最新刊期
卷 51 ， 期 4 ， 2026
- 摘要：Brain tumors, particularly highly malignant ones such as glioblastoma, have become a major challenge in contemporary medicine due to their extensive heterogeneity, invasiveness, and therapeutic resistance. This review systematically summarizes the latest research progress of targeted therapeutic drugs for brain tumors in recent years, covering multiple key targets including epidermal growth factor receptor (EGFR), isocitrate dehydrogenase (IDH), vascular endothelial growth factor receptor (VEGFR), and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The mechanisms of these targets in the occurrence and development of brain tumors, as well as the clinical application prospects of corresponding inhibitors are thoroughly discussed. Key challenges are highlighted, including drug delivery restricted by the blood-brain barrier, drug resistance caused by tumor heterogeneity, immunosuppressive tumor microenvironment, and the lack of real-world evidence. In addition, this review emphasizes the importance of multi-target combined therapy, optimized drug delivery systems, enhanced real-world studies, and the exploration of emerging technologies. In the future, with the continuous emergence of new technologies and the deepening of multidisciplinary collaboration, breakthroughs in precision therapy for brain tumors are expected to provide more effective and personalized treatment options, thereby significantly improving patient survival rates and quality of life.关键词：brain tumors;glioblastoma;targeted therapy1298|217|0更新时间：2026-05-15
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摘要：ObjectiveTo fabricate a microfluidic chip for the co-culture of oral squamous cell carcinoma cells and vascular endothelial cells, validate the interaction between the two cell types, and test the efficacy of combined chemotherapeutic and anti-angiogenic drugs.MethodsA double-layer polydimethylsiloxane (PDMS) chip was fabricated, separated by a porous parylene membrane, with human umbilical vein endothelial cells (HUVECs) seeded in the upper chamber and human tongue squamous cell carcinoma cells (WSU-HN6) seeded in the lower chamber, respectively. Hydrodynamic analysis was performed to calculate the relative pressure, flow velocity, and shear stress within the chip. Monoculture (control) and co-culture conditions were separately established for upper-layer HUVECs and lower-layer HN6 cells: HUVECs were cultured alone or co-cultured with HN6 cells in the lower chip chamber, and HN6 cells were grouped in the same way in the upper chip chamber. For HUVECs, mRNA expression levels of vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and interleukin-8 (IL-8) were detected by qRT-PCR, in the two groups, and vascular endothelial cadherin (VE-cadherin) protein expression was detected by immunofluorescence staining. Barrier function was assessed by transendothelial electrical resistance (TEER), while tube formation ability of HUVECs was evaluated using the tube formation assay. For HN6 cells, viability was determined by cell counting kit-8 (CCK-8) assay. mRNA expression levels of VEGF, basic fibroblast growth factor (bFGF), neural cadherin (N-cadherin), epithelial cadherin (E-cadherin), and Vimentin were detected by qRT-PCR. Immunofluorescence staining was performed to detect the expression of epithelial-mesenchymal transition (EMT)-related markers. HN6 cell migration was evaluated by the scratch wound assay. HN6 cell apoptosis was detected by TUNEL staining.ResultsThe medium flow rate at the chip inlet was set to 100 μm/s and was able to simulate in vivo physiological flow conditions. Hydrodynamic analysis confirmed that the flow conditions were consistent with physiological parameters. In co-culture group, HUVECs showed significantly elevated mRNA expression levels of VEGF and ICAM-1 (P<0.01), compared to monoculture control group. Co-cultured HUVECs also significantly increased the number of tube junctions (P<0.05) and total tube length (P<0.01) in the tube formation assay, along with reduced trans-epithelial electrical resistance (TEER) as well as incomplete morphology of VE-cadherin. For HN6 cells, qRT-PCR results showed that, compared with monocultured HN6 cells, co-culture with HUVECs did not significantly affect cell viability but led to significant mRNA expression changes: VEGF and N-cadherin were significantly elevated (P<0.05), E-cadherin was reduced (P<0.05). The results of immunofluorescence staining confirmed corresponding protein-level changes during EMT-related markers, consistent with the qRT-PCR results: Vimentin (P<0.001), N-cadherin (P<0.01) protein expression levels significantly increased, and E-cadherin expression significantly decreased (P<0.05). Co-cultured HN6 cells also exhibited a significantly higher 24 h scratch wound healing rate than the monoculture group (P<0.01), which was inhibited by bevacizumab in a concentration-dependent manner. Bevacizumab showed no cytotoxicity on HN6 cells nor did it change their sensitivity to chemotherapeutic agents.ConclusionThe double-layer microfluidic chip fabricated in this study can simulate the interaction between HN6 cells and HUVECs, thus enabling its use in drug screening.关键词：oral squamous cell carcinoma;microfluidic chip;endothelial cells;co-culture760|40|0更新时间：2026-05-15 -
