The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.

OBJECTIVES: We propose a novel deep learning segmentation algorithm (DSRF) based on multi-scale supervision and residual feedback strategy for precise segmentation of the optic chiasm and optic nerves in CT images of nasopharyngeal carcinoma (NPC) patients. METHODS: We collected 212 NPC CT images and their ground truth labels from SegRap2023, StructSeg2019 and HaN-Seg2023 datasets. Based on a hybrid pooling strategy, we designed a decoder (HPS) to reduce small organ feature loss during pooling in convolutional neural networks. This decoder uses adaptive and average pooling to refine high-level semantic features, which are integrated with primary semantic features to enable network learning of finer feature details. We employed multi-scale deep supervision layers to learn rich multi-scale and multi-level semantic features under deep supervision, thereby enhancing boundary identification of the optic chiasm and optic nerves. A residual feedback module that enables multiple iterations of the network was designed for contrast enhancement of the optic chiasm and optic nerves in CT images by utilizing information from fuzzy boundaries and easily confused regions to iteratively refine segmentation results under supervision. The entire segmentation framework was optimized with the loss from each iteration to enhance segmentation accuracy and boundary clarity. Ablation experiments and comparative experiments were conducted to evaluate the effectiveness of each component and the performance of the proposed model. RESULTS: The DSRF algorithm could effectively enhance feature representation of small organs to achieve accurate segmentation of the optic chiasm and optic nerves with an average DSC of 0.837 and an ASSD of 0.351. Ablation experiments further verified the contributions of each component in the DSRF method. CONCLUSIONS The proposed deep learning segmentation algorithm can effectively enhance feature representation to achieve accurate segmentation of the optic chiasm and optic nerves in CT images of NPC.
Humans ; Tomography, X-Ray Computed/methods* ; Optic Chiasm/diagnostic imaging* ; Optic Nerve/diagnostic imaging* ; Algorithms ; Nasopharyngeal Carcinoma ; Deep Learning ; Nasopharyngeal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods*

Objective To design a pH-sensitive nintedanib liposomes(Nb-Lips)which targeted the acidic microenvironment of pulmonary fibrosis.The entrapment efficiency(EE%)was optimized by the formulation process.Methods Nintedanib liposomes were prepared by membrane hydration method,and the formulation of nintedanib liposomes were optimized by single factor experiments and response surface method(RSM).The particle size,polymer dispersity index(PDI),Zeta potential and encapsulation rate was investigated by dynamic light scattering technique and microcolumn centrifugation method.The release behavior of nintedanib liposomes in artificial lung fluid with pH 7.4 and artificial lung fluid with pH 5.3 was investigated by dialysis method.Nintedanib liposomes were atomized with a compressed air atomizer and its atomization stability and aerodynamic particle size were investigated.Results The particle size of nintedanib liposomes was(100.651±7.315)nm,the PDI was(0.328±0.026),the zeta potential was(21.633±2.004)mV,and the encapsulation rate was higher than 80%.Compared with nintedanib solution at pH 7.4,the total release of nintedanib liposomes in pH 5.3 artificial lung solution was 60.78%higher,and the release of nintedanib liposomes in pH 5.3 artificial lung solution was 48h delayed,which was much higher than that of nintedanib solution.The data reveals no significant differences in particle size,potential and PDI before and after atomization of nintedanib liposomes,and the encapsulation rate decreased 4.25%.The fine particle fraction of the atomized droplets was 37.49%.Conclusion The response surface method can effectively improve the encapsulation rate of nintedanib liposomes,and successfully prepare nintedanib liposomes that are sensitive to acidic environment,and can be inhaled and released slowly.

