Volume 106 · Issue 08 · 2026

Progression-free survival (PFS) is widely used as an alternative endpoint for overall survival (OS) due to its ability to shorten clinical trial cycles and reduce interference with subsequent treatments. However, PFS based on tumor measurements is susceptible to evaluation bias, insufficient statistical power, and confounding effects of subsequent treatments, leading to doubts about its clinical value, especially in the field of ovarian cancer where controversy is significant. Although the benefits of PFS may not necessarily translate into extended OS or improved quality of life, it is not advisable to completely negate the clinical value of the drug simply because the secondary endpoint OS did not show significant benefits. This article explains the disconnect between PFS and OS in gynecological tumors, proposes the necessityofoptimizing endpoint selection to reduce statistical bias, and emphasizes the importance of precision medicine as the guide to promote clinical trial design innovation. The aim is to provide a strategic framework for balancing accelerated approval and clinical benefit verification, guiding future research to focus more on the dual improvement of endpoint selection scientificity and patient survival improvement.

Gestational trophoblastic neoplasia (GTN) represents a rare group of malignant tumors arising from trophoblastic tissue. These tumors are highly curable owing to their remarkable sensitivity to chemotherapy, yet treatment remains challenging in patients with high-risk disease, multi-drug resistance, or rare subtypes. Recent advances in immune checkpoint inhibitor (ICI) have expanded therapeutic possibilities for GTN. Some patients with recurrence or drug resistance have achieved long-term remission after treatment with programmed death receptor 1 (PD-1) and its programmed cell death ligand-1 (PD-L1) inhibitors.. Basic studies have revealed unique immunological features of GTN--including strong antigenicity, abundant immune cell infiltration, and high checkpoint expression--providing a biological rationale for immunotherapy. However, several key questions remain, including optimal treatment timing, long-term safety, fertility outcomes, and predictive biomarkers. Based on existing research findings, this review article discusses the current application status and controversies of GTN, proposes key directions for future development, and aims to provide references for clinical practice and follow-up research.

Molecular subtyping and detection of other molecular characteristics of endometrial cancer have been widely carried out and applied in clinical diagnosis and treatment. However, there are still many issues, including inconsistent molecular testing methods and the lack of high-quality evidence to guide standardized clinical diagnosis and treatment based on molecular characteristics. For molecular subtyping detection, it is recommended to conduct a comprehensive molecular subtyping assessment by combining immunohistochemistry (IHC) and next-generation sequencing (NGS). Clinically, the molecular subtyping of endometrial cancer, traditional pathological classification, and surgical pathological staging should be considered holistically, and individualized treatment plans should be formulated based on the latest available clinical evidence. POLE-mutant (POLEmut) endometrial cancer generally has a favorable prognosis, and immune checkpoint inhibitors (ICIs) may be an effective adjuvant treatment option for advanced POLEmut endometrial cancer. For stage Ⅲ and above mismatch repair-deficient (MMRd) endometrial cancer, postoperative paclitaxel plus carboplatin chemotherapy combined with ICIs and maintenance therapy are recommended. No specific molecular profile (NSMP) endometrial cancer should undergo risk stratification based on estrogen receptor (ER) expression level and pathological type, and high-risk NSMP should be treated with reference to p53-abnormal (p53abn) endometrial cancer. Precision diagnosis and treatment of endometrial cancer based on molecular characteristics are still in the stage of in-depth exploration and verification. Many issues remain to be resolved, such as whether MMRd endometrial cancer caused by MLH-1 methylation or mutations in MMR-encoding genes has consistent responses to ICIs, and how to predict treatment efficacy. The reduced cost and rapid popularization of high-throughput technologies, as well as the continuous expansion and improvement of evidence from prospective cohorts, will provide high-quality evidence for further refinement of molecular characteristics and risk stratification of endometrial cancer, and guide the implementation of precision treatment for this disease.

Chronic respiratory diseases are important contributors to the rising burden of non-communicable diseases globally. Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies, which can improve exercise capacity, reduce dyspnea, enhance health-related quality of life, stands as one of the most cost-effective treatment strategies. To better guide clinical practice in pulmonary rehabilitation of chronic respiratory diseases, Pulmonary Rehabilitation Committee of Chinese Association of Rehabilitation Medicine, Pulmonary Rehabilitation Group (preparatory) of Chinese Thoracic Society, Chinese Association of Chest Physician, jointly organized experts from multiple fields to systematically evaluated relevant guidelines and evidence from evidence-based medical research on pulmonary rehabilitation of chronic respiratory diseases published in China and abroad in the recent years. Based on the "Guidelines for respiratory rehabilitation management of chronic respiratory diseases in China (2021)", they formulated the "Guidelines for pulmonary rehabilitation of chronic respiratory diseases in China (2026 edition)" using the Delphi method. These guidelines cover the pulmonary rehabilitation defination and eligible individuals, optimal timing for initiation of pulmonary rehabilitation, pulmonary rehabilitation techniques, multimorbidity assessment and rehabilitation goals in elderly patients with CRD, education of patients and caregivers, inhalation technique, nutritional management, psychological assessment and intervention, use of assistant equipment, novel models of pulmonary rehabilitation and telerehabilitation, management of adverse events in pulmonary rehabilitation. Altogether 19 recommendations were formulated during this revision.

