1.Mechanism Study of Yinchenhao Tang Regulating Fas/Caspase-8/Caspase-3 Signaling Pathway to Improve Cholestatic Liver Injury
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Linjing SHE ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):39-46
ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury (CLI). MethodsAmong 48 Wistar rats,12 rats were randomly selected as the blank group,and the other rats were administered alpha-naphthalene isothiocyanate (ANIT) by gavage to induce a CLI model. The modeling rats were randomly divided into the model group, the ursodeoxycholic acid group(0.1 g·kg-1) and the Yinchenhao Tang group(9.23 g·kg-1),with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (γ-GT),total bilirubin (TBil) and total bile acid (TBA) in serum were detected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3,B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with those in the blank group,the levels of ALT,AST,ALP,γ-GT,TBA and TBil in serum of the model group were significantly increased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased (P<0.01). The arrangement of hepatocytes was disordered,and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly increased(P<0.05,P<0.01),while the protein and mRNA expressions of Bcl-2 were significantly decreased (P<0.05,P<0.01). Compared with those in the model group,the levels of ALP,γ-GT,TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01). The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the mRNA expression of Bcl-2 was significantly increased (P<0.05,). The levels of ALT,AST,γ-GT,TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased (P<0.05,P<0.01). The protein expression of Fas and Bax and the mRNA expression of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the protein and mRNA expression of Bcl-2 were significantly increased (P<0.05,P<0.01). Hepatocyte injury,inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI,and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.
2.Mechanism of Yinchenhao Tang in Improving Cholestatic Liver Injury by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway Through FXR
Zhengwang ZHU ; Yang YANG ; Jinghan ZHAO ; Linlin WANG ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):47-54
ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury (CLI) by inhibiting toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) pathway via regulating farnesol X receptor (FXR). MethodsA total of 40 Wistar male rats were randomly selected, with 10 as a blank group,and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate (ANIT). After modeling,they were randomly divided into the model group, the ursodeoxycholic acid (0.1 g·kg-1) group and the Yinchenhao Tang (9.23 g·kg-1) group,with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptidase (γ-GT),total bile acid (TBA),total bilirubin (TBil) and direct bilirubin (DBil) levels in serum were detected. Tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and interleukin-6 (IL-6) levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR,TLR4,MyD88,NF-κB,F4/80,TNF-α,IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR,TLR4,MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. ResultsCompared with those in the blank group,ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the model group were significantly increased (P<0.01). The levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were significantly increased (P<0.01),and the mRNA and protein expressions of FXR in liver tissue were decreased (P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased (P<0.05,P<0.01). Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group,ALT,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.05,P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased (P<0.05,P<0.01). ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.01). The mRNA and protein expressions of FXR in liver tissue were significantly increased,and the mRNA expressions of TLR4,MyD88,NF-κB,and F4/80, as well as the protein expressions of TLR4 and NF-κB were obviously decreased (P<0.05,P<0.01). The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI,and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.
