ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective: To analyze the mediating effects of self-efficacy and self-management behaviors on the relationship between depression symptoms and glycemic control among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide references for optimizing health management of elderly T2DM patients. Methods: T2DM patients aged ≥60 years from 8 community health service centers in Nanjing City were selected using a convenience sampling method. Basic information such as gender and age was collected through questionnaires. Depressive symptoms, self-efficacy, and self-management behaviors were assessed using the Patient Health Questionnaire, the Diabetes Self-Efficacy Scale, and the Diabetes Self-Management Behavior Scale, respectively. Glycated hemoglobin (HbA1c) was measured to evaluate glycemic control. A mediating effect model was constructed to analyze the mediating effects of self-efficacy and self-management behaviors on the relationship between depressive symptoms and glycemic control. Results: A total of 567 elderly T2DM patients were included, with a median age of 70.00 (interquartile range, 7.50) years. There were 248 males (43.74%) and 319 females (56.26%). The median scores of self-efficacy, self-management behaviors, depressive symptoms, and HbA1c were 3.89 (interquartile range, 0.78), 4.45 (interquartile range, 1.55), 4.00 (interquartile range, 6.00), and 6.80% (interquartile range, 1.40%), respectively. The mediating effect analysis showed that depressive symptoms indirectly affected glycemic control among elderly T2DM patients through the independent mediating effects of self-efficacy (β=0.028, 95%CI: 0.016-0.043) and self-management behaviors (β=0.009, 95%CI: 0.003-0.016), as well as the chain mediating effect of both (β=0.025, 95%CI: 0.017-0.035). The mediating effects of self-efficacy and self-management behaviors accounted for 36.66% and 11.35% of the total effect, respectively, while the chain mediating effect accounted for 32.15% of the total effect. Conclusion Self-efficacy and self-management behaviors play mediating roles in the relationship between depressive symptoms and glycemic control among elderly T2DM patients.

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Accurate staging is the fundamental basis for the treatment and prognosis of non-small cell lung cancer (NSCLC), and whether the tumor involves the pleura or chest wall is a critical aspect in assessing the staging of peripheral lung cancer. Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and positron emission tomography (PET) are widely used to determine pleural invasion in NSCLC. There has been an increasing number of studies evaluating whether NSCLC invades the pleura and the extent of such invasion. This article provides a review of the staging and the imaging diagnostic criteria of pleural invasion, aiming to offer references for peers in the precise diagnosis of pleural or chest wall invasion.
.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Lung Neoplasms/diagnosis* ; Thoracic Wall/diagnostic imaging* ; Pleura/diagnostic imaging* ; Neoplasm Invasiveness ; Tomography, X-Ray Computed

Hypertension (HT) can induce aortic dissection (AD) by increasing the tension of the aortic wall and promoting tissue degradation, and continuous HT may increase the risk of aortic-related death. It is a significant factor in poor prognosis for AD and the most important controllable factor. Research has shown that blood pressure management after AD can reduce the incidence rate and mortality of AD, so controlling HT is an important goal and means of AD treatment. This article reviews the research progress on the impact of AD on blood pressure, the significance and methods of blood pressure management after AD, with the hope of providing reference for the treatment of AD patients and benefiting them.

Objective To observe the clinical effect of neuroendoscopic minimal invasive surgery in treating the patients with intraventricular hemorrhage cast.Methods The prospective non-randomized con-trolled study was adopted.Sixty-eight inpatients with intraventricular hematoma cast receiving surgical treat-ment in the neurosurgery department of this hospital from January 2020 to January 2023 were selected as the study subjects;thirty-four cases adopting neuroendoscopic minimal invasive surgery served as the observation group and 34 cases adopting lateral ventricle drilling drainage served as the control group;the surgical time,in-traoperative bleeding volume,hospitalization duration,ICU duration,clearance time of postoperative ventricle hematoma,postoperative hydrocephalus occurrence,occurrence rate of recurrent bleeding in operating area and postoperative complications occurrence rate were observed in the two groups.The levels of serum TNF-α,L-6,CRP,GFAP,S100-β and NSE before operation and on postoperative 7 d were detected;the GCS scores,BI,NIHSS scores before operation and on postoperative 14 d were observed;the GOS scores in postoperative 6 months were observed.Results The surgical time and intraoperative bleeding amount in the control group were significantly less than those in the observation group(P＜0.05);the hospitalization duration,ICU dura-tion,clearance time of postoperative ventricular hematoma and incidence rate of hydrocephalus in the observa-tion group were significantly short or less than those in the control group(P＜0.05);there was no statistical-ly significant difference in postoperative rebleeding incidence rate between the two groups(P＞0.05);the in-cidence rates of pulmonary infection,urinary tract infection,deep venous thrombosis and surgical site infection in the observation group were significantly less than those in the control group(P＜0.05);there was no sta-tistically significant difference in organ dysfunction incidence rate between the two groups(P＞0.05);the lev-els of postoperative TNF-α,L-6,CRP,GFAP,S100-β and NSE in the both groups were significantly decreased compared with those before operation(P＜0.05);the observation group was significantly lower than the con-trol group(P＜0.05);the GCS,BI and NIHSS scores on postoperative 14 d in the two groups were signifi-cantly improved compared with before operation(P＜0.05);the observation group was significantly better than the control group(P＜0.05);the GOS score at postoperative 6 months in the observation group was bet-ter than that in the control group(P＜0.05).Conclusion Neuroendoscopic minimally invasive surgery is ef-fective in treating intraventricular hemorrhage cast with low incidence rate of postoperative complications,which is worthy of clinical promotion.