摘要：ObjectiveTo detect the expression profile of Centipeda minima miRNA, explore the expression levels and secondary structures of high-abundance miRNAs, and investigate their role in the proliferation and migration of nasopharyngeal carcinoma cells.MethodsThe miRNA expression profile of Centipeda minima was constructed by miRNA high-throughput sequencing. Bioinformatics tools were used to compare the sequence and structural differences between miRNA from Centipeda minima and those from closely related species. The downstream target genes of miRNA were identified using target gene prediction, transcriptome sequencing analysis and dual-luciferase reporter gene assays. The C666-1 human nasopharyngeal carcinoma cell line was used to analyze the effects of Centipeda minima miRNA on cell proliferation and migration by means of cell viability and scratch assays.ResultsThe miRNA expression profile of Centipeda minima was analyzed by high-throughput sequencing technology. A total of 243 miRNAs were identified, among which 13 were novel miRNA unique to this plant, and the secondary structures of miRNA precursors were predicted. Since miR396a-5p, which is expressed in the highest abundance in Centipeda minima, has unique mature and precursor sequences and structures, we named it cmi-miR396a-5p. cmi-miR396a-5p was predicted to target abundant homologous target genes in cancer-related pathways, indicating significant anti-tumor regulatory potential. The dual-luciferase reporter gene results showed that cmi-miR396a-5p directly acted on the 3' untranslated region (3'UTR) of STAT3, a gene related to the progression of nasopharyngeal carcinoma, and inhibited the mRNA and protein expression of STAT3. cmi-miR396a-5p could down-regulate Cyclin D1 and B-cell lymphoma/leukemia-2 protein (Bcl-2), downstream targets of STAT3, promote cell apoptosis, and significantly inhibit the in vitro proliferation and migration ability of C666-1 nasopharyngeal carcinoma cells.ConclusionThis study revealed the miRNA expression profile of Centipeda minima. Among them, cmi-miR396a-5p derived from Centipeda minima can exert significant anti-nasopharyngeal carcinoma activity by targeting and negatively regulating STAT3.关键词：Centipeda minima;nasopharyngeal carcinoma;miRNA cross-kingdom regulation;miR396a-5p1212|138|0更新时间：2026-05-15 -
摘要：MicroRNAs (miRNAs) are a class of small non-coding RNAs consisting of 18-25 nucleotides that participate in various biological processes, including cell proliferation, differentiation, and apoptosis, by regulating the expression of target genes. As a key tumor-suppressive miRNA, miR-141 plays a central regulatory role in the occurrence and progression of multiple malignant tumors. It can directly target key molecules such as zinc finger E-box-binding homeobox 1/2 (ZEB1/2), phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and B-cell-specific moloney murine leukemia virus insertion site 1 (BMI1), and regulate signaling pathways including epithelial-mesenchymal transition (EMT), PTEN/protein kinase B-glycogen synthase kinase 3β (Akt-GSK3β), and Wnt/β-catenin. Through these mechanisms, miR-141 inhibits the proliferation of malignant tumor cells, promotes apoptosis, and blocks their invasion, metastasis, and angiogenesis, participating in the entire regulatory process of the occurrence and development of malignant tumors. miR-141 is expected not only to serve as a potential molecular biomarker for early diagnosis and prognosis evaluation of malignant tumors, providing new directions for precise diagnosis and treatment, but also to act as a therapeutic target, restoring its expression can enhance the efficacy of chemotherapy and targeted drugs and improve patient prognosis. This review summarizes the research progress of miR-141 in the diagnosis, prognosis, and targeted therapy of malignant tumors, aiming to provide a reference for the clinical treatment of malignant tumors.关键词：miR-141;malignant tumors;mechanism of action;clinical value;therapeutic target1109|39|0更新时间：2026-05-15 -
摘要：Chemotherapy is a common treatment for cancer; however, its efficacy is often significantly limited by the development of drug resistance. Gastrointestinal tumors are among the most common malignancies worldwide, and overcoming chemoresistance is crucial for improving patient prognosis. Autophagy, a catabolic process that maintains cellular homeostasis, plays a dual role in the drug resistance of gastrointestinal tumors. On one hand, protective autophagy contributes to the development of chemoresistance; on the other hand, excessive or sustained autophagy may induce autophagic cell death, thereby reversing drug resistance. Therefore, the targeted modulation of autophagy has emerged as a promising strategy to counteract chemoresistance. This review begins with an overview of the classification and fundamental processes of autophagy, systematically elucidates its bidirectional regulatory function in gastrointestinal tumor chemoresistance, and summarizes recent advances in targeting autophagy via autophagy inhibitors or activators to overcome chemoresistance, aiming to provide new insights and rationale for anticancer therapy in gastrointestinal tumors.关键词：autophagy;drug resistance;gastrointestinal tumors718|22|0更新时间：2026-05-15