3.Effect of epigallocatechin gallate on gut microbiota during hepatocarcinogenesis in rats
TANG Yanping ; CAI Zhengmin ; TANG Yamei ; TANG Jiaying ; LI Shuang ; LI Kezhi
Chinese Journal of Cancer Biotherapy 2026;33(2):190-198
[摘 要] 目的:探讨绿茶单体表没食子儿茶素没食子酸酯(EGCG)对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法:建立二乙基亚硝胺(DEN)诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组,分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起,EGCG干预组每日给予EGCG(40 mg/kg)灌胃,正常对照组和肝癌组给予等量生理盐水灌胃,1次/日,持续至第20周。灌胃结束后,采集大鼠粪便样本,提取DNA,进行高通量16S rRNA V3-V4区测序;处死大鼠,取肝,观察肿瘤形成情况,并计算肝癌发生率。对测序数据进行生物信息学分析:经质控、聚类获得操作分类单元(OTU)表,据此计算α多样性指数(包括Observed species、Chao1、Shannon和Simpson指数),并进行β多样性分析。同时,对物种进行分类学注释,比较各组间菌群组成与丰度差异。结果: EGCG干预组大鼠(8只)肝脏肿瘤形成率明显低于肝癌组(10只)(50% vs 100%, P = 0.023),正常对照组(8只)大鼠无肿瘤发生。在肠道菌群方面,肝癌组操作分类单元(OTU)数量远低于正常对照组(P <0.001),而EGCG干预组OTU数量总体上高于肝癌组(P = 0.021)。α多样性分析显示,肝癌组Shannon指数低于正常对照组(P < 0.05);此外,与肝癌组相比,EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高(P < 0.05)。β多样性分析及主坐标分析(PCoA)表明,三组肠道菌群结构存在显著分离(PERMANOVA, R² = 0.3918, P = 0.001),其中EGCG干预组群落结构介于肝癌组与正常对照组之间,并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集,丁酸产生相关菌(如丁酸球菌属、瘤胃球菌属等)丰度显著降低(P < 0.05)。相比之下,在EGCG干预肝癌发生过程中,大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高(P < 0.05),益生菌(如双歧杆菌属、乳杆菌属等)和丁酸产生相关菌(如丁酸球菌属)富集。结论:EGCG干预可降低DEN诱导的大鼠肝癌发生率,并有助于稳定肠道菌群结构,其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。
4.Meta analysis of the efficacy of digital psychological therapies on depressive symptoms among adolescents
YANG Xuan, YANG Dong, CAI Rui, TANG Yuping, YE Sheng, LUO Yaoyue
Chinese Journal of School Health 2026;47(4):531-537
Objective:
To systematically evaluate the therapeutic efficacy and maintenance effects of digital psychological therapies on depressive symptoms among adolescents, so as to provide a reference for clinical practice.
Methods:
Randomized controlled trial(RCT) investigating digital psychological therapies to improve depressive symptoms among adolescents were searched across databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, and SinoMed, from database inception to November 20, 2025. Following literature screening, quality assessment, and data extraction, a Meta analysis was performed using Stata 18.0 software.
Results:
A total of 20 studies involving 2 042 adolescents aged 11-19 were included. The Meta analysis revealed that digital psychological therapies significantly alleviated depressive symptoms in adolescents ( SMD =-0.59, 95% CI =-0.85 to -0.32, P <0.01). The therapeutic effect was sustained at long term follow up ( SMD =-0.21, 95% CI =-0.34 to -0.09, P <0.01). Furthermore, depression scores in the intervention group showed a continued decrease from post intervention to long term follow up ( SMD =-0.28, 95% CI =-0.41 to -0.14, P <0.01). Egger s linear regression test indicated possible publication bias (Kendall s tall=0.28, P <0.01).
Conclusions
Digital psychological therapies can effectively improve depressive symptoms among adolescents, with stable long term efficacy. However, current evidence remains limited and exhibits substantial heterogeneity. Therefore, further large sample, high quality RCTs are warranted to validate the effectiveness of this intervention.
5.Research on The Genealogical Inference Efficiency of High-density SNPs
Jing LI ; Yi-Jie SUN ; Wen-Ting ZHAO ; Zi-Chen TANG ; Jing LIU ; Cai-Xia LI
Progress in Biochemistry and Biophysics 2026;53(3):740-753
ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.
