Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Cancer is one of the most lethal and burdensome diseases worldwide. Its progression not only causes irreversible damage to the body, but also imposes a substantial psychological burden on patients due to its complex prognosis. Immune imbalance, a hallmark of the tumor microenvironment (TME), accelerates tumor invasion and metastasis by impairing the function of effector immune cells, promoting the abnormal infiltration of immunosuppressive cells, and disrupting cytokine homeostasis, thereby constituting a major barrier to the efficacy of cancer immunotherapy. Compared with conventional chemotherapy and radiotherapy, aerobic exercise has shown considerable potential in antagonizing tumor progression through relatively mild but effective immunomodulatory mechanisms. On the one hand, regular aerobic exercise enhances the number and activity of key effector immune cells, such as CD8⁺ T cells, thereby strengthening their ability to recognize and eliminate tumor cells and alleviate immune imbalance. On the other hand, aerobic exercise promotes tumor vascular normalization, improves vascular maturity, and stimulates the secretion of irisin and other anti-inflammatory myokines, thereby remodeling the TME and relieving its immunosuppressive state to delay tumor progression. However, psychological stress following a cancer diagnosis can not only act as an independent disruptive factor that exacerbates immune imbalance within the TME, but also amplify the effects of other detrimental factors, such as reduced treatment adherence, thereby further weakening the antagonistic effect of aerobic exercise on tumor growth. Psychological stress, as a chronic stressor, promotes the excessive secretion of emotion-related hormones, including glucocorticoids (GCs) and norepinephrine (NE), which further suppress the activation and effector functions of antitumor immune cells such as CD8⁺ T cells and natural killer (NK) cells, while facilitating the recruitment of protumor immune cells such as regulatory T cells (Tregs). These changes ultimately disrupt immune homeostasis in the TME, promote tumor immune evasion, accelerate tumor invasion and metastasis, and offset the beneficial effects of aerobic exercise on tumor control. In addition, psychological stress induces hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal excitation of the sympathetic nervous system (SNS), thereby maintaining elevated levels of GCs, NE, and related stress hormones, suppressing inflammatory chemokine expression and immune cell recruitment, and further disturbing immune homeostasis in the TME, which accelerates tumor progression. More importantly, prolonged psychological stress can also disrupt the homeostasis of central neurotransmitters, such as 5-hydroxytryptamine (5-HT) and glutamate (Glu). This not only directly inhibits the activation and effector functions of antitumor immune cells and promotes the establishment of an immunosuppressive microenvironment, but also impairs cellular energy metabolism and continuously provides energy for tumor cells through metabolic reprogramming, thereby sustaining rapid tumor growth and adaptation to a hostile TME. Ultimately, these alterations contribute to the dysregulation of “neuro-endocrine-immune” axis and weaken the protective effect of aerobic exercise against tumor progression. Therefore, this review focuses on the interaction between psychological stress and the “neuro-endocrine-immune” axis, with particular emphasis on the mechanisms by which psychological stress induces immune imbalance and weakens the antagonistic effect of aerobic exercise on tumor progression. We further highlight the important role of psychological stress in tumor progression and propose that combining psychotropic interventions, aerobic exercise, and clinical antitumor immunotherapy may help restore the tumor-killing capacity of the immune system. Such a multimodal strategy may exert synergistic effects at multiple levels, including psychological stress relief, neuroendocrine regulation, and reconstruction of immune homeostasis, thereby providing new perspectives for identifying therapeutic targets in solid tumors, enhancing the efficacy of cancer immunotherapy, and improving patient prognosis.

