Volume 139 · Issue 20 · 2026

Esophageal cancer (EC) is a prevalent and highly aggressive malignancy with an increasing global burden that is associated with significant mortality. The principal histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), exhibit distinct etiological factors and genomic landscapes. This review systematically categorizes and synthesizes findings from key EC clinical trials conducted over the past five years. Specifically, we integrate the current understanding of molecular pathogenesis, targeted therapeutic approaches, the tumor immune microenvironment, and emerging treatment strategies. Immunotherapy has emerged as a breakthrough in the management of EC; however, the progress in the development of targeted therapies has been notably slower. To address this gap, promising future directions in targeted therapy may include tyrosine kinase inhibitors (TKIs), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, agents targeting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, and epigenetic modulators. Despite these significant therapeutic advances, EC remains a highly lethal disease, which underlines the critical and ongoing need to identify novel therapeutic vulnerabilities and explore innovative combination treatment regimens.

As global aging accelerates, sarcopenia has become an increasingly important public health concern. Although typically recognized as an age-related condition, sarcopenia can develop and progress more rapidly under certain pathological conditions, such as obesity and type 2 diabetes. With the ongoing advancement of related research, the mechanisms underlying sarcopenia are being progressively elucidated. Management strategies include both nonpharmacological and pharmacological interventions. Resistance exercise is currently regarded as one of the most effective and foundational nonpharmacological approaches. Strength-based training programs have been shown to improve muscle mass and strength, reduce functional decline, and lower the risk of falls. However, despite the growing recognition of sarcopenia as a major health issue, particularly among aging populations, no drug has yet been approved by the US Food and Drug Administration as a specific treatment for this condition, due to its complex pathophysiology. This review aims to systematically summarize the epidemiological characteristics and pathogenesis of aging-, obesity-, and diabetes-related sarcopenia and to discuss evidence-based intervention strategies. Future research should focus on elucidating the underlying biological mechanisms, identifying biomarkers for early diagnosis, and developing individualized precision treatment systems.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) are characterized by a disastrous prognosis. For most patients with R/R AML, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option. It is important to conduct mutational analysis again when the disease relapses to identify any new genetic abnormalities that can be targeted with novel treatments. As part of a conditioning regimen or post-transplant maintenance therapy, new targeted agents support HSCT in patients with R/R AML in various forms, including combination chemotherapy to improve complete remission (CR) prior to HSCT. For R/R AML patients with mutated FMS-related tyrosine kinase 3 (FLT3), sorafenib and quizartinib have shown encouraging therapeutic effects either in combination with chemotherapy for bridging to transplantation or as maintenance therapy after HSCT. Ivosidenib and enasidenib, which are inhibitors that target mutated isocitrate dehydrogenase (IDH) 1 and 2, respectively, have been approved by the US Food and Drug Administration (FDA) for the treatment of IDH1/IDH2-mutated R/R AML. Venetoclax, an inhibitor of B-cell lymphoma-2 (BCL2), is widely used in the salvage treatment of R/R AML and has better therapeutic effects and controllable drug toxicity than traditional chemotherapy. In addition, chimeric antigen receptor (CAR) T-cell immunotherapy (targeting CD33, CD123, and CLL1) has achieved encouraging clinical response rates in phase I and phase II clinical trials for R/R-AML, and subsequent bridging HSCT has significantly improved patient survival.

Background: Artificial capnothorax during surgery potentially increases the risk of tumor cell dissemination and impacts survival. This trial aimed to investigate the effect of artificial capnothorax on the prognosis of patients with esophageal cancer who underwent minimally invasive esophagectomy. Methods: This prospective, randomized controlled trial was conducted in two high-volume hospitals in China. Between August 2019 and January 2020, 110 patients with resectable esophageal cancer were randomized to undergo single-lung ventilation (n = 55) or capnothorax procedures (n = 55). The analysis was based on the intention-to-treat principle. The final follow-up occurred in January 2023. Results: A total of 110 patients were included in the intention-to-treat analysis. After surgery, the incidence of patients exhibiting incremental changes in circulating tumor cell levels was 18.6% (8/43) in the capnothorax group and 2.7% (1/37) in the single-lung ventilation group (P = 0.033) (mean changes, −3.9 ± 3.4 [FU/3 mL] vs. −2.4 ± 2.9 [FU/3 mL], respectively; P = 0.039). Compared with the capnothorax group, the single-lung ventilation group had better 3-year overall survival rates (81.6%, 95% confidence interval [CI]: 72.4–92.0% vs. 65.2%, 95% CI: 59.3–78.8%; P = 0.049) and disease-free survival rates (81.6%, 95% CI: 72.4–93.0% vs. 61.6%, 95% CI: 50.1–75.7%; P = 0.019). Multivariate analysis indicated that artificial pneumothorax potentially impaired overall survival (hazard ratio [HR]: 2.35, 95% CI: 1.05–5.24; P = 0.037) and disease-free survival (HR: 2.70, 95% CI: 1.23–5.94; P = 0.014). Conclusions: Artificial capnothorax appears to be associated with poor oncological outcomes in patients with esophageal cancer. Single-lung ventilation in minimally invasive esophagectomy is safer and more favorable than capnothorax.

