ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective:To investigate the relationship between peripheral blood amyloid protein A(SAA),C-reactive protein(CRP)/prealbumin(PA),vascular endothelial growth factor(VEGF)and the severity,pulmonary function,and prognosis of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:106 children with MPP who were admitted to Huichang County Maternal and Child Health Hospital of Ganzhou from February 2023 to August 2024 were selected as the study subjects(MPP group),they were divided into good prognosis group(n=77)and poor prognosis group(n=29)according to the 28 days prognosis,they were divided into mild group(n=61)and severe group(n=45)according to the disease severity.Another 90 healthy children who underwent physical examinations during the same period were selected as the control group.The peripheral blood SAA,CRP/PA,VEGF,and pulmonary function indicators between the control group and MPP group were compared,and the peripheral blood SAA,CRP/PA,and VEGF levels between the mild group and severe group were compared,Pearson and Spearman correlation analysis was used to investigate the correlation between peripheral blood SAA,CRP/PA,VEGF and pulmonary function indicators and disease severity in children with MPP.The levels of peripheral blood SAA,CRP/PA,and VEGF between poor prognosis group and good prognosis group were compared.Receiver operating characteristic(ROC)curve was used to analyze the value of peripheral blood SAA,CRP/PA,VEGF detection alone and in combination for evaluating the 28 days prognosis in children with MPP.Results:The peripheral blood SAA,CRP/PA,and VEGF levels in the MPP group were higher than those in the control group,while the forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),and forced vital capacity(FVC)were lower than those in the control group(P＜0.05).Peripheral blood SAA,CRP/PA,and VEGF levels in the severe group were higher than those in the mild group(P＜0.05).Peripheral blood SAA,CRP/PA,VEGF were negatively correlated with FEV1,PEF,FVC,but positively correlated with the severity of the disease(P＜0.05).Peripheral blood SAA,CRP/PA,and VEGF in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The area under the curve(AUC)values of peripheral blood SAA,CRP/PA,and VEGF for evaluating the 28 days prognosis of MPP patients were 0.514,0.562,and 0.585,respectively,the AUC of 28 days prognosis evaluation in children with MPP by combined detection of peripheral blood SAA,CRP/PA,and VEGF was 0.725,significantly higher than that of individual detection.Conclusion:Abnormal elevation of peripheral blood SAA,CRP/PA,and VEGF levels is involved in the progression of MPP,the injury of pulmonary function,and poor prognosis.combined detection of peripheral blood SAA,CRP/PA,and VEGF levels can effectively evaluate the short-term prognosis of MPP patients.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

Objective To explore the mechanism of Wenyang Yiqi Huoxue Prescription(WYYQHXP)in the treatment of chronic heart failure(CHF)by regulating miR-126-3p and PI3K/Akt signaling pathway based on network pharmacology and experimental studies.Methods Active components and targets of WYYQHXP were obtained through TCMSP,SwissTargetPrediction,SwissADME and PubChem.Four miRNA databases were used to obtain miR-126-3p targets,and four disease databases were used to obtain CHF related targets.The intersection of the three was taken as the potential target of action;the protein-protein interaction network relationships of potential targets were explored using STRING and Cytoscape 3.9.1 software,and the main active components and core targets were screened;GO and KEGG pathway enrichment analysis was performed using R 4.2.1 software;Molecular docking was performed on the main active components with the core targets.Isoproterenol was used to induce a rat model of CHF with qi deficiency and blood stasis syndrome,and intervened with WYYQHXP.MiR-126-3p and core target expression in coronary endothelial cells were detected by immunohistochemistry,RT-qPCR,and Western blot.Results Network pharmacology screened main active components of WYYQHXP,including β-sitosterol,doustanol,kaempferol,quercetin,baicalein and luteolin,and the core targets of EGFR,VEGFA and AKT1;KEGG was enriched to the signaling pathways such as PI3K/Akt,and the 3 core targets were distributed to the PI3K/Akt signaling pathway;molecular docking showed good binding ability of β-sitosterol and stigmasterol to three core targets.Animal experiments showed that WYYQHXP could increase left ventricular ejection fraction and left ventricular fractional shortening in model rats(P<0.01),reduce serum brain natriuretic peptide content(P<0.01),increase expression of miR-126-3p(P<0.05,P<0.01,P<0.001),the medium-dosage of WYYQHXP could increase mRNA and protein expressions of EGFR,PI3K,AKT1 and VEGFA in coronary endothelial cells(P<0.01).Conclusion WYYQHXP may activate PI3K/Akt signaling pathway by acting on miR-126-3p,thereby restoring endothelial dependent vasodilation of coronary arteries,repairing endothelial dysfunction of coronary arteries,and treating CHF.

Gastric cancer is a malignant tumor with high prevalence worldwide and limited therapeutic options.Chimeric antigen receptor T-cell(CAR-T)therapy has emerged as a promising approach for gastric cancer treatment;however,its application faces substantial challenges.This review provides comprehensive summary of the recent advances in CAR-T cell therapy for gastric cancer,systematic analysis of critical break throughs and core challenges from target discovery to clinical translation,and outlining of future perspectives.We describe the criter-ia for ideal target selection and highlight the current research landscape of major targets,including CLDN18.2 that demonstrated efficacy,and targets facing distinct challenges,including HER-2,CEA,EpCAM,and MUC1.This review also finely dissects three central barriers restrict-ing CAR-T cell efficacy,and discusses corresponding countermeasures:overcoming the immunosuppressive tumor microenvironment through strategies such as local delivery,armored CAR-T cells,and combination therapies;engineering approaches including affinity modula-tion and logic-gate designs to mitigate on-target/off-tumor toxicity;and optimization of manufacturing processes and reduction of costs via early leukapheresis,rapid production platforms,and universal CAR-T cell strategies.Future multidimensional,integrative,and innovative strategies are pivotal for achieving comprehensive break throughs in CAR-T cell therapy for solid tumors.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.

Objective:To explore the dosimetry optimization strategy based on filter thickness and shape selection for the bulb superficial X-ray radiotherapy unit.Methods:Monte Carlo code TOPAS was used to model tubular equipment, and the dose distribution from six X-ray energies (50-150 kV) and five conventional aluminum filters (0.5-3.0 mm) with different thickness were simulated in the water model. The percentage depth dose (PDD) curve along the central axis, the center-axis profile dose at different depths, and the lateral dose distribution were analyzed. The dose distribution of three different designs of aluminum filters (conventional cylindrical, conical and oblique cylindrical filters) was compared to evaluate the effect of dosimetric optimization of different filter shapes.Results:Under the same energy, increasing the thickness of the filter can optimize the superficial skin dose, and the optimization effect of depth dose uniformity can be increased by 26% at a depth of 5.5 mm at 70 kV energy. The raised, flat and inclined dose distribution modes can be achieved by using conventional cylindrical, conical and inclined aluminum filters.Conclusions:By selecting the appropriate X-ray energy and filter thickness, an ideal dose distribution matching the tumor depth can be achieved. The application of personalized filters is also of great significance for diverse target areas.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.