Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectiveTo investigate the risk factors for atherosclerosis （AS） in rheumatoid arthritis （RA） patients and its correlation with traditional Chinese medicine （TCM） syndromes. MethodsA cross-sectional study was conducted， enrolling 16,082 RA patients from 122 medical centers nationwide. Patient demographics， disease assessment data including disease activity （DAS-28）， tender joint count （TJC）， swollen joint count （SJC）， patient's global assessment （PGA）， evaluator's global assessment （EGA）， and visual analogue scale （VAS）， major clinical symptoms including insomnia， loss of appetite， irritability， and fatigue， and laboratory indicators including blood routine， inflammatory markers， liver and kidney function， metabolic indices， and coagulation markers were collected through questionnaire. Based on the four examinations in TCM， patients were classified into eight TCM syndromes， which were wind-damp obstruction， cold-damp obstruction， damp-heat obstruction， phlegm-stasis obstruction， blood stasis obstructing the collaterals， qi-blood deficiency， liver-kidney insufficiency， and qi-yin deficiency. Patients who experienced AS events were included in the event group （564 cases）， while those without AS events were included in the non-event group （15,518 cases）. Intergroup difference tests were used to screen potential risk factors， and binary logistic regression analysis was employed to assess the correlation between TCM syndromes and rheumatoid arthritis with atherosclerosis （RA-AS）. ResultsCompared to the non-event group， patients in the event group had longer disease duration， higher body weight， and older age （P＜0.05）， and showed significantly higher DAS28， TJC， SJC， PGA， EGA， VAS， ESR， low-density lipoprotein cholesterol （LDL-C）， triglycerides （TG）， total cholesterol （TC）， and D-dimer levels， and lower high-density lipoprotein cholesterol （HDL-C）， with more severe symptoms of insomnia， irritability， and fatigue （P＜0.05）. Damp-heat obstruction syndrome was the most prevalent in both groups， with a higher proportion in the event group （393/564， 69.68%） than in the non-event group （4578/15,518， 29.50%） showing significant difference （P＜0.05）. Logistic regression analysis showed that patients with damp-heat obstruction syndrome had a 5.326-fold higher risk of developing RA-AS compared to those without this syndrome （OR=5.326， 95%CI 4.517 to 7.089， P＜0.001）. ConclusionThe occurrence of RA-AS is associated with TCM syndromes， disease activity， inflammatory markers and lipid metabolic indices， and damp-heat obstruction syndrome is an independent risk factor for RA-AS.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

ObjectiveTo investigate the efficacy and safety of stereotactic body radiotherapy （SBRT） combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma （uHCC） and related prognostic factors. MethodsA total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology， The Fifth Medical Centre of PLA General Hospital， from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36‍ ‍—‍ ‍50 Gy in 5‍ ‍—‍ ‍6 fractions for continuous irradiation， followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival （OS） rate and progression-free survival （PFS） rate， and the log-rank test was used for comparison between groups； the Cox proportional hazards model was used to investigate the influencing factors for prognosis. ResultsThe median follow-up time was 21.6 months， with an objective response rate of 69%， a disease control rate of 85.7%， a median PFS of 10.0 months （95% confidence interval ［CI］： 6.7‍ ‍—‍ ‍13.0）， and a median OS of 23.3 months （95%CI： 14.7‍ ‍—‍ ‍31.8）. Most adverse events were grade 1‍ ‍—‍ ‍2 events， and there were no fatal adverse events. At 6‍ ‍—‍ ‍8 weeks after treatment， the AFP response group had a significantly better OS than the non-AFP response group （not reached vs 11.8 months， P=0.007）. The multivariate analysis showed that AFP response was associated with the good prognosis of patients （hazard ratio=0.31， 95%CI： 0.13‍ ‍—‍ ‍0.75， P=0.009）. ConclusionFor patients with uHCC， SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile， and a >50% reduction in AFP at 6‍ ‍—‍ ‍8 weeks after treatment can be used as a potential prognostic indicator.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Heart failure(HF)is a cardiovascular disease with a high prevalence and mortality rate worldwide,and despite the widespread use of existing drugs,device intervetions and surgical procedures,the clinical outcomes are still unsatisfactory.The exploration of new methods to treat HF is still an urgent problem.Gene therapy provides a new therapeutic strategy for HF by targeting the regulation of pathogenic genes.This article systematically reviewed the delivery system optimization,key targets and clinical translational challenges of gene therapy for HF,aiming to provide a theoretical basis for the optimization of treatment strategies.

Objective To investigate the differences in BMD,T-scores,lumbar HU values,and modified VBQ scores in patients with thoracolumbar fractures,analyze their correlations,and evaluate their predictive efficacy for thoracolumbar fractures.Methods Patients with thoracolumbar fragility fractures and hospitalized in the Department of Orthopedics at the Second Affiliated Hospital of Kunming Medical University from January 2022 to March 2025 were retrospectively enrolled.Among them,132 eligible patients were divided into the fracture group(n=63)and the non-fracture group(n=69).BMD and T-scores of L1～L4 vertebrae were measured via DEXA,lumbar HU values were obtained from CT scans,and modified VBQ scores were calculated using lumbar MRI.Intergroup comparisons were performed using independent samples t-tests.Pearson's correlation analysis was used to assess the relationships among BMD,T-scores,HU values,and modified VBQ scores.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate their predictive performance for thoracolumbar fractures.Results The fracture group exhibited significantly lower mean BMD,T-scores,and HU values in L1～L4 compared to the non-fracture group,while modified VBQ scores were significantly higher(P<0.001).Correlation analysis revealed a significant positive correlation between BMD,T-scores,and HU values in L1～L4,whereas all three parameters showed a significant negative correlation with modified VBQ scores(P<0.001).The AUC values for predicting thoracolumbar fractures were 0.826(T-score),0.836(BMD),0.759(HU value),and 0.875(modified VBQ score),with optimal cutoff thresholds of-1.65(T-score),0.836 g/cm2(BMD),68.4(HU value),and 3.01(modified VBQ score),respectively.Conclusion BMD,T-scores,HU values,and modified VBQ scores in L1～L4 vertebrae are significantly correlated and can serve as the predictive indicators for thoracolumbar fractures.Among them,the modified VBQ score demonstrates the best predictive performance,making it a valuable auxiliary tool for assessing the vertebral bone quality.