Research and Application of Tumor Targeted Drugs
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摘要：ObjectiveTo compare the efficacy and safety of argon-helium cryoablation (CRYO) combined with lenvatinib (LEN) and transarterial chemoembolization (TACE) combined with LEN in the treatment of unresectable hepatocellular carcinoma (uHCC).MethodsThis was a retrospective cohort study. A total of 234 patients with uHCC admitted to the Hepatology Medical Center of Chinese PLA General Hospital from May 2020 to March 2023 were enrolled, including 107 patients treated with TACE+LEN (TACE+LEN group) and 127 patients treated with CRYO+LEN (CRYO+LEN group). A 1:1 propensity score matching (PSM) was used to balance baseline characteristics, and 192 patients were finally enrolled. Study endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Survival differences were analyzed using Kaplan-Meier method, and independent prognostic factors were screened using Cox regression and LASSO regression analyses.ResultsAfter PSM, baseline characteristics were well balanced between the two groups (P>0.05). Of the 192 patients, 178 (92.7%) were male, 182 (94.8%) had liver cirrhosis, 149 (77.6%) were Child-Pugh class A, and 130 (67.7%) were at Barcelona Clinic Liver Cancer (BCLC) stage C. No significant differences were observed between CRYO+LEN and TACE+LEN groups in median OS (24.2 months vs. 22.0 months, HR=1.10, P=0.635), median PFS (8.7 months vs. 11.9 months, HR=0.89, P=0.477), ORR (53.1% vs. 53.1%, P=1.000), or DCR (78.1% vs. 86.5%, P=0.186). Multivariate Cox regression analysis identified hepatitis B virus (HBV) infection (HR=0.231, P=0.014), Child-Pugh class (HR=1.757, P=0.017), maximum tumor diameter (HR=1.908, P=0.003), and subsequent anti-programmed cell death protein-1 (PD-1) therapy (HR=0.652, P=0.045) as independent factors influencing OS. CRYO+LEN group had higher incidences of pleural effusion (6.2% vs. 0%, P=0.038) and skin frostbite (8.3% vs. 0%, P=0.011), while TACE+LEN group was more prone to abdominal pain (7.3% vs. 0%, P=0.021) and non-infectious fever (24% vs. 5.2%, P=0.001). There were no significant differences in other AEs between the two groups (P>0.05).ConclusionsCRYO combined with LEN demonstrates similar clinical benefits and manageable safety profiles to TACE combined with LEN in the treatment of uHCC, providing an effective alternative therapeutic option for patients unsuitable for TACE.关键词：unresectable hepatocellular carcinoma;transarterial chemoembolization;cryoablation;lenvatinib33|80|0更新时间：2026-05-15 -
摘要：ObjectiveTo explore the potential causal relationships between multiple dietary factors and chronic kidney disease (CKD) using Mendelian randomization (MR) methods based on genome-wide association study (GWAS) data, as well as the underlying molecular mechanisms.MethodsMR methods with inverse variance weighted (IVW) as the primary approach were employed to evaluate the causal effects of seven dietary composition (coffee, tea, alcohol, fruits, vegetables, red meat, and nuts) on CKD. GWAS data of seven dietary composition was selected from UK Biobank, IEU Open GWAS, and NHGRI-EBI GWAS database, while GWAS data of CKD from FinnGen database. Heterogeneity tests, horizontal pleiotropy tests, and sensitivity analyses were conducted to assess the robustness of the MR results. Functional Mapping and Annotation (FUMA) platform was used to perform nearby gene annotation and pathway enrichment analysis on significant single nucleotide polymorphisms (SNPs), so as to explore CKD-related biological pathways. In addition, expression quantitative trait loci (eQTL) data of kidney cortex tissues from the Genotype-Tissue Expression (GTEx) database were integrated to identify key CKD-related genes, and their expression levels were validated using the Human Protein Atlas (HPA).ResultsMR analysis showed that coffee, tea, and fruit intake were significantly negatively associated with the risk of CKD (P<0.05, ORs<1, and 95%CIs not crossing 1), suggesting that they may be potential protective factors against CKD. In contrast, no significant causal associations were observed between the intake of alcohol, vegetables, red meat, or nuts and CKD. Sensitivity analyses indicated no evidence of horizontal pleiotropy or heterogeneity, and the leave-one-out analysis further confirmed the robustness of the results. Enrichment analysis indicated that coffee-related genes were mainly involved in CYP450-mediated xenobiotic metabolism, reactive oxygen species response, and tryptophan metabolism; tea-related genes were enriched in glycosaminoglycan degradation and lysosomal pathways; fruit-related genes were primarily enriched in inositol phosphate metabolism and phosphatidylinositol signaling system. eQTL analysis identified proline-rich protein HaeⅢ subfamily 1 (PRH1), G protein-coupled receptor kinase 4 (GRK4), and Rho guanine nucleotide exchange factor 35 (ARHGEF35) as potential key genes. Expression level of ARHGEF35 is intermediate or high, and GRK4 is intermediate in kidney.ConclusionThe consumption of coffee, tea, and fruits may reduce the risk of CKD, and their protective effects may be mediated through biological pathways involving antioxidative stress, anti-inflammation, metabolic regulation, and autophagy.关键词：dietary habits;chronic kidney disease;causal inference;Mendelian randomization48|36|0更新时间：2026-05-15 -