To compare the clinical features and acoustic characteristics of native arteriovenous fistulas (AVF) between maintenance hemodialysis (MHD) patients with and without diabetes mellitus.

In this cross-sectional study, MHD patients using AVF from the Blood Purification Center of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University between March and August 2024 were enrolled. AVF morphology and hemodynamics were assessed via ultrasonography, while concomitant audio recordings were obtained for acoustic analysis. Participants were stratified by diabetes status, and differences in clinical, ultrasonographic, and acoustic features were analyzed.

A total of 192 patients (119 males and 73 females) aged (58.6±12.7) years were enrolled. Those with diabetes had greater height, weight, and body surface area but shorter dialysis duration and lower albumin, prealbumin, and hemoglobin levels (all P<0.05). Ultrasonography revealed smaller vascular diameters at the anastomosis, within 3 cm proximally, at the puncture site, and in the radial artery 2 cm from the brachial artery bifurcation in the diabetic group (all P<0.05). Resistive indices (at the anastomosis and within 3 cm proximally) and puncture depth were higher in diabetic patients (all P<0.05). The multiple linear regression analysis indicated that diabetes mellitus (β=0.102, 95%CI: 0.051-0.153, P<0.001) was associated with an increased anastomosis resistive index. The diabetic group demonstrated a significantly higher zero-crossing rate [0.011 (0.009, 0.012) vs 0.008 (0.007, 0.011), P<0.001], but lower acoustic wave amplitude [-13.2 (-20.6, -10.6) dB vs -11.5 (-14.3, -10.3) dB, P=0.049], mean mel-frequency cepstral coefficients (MFCC) [7.6 (0.4, 10.2) vs 10.4 (7.2, 12.2), P<0.001], and mean extended Geneva minimalistic acoustic parameter set (eGEmaps) values [112 (109, 114) vs 113 (112, 115), P=0.011] compared to the non-diabetic group.

MHD patients with diabetes exhibit distinct AVF profiles characterized by smaller vascular diameters, greater puncture depth and resistance indices, higher acoustic zero-crossing rates, and lower mean MFCC and eGEMAPS values compared to non-diabetic patients.

To investigate the prefrontal cortex activation characteristics in patients with schizophrenia (SZ) during a verbal fluency task (VFT) using functional near-infrared spectroscopy (fNIRS), and to explore their relationship with treatment efficacy.

In this prospective study, SZ patients hospitalized at the Second Affiliated Hospital of Xinxiang Medical University between March 2022 and October 2024, and healthy controls (HCs) from the same hospital during the same period were enrolled. At baseline, prefrontal cortical activation was assessed by measuring changes in oxygenated hemoglobin (oxy-Hb) concentration using fNIRS during the VFT. Symptom severity in SZ patients was evaluated with the Positive and Negative Syndrome Scale (PANSS). After 4 weeks of treatment, PANSS assessment and fNIRS measurements were repeated. Patients were then classified into responders and non-responders based on whether the PANSS score reduction rate was≥25%. Differences in brain activation were compared between: (1) SZ patients and HCs at baseline; (2) SZ patients before and after treatment; and (3) responders versus non-responders.

Eighty SZ patients [40 males, 40 females, mean age (32.4±8.8) years] and 80 HCs [39 males, 41 females, mean age (31.0±10.2) years] were included, with no significant differences in age or gender between groups (all P>0.05). During the VFT, the SZ group showed significantly fewer activated channels than the HC group (9 vs 31 channels). In the SZ group, total PANSS score and subscale scores were significantly correlated with oxy-Hb concentrations in channels covering the Broca′s area, frontopolar region, and dorsolateral prefrontal cortex (all P<0.05). After 4 weeks of treatment, the SZ group exhibited a significant reduction in PANSS scores [(94.2±12.1) score vs (73.1±14.6) score]and an increased number of activated channels (9 vs 12 channels), with channels ch21 and ch48 showing significantly greater activation post-treatment [(0.26±0.73) vs (0.06±0.84) and (0.44±0.90) vs (0.19±0.62), respectively] (all P<0.05). The responders had more activated channels than non-responders (15 vs 1 channel), with 7 channels showing statistically significant between-group differences in activation values (all P<0.05).

SZ patients exhibited significantly impaired prefrontal cortex activation as measured by fNIRS. Following 4-week treatment, the extent of prefrontal activation increased, particularly in responders.

