Objective: To investigate the effect of intraarticular hemorrhage on extending knee joint contracture model in rats . Methods: 18 mature male SD rats were divided into 3 groups by random number table method . The control group ( group C) was not immobilized and was killed after 4 weeks of feeding . In the simple fixation group( M1 group) , the left lower limb knee joint was immobilized in straight position for 4 weeks . The blood fixationgroup (M2 group) was injected into the knee cavity with body blood and immobilized in a straight position for 4 weeks . The knee joint motion of each group was measured by the joint motion measuring instrument under a stand⁃ard torque . The contracture degree was calculated by the joint range of motion of the knee joint before and after muscles separation . HE staining and Masson staining were used to detect the number of cells and collagen deposi⁃tion in the anterior joint capsule . The protein expressions of transforming growth factor 1 (TGF⁃ β1) , wingless⁃type MMTV integration site family , member 1 ( Wnt1) and beta⁃catenin ( β⁃catenin) in the anterior articular capsule were detected by Western blotting . Results: Compared with group C , total knee contracture and arthrogenic con⁃tracture of rats in M1 and M2 groups increased , and the difference was statistically significant (P < 0. 05) . At the same time , the degree of total contracture and arthrogenic contracture in M2 group was higher than that in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the number of anterior joint capsule cells and collagen deposition in M1 and M2 groups increased , and the difference was statistically sig⁃group were higher than those in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the protein expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of rats in M1 expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of the knee joint in M2 group were sig⁃nificantly higher than those in M1 group , with statistical significance (P < 0. 05) . Conclusion Joint immobiliza⁃ tion can lead to joint contracture , and joint bleeding aggravates the degree of joint capsule fibrosis induced by im⁃mobilization .

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

OBJECTIVE To conduct qualitative analysis of chemical constituents in the crude extract of Modified Ermiao Formu-la,along with its blood-absorbed components and metabolites in rats post-administration employing ultra-performance liquid chroma-tography coupled with quadrupole-exactive orbitrap tandem mass spectrometry(UPLC-Q-Exactive Orbitrap-MS/MS).METHODS Separation was performed on a Waters HSS T3 column(100 mm×2.1 mm,1.8 μm)using gradient elution with 0.1%formic acid in water(mobile phase A)and 0.1%formic acid in acetonitrile(mobile phase B),under controlled conditions:column temperature maintained at 40℃,flow rate set to 0.3 mL·min-1,and injection volume fixed at 2 μL.Mass spectrometric data acquisition utilized an electrospray ionization(ESI)source with scanning in both positive and negative ion modes.RESULTS By analyzing precise mo-lecular weights,retention times,and MS/MS fragmentation patterns,and cross-referencing these against established databases and published literature,173 chemical constituents were definitively identified in the Modified Ermiao Formula crude extract.These prima-rily comprised flavonoids,organic acids,and alkaloids.Additionally,32 prototype components and 13 metabolites were characterized in the serum of dosed rats.Organic acids constituted the predominant class of serum prototype components,undergoing in vivo metabo-lism principally through demethylation and carboxyl glucuronidation.CONCLUSION This study provides the initial delineation of blood-absorbed prototype components derived from Modified Ermiao Formula,with concomitant identification of their metabolites,thereby establishing a foundational framework for elucidating the pharmacologically active constituents of this formula.