摘要：ObjectiveTo investigate the independent predictive factors for the failure of methotrexate (MTX) in treating gestational sac-type cesarean scar pregnancy (CSP), and to construct and preliminarily validate a risk stratification prediction model.MethodsThe clinical data of 55 patients with gestational sac-type CSP who underwent ultrasound-guided local MTX injection at the First Medical Center of PLA General Hospital between January 2014 and June 2025 were retrospectively analyzed. Patients were divided into successful drug treatment group (n=41) and failed drug treatment group (n=14) according to whether surgical intervention was required after treatment. Univariate and multivariate logistic regression analyses were performed to identify independent predictive factors for MTX treatment failure. A risk stratification model was constructed based on these predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated, and internal validation was conducted using the Bootstrap method (1000 repeated samplings) to assess the discriminatory power and stability of the model.ResultsThe overall success rate of MTX treatment was 74.5% (41/55). Univariate analysis showed significant associations between treatment failure and Jordans classification (P=0.036), embryonic bud grouping (P=0.008), preoperative serum β-human chorionic gonadotropin (β-hCG) (P=0.009), and mean gestational sac diameter (P=0.026). Multivariate logistic regression analysis revealed that Jordans type Ⅱ (OR=5.318, 95%CI 1.030-27.446, P=0.046) and embryonic bud length ≥4.0 mm (OR=10.893, 95%CI 2.233-53.138, P=0.003) were independent predictive factors for treatment failure. Based on these results, CSP patients were stratified into three groups: low-risk group (Jordans type Ⅰ+embryonic bud length <4.0 mm), intermediate-risk group (Jordans type Ⅰ+embryonic bud length ≥4.0 mm or Jordans type Ⅱ+embryonic bud length <4.0 mm), and high-risk group (Jordans type Ⅱ+embryonic bud length ≥4.0 mm). The actual failure rate was 3.8% (1/26) in low-risk group (n=26), 25.0% (6/24) in intermediate-risk group (n=24), and 80.0% (4/5) in high-risk group (n=5). ROC analysis demonstrated that the model had moderate discriminatory power (AUC=0.780), and Bootstrap validation confirmed good stability of the model with a mean AUC of 0.782 (95% CI 0.632-0.904) and a median AUC of 0.788 (0.740, 0.832).ConclusionsJordans classification and embryonic bud length are important indicators for predicting the treatment failure of ultrasound-guided local MTX injection in gestational sac-type CSP. The preliminary risk stratification model based on these predictors provides a decision-making reference for the individualized treatment of CSP.关键词：gestational sac-type cesarean scar pregnancy;methotrexate;Jordans classification;risk stratification prediction model38|109|0更新时间：2026-05-15 -
摘要：ObjectiveTo compare the effects of ultrasound-guided single-shot iliopsoas plane block (IPB) and single-shot pericapsular nerve group block (PENGB) on postoperative lower limb motor function in elderly patients with hip fracture.MethodsA retrospective analysis was performed on the clinical data of 60 elderly patients with hip fractures admitted to the Department of Orthopedics, Hainan Hospital of Chinese PLA General Hospital from May 2023 to March 2024. According to different block regimens, the patients were divided into IPB group and PENGB group, with 30 cases in each group. IPB group received ultrasound-guided single-shot IPB combined with lateral femoral cutaneous nerve block (LFCNB), and PENGB group received ultrasound-guided single-shot PENGB combined with LFCNB, followed by general anesthesia in both groups. After surgery, both groups were given intravenous infusion of flurbiprofen axetil injection at a dose of 100 mg/d for analgesia. If the visual analogue scale (VAS) score was ≥4, dezocine 5 mg was intravenously injected for rescue analgesia per time. The two groups were compared regarding the quadriceps manual muscle test (MMT) grade at 3, 6, 12, 24, and 48 h postoperatively, the time to first ambulation after surgery, VAS scores at rest and during activity (passive straight leg raising to 45°) at 3, 6, 12, 24, and 48 h postoperatively, the intraoperative dosage of sufentanil, and the number of rescue analgesia administration required within 48 h postoperatively. Additionally, the incidences of perioperative complications such as delirium, nausea and vomiting, deep vein thrombosis, neurovascular injury, local anesthetic toxicity, and puncture site infection were compared between the two groups.ResultsCompared with PENGB group, IPB group had significantly higher MMT grades of quadriceps at 3, 6 and 12 h after surgery (P<0.001, P<0.001, P=0.021), a significantly shorter time to first ambulation after surgery (P<0.001), and significantly higher active VAS scores at 3, 6 and 12 h after surgery (P=0.011, P=0.016, P=0.028). There was no statistically significant difference in resting VAS scores after surgery, intraoperative sufentanil dosage, frequency of rescue analgesia administration within 48 h after surgery, and incidences of various perioperative complications between the two groups (P>0.05).ConclusionUltrasound-guided single-shot IPB has a less impact on lower limb muscle strength, and can ensure a good perioperative analgesia effect and safety, making it a more preferable nerve block technique for the early postoperative rehabilitation program of elderly patients with hip fractures.关键词：hip fracture;iliopsoas plane block;pericapsular nerve group block;motor block46|135|0更新时间：2026-05-15