To investigate the expression of miR-199a-5p in intrahepatic cholangiocarcinoma (ICC) and its regulatory mechanism in tumor invasion and metastasis.

Tumor tissues and adjacent normal tissues from 38 ICC patients (aged 40-80 years, including 14 males) were collected at the First Affiliated Hospital of Nanhua University from January 2020 to April 2023. Differential genes and target genes were screened using transcriptome sequencing and multi-database bioinformatics analysis. Transcriptome sequencing was performed to detect the expression of miR-199a-5p and hypoxia-inducible factor 1α (HIF-1α). At the same time, clinical and pathological data such as patients′ TNM staging and pathological differentiation were collected to analyze the correlation between the expression levels of miR-199a-5p and HIF-1α and clinicopathological features. Transcriptome sequencing was used to detect the RNA expression of miR-199a-5p and HIF-1α in tumor tissues and adjacent non-cancerous tissues of ICC patients. Immunohistochemistry was employed to detect HIF-1α expression in the tissues. Human normal bile duct epithelial cells, HuCC-T1 and RBE cell lines were cultured and used. The targeting relationship between miR-199a-5p and HIF-1α was verified by dual-luciferase reporter assay. The expression levels of miR-199a-5p and HIF-1α at the cellular level were detected using real-time quantitative PCR (qRT-PCR). RBE cells were divided into three groups through transfection using Lipofectamine 3000 reagent: control group, miR-199a-5p mimic group, and miR-199a-5p inhibitor group. The transfection efficiency and HIF-1α mRNA expression levels were assessed by qRT-PCR. Western blot analysis was used to detect the protein expression levels of HIF-1α, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9), and Cleaved caspase3. Cell migration and invasion abilities were assessed using wound healing and Transwell assays. HIF-1α knockdown cell models were established in RBE cells by transfecting them with HIF-1α-specific small interfering RNA (si-HIF-1α), with a negative control group (si-NC) set up simultaneously. After verifying the knockdown efficiency by qRT-PCR and Western blotting, changes in biological behavior of cholangiocarcinoma cells following HIF-1α suppression were observed by examining the expression of proliferation-related protein PCNA, performing wound healing assays, and conducting Transwell migration and invasion assays. This was aimed at clarifying the central role of HIF-1α in cholangiocarcinoma migration and invasion, further supporting that miR-199a-5p exerts its tumor-suppressive effect by targeting and inhibiting HIF-1α. All experimental data were repeated three times.

Transcriptome sequencing and multi-database analysis identified miR-199a-5p and HIF-1α as targets. Dual-luciferase reporter assays confirmed that miR-199a-5p directly targets the 3′-UTR of HIF-1α. Transcriptome sequencing tissue expression analysis showed that compared with adjacent non-cancerous tissue, the expression of miR-199a-5p was decreased in ICC (FPKM: 1.24±0.31 vs 3.87±0.56), while the expression of HIF-1α was significantly increased (FPKM: 18.76±6.23 vs 56.15±8.42) (both P<0.05). Immunohistochemistry results showed high expression of HIF-1α in ICC. Analysis of clinical pathological features indicated that ICC patients in the low miR-199a-5p expression group and the high HIF-1α expression group both had later TNM staging and poorer pathological differentiation (both P<0.05). Mechanistically, overexpression of miR-199a-5p downregulated PCNA and MMP9 and upregulated Cleaved caspase 3, while inhibition of miR-199a-5p led to the opposite changes (all P<0.05). Overexpression of miR-199a-5p inhibited the expression of HIF-1α and suppressed cell migration and invasion, whereas inhibition of miR-199a-5p produced the opposite effects (all P<0.05). After knocking off HIF-1α, both the number of migrating and invading cells decreased (both P<0.05).

miR-199a-5p is downregulated in ICC and suppresses tumor migration and invasion by directly targeting HIF-1α and regulating downstream molecules involved in proliferation, invasion and apoptosis.

A total of 31 patients [17 males and 14 females, with a median (Q₁, Q₃) age of 73 (71, 75) years] over 70 years old with acute type A aortic dissection who underwent Sun′s operation in Fuwai Central China Cardiovascular Hospital from October 2023 to June 2025 were included, and 11 patients [two males and nine females, with a median (Q₁, Q₃) age of 73 (71, 74) years] who underwent simplified ascending aorta replacement were included as the control group. In the Sun′s procedure group, bilateral antegrade cerebral perfusion under mild hypothermia (28.1-32.0 ℃) was used for cerebral protection during circulatory arrest. The operation time was (6.6±1.5) h and (6.8±1.5) h, the tracheal intubation time was 39 (21, 132) h and 34 (16, 71) h, and the intensive care time was 113 (68, 179) h and 111 (43, 178) h in the Sun′s procedure group and the control group, respectively, with no significant differences between the two groups (all P>0.05). In the Sun′s procedure group, one patient died of intraoperative bleeding and another died of a new postoperative cerebral infarction. Therefore, the in-hospital mortality rate was 6.5% (2/31). There were no deaths in the control group. The results suggest that Sun′s procedure under mild hypothermia combined with bilateral antegrade cerebral perfusion is an effective surgical treatment for patients over 70 years old with acute type A aortic dissection.

