ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Objective To investigate the expression of small nuclear ribonucleoprotein D1 (SNRPD1) in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1. Methods The UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway. Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer (P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue (P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen (P<0.001),carbohydrate antigen 19-9 (P<0.001),G stage (P=0.042),T stage (P=0.002),and N stage (P=0.027) in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer (P<0.001),and it was an independent risk factor for the death of gastric cancer patients (P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed that SNRPD1 was involved in the regulation of the cell cycle.The results of CCK-8 and colony formation assays showed that up-regulation of SNRPD1 promoted the proliferation of gastric cancer cells (P<0.001,P<0.001).The up-regulation of SNRPD1 up-regulated the expression of cyclin-dependent kinase 6 and G₁/S-specific cyclin-D1 (P<0.001,P=0.002),whereas the interference in SNRPD1 led to opposite results (P=0.004,P<0.001).SNRPD1 accelerated the G₁/S phase transition of gastric cancer cells (P<0.001).The overexpression of SNRPD1 promoted the expression of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in gastric cancer cells (P=0.043,P<0.001),whereas disruption of SNRPD1 inhibited their expression (both P<0.001).Insulin-like growth factor 1,an agonist of the PI3K/Akt signaling pathway,promoted the proliferation of gastric cancer cells with SNRPD1 disturbed (P=0.002). Conclusion High expression of SNRPD1 in the gastric cancer tissues is associated with poor prognosis,and it may promote tumor cell proliferation and regulate the cell cycle by activating the PI3K/Akt signaling pathway.
Humans ; Stomach Neoplasms/pathology* ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Retrospective Studies ; Cell Cycle ; Male ; Female

Objective To investigate the role and mechanism of afzelin(AFZ)in treating Crohn's disease-like colitis.Methods A mouse model of 2,4,6-trinitrobenzene sulfonic acid-induced colitis was established to assess the effect of AFZ on experimental colitis in vivo.A Caco-2 cell model of tumor necrosis factor(TNF)-α-induced inflammation was established to evaluate the effects of AFZ on the intestinal barrier function,intestinal epithelial cell apoptosis,and mitochondrial function in vitro.The animal and cell experiments were performed to validate the regulatory role of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulater 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator(PGC)-1α pathway in the treatment of colitis with AFZ.Results AFZ reduced the disease activity index(P=0.003),weight loss(P<0.001),colon shortening(P<0.001),inflammation score(P=0.002),pro-inflammatory cytokine release(interleukin-6:P<0.001;TNF-α:P=0.010),and intestinal barrier permeability(fluorescein isothiocyanate dextran 4:P<0.001;intestinal-type fatty acid-binding protein:P=0.013).Meanwhile,AFZ increased the colonic transepithelial electric resistance(P=0.001),reduced bacterial translocation(P<0.001),and promoted the localization and up-regulated the expression of tight junction proteins [zonula occluden-1(P=0.005) and Claudin-1(P=0.024)].AFZ exerted a protective effect on the Caco-2 cells exposed to TNF-α in terms of intestinal epithelial cell permeability(P=0.017),transepithelial electric resistance(P=0.014),and tight junction protein[zonula occluden-1(P=0.014) and Claudin-1(P=0.006)] localization and expression.Furthermore,the cell and animal experiments confirmed that AFZ reduced the percentage of apoptosis(P<0.001,P=0.013)and the expression of cleaved-caspase 3(P=0.028,P=0.004)and Bax(P=0.004,P=0.020),and upregulated the Bcl2(P=0.020,P=0.006)level in intestinal epithelial cells.Additionally,AFZ increased the number of mitochondria,mitochondrial membrane potential,and copy number of mitochondrial DNA(P=0.007)in intestinal epithelial cells,while enhancing the activities of mitochondrial respiratory chain complex Ⅰ(P=0.005)and complex Ⅳ(P=0.001).The activation of the AMPK/SIRT1/PGC-1α pathway was involved in the protective effects of AFZ on mitochondrial function and apoptosis in intestinal epithelial cells.Conclusion AFZ alleviates mitochondrial dysfunction and apoptosis in intestinal epithelial cells by activating the AMPK/SIRT1/PGC-1α pathway,thereby ameliorating intestinal barrier dysfunction and experimental colitis.
Animals ; Colitis/drug therapy* ; Humans ; Caco-2 Cells ; Mice ; Trinitrobenzenesulfonic Acid ; Apoptosis/drug effects* ; Disease Models, Animal ; AMP-Activated Protein Kinases/metabolism* ; Sirtuin 1/metabolism*

