Objective:To investigate the predictive value of neutrophil extracellular traps (NETs) on the prognosis of patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma.Methods:A total of 132 surgical paraffin specimens of EGFR wild-type lung adenocarcinoma diagnosed at the Tumor Hospital Affiliated to Xinjiang Medical University from January 2016 to December 2023 and 12 pairs of cancer and paracancerous fresh tissues from patients with EGFR wild-type lung adenocarcinoma diagnosed in March-July 2024 were collected with their clinical information. Western blotting and immunofluorescence were used to detect the expression levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in cancerous and paraneoplastic tissues. Immunohistochemistry was used to detect the infiltration of PD-L1, CD4 + T cells and CD8 + T cells in the tumors. The clinical and prognostic correlations between NETs and EGFR wild-type lung adenocarcinoma patients were analyzed. Results:The expression of MPO ( P＜0.001) and CitH3 ( P=0.009) was significantly increased in the tumors compared with the paracancerous tissues. The rate of high expression of NETs in cancer tissues was higher in patients with EGFR wild-type lung adenocarcinoma who were in stage Ⅲ and Ⅳ, with lymph node metastasis, distant metastasis, pleural invasion, high expression of Ki-67, low expression of CD8 + T, and lowered lymphocyte counts when compared to paraneoplastic tissues ( P＜0.05). Patients were stratified based on TNM stage Ⅱb for prognostic analysis. Kaplan-Meier univariate analysis showed that the median overall survival (OS) (stage Ⅰ to Ⅱb: 47 vs 87 months; stage Ⅲ to Ⅳ: 27 months vs not reach) and the median disease-free survival (DFS) (stage Ⅰ to Ⅱb: 42 vs 78 months; stage Ⅲ to Ⅳ: 18 vs 39 months) of patients with high expression of NETs in stage Ⅰ to II b and stage Ⅲ to Ⅳ were lower than those with low expression (stage Ⅰ to Ⅱb: OS, P＜0.001; DFS, P＜0.001; stage Ⅲ to Ⅳ: OS, P=0.001; DFS, P=0.022). The OS (stage Ⅰ to Ⅱb: HR=3.513, 95% CI: 1.966-6.277, P＜0.001; stage Ⅲ to Ⅳ: HR=3.215, 95% CI: 1.324-7.806, P=0.010) and the DFS (stage Ⅰ to Ⅱb: HR=2.478 ,95% CI: 1.396-4.400, P=0.002; stage Ⅲ to Ⅳ: HR=2.248, 95% CI: 1.089-4.638, P=0.028) in the group with high expression of NETs in either stage Ⅰ to Ⅱb or stage Ⅲ to Ⅳ were significantly shorter than those in the group with low expression. Conclusion:The EGFR wild-type lung adenocarcinoma patients with high expression of NETs have relatively shorter DFS and OS, which are independent risk factors for the prognosis of patients with EGFR wild-type lung adenocarcinoma, and are likely to be the potential biomarkers for the diagnosis and treatment of EGFR wild-type lung adenocarcinoma.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

The early prediction of axillary lymph node metastasis is crucial to the treatment and prognosis of breast cancer patients. Radiomics, as a non-invasive, convenient and efficient emerging technology, can achieve deep exploration and processing of imaging images and plays an increasingly important role in the evaluation of benign and malignant breast tumors, prediction of lymph node metastasis and other aspects. This article reviews the studies on the prediction of axillary lymph node metastasis of breast cancer based on radiomics of mammography, ultrasound and magnetic resonance imaging.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Terahertz(THz)technology,as an emerging tool for characterizing biomacromolecules,has rapidly developed over the past few decades,demonstrating significant application potential in multiple fields.Defensive qi is a vital energy in the human body,responsible for defense functions by warming the skin,regulating the opening and closing of the striae and interstices,and resisting the invasion of external pathogens.Defensive qi is one of the core concepts for disease prevention and health maintenance in traditional Chinese medicine(TCM).However,due to the high abstraction and complexity of TCM theory,the scientific connotation and mechanism of action of defensive qi remained incompletely elucidated.THz waves have the unique physical properties of molecular vibration sensitivity,penetrability,and thermal radiation effects,and are highly sensitive to biological tissues,which make THz technology a promising tool for defensive qi research.By analyzing the characteristics of THz waves,this paper explores the feasibility of applying THz technology to investigate the circulation patterns of defensive qi,the prevention and treatment of disorders related defensive qi,the pathological essence of defensive qi diseases,the material basis of defensive qi,the screening of defensive qi disorders,and the development of novel drugs targeting defensive qi disorders.This approach provides a new perspective and methodology for the research of TCM fundamental theory.