Clinical Research
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摘要：ObjectiveTo investigate the effect of inhibiting the expression of solute carrier family 31 member 1 (SLC31A1) on alcoholic fatty liver disease (AFLD) in mice by regulating copper homeostasis and its underlying mechanisms.MethodsThirty healthy male C57BL/6N mice aged 6-8 weeks were randomly divided into control group, ethanol group, and plasmid group (n=10). Control group was fed a control liquid diet daily, while ethanol and plasmid groups were fed an ethanol-containing liquid diet daily. Plasmid group was injected with 0.2 ml of SLC31A1-sgRNA plasmid (2 mg/kg) via the tail vein by hydrodynamic injection, and ethanol and control groups were injected with an equal volume of normal saline via the tail vein. At the end of the 8th week, the mice were euthanized after ocular blood collection, and liver tissue were harvested. qPCR and Western blotting were used to detect the mRNA and protein expression levels of SLC31A1 in liver tissue. Immunohistochemistry (IHC) was employed to detect the expression of SLC31A1 in liver tissue. Colorimetric assay was adopted to determine the copper content in liver tissue and serum. Microplate assay was used to detect the activity of superoxide dismutase (SOD), and the contents of glutathione (GSH), malondialdehyde (MDA), total cholesterol (TC), and triglycerides (TG) in liver tissue, as well as the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the contents of TC and TG in serum. HE staining, Oil Red O staining, and periodic acid-Schiff (PAS) staining were conducted to assess liver injury, lipid accumulation, and glycogen changes, respectively. Western blotting was used to detect the protein expression levels of nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1), peroxisome proliferator-activated receptor alpha (PPAR-α), nuclear factor κB p65 subunit (NF-κB p65), inhibitor of nuclear factor κB alpha (IκB-α), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK).ResultsThe results of qPCR, Western blotting, and IHC showed that SLC31A1-sgRNA plasmid could effectively inhibit the expression of SLC31A1 (P<0.001). Compared with control group, ethanol group had increased liver injury scores and lipid droplet area ratio, and decreased collagen area ratio; the SLC31A1-positive area ratio, mRNA and protein expression levels of SLC31A1, and copper content in liver tissue and serum were increased; the activities of ALT and AST, and the contents of MDA, TC, and TG were increased, while the SOD activity and GSH content were decreased; the protein expression level of CYP2E1, and the ratios of p-JNK/JNK, p-p38 MAPK/p38 MAPK, p-NF-κB p65/NF-κB p65, and p-IκB-α/IκB-α were up-regulated, whereas the protein expression levels of Nrf2 and PPAR-α, and the ratio of p-AMPKα1/AMPKα1 were down-regulated (P<0.05). Compared with ethanol group, plasmid group had decreased liver injury score and lipid droplet area ratio, and increased collagen area ratio; the SLC31A1-positive area ratio, mRNA and protein expression levels of SLC31A1, and copper content in liver tissue and serum were decreased (P<0.001); the activities of ALT and AST, and the contents of MDA, TC, and TG were reduced, while the SOD activity and GSH content were elevated; the protein expression levels of CYP2E1, and the ratios of p-JNK/JNK, p-p38 MAPK/p38 MAPK, p-NF-κB p65/NF-κB p65, and p-IκB-α/IκB-α were down-regulated; and the protein expression levels of Nrf2 and PPAR-α, and the ratio of p-AMPKα1/AMPKα1 were up-regulated (P<0.05).ConclusionInhibition of SLC31A1 may alleviate ethanol-induced fatty liver lesions in AFLD mice by reducing copper content, thereby attenuating oxidative stress injury, lipid metabolism disorder, and inflammatory injury.关键词：alcoholic fatty liver disease;solute carrier family 31 member 1;copper;oxidative stress;lipid metabolism;inflammatory injury36|480|0更新时间：2026-05-15 -