OBJECTIVES: To study the risk factors for hypoxemia in children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A retrospective collection of clinical data from children diagnosed with SMPP at the Third Affiliated Hospital of Zhengzhou University from June to December 2023 was conducted. The patients were categorized into hypoxemia and non-hypoxemia groups. Logistic regression analysis was used to assess the risk factors for hypoxemia, and receiver operating characteristic (ROC) curve analysis was employed to analyze the diagnostic performance of various indicators. RESULTS: A total of 113 children with SMPP were included. Univariate logistic regression analysis showed that ferritin, aspartate aminotransferase, creatinine, creatine kinase isoenzyme, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, immunoglobulin G, complement C3, complement C4, age, extrapulmonary complications, and a chest computed tomography (CT) scan showing a bronchiolitis pattern were significant factors for hypoxemia in children with SMPP (P<0.05). Multivariate logistic regression analysis revealed that elevated ferritin levels, presence of extrapulmonary complications, and a bronchiolitis pattern on lung CT were independent risk factors for hypoxemia in these patients (P<0.05). The ROC curve analysis indicated that the combination of these three indicators for predicting hypoxemia had a sensitivity of 71.9%, a specificity of 95.1%, and an area under the curve of 0.888 (95%CI: 0.809-0.968). CONCLUSIONS In children with SMPP, when there are elevated ferritin levels, a bronchiolitis pattern on chest CT, and the presence of extrapulmonary complications, there should be a high level of vigilance for the potential development of hypoxemia.
Humans ; Pneumonia, Mycoplasma/complications* ; Male ; Female ; Risk Factors ; Child, Preschool ; Hypoxia/etiology* ; Retrospective Studies ; Child ; Logistic Models ; Infant ; ROC Curve ; Adolescent

OBJECTIVES: To investigate the underlying causes and clinical manifestations in infants undergoing colonoscopy, and to analyze changes in disease spectrum. METHODS: Clinical data from 180 infants who underwent a total of 184 colonoscopies at the Department of Gastroenterology, Children's Hospital Affiliated to Shandong University from January 2015 to December 2024 were retrospectively analyzed. Patients were grouped by age: ≤6 months (n=41) and >6-12 months (n=139); and by examination period: 2015-2019 (n=83) and 2020-2024 (n=97). Primary causes for performing colonoscopy, final diagnoses, and disease spectrum evolution were assessed. RESULTS: Among 184 colonoscopies, the leading causes prompting examination were hematochezia (37.8%, 68/180), diarrhea (36.7%, 66/180), and co-occurring hematochezia and diarrhea (21.1%, 38/180). Causes for performing colonoscopy differed significantly by age group (P<0.05). Colonic polyps were only detected in the >6-12 months group (P<0.05). Compared to the 2015-2019 group, the 2020-2024 group had fewer food allergy-related gastrointestinal diseases (P<0.05) but more colitis (P<0.05). CONCLUSIONS Colonoscopy is essential for diagnosing infantile digestive disorders, with disease spectra varying by age and time period.
Humans ; Infant ; Colonoscopy ; Male ; Female ; Retrospective Studies ; Infant, Newborn ; Diarrhea/etiology* ; Gastrointestinal Hemorrhage/etiology*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.