Objective:To investigate the effects of radiation dose to the host immune system during radiotherapy on disease progression and survival in patients with peripheral early-stage non-small cell lung cancer (ES-NSCLC) receiving stereotactic body radiation therapy (SBRT).Methods:Clinical data of pathologically confirmed ES-NSCLC patients who were treated with SBRT at Tianjin Medical University Cancer Institute and Hospital between January 2007 and December 2020 were retrospectively analyzed. The prognostic significance of the estimated dose of radiation to immune cells (EDRIC) in ES-NSCLC patients undergoing SBRT was cited and validated. EDRIC was calculated using the model developed by Kong et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate cancer-specific survival (CSS), progression-free survival (PFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS). Pearson's correlation was used to assess the correlation between variables. Results:The median prescription dose/fraction was 60 Gy/5 fractions (range: 48-60 Gy in 3-10 fractions). The median follow-up time was 52.17 (1.17-154.77) months. The median gross tumor volume (GTV) and EDRIC were 10.98 (0.91-120.34) cm 3 and 2.064 (0.426-6.015) Gy, respectively. Person's correlation analysis showed that GTV was positively correlated with EDRIC ( r=0.712, P<0.001). In multivariate analysis, EDRIC was an important prognostic variable of CSS and DMFS. Higher EDRIC was significantly associated with worse CSS ( HR=1.763, P=0.004) and DMFS ( HR=1.902, P=0.004). Compared to patients with EDRIC ≤ 1.56 Gy, those with EDRIC > 2.64 Gy and EDRIC between <2.06-2.64 Gy exhibited significantly lower CSS ( P<0.001, P=0.049). There were significant differences in DMFS among the groups divided by quartiles of EDRIC (compared to EDRIC ≤1.56 Gy, the P values were <0.001, 0.004, and 0.022 respectively). Conclusions:EDRIC is an important predictor of CSS and DMFS in ES-NSCLC patients treated with SBRT, suggesting that radiation dose to the immune system is a critical determinant of treatment outcomes. EDRIC can be used to quantify the effects of radiation therapy on the host immune system.

Objective:To investigate the variations in peripheral lymphocyte count (PLC) and evaluate the impact of PLC on clinical prognosis of patients with early-stage non-small cell lung cancer (NSCLC) during stereotactic body radiation therapy (SBRT).Methods:Clinical data of early-stage NSCLC patients who received SBRT at Tianjin Medical University Cancer Institute and Hospital from January 2007 to January 2021 were retrospectively analyzed. The PLC of early-stage NSCLC patients was recorded at four different time points: 1 week before SBRT, 1 week after SBRT, 1 month after SBRT, and 3 months after SBRT. Kaplan-Meier method and Cox proportional hazards regression analysis were used to estimate cancer-specific survival (CSS), progression-free survival (PFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) and their influencing factors. Pearson correlation analysis was used to evaluate the correlation among different variables. The optimal cut-off value of nadir-PLC is determined using the 'maxstat package' in R language.Results:Throughout the treatment process, the nadir-PLC generally occurred approximately at 1 week after SBRT, and was gradually increased thereafter, and almost restored to the level before SBRT at approximately 3 months after SBRT. The median nadir-PLC was 1.03×10 9/L, significantly lower than the baseline value of 1.90×10 9/L before treatment ( P<0.001). The nadir-PLC in patients with central NSCLC was lower compared with that of patients with peripheral NSCLC ( P=0.030). The median survival for the entire group was 91.5 months, and 89.8%, 78.6%, 93.2%, and 82.5% for the 2-year CSS, PFS, LPFS, and DMFS rates, respectively. In multivariate analysis, nadir-PLC ≥1.01×10 9/L was an important favorable prognostic factor for CSS, PFS and DMFS. Pearson correlation analysis showed that gross tumor volume (GTV) was negatively correlated with nadir-PLC ( r=-0.55, P<0.001). Conclusions:In early-stage NSCLC patients treated with SBRT, PLC will decline after treatment. The nadir-PLC is an important favorable prognostic factor for CSS, PFS and DMFS.

There are few reports in China on the laparoscopic Burch procedure in the treatment of female stress urinary incontinence. Twenty-two female stress urinary incontinence patients admitted to our hospital were treated with laparoscopic Burch procedure, with an overall effective rate of 100%. The score of the International Continence Advisory Committee Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF) at one month after treatment was lower compared to that before the procedure. There were no complications during two months of follow-up.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.