摘要：ObjectiveTo investigate the therapeutic effect of lycium barbarum polysaccharide (LBP) on Alzheimer's disease (AD) model mice, as well as its effect on neuronal pyroptosis and the underlying mechanisms.MethodsSixteen 6-month-old amyloid precursor protein/presenilin-1 (APP/PS1) double-transgenic mice were randomly divided into AD group and AD+LBP group, with 8 mice in each group. Sixteen age-matched wild-type (WT) C57BL/6 mice were randomly divided into WT group and WT+LBP group, with 8 mice in each group. Morris water maze and Y-maze tests were performed to evaluate the cognitive function of mice in each group. Western blotting was used to detect the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF‑κB) subunit p65, nucleotide-binding domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, Gasdermin D (GSDMD), GSDMD-N terminal, interleukin (IL)-18 and IL-1β in mouse brain tissues. Immunofluorescence staining was conducted to detect the co-localization of β-amyloid 1-42 (Aβ1-42), NLRP3, caspase-1, GSDMD and IL-1β with microglia in the mouse brain.ResultsCompared with WT and WT+LBP groups, AD group exhibited significant cognitive decline (P<0.01 or P<0.001) and increased protein expression of Aβ1-42, TLR4, MyD88, NF-κB p65, NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β in brain tissues (P<0.05 or P<0.01 or P<0.001). Compared with AD group, AD+LBP group showed markedly improved cognitive function (P<0.01 or P<0.001) and decreased protein expression of Aβ1-42, TLR4, MyD88, NF-κB p65, NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β (P<0.05, P<0.01 or P<0.001).ConclusionLBP may reduce Aβ1-42 deposition and pyroptosis in the brain, and improve cognitive function in mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway and the activity of the NLRP3 inflammasome.关键词：lycium barbarum polysaccharide;Alzheimer's disease;NLRP3 inflammasome;pyroptosis43|490|0更新时间：2026-05-15 -
摘要：ObjectiveTo investigate the role of exosomes derived from hepatocyte growth factor-overexpressing mesenchymal stem cells (HGF-MSCs, HGF-MSCs-EXO ) in regulating epithelial-mesenchymal transition (EMT) and inflammation in airway epithelial cells of obliterative bronchiolitis (OB) by modulating autophagy via the miR-221-5p/NLRP1 axis.MethodsUmbilical cord mesenchymal stem cells (UC-MSCs) were transfected to overexpress HGF, and HGF-MSCs-EXO were isolated from the transfected cells. Transmission electron microscopy (TEM) was used to observe the morphology of HGF-MSCs-EXO, and nanoparticle tracking analysis (NTA) was performed to assess their particle size distribution. Western blotting was used to detect the expression of exosome marker proteins CD63 and tumor susceptibility gene 101 (TSG101). qRT-PCR was employed to detect the expression of HGF mRNA to verify the successful construction of HGF-MSCs-EXO. An in vivo OB mouse model and an in vitro OB model of TC-1 cells induced by lipopolysaccharide (LPS) were established. HGF-MSCs-EXO were administered to intervene in both models. Histopathological examination was performed to evaluate tracheal tissue damage. Western blotting was used to detect the expression of autophagy-related proteins [such as Beclin1, autophagy-related gene 5 (ATG5), p62], and EMT marker proteins [such as α-smooth muscle actin (α-SMA), Vimentin, and E-cadherin]. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the concentrations of pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, and interferon-γ (IFN-γ)]. Additionally, to clarify the regulatory mechanism, miR-221-5p inhibitor or agomir was transfected, and NLRP1 was knocked down in cells/mice. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR (CHIP-qPCR) were conducted to confirm the targeting relationship between miR-221-5p and NLRP1.ResultsHGF-MSCs-EXO were successfully constructed and identified: TEM showed cup-shaped or vesicular structures, with a diameter range of 30-150 nm, the exosomal marker proteins CD63 and TSG101 were expressed, and HGF mRNA was highly expressed in HGF-MSCs-EXO. In vivo experiments, compared with control group, model group showed severe tracheal tissue damage, abnormal activation of autophagy (increased Beclin1 and ATG5, decreased p62), enhanced inflammation (elevated IL-6, IL-1β, IFN-γ), and obvious abnormal EMT (decreased E-cadherin, increased α-SMA and Vimentin) (P<0.05). These indicators and pathological damage were significantly improved in the HGF-MSCs-EXO group (P<0.05). In vitro experiments, PKH26 fluorescence confirmed that TC-1 cells could internalize HGF-MSCs-EXO. Consistent with in vivo results, the LPS-induced model group exhibited abnormal autophagy, inflammation, and EMT, accompanied by downregulated miR-221-5p and upregulated NLRP1 (P<0.05), which were reversed by HGF-MSCs-EXO treatment (P<0.05). HGF modification significantly increased the expression of miR-221-5p in MSCs and their exosomes, while transfection of miR-221-5p inhibitor abrogated the autophagy-inhibitory effect of HGF-MSCs-EXO (P<0.05). Administration of miR-221-5p agomir in vivo and in vitro upregulated miR-221-5p expression, remarkably alleviated pathological damage, and inhibited autophagy, inflammation, and EMT (P<0.05). Dual-luciferase reporter gene assay and CHIP-qPCR confirmed that miR-221-5p directly targeted NLRP1. miR-221-5p mimics decreased NLRP1 mRNA and protein expression, while miR-221-5p inhibitor increased them (P<0.05). NLRP1 knockdown mimicked the regulatory effect of miR-221-5p, and this effect was reversed by miR-221-5p inhibitor (P<0.05). In vivo verification showed that NLRP1 mRNA and protein expression in tracheal tissues of the model group was significantly higher than that of the control group, lower in the miR-221-5p agomir group than in the model group, and higher in the HGF-MSCs-EXO group than in the miR-221-5p agomir group (P<0.05). Furthermore, compared with the HGF-MSCs-EXO+negative control knockdown group, the HGF-MSCs-EXO+NLRP1 knockdown group showed lower NLRP1 expression, more significant improvement in pathological damage, and stronger regulatory effects on autophagy, inflammation, and EMT indicators (P<0.05).ConclusionHGF-MSCs-EXO can target and inhibit NLRP1 expression by delivering miR-221-5p, thereby modulating autophagy and ultimately alleviating EMT and inflammatory responses in airway epithelial cells of OB. This provides a novel potential target for OB.关键词：hepatocyte growth factor-overexpressing mesenchymal stem cells;exosomes;autophagy;bronchiolitis obliterans39|279|0更新时间：2026-05-15 -