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

The early prediction of axillary lymph node metastasis is crucial to the treatment and prognosis of breast cancer patients. Radiomics, as a non-invasive, convenient and efficient emerging technology, can achieve deep exploration and processing of imaging images and plays an increasingly important role in the evaluation of benign and malignant breast tumors, prediction of lymph node metastasis and other aspects. This article reviews the studies on the prediction of axillary lymph node metastasis of breast cancer based on radiomics of mammography, ultrasound and magnetic resonance imaging.

Objective:To investigate the predictive value of neutrophil extracellular traps (NETs) on the prognosis of patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma.Methods:A total of 132 surgical paraffin specimens of EGFR wild-type lung adenocarcinoma diagnosed at the Tumor Hospital Affiliated to Xinjiang Medical University from January 2016 to December 2023 and 12 pairs of cancer and paracancerous fresh tissues from patients with EGFR wild-type lung adenocarcinoma diagnosed in March-July 2024 were collected with their clinical information. Western blotting and immunofluorescence were used to detect the expression levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in cancerous and paraneoplastic tissues. Immunohistochemistry was used to detect the infiltration of PD-L1, CD4 + T cells and CD8 + T cells in the tumors. The clinical and prognostic correlations between NETs and EGFR wild-type lung adenocarcinoma patients were analyzed. Results:The expression of MPO ( P＜0.001) and CitH3 ( P=0.009) was significantly increased in the tumors compared with the paracancerous tissues. The rate of high expression of NETs in cancer tissues was higher in patients with EGFR wild-type lung adenocarcinoma who were in stage Ⅲ and Ⅳ, with lymph node metastasis, distant metastasis, pleural invasion, high expression of Ki-67, low expression of CD8 + T, and lowered lymphocyte counts when compared to paraneoplastic tissues ( P＜0.05). Patients were stratified based on TNM stage Ⅱb for prognostic analysis. Kaplan-Meier univariate analysis showed that the median overall survival (OS) (stage Ⅰ to Ⅱb: 47 vs 87 months; stage Ⅲ to Ⅳ: 27 months vs not reach) and the median disease-free survival (DFS) (stage Ⅰ to Ⅱb: 42 vs 78 months; stage Ⅲ to Ⅳ: 18 vs 39 months) of patients with high expression of NETs in stage Ⅰ to II b and stage Ⅲ to Ⅳ were lower than those with low expression (stage Ⅰ to Ⅱb: OS, P＜0.001; DFS, P＜0.001; stage Ⅲ to Ⅳ: OS, P=0.001; DFS, P=0.022). The OS (stage Ⅰ to Ⅱb: HR=3.513, 95% CI: 1.966-6.277, P＜0.001; stage Ⅲ to Ⅳ: HR=3.215, 95% CI: 1.324-7.806, P=0.010) and the DFS (stage Ⅰ to Ⅱb: HR=2.478 ,95% CI: 1.396-4.400, P=0.002; stage Ⅲ to Ⅳ: HR=2.248, 95% CI: 1.089-4.638, P=0.028) in the group with high expression of NETs in either stage Ⅰ to Ⅱb or stage Ⅲ to Ⅳ were significantly shorter than those in the group with low expression. Conclusion:The EGFR wild-type lung adenocarcinoma patients with high expression of NETs have relatively shorter DFS and OS, which are independent risk factors for the prognosis of patients with EGFR wild-type lung adenocarcinoma, and are likely to be the potential biomarkers for the diagnosis and treatment of EGFR wild-type lung adenocarcinoma.