ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Objective To explore the expression of coagulation indexes in rheumatoid arthritis (RA) and dry syndrome (pSS) and their relationships with inflammation and immune function. Methods A total of 61 patients with RA who were hospitalized in the Department of Rheumatology of Anhui Provincial Hospital of Traditional Chinese Medicine from March 12 to September 9, 2024 were selected as the RA group. And 61 patients with pSS who were hospitalized in the Department of Rheumatology of the same hospital September 4, 2023, to August 17, 2024, were selected as the pSS group. 61 healthy individuals who underwent routine medical checkups at the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine during the same period were included as the control group. Baseline clinical indexes before treatment were collected from patients in each group, including prothrombin time(PT), international normalized ratio(INR), thrombia time(TT), fibrinogen(FBG), activated partial thromboplastin time(APTT), fibrin (ogen) degradation products(FDP) and D-Dimer(D-D). Results The expression levels of PT, FBG, TT, FDP, and D-D in the RA group, the pSS group, and the normal group were significantly different. The expression levels of PT, FBG, FDP, and D-D in the RA group were all higher than those in the pSS group and the control group, respectively. And the expression level of TT in the pSS group was lower than that in control group. ROC curve analysis showed that the AUC of PT was 0.638, the AUC of FBG was 0.899, the AUC of FDP was 0.866, and the AUC of D-D was 0.919 in the RA group compared with the normal group. And the AUC of coagulation indexes for joint diagnosis of RA was higher than that of the indexes detected individually. pSS group had an AUC of PT of 0.618 compared with that of the normal group. The AUC of TT was 0.645, and the AUC of coagulation indexes for the joint diagnosis of pSS was higher than the AUC of each index detected separately. Association rule analysis showed that elevated D-D in RA patients had a significant correlation with elevated hs-CRP, CCP and RF, and elevated FBG had a significant correlation with elevated hs-CRP, ESR, RF and CCP. Elevated D-D in pSS patients had a correlation with elevated hs-CRP and anti-SSA, and elevated INR has correlation with elevated hs-CRP, anti-SSA and anti-SSB. Correlation analysis showed that PT, INR, FBG, FDP, and D-D were positively correlated with CRP and ESR, and TT was negatively correlated with CRP and ESR in the RA group. FBG, FDP, and D-D were positively correlated with CRP and ESR in the pSS group. Moreover, coagulation indexes were positively correlated with immune indexes in RA group and pSS group which were all significant. The results of multiple linear regression analysis showed that FBG was a positive correlate of hs-CRP and ESR in RA patients. For PSS patients, FBG and FDP were positive correlates of hs-CRP. APTT and FBG were positive correlates of ESR. Conclusion Compared with pSS, coagulation indexes (especially PT, FBG, FDP and D-D) are more informative for the early diagnosis of RA and the judgment of the degree of the disease, and can be used as an important predictor for the confirmation of the diagnosis of RA.
Humans ; Female ; Male ; Arthritis, Rheumatoid/diagnosis* ; Middle Aged ; Fibrin Fibrinogen Degradation Products/analysis* ; Blood Coagulation ; Adult ; Fibrinogen/metabolism* ; Partial Thromboplastin Time ; Prothrombin Time ; Aged ; Inflammation/immunology* ; ROC Curve

Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis（CLNM） in patients with laryngeal squamous cell carcinoma（LSCC）, and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein（CRP）, fibrinogen, neutrophil-to-lymphocyte ratio（NLR）, platelet-to-lymphocyte ratio（PLR）, systemic immune-inflammation index（SII）, systemic inflammation response index（SIRI）, and prognostic inflammatory index（PIV） between the CLNM-positive and CLNM-negative groups（P<0.05）. Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width（RDW） -coefficient of variation（RDW-CV）, CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio（LMR） were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients（P<0.05）. A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837（95%CI 0.766-0.908） in the training cohort and 0.809（95%CI 0.698-0.920） in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans ; Nomograms ; Laryngeal Neoplasms/blood* ; Retrospective Studies ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/blood* ; Lymph Nodes/pathology* ; Male ; Female ; Middle Aged ; Neck ; C-Reactive Protein ; Aged ; Logistic Models ; Neutrophils ; Prognosis