摘要：ObjectiveTo explore the effect of DNA methyltransferase 1 (DNMT1)-mediated promoter methylation on the regulation of von Hippel-Lindau tumor suppressor (VHL) gene expression and its impact on tumor growth in lung adenocarcinoma (LUAD).Methods(1) Based on the Gene Expression Profiling Interactive Analysis (GEPIA) database, the expression levels of DNMT1 and VHL in LUAD tissues and their correlations with the overall survival of LUAD patients were analyzed. (2) A total of 100 pairs of LUAD tissues and their adjacent non-tumor tissues were collected from patients admitted to Nanyang First People's Hospital from January 2020 to December 2021. Methylation-specific PCR (MSP), reverse transcription-quantitative PCR (RT-qPCR) and Western blotting were performed to detect VHL gene promoter methylation status, as well as the mRNA and protein expression levels of DNMT1 and VHL in LUAD tissues. The correlation between DNMT1 and VHL expression was analyzed, and the association of VHL expression level with clinicopathological parameters of patients was also analyzed. (3) Human LUAD A549 cells were randomly divided into control group, DNMT1 group, sh-NC group, sh-DNMT1 group, 5-Aza-CdR group, and DNMT1+5-Aza-CdR group. After the cells were treated with the corresponding lentiviral infection and the methylation inhibitor 5-Aza-CdR, VHL promoter methylation status, mRNA and protein levels of DNMT1 and VHL were detected; the Cell Counting Kit-8 (CCK-8) assay was used to evaluate the proliferative capacity of the cells. (4) Thirty nude mice were randomly divided into sh-NC group and sh-DNMT1 group, with 15 mice in each group. The lentivirus-infected A549 cells were subcutaneously injected into the nude mice of each group. One month after tumor model establishment, the tumor volume and weight were measured; VHL promoter methylation status, as well as the mRNA and protein expression levels of DNMT1 and VHL in tumor tissues were detected.Results(1) Compared with normal lung tissues, the expression level of DNMT1 was significantly increased (P<0.05) and the expression level of VHL was significantly decreased in LUAD tissues (P<0.05). LUAD patients with high DNMT1 or low VHL expression had a shorter overall survival time (P<0.05). (2) Compared with adjacent non-tumor tissues, VHL promoter methylation level and DNMT1 expression level in LUAD tissues were significantly elevated (P<0.05), while VHL expression level was reduced (P<0.05). DNMT1 expression level was negatively correlated with VHL expression level in LUAD tissues (P<0.05). LUAD patients with low VHL expression level had a higher TNM stage and a lower degree of tumor differentiation (P<0.05). (3) Compared with control group, VHL promoter methylation level, DNMT1 expression level and cell proliferative capacity were significantly increased (P<0.05), while VHL expression level was decreased in DNMT1 group (P<0.05). Compared with sh-NC group, VHL promoter methylation level, DNMT1 expression level, and cell proliferative capacity were significantly reduced (P<0.05), while VHL expression level was elevated in sh-DNMT1 group (P<0.05). Compared with 5-Aza-CdR group, VHL promoter methylation level and cell proliferative capacity were significantly increased (P<0.05), while VHL expression level was decreased in DNMT1+5-Aza-CdR group (P<0.05). (4) Compared with sh-NC group, the tumor volume and weight of nude mice in sh-DNMT1 group were significantly reduced (P<0.05), VHL promoter methylation level and DNMT1 expression level in tumor tissues were significantly decreased (P<0.05), while VHL expression level was increased (P<0.05).ConclusionDNMT1-mediated promoter methylation can inhibit VHL gene expression and thereby promote LUAD tumor growth.关键词：lung adenocarcinoma;DNA methyltransferase 1;promoter methylation;von Hippel-Lindau tumor suppressor26|107|0更新时间：2026-05-15
Basic Research
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Research progress on the mechanism and application of adiponectin in idiopathic pulmonary fibrosis AI导读