Objectives:To explore the correlation between preoperative frailty and postoperative pulmonary complications in elderly patients undergoing cardiac surgery,and to provide a scientific basis for the comprehensive perioperative management of these patients.Methods:In this prospective cohort study,elderly patients(≥60 years old)who were scheduled to undergo coronary artery bypass grafting(CABG)and/or heart valve surgery at Fuwai Hospital,Chinese Academy of Medical Sciences from December 2022 to December 2023 were consecutively enrolled.Patients were divided into the postoperative pulmonary complication group and the non-postoperative pulmonary complication group based on whether they developed postoperative pulmonary complications.Demographic data,preoperative frailty status,physical function indicators(6-meter walking speed,pulmonary function),laboratory test indicators,and surgical data of the two groups were collected and compared.Multivariate logistic regression analysis was used to evaluate the correlation between preoperative frailty and postoperative pulmonary complications in these patients.Results:A total of 522 patients were included in the study,66(12.6%)had preoperative frailty.There were 159 cases(30.5%)in the postoperative pulmonary complication group and 363 cases(69.5%)in the non-postoperative pulmonary complication group.Compared with the non-postoperative pulmonary complication group,the postoperative pulmonary complication group had a higher prevalence of preoperative frailty,cerebral infarction,and pulmonary hypertension,lower maximal inspiratory pressure,slower 6-meter walking speed,a higher proportion of patients undergoing heart valve surgery and CABG+heart valve surgery,and significantly longer mechanical ventilation time,intensive care unit stay,and postoperative hospital stay(all P<0.05).Multivariate logistic regression analysis showed that preoperative frailty(OR=1.998,95%CI:1.005-3.973,P=0.048),maximal inspiratory pressure(OR=0.987,95%CI:0.977-0.997,P=0.011),6-meter walking speed(OR=0.003,95%CI:0.001-0.017,P<0.001),mechanical ventilation time(OR=2.295,95%CI:1.601-3.290,P<0.001),and CABG+heart valve surgery(OR=1.772,95%CI:1.294-2.428,P<0.001)were independent risk factors of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.Conclusions:Preoperative frailty increases the risk of postoperative pulmonary complications in elderly patients undergoing cardiac surgery.

Objective To determine the basic and clinical issues to be included in the Guidelines for the Prevention and Treatment of Adenomyosis based on the Delphi method.Methods Based on literature review,preliminary general research,and expert interviews,this study drafted a survey questionnaire for guideline questions.After selecting the expert group,two rounds of Delphi method were conducted to determine the basic and clinical issues included in the guidelines.The questionnaire results were statistically analyzed to evaluate the quality control of Delphi method.Results A total of 15 experts were selected to participate in two rounds of Delphi questionnaire surveys.Finally,39 basic and clinical questions were included,which were condensed into 8 guideline questions.The expert positivity coefficient was 100%,the average coefficient of variation of the two rounds of coordination was 0.23 and 0.30,respectively,and the expert authority coefficient was 0.903.The quality control of the two rounds of Delphi method was good.Conclusion Based on the Delphi method,the basic and clinical issues of the Guidelines for the Prevention and Treatment of Adenomyosis are determined,laying the foundation for the subsequent development of the guidelines.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

Objective To identify the basic and clinical questions of the Guidelines for Preventive Treatment of Diseases in Endometriosis based on the Delphi method.Methods Based on the preliminary literature review,preliminary pan-research and expert interviews,the questions of the Guidelines for Preventive Treatment of Diseasesin in Endometriosis were drafted.Totally 15 experts were selected for two rounds of Delphi method expert correspondence and the results were statistically analyzed to finalize the questions for inclusion in the guidelines.Results A total of 65 entries were finally identified for inclusion in the guideline questions and condensed into 8 guideline questions.The quality control of the two rounds of Delphi method was good.The positive coefficient of experts in both rounds was 100%.The coefficient of authority of experts was>0.70.In the degree of Delphi coordination,the mean coefficients of variation were 0.23 and 0.26,and the coefficients of Kendall's concordance were 0.510 and 0.309,respectively(P<0.05).Conclusion This study uses two rounds of Delphi method to determine the issues included in the Guidelines for Preventive Treatment of Diseases in in Endometriosis,laying a solid foundation for the subsequent development of the guidelines.

Antibody-drug conjugates(ADCs)represent a major breakthrough in the treatment of human epidermal growth factor receptor-2(HER-2)-positive breast cancer as they are responsible for significantly improving clinical outcomes.However,their widespread use is accom-panied by severe adverse effects that not only impact the quality of life of patients and treatment adherence but also life-threatening,ulti-mately leading to treatment discontinuation.This article systematically reviews the underlying mechanisms and management strategies for ADC-related toxicities in HER-2-positive breast cancer.Additionally,it focuses on key adverse events,including thrombocytopenia,interstitial lung disease,and cardiotoxicity,that are induced by ADCs such as trastuzumab emtansine(T-DM1)and trastuzumab deruxtecan(T-DXd).Based on the clinical evidence,we proposed early monitoring and standardized intervention measures,emphasizing the importance of timely recognition and systematic management to mitigate risks.Furthermore,we explored future directions for optimizing ADC design to reduce their toxicity and provide valuable insights into their safe clinical application.