Objective To explore the value of Turbo-Flash mode CT scanning for displaying calcification of ligamentum arteriousum(CLA)in infants and young children.Methods Chest CT data obtained with Turbo-Flash mode scanning of 1 762 infants and young children(aged 1 to 36 months)with suspected lung,trachea or bronchi lesions were retrospectively analyzed.Children were divided into group A to L according to age at 3-month intervals.CLA was evaluated and its CT manifestations were analyzed.The incidence of CLA in each group was counted,the density of CLA was measured,and their correlations with age were observed.Results Among 1 762 children,912 was found with CLA(912/1 762,51.76%).The incidence of CLA in group A—L was 34.29%(12/35)—59.35%(92/155),respectively.All CLA located in the arterial ligaments between the left side of pulmonary trunk and the origin level of left subclavian artery of the aorta and shaped differently.The density of CLA in group A—L was(183.36±50.16)—(295.80±105.91)HU,respectively.The incidence of CLA in group A—F was positively(r=0.945,P=0.002),while in group F—L was negatively correlated with age(r=-0.765,P=0.045).Meanwhile,the density of CLA in group A—F was positively correlated with age(r=0.775,P=0.020),but no significant correlation between CLA density and age was found in G—L group(P=0.593).Conclusion Turbo-Flash mode CT scanning had high clinical application value for displaying CLA in infants and young children.

Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)％,(18.57±1.63)％,(9.61±1.04)％,and(15.43±1.38)％,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P＜0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P＜0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.

Objective:To construct a risk classification model for adverse events of medical consumables,so as to achieve automatic evaluation for risk level of such events,and enhance the capability for risk management of adverse events of medical consumables,and ensure the safety of medical apparatuses.Methods:The data of adverse events of medical consumables of 370 cases of 148 types that were reported by Shandong Provincial Third Hospital from 2020 to 2023 were selected,and they were divided into high-risk and low-risk types.Eight key factors of them,which included the number of cases,injury level,type of registration certificate,with source and without source,high-value and low-value,domestic and imports,product classification,and risk levels,were counted to form a dataset.K-nearest neighbor(KNN),support vector machine(SVM)and decision tree algorithms in machine learning were used to construct a risk classification model for adverse events of medical consumables.The data of 12 adverse events of medical consumables of 5 types of our hospital,which were newly reported in 2024,were integrated for their parameters.Then,the accuracy rate and prediction performance of the model were further analyzed.Results:By comparing the KNN,SVM and decision tree algorithm models,the effect of SVM algorithm model was better,and its accuracy rate was 90.54%,and its area under curve(AUC)value of the receiver operating characteristic(ROC)curve was 0.944,and its Kolmogorov-Smirnov(KS)test value was 0.808.The model had favorable predictive performance.The results,that invoked SVM algorithm model to conduct verification of actual prediction for 12 adverse events of medical consumables of 5 types,indicated it was same between predictive outcomes and risk levels of manual evaluation.Conclusion:The risk classification model of adverse events of medical consumables has established an operational model for assessing the risk level of such events,which can assist monitoring personnel for adverse event of medical apparatuses to quickly and accurately find risk signals of adverse events of medical consumables,and improve the monitoring capability of them for these adverse events.

Objective:To investigate the X-chromosome inactivation (XCI) patterns and origin in four children with Rett syndrome (RTT), and to explore the genetic basis of their phenotypic variability.Methods:Four pediatric RTT cases diagnosed at Northwest Women′s and Children′s Hospital between August 1, 2022 and October 31, 2024 were enrolled. Clinical data were collected, and whole exome sequencing (WES) and Sanger sequencing were performed on the children and their parents to identify pathogenic variants. XCI analysis and linkage studies were conducted to determine the origin of variants and assess skewed XCI. This study was approved by the Medical Ethics Committee of the Northwest Women′s and Children′s Hospital (Ethics No. 21-036).Results:① WES and Sanger sequencing revealed that the four children carried the following MECP2 (NM_001110792.2) variants: c. 916C>T (p.Arg306Cys), c. 842delG (p.G281Afs*20), c. 763C>T (p.R255X), and c. 686C>T (p.Pro229Leu). The c. 916C>T variant was maternally inherited, while the other three were de novo. ② All four variants have been previously reported. c. 916C>T, c. 842delG, and c. 763C>T were classified as pathogenic, whereas c. 686C>T was deemed likely pathogenic. ③ XCI analysis demonstrated skewed inactivation in child 2 and 3 and their mothers, with maternal X-chromosome recombination during gametogenesis observed in child 3. All variants were located on the maternal X chromosome. Conclusion:Skewed XCI is a common pathogenic mechanism in MECP2-related RTT, and MECP2 variants may exhibit a maternal origin bias. Clinical evaluation should incorporate XCI status for comprehensive genetic analysis.

OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.