6.Establishment of a predictive model for the risk of hypoalbuminemia after partial hepatectomy based on machine learning methods
Dongqing CAI ; Shanhua TANG ; Yuancan XIAO ; Xiru LEI ; Suicheng LI ; Jie ZHOU
Journal of Clinical Hepatology 2026;42(5):1109-1118
ObjectiveTo investigate the application value of a machine learning model based on preoperative clinical indicators in predicting the risk of hypoalbuminemia after partial hepatectomy. MethodsA retrospective analysis was performed for the clinical data of 700 patients who underwent partial hepatectomy in Nanfang Hospital, Southern Medical University, from January 2018 to January 2023, including demographic data, history of underlying diseases, tumor characteristics, preoperative laboratory markers, and perioperative indicators. The research data were divided into a training set and a test set at a ratio of 7∶3. The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups; the two-independent-samples Wilcoxon rank-sum test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify characteristic variables, and 7 machine learning algorithms were used to construct predictive models, i.e., logistic regression, decision tree, artificial neural network, K-nearest neighbors (KNN), support vector machine, eXtreme gradient boosting, and light gradient boosting machine. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the discriminatory ability of models, and the DeLong test was used for comparison of AUC. The calibration curve and decision curve analysis were used to assess the calibration and clinical practicability of models, and the models were compared with albumin-bilirubin (ALBI) score and Model for End-Stage Liver Disease (MELD) score. SHapley Additive exPlanations (SHAP) were used to interpret the key influencing factors for the optimal model. ResultsA total of 700 patients were finally enrolled, 283 (40.42%) developed hypoalbuminemia after surgery. The LASSO regression analysis identified 8 predictive factors of age, hepatitis B, fatty liver, blockade time, preoperative albumin (Alb), time of operation, intraoperative blood loss, and preoperative aspartate aminotransferase (AST). Among the 7 machine learning models, the KNN model showed the best overall predictive performance, with an AUC of 0.835 (95% confidence interval: 0.781 — 0.889), a sensitivity of 84.0%, and a specificity of 65.5% in the test set. ALBI and MELD scores had an AUC of 0.652 and 0.524, respectively, and the KNN model had a better predictive performance than these two scores (Z=5.309 and 8.945, both P <0.001). The calibration curve showed good consistency between predicted probabilities and actual incidence rates, and the decision curve analysis showed that the KNN model had net clinical benefit across a wide threshold range. The SHAP analysis showed that preoperative Alb, hepatitis B, time of operation, and age were the most significant influencing factors, and a synergistic effect was observed between hepatitis B and age/time of operation. ConclusionThe KNN machine learning model constructed based on preoperative clinical indicators can effectively predict the risk of hypoalbuminemia after partial hepatectomy and has a better performance than traditional scoring models, which provides a reference for the early identification of high-risk patients in clinical practice.
7.Pseudolaric Acid B-linked Double-network Hydrogel Alleviates Pruritus by Inhibiting The Growth of Staphylococcus aureus
Ye YOU ; Yan YANG ; Tong-Yu LI ; Cheng-Long CAI ; Ting WANG ; Chan ZHU ; Zong-Xiang TANG
Progress in Biochemistry and Biophysics 2026;53(6):1734-1745
ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.
8.Effects of Electro-Acupuncture Based on the Midnight-Noon Ebb-Low Method with Hour-Prescription on BMAL1 Protein and NETs Markers in Lung Tissue of Chronic Obstructive Pulmonary Disease Model Rats with Lung-Qi Deficiency Syndrome
Changtian JIAO-LI ; Nise Pantaleo SHIO ; Lianqing CAI ; Qingyao JIANG ; Siyu TANG ; Qianqian WAN ; Mengchen WAN ; Yuqi YE ; Jie ZHU
Journal of Traditional Chinese Medicine 2026;67(13):1422-1430
ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease (COPD) with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 (BMAL1) as well as neutrophil extracellular traps (NETs). MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation, 24 rats were randomly allocated into control group 1, model group 1, midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group, with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide (LPS). After successful modelling, rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan (LU 9)", "Feishu (BL 13)" and "Zusanli (ST 36)" during 05:00—07:00, 30 minutes per treatment once every other day for 14 consecutive days (7 sessions in total). Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours (08:00—18:00). Pulmonary function parameters including forced expiratory volume in 0.3 second (FEV0.3), forced vital capacity (FVC) and FEV0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin (HE) staining. Plasma levels of pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as pulmonary reactive oxygen species (ROS) content, BMAL1 protein expression and the levels of neutrophil extracellular traps (NETs) biomarkers such as myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (CitH3) in lung tissue were determined. For the mechanistic verification phase, 36 rats were divided into control group 2, model group 2, midnight-noon electro-acupuncture group 2, overexpression empty group, overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group, with 6 rats in each group. At the 5th week of model construction, rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally, pulmonary levels of MPO, NE and CitH3 were measured in all groups. ResultsCompared with the control group 1, the model group 1 exhibited decreased FEV0.3, FVC and FEV0.3/FVC ratio, elevated plasma IL-1β, TNF-α and pulmonary ROS levels, downregulated lung BMAL1 protein expression, and increased contents of MPO, NE and CitH3 (all P<0.05); typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy; HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1, both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators, with superior therapeutic effects in midnight-noon electro-acupuncture group 1 (P<0.05). Consistently, midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2, the average optical density of MPO as well as the protein levels of MPO, NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2, overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group (P<0.05); furthermore, these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 (P<0.05). ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.