Background: Benvitimod (tapinarof), an aryl hydrocarbon receptor (AhR) agonist approved for treating plaque psoriasis, is being investigated as a potential treatment for atopic dermatitis (AD). The aim of this study was to evaluate the efficacy and safety of benvitimod 1% cream in patients aged 2 years or older with AD. Methods: This randomized controlled trial enrolled 271 Chinese patients with AD aged ≥2 years, who received either benvitimod 1% cream (n = 183) or vehicle cream (n = 88) twice daily for 8 weeks in a 2:1 ratio at 35 sites in China from June to November 2023. The primary endpoint was the proportion of patients achieving a 75% improvement in the Eczema Area and Severity Index (EASI) 75 at week 8. Secondary endpoints included achievement of Investigator’s Global Assessment (IGA) scores of 0/1, 90% EASI improvement (EASI 90), and ≥3-point reduction in Peak Pruritus Numerical Rating Scale (PP-NRS). Treatment-emergent adverse events (TEAEs) were monitored for safety evaluation. Furthermore, a subset of patients (n = 43) opted into a 44-week open-label extension. Results: At week 8, a significantly higher proportion of patients treated with benvitimod achieved EASI 75 compared to those receiving vehicle (54.4% [n = 183] vs. 25.5% [n = 88]; P <0.001). The benvitimod group also showed superior results across all secondary endpoints: IGA 0/1 (46.2% [n = 183] vs. 21.4% [n = 88]; P <0.001), EASI 90 (33.9% [58/171] vs. 13.5% [10/74]; P<0.001), and ≥3-point decrease in PP-NRS (54.0% [47/87] vs. 27.9% [12/43]; P <0.01). TEAEs occurred in 51.4% (94/183) of benvitimod-treated patients vs. 43.2% (38/88) of vehicle-treated patients, with most events being mild to moderate in severity. Conclusion: Benvitimod 1% cream demonstrated favorable efficacy and safety in adult and pediatric patients with AD, supporting its potential as a novel topical treatment option.

Background: Acute graft-versus-host disease (aGVHD) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The development of methods that preserve graft-versus-leukemia (GVL) activity while preventing aGVHD remains a long-sought goal. Recent studies suggest that mesenchymal stem cells (MSCs), particularly human umbilical cord-derived MSCs (HUC-MSCs), are effective at mitigating aGVHD, yet their varied efficacy remains poorly understood. Methods: We performed a comprehensive analysis of MSCs heterogeneity through single-cell transcriptomic mapping across nine human tissue sources and identified the keratin 8 high-expression (KRT8+) subpopulation of HUC-MSCs with enhanced functional properties. We further validated the functional roles of the KRT8+ subpopulation through lentivirus-mediated KRT8 overexpression. Bulk RNA sequencing was used to analyze the genomic impact of KRT8 overexpression. Additionally, we examined the effects of KRT8 overexpression on cellular senescence via Western blotting and β-galactosidase (SA-β-gal) staining. The immunosuppressive function of HUC-MSCs was evaluated by coculturing them with CD3+ T cells and liver organoids. Cell migration ability was assessed through Transwell assays and PKH26 dye labeling in vivo. An MHC-mismatched GVHD mice model (C57BL/6J to BALB/c) was established to test the therapeutic effect of HUC-MSCs. Clinical signs of aGVHD were monitored, and pathological changes were analyzed using hematoxylin and eosin staining. The GVL effect was evaluated through the inoculation of luciferase-transfected A20 cells and bioluminescence imaging. Results: KRT8 was expressed predominantly in HUC-MSCs. Compared with the KRT8 low-expression (KRT8lo) subpopulation of HUC-MSCs, the KRT8+ subpopulation presented increased stemness and reduced immunogenicity. KRT8 overexpression in HUC-MSCs significantly ameliorated aGVHD in vivo. Importantly, increased KRT8 expression in HUC-MSC did not impaire GVL activity in A20 lymphoma cells. Functional experiments further confirmed that HUC-MSCs with increased KRT8 expression significantly reduced cellular senescence by increasing enhancer of zeste homolog 2 (EZH2)-mediated histone h3 lysine 27 trimethylation (H3K27me3). This upregulation resulted in increased secretion of hepatocyte growth factor (HGF). This, in turn, suppressed T-cell proliferation and activation, significantly reducing liver organoid damage in vitro. Conclusions: Our results suggest that the infusion of KRT8+ HUC-MSCs enhances the efficacy of preventing aGVHD but does not interfere with the GVL effect. This strategy represents a promising therapeutic advancement in the setting of allo-HSCT.

