ObjectiveThis study aims to analyze the pharmacodynamic material basis and multi-target mechanism of action of Banxia Baizhu Tianmatang combined with Danggui Shaoyaosan in the treatment of Meniere's disease（MD）. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS） （mobile phase： gradient elution with 0.1% formic acid aqueous solution-acetonitrile. Mass spectrometry scanning range： m/z 90-1 300） was used to identify the chemical components of the compound recipe and components absorbed into blood. The core mechanism was predicted by combining network pharmacology （target screening via SwissTargetPrediction and GeneCards databases， and construction of protein-protein interaction （PPI） network by STRING） and molecular docking （evaluated by Autodock， with binding energy ≤ -5.0 kcal·mol^-1）. For animal experiment validation， 36 Sprague Dawley （SD） rats were divided into a blank group， a model group （postauricular injection of lipopolysaccharide （LPS） at 1 mg·kg^-1）， low/medium/high-dose Chinese medicine groups （5.94， 11.88， and 23.76 g·kg^-1·d^-1， respectively）， and Western medicine group （betahistine at 0.1 mg·kg^-1·d^-1）. After eight weeks of intervention， the gene and protein expressions in cochlear tissue were detected. Results①A total of 2 831 chemical components and 173 components absorbed into blood were identified， with terpenoids showing the highest absorption rate into blood（10.28%）. ②60 common drug-disease targets were screened， with core targets including tumor necrosis factor-α（TNF-α），interleukin-6（IL-6）， Toll-like receptor 4（TLR4）， angiotensin-converting enzyme（ACE）， and endothelial nitric oxide synthase 3（NOS3）.These targets were enriched in the nuclear factor-κB（NF-κB） signaling pathway and renin-angiotensin system（P<0.05）. Molecular docking showed that the active component YC-1 had a strong binding ability to TNF（binding energy-9.66 kcal·mol^-1）. ③In animal experiments， the high-dose Chinese medicine group significantly down-regulated the expression of pro-inflammatory factors TNF mRNA（P<0.01）and up-regulated vascular regulatory factors NOS3 protein（P<0.01）， and alleviated cochlear pathological damage［hematoxylin eosin （HE） score： from 4 to 2］. ConclusionThis compound recipe synergistically regulates the TNF/NF-κB inflammatory pathway and ACE/NOS3 vascular homeostasis pathway through flavonoids， triterpenoids， and other components， thereby inhibiting endolymphatic hydrops and cochlear damage. It provides a scientific basis for the theory of "simultaneous treatment of phlegm and blood stasis" in traditional Chinese medicine.

Large bone defects in load-bearing bone can result from tumor resection, osteomyelitis, trauma, and other factors. Although bone has the intrinsic potential to self-repair and regenerate, the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge. Traditionally, repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites, and autogenous bone grafting remains the "gold standard" treatment. However, the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone, donor-site morbidities, and the risk of rejection. In recent years, the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes. In addition to osteoconductivity and osteoinductivity, optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects, but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength. A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements. In this review, the use of traditional bone grafts in load-bearing bone defects, as well as their advantages and disadvantages, is summarized and reviewed. Furthermore, we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance, structural, and functional bionics to provide ideas and directions for future research.
Humans ; Bone Transplantation/methods* ; Weight-Bearing ; Bone Regeneration ; Bone Substitutes ; Bone and Bones ; Animals ; Tissue Scaffolds

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI radiomics and signal intensity in hepatobiliary phase(HBP)in predicting the pathological differentiation degree of hep-atocellular carcinoma(HCC).Methods The clinical and imaging data of 224 patients pathologically confirmed with HCC were col-lected.All patients were randomly divided into test group(68 cases)and training group(156 cases)at a ratio of 7︰3.The ITK-SNAP software was used to delineate region of interest(ROI)on arterial phase(AP),portal venous phase(PVP)and HBP,the radiomics features of the tumor tissues were extracted and the radiomics models were established using the FAE software.Logistic regression analysis was used to determine the clinical independent predictors associated with the pathological differentiation degree of HCC and to construct clinical model and clinical-radiomics model.Receiver operating characteristic(ROC)curve was plotted for each model and the area under the curve(AUC)was calculated to compare the diagnostic efficacy of the models.Results Age,alpha-fetoprotein(AFP),and r-glutamyltransferase(r-GT)were independent risk factors for predicting the degree of pathological differentiation of HCC.The AUC of the clinical-radiomics model in the training group and test group were 0.825 and 0.779,respectively,which were higher than those of the radiomics model(0.812 and 0.771)and the clinical model(0.687 and 0.666).Conclusion Gd-EOB-DTPA enhanced MRI radiomics have certain value in predicting the degree of pathological differentiation of HCC,while the predictive value of the signal intensity on HBP and the signal intensity ratio(SIR)on HBP is limited.