9.Application analysis of flux smoothness modes in the Monaco system: balancing dose safety and equipment operating costs in cervical cancer radiotherapy
Yongjuan SU ; Yuhua GAO ; Shaolin MA ; Chao GUO ; Cai TANG
Chinese Journal of Radiological Health 2026;35(3):354-361
Objective To investigate the effects of low, mid, and high flux smoothness modes on plan quality, treatment efficiency, equipment loss, and clinical economic benefits in fixed-field intensity-modulated radiotherapy for cervical cancer, and establish a decision-making model for parameter optimization and economic benefits. Methods Fifteen patients with cervical cancer undergoing radiotherapy were selected. Using the Monaco system and adjusting only the flux smoothness parameter, low, mid, and high plans were designed for each patient. Dosimetric differences were compared for the target volume (D2, D98, Dmean, homogeneity index, conformity index) and organs at risk (small intestine, rectum, colon, bladder, femoral head). The number of segments, monitor units, and their correlations with treatment efficiency and equipment loss were analyzed, as well as the potential impact on clinical costs. Results There were statistically significant differences in the three groups' planned target areas D2, D98, Dmean, CI, HI, and the dose parameters of organs at risk (P<0.001), but the absolute differences were all lower than the clinical tolerance limits in the ICRU 83 report (±3% – ±5%), with an effect size d<0.5 (except for the small intestine with d = 0.51). There was no clinical significance. Compared with the mid mode, the high mode had a 13.3% reduction in the number of subfields (effect size d = 0.85), a 11.6% reduction in machine jumps (d = 1.0), and a 13.0% reduction in treatment time. Based on the mid mode, the relative loss rate of the accelerating tube in the high mode was 11.6%, the theoretical risk change rate of equipment failure was 12.7%, and the accelerating tube lifespan was extended by approximately 1.2 years. Comprehensive economic benefits: Calculated based on 1,200 treatments per year, the annual cost savings are approximately 920,000 yuan. Conclusion Adoption of the high flux smoothness mode in fixed-field intensity-modulated radiotherapy for cervical cancer using the Monaco system can significantly enhance treatment efficiency and reduce operating costs while ensuring dosimetric quality. It is recommended for routine clinical use.
10.Kupffer cells: Orchestrators of liver physiology
Liver Research 2026;10(2):99-108
As the central metabolic organ, the liver coordinates fundamental biological processes through its specialized cellular architecture and regulatory networks, encompassing metabolism, immunity, and regeneration. Kupffer cells (KCs), the liver-resident macrophages, exhibit functional heterogeneity beyond classical polarization paradigms. Currently, multiple classification systems for KCs have been established utilizing distinct surface markers. However, there is no systematic theoretical framework for the classification of KCs. The strategic positioning of KCs within the hepatic Disse space enables intricate intercellular communication networks with neighboring hepatocytes for coordinated physiological regulation. Their functional plasticity critically regulates systemic iron and metabolic homeostasis, with KC-driven metabolic reprogramming directly influencing hepatic pathophysiology. Furtherly, KC activity shows spatiotemporal regulation by circadian rhythms and nutrient signals, reshaping the liver microenvironment to affect function. This review summarizes advances in liver macrophage biology, highlighting the classification challenges of KCs and their roles in hepatic physiology. Additionally, we discuss how circadian rhythms, aging, diet, and exercise dynamically influence KC functionality, which provides a framework to interpret their regulatory logic and dysfunction in disease.


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