Objective To analyze the distribution characteristics of traditional Chinese medicine(TCM)syndrome types in patients with osteoporosis and the distribution differences of clinical and serological indicators in TCM syndrome types.Meth-ods A total of 69 patients with osteoporosis were collected from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine and Qifu Hospital Affiliated to Jinan University.The general information,bone mineral density T value,fasting periph-eral venous blood in the morning were collected.The expression of telomerase protective factor 1(POT1),telomerase reverse transcriptase(TERT),serum 8-hydroxy-2'-deoxyguanosine(8-OHdG)and superoxide dismutase 2(SOD2)were detected by ELISA.Finally,the above data were statistically analyzed.Results There were significant differences in body weight,height,bone mineral density,POT1,TERT,and 8-OHdG among the four syndromes(P＜0.05).In terms of correlation,the relation-ship between bone mineral density and each parameter in different syndrome types was explored.The bone mineral density of qi stagnation and blood stasis syndrome was positively correlated with SOD2 value.There is a positive correlation between bone min-eral density and 8-OHdG in patients with Yin deficiency of liver and kidney.TERT was positively correlated with qi stagnation and blood stasis syndrome.Liver and kidney Yin deficiency syndrome was positively correlated with weight and bone mineral den-sity,and negatively correlated with TERT value.Weight was negatively correlated with qi and blood stasis syndrome.Conclusion In TCM syndrome differentiation of osteoporosis,there were statistical differences in weight,height,bone mineral density,ser-um POT1,TERT and 8-OHdG among Qi-stagnation and blood stasis,spleen-kidney Yang deficiency,liver-kidney Yin deficiency and Qi-blood-peace syndrome.In different syndrome types,serum SOD2 and 8-OHdG were the influencing factors of bone miner-al density.Serum TERT and 8-OHdG are the main factors affecting the dialectical classification of osteoporosis.

Although a great deal of research has been done on sepsis in children，its pathogenesis remains controversial and unresolved，one of which is immune dysfunction.Immunosuppression is the core part of immune dysfunction，and it is related to the disease progression，treatment options，and prognosis changes in patients with sepsis.Since T lymphocytes play a crucial role in immune function，they have been regarded as an important indicator for judging changes in immune function in clinical practice.This review explained the mechanism of immunosuppression caused by some T lymphocyte subsets and its clinical application value in the evaluation，prognosis and immune intervention of sepsis.

Objectives:To explore the safety and early effectiveness of decompression under full-endoscope and percutaneous pedicle screw fixation in the treatment of single-level thoracolumbar burst fractures.Methods:The clinical data of 9 patients with single-segment thoracolumbar burst fracture treated with spinal canal decompression under full-endoscope and percutaneous pedicle screw fixation from April 2021 to June 2022 in our hospital were analyzed retrospectively,including 7 males and 2 females.The age ranged from 23 to 61(39.3±9.1)years old.According to AO classification,there were 6 cases of type A,2 cases of type B and 1 case of type C.Fracture segments were T12 in 2 cases,L1 in 3 cases,L2 in 3 cases,and L3 in 1 case.According to the classification of American Spinal Injury Association(ASIA)grading,there were 2 cases of type C,2 cases of type D,and 5 cases of type E.The decompression and percutaneous pedicle screw fixation were operated through the same incision in the injured vertebrae for screw placing.The operation-related indexes and complications were recorded.The patients'low back pain was evaluated by visual analogue scale(VAS)score before operation,on 3rd day after operation and at the last follow-up.The sagittal Cobb angle,height ratio of vertebral anterior edge,and the rate of spinal canal occupation were measured on spinal X-ray and CT images,and the recovery of neurological function was evaluated at the last follow-up.Results:All 9 patients successfully completed the operation,and the operative time was 105-145min(1 12.4± 21.2min),bleeding volume was 50-110mL(83.9±19.6mL),and hospitalization time was 7-13d(9.1±1.3d).No serious complications such as wound infection,cerebrospinal fluid leakage,aggravated nerve injury occurred.The follow-up time was 6-13months(8.4±3.9 months),all the fractures healed successfully,and the healing time was 3-6 months(4.7±1.6 months).The VAS score of low back pain on the 3rd day after operation and at final follow-up significantly improved compared with that before operation(P＜0.05),and it was also significantly improved at the last follow-up compared with that on the 3rd day after operation(P＜0.05).The Cobb angle,anterior height ratio of injured vertebrae,and invasion rate of spinal canal were significantly improved compared with those before operation(P＜0.05),respectively,but there was no statistical difference between the last follow-up and postoperative 3d(P＞0.05).One patient recovered from grade C to grade D of ASIA classification,while another three patients with neurological injury recovered completely.Conclusions:Decompression under full-endoscope and percutaneous pedicle screw fixation through the same incision in the injured vertebrae for screw placement in the treatment of single-level thoracolumbar burst fractures can obtain effective nerve root and spinal canal decompression,with good correction and small operative trauma,which is a safe and effective option.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.