OBJECTIVE To explore the optimal parameters of simmered Rhei Radix et Rhizoma and the correlation between the chroma values and the intrinsic composition of simmered Rhei Radix et Rhizoma decoction pieces powder.METHODS The single-factor-response surface method was used to investigate the simmering temperature,simmering time,paper dosage and plant ash dos-age,the response surface experiment was carried out on the basis of the single factor experiment,the appearance traits,total anthraqui-nones,free anthraquinones,leachables,sennoside A and B contents were taken as indicators,the analytic hierarchy process(AHP)was used to give weights to each index,and the process was optimized.The chroma values of raw and simmered products were deter-mined by electronic eye,the correlation and regression analysis were carried out by SPSS22.0 software,and the chroma-component re-gression equation was constructed.RESULTS The optimal process of simmering Rhei Radix et Rhizoma was 140 ℃,5 times of plant ash,2 layers of wet paper wrapped and being simmered for 2.5 h.CONCLUSION The simmering process of Rhei Radix et Rhizoma optimized by AHP combined with response surface method is reasonable and feasible,the color of decoction pieces has a significant correlation with the component content,and the regression equation constructed is reliable,which can predict the intrinsic component content of decoction pieces through chroma values.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To investigate the safety of intravascular lithotripsy(IVL)and coronary rotational atherectomy(RA)in the management of coronary artery calcification(CAC).Methods In this retrospective,matched-pair cohort study,210 patients with severe CAC treated at Zhongshan Hospital,Fudan University between December 2021 and April 2025 were enrolled.The cohort was equally divided into two interventional groups:IVL group(n=105)and RA group(n=105),based on the revascularization strategy employed.Procedure parameters,postoperative biochemical markers of myocardial injury,and incidence of in-hospital major adverse cardiovascular events(MACE)were compared between the two groups.Results Before propensity score matching(PSM),statistically significant differences were observed in terms of the proportions of the left anterior descending artery(77.1％vs.63.8％,P=0.034),the right coronary artery(14.3％vs.30.5％,P=0.005),and the percentage of target vessel stenosis[85％(80％,90％)vs.80％(80％,90％),P=0.014]between the IVL and RA groups.After PSM,these differences became insignificant(all P＞0.05).There is no statistically significant differences in stent implantation rate,drug-coated balloon usage rate,stent diameter,or total stent length between the IVL and RA groups(all P＞0.05).Compared to the RA group,although the IVL group had a higher utilization of tirofiban after the procedure,and a lower rate of intravenous nitrate during the procedure,these differences were not statistically significant(all P＞0.05).cTnT levels increased significantly after the procedure in both the IVL and RA groups(all P＜0.001).Before PSM,the preoperative cTnT levels were comparable between the IVL and RA groups(P=0.525),while a statistically significant difference emerged postoperatively(P=0.038).The incidence of in-hospital myocardial infarction showed no significant intergroup difference(8.6％vs.16.2％,P=0.094),and no events of death or target vessel revascularization occurred in either group.After PSM,despite no significant difference in preoperative cTnT levels between the IVL and RA groups(P=0.235),a significant difference was observed postoperatively(P=0.014).Furthermore,while no deaths or target vessel revascularization occurred in either group,the IVL group demonstrated a significantly lower incidence of in-hospital myocardial infarction compared to the RA group(9.9％vs.23.9％,P=0.025).Conclusions The use of intravascular lithotripsy for the pretreatment in patients with severe CAC is safe and promising.

Sweat pores function is the ascending and descending of Qi. The human body maintains a continuous, holistic, and dynamic balance through the functioning of sweat pores as well as the Qi movement and transformation in the spleen, stomach, and triple energizer. Sweat pores play a crucial role in the generation and development of Zang-fu organs, essence and spirit, and body and orifices, as well as in the onset and progression of diseases. Oxidative stress significantly affects the regulation of inflammation in allergic rhinitis(AR), induces the pathological damage to nasal epithelial cells, and alters immune activity, serving as a key mechanism exacerbating AR symptoms. This mechanism closely aligns with the pathogenesis associated with dysfunction in the sweat pore-Qi-triple energizer system. In recent years, oxidative stress and antioxidants in AR have received increasing attention. Elevated levels of reactive oxygen species, fractional exhaled nitric oxide, and malondialdehyde have become key indicators for the early diagnosis of AR. Classical prescriptions, empirical prescriptions, and newly developed preparations of traditional Chinese medicine(TCM) for external use with anti-inflammatory, anti-allergic, and immune-regulatory effects via antioxidant pathways have demonstrated definite efficacy in treating AR. This provides a basis for understanding the pathogenesis of AR in TCM from a modern medical perspective. Therefore, this paper systematically examines the relationship between the sweat pore-Qi-triple energizer system and AR, incorporating the oxidative stress mechanism into the research on pathogenesis of the disorders. Furthermore, methods for treating AR in children are proposed with TCM preparations for external use which aimed at opening nasal sweat pores, dispersing, searching, channeling with aroma, warming, and dredging, regulating Qi movement in spleen, warming Yang Qi to promote urination, and clearing latent wind to inhibit liver depression.
Humans ; Oxidative Stress/drug effects* ; Rhinitis, Allergic/metabolism* ; Child ; Qi ; Sweat/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Medicine, Chinese Traditional