Background: Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which effective treatments capable of suppressing local autoimmune injury remain limited. This study aimed to develop an ultrasound-responsive anti-inflammatory nano-contrast agent (AINA) for the targeted delivery of MHC class II transactivator (CIITA)-small interfering ribonucleic acid (CIITA-siRNA) and rapamycin to thyroid tissue. Methods: Thyroid tissue samples were obtained from patients undergoing total thyroidectomy at Qilu Hospital of Shandong University from March to April 2024. After pathological evaluation, samples from three patients with HT and three patients without HT were included. CIITA and human leukocyte antigen DR isotype (HLA-DR) expression was assessed using transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction. AINAs were constructed with an erythrocyte-membrane shell carrying rapamycin and a core containing CIITA-siRNA-loaded, trans-activator of transcription (TAT)-modified mesoporous silica nanoparticles and liquid perfluorohexane. Their physicochemical properties, ultrasound imaging performance, cellular uptake, therapeutic effects, and preliminary safety were evaluated in Nthy-ori 3-1 cells, Jurkat cells, and NOD.H-2h4 mice. Results: AINAs had a mean diameter of 255 nm and a polydispersity index of 0.23. More than 90% of CIITA-siRNA was loaded onto the mesoporous silica nanoparticles, and the optimized preparation achieved a rapamycin encapsulation efficiency of approximately 75%. In vitro, ultrasound-assisted AINAs reduced Interleukin-23-induced reactive oxygen species accumulation and apoptosis in thyroid cells and suppressed CIITA and HLA-DR expression, antigen presentation, and Jurkat T-cell activation. In vivo, ultrasound enhanced the accumulation of AINAs in thyroid tissue. Treatment with AINAs plus ultrasound alleviated thyroid inflammation, reduced local CD3+ and CD4+ T-cell infiltration and serum thyroid autoantibody levels, and caused no apparent pathological injury to major organs. Conclusions: Ultrasound-responsive AINAs enabled the targeted delivery of CIITA-siRNA and rapamycin to thyroid tissue and showed anti-inflammatory and thyroid-protective effects in cellular and animal models of HT.

Background: Chronic hepatitis B virus (HBV) infection accounts for more than 40% of hepatocellular carcinoma (HCC) cases worldwide. The GALAD (Gender, Age, alpha fetoprotein heterogeneity [AFP-L3], AFP, and des-gamma-carboxy prothrombin [DCP]) model has potential for enhancing HCC diagnosis. However, its diagnostic performance in HBV-associated chronic liver disease requires further optimization. This study aimed to establish a diagnostic model for HBV-associated HCC. Methods: The data from 2190 patients with HBV-related liver diseases, including chronic hepatitis B (CHB), cirrhosis, and HCC were analysed. The GADA model was developed by omitting AFP-L3 for improved accessibility, and its performance was assessed via the area under the receiver operating characteristic curve (AUC). Validation was performed on 20,908 patients across ten hospitals. Results: The simplified GADA model demonstrated exceptional diagnostic performance in identifying HBV-related HCC in the modeling group, achieving an AUC of 0.940 (95% CI, 0.927–0.952), with a sensitivity and specificity of 82.57% and 91.53%, respectively, surpassing the original GALAD model’s AUC of 0.907 (95% CI, 0.891–0.921). In the internal validation cohort, the GADA model had an AUC of 0.935 (95% CI, 0.914–0.953), sensitivity of 82.04%, and specificity of 92.65%. For early-stage HCC detection, the AUC in the modeling group was 0.858 (95% CI, 0.837–0.877), and in the internal validation group was 0.868 (95% CI, 0.836–0.895), significantly better than the original GALAD model. External validation with 20,908 participants yielded an AUC of 0.919 (95% CI, 0.916–0.923), with sensitivity of 86.00% and specificity 81.88%. For early-stage HCC diagnosis, the AUC was 0.903 (95% CI: 0.898–0.907), with sensitivity of 88.16% and specificity 74.50%. Conclusions: The GADA model shows exceptional promise for diagnosing HBV-related HCC, enhancing early detection and reducing misdiagnosis rates. Its clinical utility is supported by robust validation, indicating significant implications for patient prognosis and treatment options.

