with an emphasis on their relevance to cancer. Furthermore, the potential applications of SRTs in diagnosing and treating diseases, especially malignancies, are discussed. By serving as diagnostic markers and therapeutic targets, SRTs hold significant promise in the development of personalized medicine and precision therapies. This review aims to provide new insights into the importance of SRTs in advancing the understanding and treatment of human diseases.

Lecanemab has shown promise in treating early Alzheimer’s disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.

In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.

A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs. 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs. 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs. 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.

Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab’s use in China, supporting further investigation in larger controlled studies.

The burden of breast cancer for older adults has been rising with the increasing population aging. This study aims to describe the burden of breast cancer in older adults worldwide, analyze the temporal trends for older breast cancer incidence, and assess the socioeconomic inequalities of breast cancer incidence and mortality with human development index (HDI) levels, which will provide valuable information in preventing and controlling the increasing breast cancer burden in older women.

The incidence and mortality rates of specific cancer types in older individuals in 2022 were sourced from the Global Cancer Today database. Trends in breast cancer incidence acquired from the Cancer Incidence in Five Continents (CI5) database. HDI and other risk factors were obtained from the United Nations. We used a generalized linear model to estimate the rate ratio and 95% confidence interval (CI) between HDI levels and breast cancer burden in older people.

It was estimated approximately 1,058,466 newly diagnosed breast cancer cases and 383,774 breast cancer deaths in women ≥60 years, accounting for 18.9% and 12.7% of global cancer cases and deaths. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were 172.9 and 57.7 per 100,000, ranking first and second among all cancer incidence and mortality in older women. The highest ASIR and ASMR were four-fold higher than the lowest, with ASIR ranging from a peak of 399.1 per 100,000 in Australia-New Zealand to a low of 90.6 per 100,000 in South Central Asia, and ASMR varying from a high of 118.6 per 100,000 in Melanesia to a low of 28.8 per 100,000 in East Asia. The largest increases in ASIR from 1998-2002 to 2013-2017 were observed in South Korea, China, and Estonia. The corresponding estimated 5-year average percentage changes (EAPC) were 6.01%, 2.89%, and 1.93%, respectively.

The global burden of breast cancer in older women is increasing fast and varies greatly across countries. Effective prevention strategies are essential to address the increasing breast cancer burden for older women.

Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults.

By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs. with offspring; more than one vs. one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models.

Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men (vs. one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring (P_nonlinear <0.0001).

Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.

Owing to the high prevalence of antibiotic resistance in Helicobacter pylori (H. pylori) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs. esomeprazole for H. pylori eradication in a patient population in China.

This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori, evaluated using a ¹³C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.

The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.

Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.

Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD’s impact in countries and regions worldwide, providing insights into its prevalence.

Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI).

Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2-0.2%, P <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1-0.1%, P <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high-middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries.

In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.

Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels may not fully translate into patient-reported health status in patients with heart failure (HF). We aimed to evaluate the correlation between NT-proBNP levels and patient-reported health status changes at one month after discharge of patients, and their associations with risk of death and rehospitalization in patients with acute HF.

We used data from the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (PEACE 5p-HF Study). Patient-reported health status was measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Patients who were hospitalized for HF and completed the KCCQ-12 and NT-proBNP tests before and one month after discharge were eligible in our study. We stratified patients into different groups based on NT-proBNP levels (i.e., improved, stable, and deteriorated) and KCCQ-12 scores (i.e., not deteriorated and deteriorated). We also examined the associations of the joint NT-proBNP and KCCQ-12 change with the risk of one-year and four-year clinical outcomes.

A total of 2461 patients were included in the analysis. The mean age was 64.06 ± 13.51 years, and 36.37% (895/2461) of the study population were female. Among patients with improved NT-proBNP levels, 115 (10.95%) patients had deteriorated KCCQ-12 scores. The correlation between the change in the KCCQ-12 score and NT-proBNP level was weak (r² = 0.002, P = 0.013). Stratification by changes in the KCCQ-12 score revealed subgroups with distinctive risks, such that patients with deteriorated KCCQ-12 scores in any of the NT-proBNP change groups exhibited an increased risk of one-year all-cause death than participants with not deteriorated KCCQ-12 scores in any of the NT-proBNP change groups. Patients with improved NT-proBNP levels and deteriorated KCCQ-12 scores presented greater risks of one-year all-cause death (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.34-4.48) than patients with stable NT-proBNP levels and not deteriorated KCCQ-12 scores (HR [95% CI], 1.77 [1.25-2.53]).

A discrepancy between changes in NT-proBNP levels and KCCQ-12 scores was common. The change in NT-proBNP levels was not sufficient to characterize critical aspects related to HF during one month after discharge of patients. Changes in the KCCQ-12 score exhibit complementary information to NT-proBNP levels for the prediction of clinical outcomes in patients with acute HF.

Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients’ clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens.

This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.

With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS (P = 0.012) and EFS (P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs. 6 [4, 7] days, Z = -0.227, P = 0.820).

NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.

While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients.

This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS (n = 178,883) and non-BS-GPS (n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively.

The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge.

Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.

The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported.

This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10⁷ cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits.

In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs. 2.11 [1.96, 2.35], P = 0.008; VCmax, 2.92 [2.55, 3.60] vs. 2.47 [2.18, 2.68], P = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs. 2.38 [2.24, 2.63], P = 0.017; VCmax, 3.52 [3.02, 3.80] vs. 2.59 [2.45, 3.15], P = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs. 2.30 [2.16, 2.70], P = 0.019; VCmax,3.61 [3.35, 3.97] vs. 2.69 [2.56, 3.23], P = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 (P = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups.

Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment.

Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.

In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.

A low dose of ATO (0.75 µmol/L in vitro and 1 mg/kg in vivo) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.

Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.

The 2023 edition of the International Working Group on the Diabetic Foot (IWGDF) Guidelines for the Prevention and Management of Diabetes-related Foot Disease was released during the 9th International Symposium on the Diabetic Foot in Hague, Netherlands, on May 13, 2023. These guidelines include changes to relevant terminology and definitions, notably replacing "diabetic foot" with "diabetes-related foot disease" and substituting "diabetic foot ulcer" with "diabetes-related foot ulcer". The former change encompasses not only modifications in terminology but also alterations in definition, whereas the latter constitutes merely a textual adjustment without altering the underlying definition.^[1]

To the Editor: Intrahepatic cholangiocarcinoma (ICC) ranks second among liver malignancies, and system chemotherapy is the current choice for controlling the tumor for patients with advanced ICC.^[1]Gemcitabine (Gem)-based chemotherapy has been a dominating treatment for advanced ICC.^[2]Generally, the outcome of systemic chemotherapy is poor and dissatisfied, and patients easily obtain therapy resistance.^[2]Recently, programmed cell death 1 (PD-1) blockade has shown great potential in tumor-specific immune therapy.^[3]Lenvatinib which targets multi-vascular endothelial growth factor receptors (VEGFR), and lenvatinib alliance of PD-1 blockade have shown great promise in advanced ICC.^[4]This retrospective multicenter research compares the prognosis of triple therapy with Gemox, lenvatinib, and PD-1 blockade with Gemox monotherapy for treating ICC with extrahepatic metastases.

To the Editor: HIV-associated lymphoma, particularly diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), is the most common malignancy among people living with HIV (PWH), contributing significantly to morbidity and mortality.^[1]The National Comprehensive Cancer Network (NCCN) guidelines recommend that the R-CODOX-M/IVAC and R-DA-EPOCH regimens be prioritized for patients with HIV-associated Burkitt lymphoma (HIV-BL), and the NCCN risk stratification criteria are also available. However, a randomized trial comparing the efficacy of these two regimens in high-risk patients revealed no significant difference in survival, and R-DA-EPOCH was the preferred regimen for most patients without central nervous system (CNS) involvement.

To the Editor: In the evolving landscape of prostate cancer management, particularly metastatic prostate cancer (mPCa), the transition to castration-resistant prostate cancer (CRPC) represents a pivotal challenge.^[1]This progression marks a critical phase in which the disease prognosis typically deteriorates and therapeutic options become increasingly limited. Traditional prognostic models heavily depend on clinical indicators such as Prostate Imaging Reporting and Data System (PI-RADS) scores, prostate-specific antigen (PSA) levels, and Gleason scores.^[2]While these markers are invaluable in the diagnostic context, their ability to predict progression to CRPC is notably limited. Furthermore, these prognostic markers do not fully capture the complex biological interactions within tumors or the dynamic nature of cancer progression.

To the Editor: Anterior cruciate ligament (ACL) rupture is a frequent knee injury that modifies knee joint kinematics, including intra-articular motions and forces, leading to recurrent functional instability of the knee. With an estimated 200,000 ACL ruptures annually in the United States, ACL ruptures are prevalent, especially in young, physically active individuals.^[1]Restoring knee morphology, stability, and function is the aim of conventional therapy, which is ACL reconstruction (ACLR).^[2]Previous studies have evaluated gait function at different time points before and after ACLR to quantify impairments in movement patterns and knee joint biomechanics.^[3]These investigations have consistently revealed substantial alterations in gait patterns induced by ACLR, with recovery persisting for at least 6 months post-procedure.^[4]Majewskaet al^[4]pointed out that most studies focus on short-term follow-up within 6 months after surgery, while time-dependent changes in long-term dynamic functional recovery remain poorly studied. Accordingly, we aimed to perform gait analysis both pre-ACLR and throughout the 12 months postoperatively, complemented by standard assessments of knee joint function.

