OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

[摘 要] 树突状细胞（DC）作为抗肿瘤免疫应答的核心启动者与调控者，已成为肿瘤免疫治疗的重要靶点。DC疫苗等靶向DC的免疫治疗策略在抗肿瘤治疗中展现出独特优势，但仍存在抗原提呈效率不足、免疫抑制微环境抵抗、功能特异性调控困难等瓶颈问题。肿瘤微环境（TME）中的DC存在高度异质性，不同DC亚群在分化发育、免疫调控及效应转归方面呈现复杂的多样性。解析DC亚群的精确表型与功能机制对于开发新型DC靶向性免疫治疗策略具有重要意义。TME中募集的经典DC、浆细胞样DC、单核细胞来源DC能与肿瘤浸润免疫细胞和微环境中的非免疫细胞（包括肿瘤细胞、成纤维细胞、内皮细胞等）相互作用激活抗肿瘤免疫应答，而TME还会通过转录调控、表观遗传调控、代谢重塑等多种方式抑制DC招募和抗原提呈能力，甚至诱导其向耐受性DC转化。值得注意的是，新近发现的富含免疫调节分子的成熟DC具有双向免疫调控作用，其起源路径和免疫调控网络仍有待深入研究。随着单细胞分析与空间组学分析等技术的发展，有望在单细胞分辨率下系统解析DC亚群的功能多样性及其与TME的时空相互作用网络，为开发下一代精准免疫治疗策略提供新靶点和新思路。

OBJECTIVE To analyze the impact of the diagnosis-related groups （DRG） payment reform on the length of stay and medical costs in patients with chronic obstructive pulmonary disease （COPD） in Kashgar region， aiming to provide localized empirical evidence for the optimization of regional medical insurance payment methods. METHODS Based on the inpatient settlement database of the Xinjiang Uygur Autonomous Region Healthcare Security Administration， settlement data of COPD inpatients from 17 medical institutions in Kashgar region between January 1， 2022， and December 31， 2024， were extracted. The overall changes in patients’ length of stay and costs were compared before and after the reform. Subsequently， interrupted time series analysis （ITSA） was employed to explore the impact of the DRG payment reform on these variables. RESULTS Following the reform， both the average length of stay and various cost decreased significantly compared to the pre-reform period （ P ＜0.001）. At the overall sample level， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission all demonstrated significant long-term downward trends after the reform （ P ＜0.05）. However， the decrease in average out-of-pocket costs and the increase in average consumable costs per admission were not statistically significant （ P ＞0.05）. In tertiary medical institutions， the average length of stay and all categories of costs （except average consumable costs per admission） exhibited significant long-term upward trends after the reform （ P ＜0.05）； conversely， in secondary and lower-level medical institutions， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission showed significant long-term downward trends （ P ＜0.05）. CONCLUSIONS The DRG payment reform has achieved an overall effect of reducing the length of stay and controlling costs in COPD patients from Kashgar region. However， the effects vary across different levels of medical institutions： secondary and lower-level institutions show a long-term downward trend in length of stay and costs， whereas tertiary institutions exhibit a long-term upward trend. Furthermore， patients’ out-of-pocket financial burden does not show significant improvement.

This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

This paper summarizes clinical insights on treating the syndrome of coexisting dryness and dampness in Sjögren's syndrome （SS） based on the "three methods for liver diseases". It is proposed that the core pathogenesis of this subtype lies in the liver's failure to regulate and disperse， leading to fluid retention and transformation into dryness； disharmony between wood （liver） and earth （spleen）， resulting in internal generation of dryness and dampness； and liver impairment affecting the kidney， eventually causing extreme dryness to transform into dampness. This syndrome is thus characterized by disharmony between the liver and spleen， as well as dysfunction between ti （character， 体） and yong （function， 用）. Drawing from the Guide to Clinical Case （《临证指南医案》）， the "three methods for liver diseases" are applied as follows，i.e. using pungent and dispersing herbs to regulate the liver and resolve qi stagnation； using sweet and gentle herbs to soothe the liver and address the root of concurrent dryness and dampness； and using sour and purgative herbs to soften the liver and restore fluid balance. The coordinated use of these three methods， treating both ti and yong， facilitates the separation of dryness and dampness， providing a novel approach to syndrome differentiation and treatment for this subtype of SS.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