Objective To explore the nutritional status in elderly patients with type 2 diabetes mellitus (T2DM) and analyze its relationship with the risk of sarcopenia. Methods A retrospective analysis was conducted on 312 elderly patients with T2DM admitted to the 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army between January 2023 and December 2025. Based on the presence or absence of sarcopenia, the patients were classified into a sarcopenia group (121 cases) and a non-sarcopenia group (191 cases). The nutritional status and related factors were compared between the two groups. Binary logistic regression analysis was adopted to analyze the correlation and influencing factors. Results The incidence rate of sarcopenia among elderly patients with T2DM was 38.78%. Compared with the non-sarcopenia group, the sarcopenia group had older age and higher proportions of patients with daily activity dependence, coronary heart disease, and gastrointestinal diseases. Conversely, the proportions of patients exercising ≥4 times per week and those paying attention to nutritional knowledge were lower in the sarcopenia group than those in the non-sarcopenia group (P<0.05). The body mass index (BMI), calf circumference (CC), body weight, albumin (ALB), hemoglobin (Hb), and MNA-SF score in the sarcopenia group were lower compared with those in the non-sarcopenia group (P<0.05). After logistic regression analysis, it was found that low BMI, exercising ≥4 times per week, dependence on daily activity, and low ALB and Hb were independent factors influencing sarcopenia in elderly patients with T2DM (P<0.05). Conclusion The incidence rate of sarcopenia is relatively high in elderly patients with T2DM. Low BMI, low ALB, low Hb, reduced weekly exercise frequency, and daily activity dependence are independent related factors. It is necessary to pay clinical attention to nutritional assessment and intervention.

Adipose tissue macrophages (ATMs) are crucial immunomodulatory factors in the adipose tissue (AT) microenvironment, playing an irreplaceable role in maintaining the balance of the local immune system and regulating metabolic homeostasis. Under obese conditions, the excessive accumulation of lipids leads to abnormal expansion of adipose tissue, which further disrupts the homeostasis of the local microenvironment, including the imbalance of inflammatory factors, the occurrence of oxidative stress, and the damage of microcirculation. As an essential immune cell population in adipose tissue, ATMs are deeply involved in the occurrence and progression of metabolic disorders and multiple obesity-related diseases, and their functional abnormalities are closely related to the initiation and development of adipose tissue inflammation and systemic metabolic disorders. The interaction between ATMs and adipokines, including adiponectin, leptin, resistin and retinol-binding protein 4 (RBP4), acts as the core immunological and molecular mechanism linking adipose tissue inflammation to continuous disease deterioration, and this interaction is also a key research focus in the field of obesity-related diseases in recent years. This review discusses in detail the facilitating effect of the AT inflammatory microenvironment on the differentiation of peripheral monocytes into ATMs, elaborating on the specific molecular mechanisms by which various inflammatory mediators and abnormal metabolic products in the inflammatory microenvironment induce the differentiation of peripheral monocytes into functional ATMs. It also focuses on the regulatory mechanisms of chemokine-mediated ATM polarization and recruitment, including the specific roles of key chemokines like monocyte chemoattractant protein‑1 (MCP-1) and C‑X‑C motif chemokine ligand 10 (CXCL10) in mediating the recruitment of ATMs to adipose tissue, as well as the molecular pathways that regulate the switch between M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype of ATMs. In addition, this review explores the specific process by which ATMs trigger AT inflammation by secreting various pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, which further amplify the local inflammatory response and disrupt the metabolic homeostasis of adipose tissue. Furthermore, it analyzes the specific binding patterns and molecular characteristics of adiponectin, leptin, resistin and RBP4 with ATM surface receptors, and clarifies how the activation of downstream immune signaling pathways, such as Janus kinase‑signal transducer and activator of transcription (JAK-STAT), nuclear factor‑κB (NF‑κB), and phosphatidylinositol 3‑kinase‑protein kinase B (PI3K-AKT), triggered by these binding processes, induces the occurrence and development of various obesity-related diseases, including insulin resistance, cancer, metabolic-associated steatohepatitis (MASH) and cardiovascular diseases. This paper highlights the unique and crucial role of the interaction between ATMs and adipokines in the occurrence and progression of obesity-related diseases, emphasizing that this interaction is a key link connecting local adipose tissue inflammation to systemic metabolic disorders. It further summarizes the potential therapeutic strategies targeting the ATM-adipokine axis, and comprehensively illustrates three major clinical application barriers, namely biological complexity, technical bottlenecks, and clinical translation obstacles, in the process of applying these therapeutic strategies. For each barrier, this review puts forward corresponding feasible solutions and clear research directions, which not only enrich the theoretical system of the ATM-adipokine axis in the field of obesity research, but also provide a solid theoretical basis and practical ideas for the clinical intervention, prevention and treatment of obesity and its related diseases.

Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Anterior cruciate ligament (ACL) reconstruction yields favorable outcomes for restoring anteroposterior stability of the knee joint in patients with ACL tears. However, some patients still exhibit positive knee pivot shift after ACL reconstruction. Currently, combined ACL and anterolateral ligament(ALL) reconstruction has been accepted by most scholars. This surgical technique can restore the rotational stability of the knee joint in patients postoperatively and facilitate the early besumption of sports training after surgery. This article reviews the anatomical research, isometry-like point research, and reconstruction indications of the anterolateral ligament, as well as the surgical approaches, graft tunnel convergence, and reconstruction outcomes of combined anterior cruciate ligament and anterolateral ligament reconstruction.

Objective To evaluate the clinical efficacy of haloperidol combined with auricular point pressing therapy in children with tic disorders.Methods A total of 120 pediatric patients diagnosed with tic disorders at the Department of Pediatric Rehabilitation,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Hebei Province from March 2022 to March 2024 were enrolled.Participants were randomly divided into an observation group(n=60)and a control group(n=60)using a random number table.The control group received haloperidol alone,while the observation group received additional auricular point pressing therapy.Treatment duration was 12 weeks.After 3 months,clinical efficacy was assessed by comparing:Yale Global Tic Severity Scale(YGTSS)scores,serum 5-hydroxytryptamine(5-HT)and dopamine(DA)levels,immune function markers(CD3+,CD4+),and incidence of adverse reactions between groups.Results(1)The overall efficacy rate in the observation group was 91.67％(55/60),while that in the control group was 76.67％(46/60).The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the YGTSS scores of children in both groups was significantly improved(P＜0.05),and the observation group showed a significantly greater improvement in YGTSS scores than the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the levels of 5-HT and DA in both groups of children were significantly improved(P＜0.05),and the observation group showed a significantly greater improvement in 5-HT and DA levels than the control group,with a statistically significant difference(P＜0.05).(4)After treatment,CD3+and CD4+levels were significantly improved in both groups(P＜0.05),and the observation group showed a significantly greater improvement in CD3+and CD4+levels than the control group,with a statistically significant difference(P＜0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group,with a statistically significant difference(P＞0.05).Conclusion The combination of haloperidol and auricular point pressing therapy significantly improves clinical symptoms and immune function in children with tic disorders,demonstrating both efficacy and safety.

The health of women and children serves as the cornerstone of comprehensive public health and represents a crucial barometer for measuring social progress and civilization. It directly impacts family well-being and social harmony. As a national-level guidance center for complex disease diagnosis and treatment, Beijing's critical maternal care center, and the designated consultation hospital for pregnancy complicated by rheumatic immune and endocrine disorders, Peking Union Medical College Hospital bears significant responsibilities in managing complex medical cases and implementing counterpart assistance programs. Confronted with diverse and complicated maternal sources, particularly emergency cases lacking standardized prenatal care, the hospital has established a multi-tiered, whole-process, and comprehensive maternal-infant safety management system. Through implementing high-risk maternal management protocols, optimizing critical care procedures, promoting informatization development, and enhancing multidisciplinary collaboration, Peking Union Medical College Hospital has substantially improved the efficiency of critical maternal care and maternal-infant safety assurance. This paper systematically summarizes the institutional development experience in maternal management and explores potential optimization approaches, aiming to provide valuable references for enhancing maternal-infant safety management systems in domestic healthcare institutions.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.