Background: Sjögren’s disease (SjD) is an autoimmune disorder characterized by sicca syndrome with undetermined roles of reactive oxygen species (ROS) and mitochondrial dynamics in the damaged glands. This study aimed to clarify the roles of ROS and mitochondrial dynamics in SjD-related hyposalivation and explored the therapeutic effect of targeting mitochondrial fission to treat hyposalivation in murine SjD. Methods: Single-cell sequencing analysis of submandibular glands (SMGs) from mice with SjD was performed. ROS and mitochondrial dynamics and function were evaluated. Mitochondrial division inhibitor-1 (Mdivi-1) was intraductally infused into the SMGs of mice with SjD. The saliva flow rate was measured after intraperitoneal injection of pilocarpine. Results: Single-cell sequencing analysis revealed that oxidative stress damage in SMGs might play a critical role in hyposalivation caused by SjD. Intraperitoneal injection of Mito-TEMPO (a mitochondrion-targeted antioxidant) increased the salivary flow rate in murine SjD. In vitro, Mito-TEMPO preincubation alleviated mitochondrial dysfunction. Furthermore, the increased ROS levels promoted mitochondrial fission and decreased fusion in vivo and in vitro. Dynamin-related protein 1 (Drp1) and its Ser616 site mediated mitochondrial dysfunction in glandular epithelial cells induced by interferon-γ. Finally, Mdivi-1 and Drp1 inhibitor intraductally infused into the SMGs promote the saliva flow rate in SjD mice, accompanied by improvements in glandular mitochondrial function and cell survival. Conclusions: The elevated ROS in salivary gland epithelial cells participates in hyposalivation in SjD. The excess ROS results in the increased mitochondrial fission via Drp1 and its Ser616 site, further worsening mitochondrial dysfunction in glandular cells. Mdivi-1 intraductal infusion can significantly ameliorate hyposalivation in murine models of SjD.

Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. Solute carrier family 38 member 7 (SLC38A7), a lysosome-localized glutamine transporter, has been implicated in poor cancer prognosis and chemoresistance, but its biological role in GC is not well understood. This study aimed to investigate the biological function of SLC38A7 in GC progression and to elucidate the underlying signaling mechanism. Methods: The expression pattern and clinical relevance of SLC38A7 were analyzed using public datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project, and validated in 60 paired GC tissues collected at the Chinese People’s Liberation Army General Hospital. Gain- and loss-of-function experiments were conducted in MKN-28 and MGC-803 to evaluate the effects of SLC38A7 on cell proliferation, migration, and invasion under glutamine-replete and glutamine-deprived conditions. Protein–protein interactions were assessed by co-immunoprecipitation and mass spectrometry. Site-directed mutagenesis was performed to identify key residues mediating SLC38A7 function. Downstream signaling was analyzed by western blotting and ubiquitination assays. A xenograft mouse model was established to determine the role of SLC38A7 in tumor growth in vivo. Results: SLC38A7 expression was significantly upregulated in GC tissues and cell lines and was associated with poor patient prognosis. Functional assays demonstrated that SLC38A7 promoted GC cell proliferation, migration, and invasion, particularly under glutamine-deprived conditions. Mechanistically, SLC38A7 interacted with myosin heavy chain 9 (MYH9), facilitating glycogen synthase kinase-3β (GSK-3β) ubiquitination and degradation, which led to activation of the wingless/int-1 (Wnt)/β-catenin signaling pathway. Mutation of key SLC38A7 residues (E12 and Q3) disrupted its interaction with MYH9 and attenuated downstream signaling. Pharmacological inhibition of GSK-3β partially rescued the effects of SLC38A7 silencing in vitro. In vivo, SLC38A7 knockdown significantly suppressed tumor growth. Conclusion: SLC38A7 promotes gastric cancer progression by activating the Wnt/β-catenin signaling pathway through MYH9-dependent regulation of GSK-3β ubiquitination.