摘要：Idiopathic pulmonary fibrosis (IPF) is a prevalent interstitial lung disease characterized by a progressive decline in lung function. Given that current anti-fibrotic agents merely slow disease progression without offering a cure, and therapeutic options remain limited, there is an urgent need to explore novel therapeutic strategies to improve survival outcomes in IPF patients. Adiponectin (APN) is a bioactive protein predominantly secreted by adipocytes, which has the functions of insulin sensitization, anti-oxidative stress, attenuating inflammatory responses, and exerting cardioprotective effects. Recent studies indicated that APN also plays a regulatory role in the pathogenesis and progression of hepatic, renal, and pulmonary fibrosis. This review summarizes the research progress regarding the mechanisms of action and potential therapeutic applications of adiponectin in IPF, aiming to provide a theoretical foundation for achieving anti-fibrotic effects through the activation of APN signaling pathways.关键词：adiponectin;adiponectin receptor agonist;idiopathic pulmonary fibrosis;signal pathway;targeted therapy33|266|0更新时间：2026-05-15 - 摘要：Rosacea is a complex inflammatory disease characterized primarily by erythema, papules, and pustules in the central facial region. Its pathophysiological mechanisms are influenced by various external and genetic factors, with overactivation of the immune system further complicating the disease's pathogenesis. Recent research shows that different T lymphocyte subsets exhibit varying degrees of expression in the skin lesions of rosacea patients, which play crucial roles in regulating immune responses, triggering inflammation, and maintaining immune homeostasis. However, the specific mechanisms underlying their actions in rosacea remain to be fully elucidated. This review outlines the role of T cells in the pathogenesis of rosacea, with a focus on the research progress regarding the roles of CD4+ T cell subsets, especially T helper (Th)1, Th2, Th17 cells, and their related signaling factors, aiming to provide a theoretical basis for future therapeutic strategies targeting these specialized cells.关键词：rosacea;T lymphocyte subsets;immunity;cytokines;pathogenesis26|210|0更新时间：2026-05-15
- 摘要：Copper is one of the essential trace elements in human body, with its participation in crucial physiological processes in the body as the cofactors of enzymes. Cuproptosis is a programmed cell death caused by accumulation of copper ion in cell and mitochondrial dysfunction. Its main features are accumulation of copper ion and the metabolic disorder in tricarboxylic acid cycle, and is closely related to the pathogenesis and progression of ophthalmic diseases such as uveal melanoma, age-related macular degeneration, and glaucoma. This review summarizes progress on the core mechanisms and signaling pathways of cuproptosis, explores the role of copper ion dyshomeostasis in ophthalmic diseases, and analyzes potential therapeutic strategies based on cuproptosis intervention, aiming to provide insights for investigating the pathogenesis of ophthalmic diseases and developing novel therapeutic targets.关键词：cuproptosis;copper ion transporters;uveal melanoma;cell death;mechanism30|229|0更新时间：2026-05-15
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摘要：Histone lysine demethylase 2B (KDM2B), a member of the KDM2 family, is localized in the nucleolus and is widely expressed across various organs. KDM2B plays a role in numerous cell biological processes, including the inhibition of cellular senescence, promotion of cell proliferation, maintenance of an undifferentiated state, facilitation of somatic cell reprogramming, self-renewal of stem cells, and regulation of organ development. It is also crucial for processes such as spermatogenesis, embryonic development, and the formation of the neural tube and hippocampus. Additionally, KDM2B is involved in the regulation of various diseases, including solid tumors, neurological disorders, hematological diseases, as well as inflammation and viral infections. This review aims to summarize the biological functions of KDM2B and its roles in the pathogenesis of multiple diseases, thus providing theoretical basis for its further basic research and clinical application.关键词：lysine demethylase 2B;tumors;neurological disorders;hematopoietic diseases;inflammation32|146|0更新时间：2026-05-15 -
摘要：Mycobacterium tuberculosis (Mtb) can survive for a long time in a dormant state in the host. When in a latent infection state, it has no significant response to most anti-tuberculosis drugs and cannot be tested in clinical practice. It is activated and transformed into active tuberculosis (aTB) under such conditions as hypoxia, oxidative stress, or impaired immune system function, causing great trouble for the prevention and control of tuberculosis. Dormancy oxygen sensor histidine kinase (DosS)/dormancy survival regulon (DosR) two-component regulatory system (TCSs) is an important regulatory system for mediating Mtb latent infection. Its regulatory proteins have a broad application prospect in the development of diagnostic reagents for Mtb latent infection and new tuberculosis vaccines. In this review, the structural characteristics, biological functions, and interaction with host immune cells of Mtb DosS/DosR TCSs were summarized, as well as its potential in new vaccine development.关键词：Mycobacterium tuberculosis;DosS/DosR two-component regulatory system;latent tuberculosis infection;immune cells;vaccine35|240|0更新时间：2026-05-15
Review
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