Aortic stenosis (AS) and chronic kidney disease (CKD) show high comorbidity rates in the elderly population, and CKD can accelerate valve calcification through chronic inflammation, calcium and phosphorus metabolism disorders, and increased hemodynamic load, promoting the rapid progression of AS and significantly reducing long-term survival rate. In this paper, the main risk factors of AS and CKD and their interaction mechanisms were combed out, and the pathological basis of promoting valvular lesions in CKD patients was emphasized at the early stage of the disease, which suggested that the comprehensive management of risk factors such AS blood pressure, blood lipid, blood glucose and calcium and phosphorus metabolism was of great significance. In recent years, new lipid-lowering therapies and cardiorenoprotective drugs have been of potential value in improving metabolic status and delaying the progression of AS. In the treatment of severe AS, transcatheter aortic valve replacement (TAVR) has a better safety and benefit ratio than traditional surgical aortic valve replacement (SAVR) in patients with CKD. This paper reviews the epidemiological characteristics, pathophysiological mechanisms and treatment strategies of CKD combined with AS, aiming to provide reference for clinical practice and provide ideas for future research directions.

As an emerging three-dimensional tumor model, patient-derived organoids (PDOs) have shown significant advantages in simulating the tissue structure, molecular characteristics and function of tumors. Compared with traditional two-dimensional cell lines and patient-derived xenograft models, PDO can more truly reflect the heterogeneity of tumors and their interactions with the microenvironment. This article reviews the recent progress in the construction and optimization of PDO in head and neck tumors, with emphasis on its applications in genomic and single cell analysis, drug screening, and tumor immune microenvironment modeling. At the same time, the main challenges limiting the widespread application of PDO, including establishment efficiency, clone drift and standardization of culture conditions, were further analyzed. Finally, the future development prospects of PDO in the construction of biological sample banks, organ chip platforms, and artificial intelligence (AI) -assisted analysis are prospected, in order to maximize its translational potential in guiding individualized treatment of patients with head and neck tumors.

The patient, a 73-year-old female, was admitted to the respiratory department of Qingdao Municipal Hospital on October 21, 2024 due to "pulmonary nodules found for 3 weeks". Previously, he underwent "hysterectomy" in December 2021 due to "endometrial malignant tumor". Specialist examination showed clear breathing sounds in both lungs, and no dry or wet rales were heard. The detection of carcinoembryonic antigen, neuron-specific enolase, squamous cell carcinoma antigen and anti-tuberculosis antibody were negative at admission. On October 22, 2024, the results of chest enhancement CT showed a nodular focus near the pleura in the lower lobe of the right lung, with clear boundaries and a size of about 17 mm ×12 mm. The enhancement around the enhancement scan was more obvious than the center, and the hilum of both lungs was not large (shown by arrows in Figures A and B). In order to confirm the diagnosis and treatment, thoracoscopic wedge resection of the right lower lobe of the lung under general anesthesia was performed on October 25, 2024. The pathological results showed that the lymphoid tissue in the right lower lobe of the lung tissue diffusely proliferated and invaded blood vessels, and abnormal large lymphocytes were seen in the background of small lymphocytes, and large lymphocytes were diffusely distributed in patches in some areas (Figure C, hematoxylin-eosin staining ×100). In situ hybridization showed positive expression of Epstein-Barr virus-encoding RNA in situ hybridization (EBER-ISH) in tumor cells (panel D, chromogenic in situ hybridization ×400). Immunohistochemistry showed positive expression of CD20 and MUM1 in tumor cells, CD30 (scattered positive,<5%), CD3, BCL6, CD10, CD21 were all negative, combined with histopathology, immunohistochemistry and Epstein-Barr virus detection results were positive, consistent with lymphomatoid granuloma (LYG), grade 3. LYG is a rare vasocentric and vasodestructive lymphoproliferative disease that occurs outside lymphoid organs. It consists of Epstein-Barr virus-positive B cells and reactive T cells. The distribution of nodular LYG was mainly in the middle and lower lung fields, and the nodules were mostly irregular, with less sharp edges but no obvious burrs. After enhanced imaging scan, nodular LYG mostly showed mild to moderate uniform enhancement. The pathology of LYG is characterized by vasocentric and vasodestructive pleomorphic lymphoid infiltration. Treatment includes drugs that act on the immune system, chemotherapy, and bone marrow transplantation.