To the Editor: Breast cancer remains a leading cause of cancer incidence and mortality among women globally.^[1]While population-based screening programs in countries like the U.S., Germany, and Japan have reduced mortality through early detection,^[2]Family history—a major non-modifiable risk factor—significantly influences individual breast cancer risk and age of onset, warranting tailored screening strategies. In China, national initiatives such as the Cancer Screening Program in Urban China and the Breast and Cervical Cancer Project for Rural Women have improved early detection. Nevertheless, current guidelines remain largely age-centered, with limited integration of family history for personalized screening. This study aims to provide empirical evidence for optimizing breast cancer screening initiation based on familial risk in a large Chinese cohort.

To the Editor: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory condition characterized by persistent pelvic pain, urinary urgency, frequency, and bladder fibrosis, which significantly diminishes the quality of life of patients.^[1]Despite its global prevalence of approximately 300 cases per 100,000 females, the condition remains poorly recognized and underdiagnosed in China, with reported incidences ranging from 21.8 to 100.0 per 100,000 individuals. Currently, IC/BPS diagnosis primarily relies on symptom evaluation and exclusion of bacterial infection, leading to frequent misdiagnoses.^[2]While therapies such as antihistamines, amitriptyline, and pentosan polysulfate provide partial relief, their efficacy is limited, and adverse effects remain common.^[3]Although the precise pathogenesis of IC/BPS remains unclear, accumulating evidence has suggested that immune dysregulation, chronic inflammation, and urothelial dysfunction may play pivotal roles.^[4]Understanding the correlation between molecular mechanisms and clinical manifestations such as pain, fibrosis, and immune responses is crucial. The identification of phenotype-related genes associated with immune cell infiltration may uncover potential biomarkers, advancing diagnostic accuracy and targeted therapies. Recently, machine learning (ML) methods have provided powerful tools for identifying disease-associated biomarkers and gene expression signatures.^[5]Utilizing ML algorithms to analyze transcriptomic data can reveal underlying molecular patterns, enhancing our understanding of complex diseases such as IC/BPS.

To the Editor: Lipoprotein(a) (Lp[a]) is a cholesteryl ester-rich lipoprotein exclusively produced in the liver, comprising two major components: a low-density lipoprotein (LDL)-like particle containing apolipoprotein B (apoB) and a glycoprotein apolipoprotein(a) (apo[a]) linked to apoB by a disulfide bridge.^[1]Both genomic and epidemiological evidence support the strong pathogenic role of elevated serum Lp(a) levels in cardiovascular disease (CVD) risk, independent of well-controlled LDL cholesterol (LDL-C) levels.^[1]

To the Editor: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and an excellent long-term prognosis is attained in most patients.^[1]However, aggressive variants of PTC, including tall cells, columnar cells, insular cells, solid cells, and diffuse sclerosing subtypes, are associated with higher recurrence and reduced survival rates.^[2]The role of radioactive iodine (RAI) therapy in managing these aggressive variants remains controversial, particularly regarding its impact on cancer-specific survival (CSS).^[3]

To the Editor: The standardized management of pain-agitation-delirium (PAD) represents a fundamental component of clinical practice in intensive care units (ICUs).^[1]Evidence-based analgesia and sedation strategies not only alleviate patients’ physiological discomfort and psychological distress, but also significantly reduce mechanical ventilation duration, improve long-term prognosis, and optimize healthcare resource allocation.^[1,2]Equally crucial is delirium management, as evidenced by studies demonstrating that delirium duration independently predicts mortality risk, hospital stay length, healthcare expenditures, and acquired dementia incidence.^[3]

To the Editor: Rearrangements involving lysine methyltransferase 2A (KMT2A) represent recurrent genetic abnormalities in acute leukemia (AL), which are commonly associated with poor clinical outcomes.^[1]Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve long-term survival ofKMT2A-rearranged (r) AL, but relapse remains the most important cause of transplant failure.^[2]Measurable residual disease (MRD) can predict post-HSCT relapse, and MRD-directed therapies improve clinical outcomes.^[3,4]Studies from our center indicate that monitoring theKMT2Alevel with real-time quantitative polymerase chain reaction (RT-qPCR) can predict relapse and survival post-allo-HSCT.^[5,6]Patients positive forKMT2Ahave a significantly higher cumulative incidence of relapse (93.5%vs. 12.5%,P<0.001), a worse overall survival (OS: 12.5%vs. 77.8%,P<0.001), and a worse leukemia-free survival (LFS, 0vs. 72.2%,P<0.001) compared with those continuously negative forKMT2A.^[6]