Diabetic kidney disease(DKD)is one of the serious complications of diabetes.Ferroptosis causes pathological damage and is involved in the progression of DKD.How to inhibit ferroptosis and delay DKD is a new academic hotspot.The author's team further enriched and proposed the core pathogenesis theory of"internal heat induced disease"on the basis of the traditional DKD"yin deficiency and dryness-heat"theory,and explained the general development law of DKD.In this article,"internal heat"and"Zhengjia"in the theory of DKD"internal heat induced diseases"are used as the starting point to explore the relationship of the main pathological damage of ferroptosis such as activating inflammatory response,enhancing oxidative stress,promoting fibrosis and so on with the internal mechanism of the theory of"internal heat induced diseases",further explained the scientific connotation of DKD"internal heat induced diseases",in order to provide ideas and theoretical basis for the TCM prevention and treatment of DKD.

Objective To explore the value of dynamic contrast-enhanced(DCE)-MRI quantitative parameters based on differential sub-sampling with Cartesian ordering(DISCO)technology for differentiating high-and low-grade breast cancer.Methods A total of 80 patients with single breast cancer confirmed by biopsy pathology were retrospectively enrolled,including 40 cases of low-grade(L group)and 40 cases of high-grade breast cancer(H group).Then quantitative parameters obtained from DISCO-DCE-MRI before treatment were compared between groups,including extravascular extracellular volume fraction(Ve),rate constant(Kep),contrast enhancement ratio(CER),maximum slope(MaxSlope)and volume transfer constant(Ktrans),and their correlations with histological grade were analyzed.Receiver operating characteristic(ROC)curves of DISCO-DCE-MRI quantitative parameters being significantly different between groups were plotted,and the area under the curves(AUC)were calculated to evaluate their efficacy for differentiating high-and low-grade breast cancer.Results Ve(0.91[0.59,0.99]),CER(2.76±0.54)and MaxSlope(0.02[0.01,0.03])in L group were all higher than those in H group(0.52[0.34,0.73],[2.31±0.74],0.01[0.01,0.02],all P＜0.05),and no significant difference of Kep nor Ktrans was found between groups(both P＞0.05).Ve,CER and MaxSlope of breast cancer were all negatively correlated with histological grade(rs=-0.43,-0.39,-0.35,all P＜0.05),while Kep andKtranshad no significant correlation with histological grade(both P＞0.05).The AUC of Ve,CER and MaxSlope for differentiating high-and low-grade breast cancer was 0.749,0.725 and 0.700,respectively.Conclusion Among DISCO-DCE-MRI quantitative parameters,Ve,CER and MaxSlope could be used for differentiating high-and low-grade breast cancer.

Objective To explore the value of clinical-MRI radiomics combined model for differentiating borderline ovarian tumor(BOT)from epithelial ovarian cancer(EOC).Methods Totally 139 patients with BOT(BOT group)and 307 patients with EOC(EOC group)confirmed by postoperative pathology and underwent preoperative pelvic MRI were retrospectively enrolled and randomly divided into training set(n=312)and test set(n=134)at a ratio of 7∶3.Multivariable logistic regression was used to identify independent clinical predictors for differentiating BOT and EOC,then a clinical model was constructed.Radiomics features were extracted from the volumes of interest(VOI)of lesions on T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images,respectively,and single-sequence and multi-sequence MRI radiomics models were built using extreme gradient boosting(XGBoost)based on data in training set.The optimal MRI radiomics model was selected according to the highest area under the curve(AUC)in test set,and a clinical-MRI radiomics combined model was constructed combined the optimal radiomics model with independent clinical predictors.The performances of clinical model,the optimal MRI radiomics model and the combined model for differentiating BOT and EOC were compared in test set.SHapley Additive exPlanations(SHAP)analysis was applied to interpret key predictive features in the best model.Results Patients' age,carbohydrate antigen 153(CA153)and carbohydrate antigen 125(CA125)were all independent predictors for differentiating BOT and EOC(all P＜0.05).Multi-sequence MRI radiomics model was the optimal MRI radiomics model.The combined model showed superior performance(AUC=0.929)for discriminating BOT and EOC compared with clinical model(AUC=0.881)and multi-sequence MRI radiomics model(AUC=0.871)(both P＜0.05).SHAP beeswarm plot revealed that the top 10 important features of combined model included age,CA153 and CA125,as well as entropy,kurtosis and gray level non-uniformity from ADC and DWI sequences.Conclusion Clinical-MRI radiomics combined model based on multi-sequence MRI radiomics features and clinical features could be used to effectively differentiate BOT from EOC.