Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective:To evaluate lung ultrasound (LUS) for assessing lung aeration heterogeneity in neonatal respiratory distress syndrome (NRDS) across gestational ages and analyze its correlation with oxygenation.Methods:This retrospective cohort study enrolled 125 ventilated NRDS neonates from the neonatal intensive care unit of Hebei Children's Hospital (from March 2023 to May 2024), who were stratified as <32 gestational weeks ( n=47) and ≥32 gestational weeks ( n=78). All underwent LUS, chest X-ray, and blood gas analysis within 2 h of admission. The lung ultrasound score (LUSsc) quantified impaired lung volume percentage (graded: A=normal, B=coalescent B-lines, C=dense B-lines/focal consolidation, D=lobar consolidation). Aeration heterogeneity was measured by coefficient of variation (CV, within-patient) and Gini-Simpson index (between-patients), while oxygenation was assessed by arterial oxygen partial pressure/inhaled oxygen concentration (P/F). Group comparisons, including basic information, lung aeration, and lung aeration heterogeneity, used two independent sample t-tests, Mann-Whitney U tests, Chi square tests, or Wilcoxon tests; partial correlation analyzed aeration-oxygenation relationships. Results:(1) Analysis of impaired lung volume percentage revealed similar distribution patterns between groups, with the <32-week cohort ( n=47, 564 lung segments) showing proportions of 15.6% (88/564), 14.9% (84/564), 35.5% (200/564), and 34.0% (192/564) for graded patterns A through D, respectively, while the ≥32-week cohort ( n=78, 936 segments) demonstrated corresponding proportions of 15.7% (147/936), 16.3% (153/936), 31.7% (297/936), and 36.2% (339/936), with no statistically significant difference between groups ( Z=－0.24, P=0.812). (2) Within-patient heterogeneity analysis revealed no significant CV difference between <32-week group and ≥32-week group [0.33 (0.20-0.84) vs. 0.43 (0.21-0.73), Z=－0.99, P=0.321]. (3) Between-patient heterogeneity was significantly higher in the ≥32-week group, as reflected by the Gini-Simpson index [0.12 (0.09-0.14) vs. 0.09 (0.06-0.14), Z=－1.99, P=0.046], with heterogeneous aeration predominantly located in non-gravity-dependent regions—specifically the left upper lung in the <32-week group and anterior lungs in the ≥32-week group. (4) Correlation analyses demonstrated significantly inverse relationships between CV and LUSsc in <32-week and ≥32-week groups ( r=－0.912, P<0.001; r=－0.886, P<0.001), while the ≥32-week group additionally showed positive CV-P/F correlation ( r=0.373, P=0.001) and inverse LUSsc-P/F association ( r=－0.287, P=0.013). Conclusions:LUS effectively evaluates aeration and its heterogeneity in early NRDS. Infants ≥32 weeks exhibit greater between-patient heterogeneity, with ventilation parameters correlating significantly with oxygenation status.

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

Objective:To evaluate lung ultrasound (LUS) for assessing lung aeration heterogeneity in neonatal respiratory distress syndrome (NRDS) across gestational ages and analyze its correlation with oxygenation.Methods:This retrospective cohort study enrolled 125 ventilated NRDS neonates from the neonatal intensive care unit of Hebei Children's Hospital (from March 2023 to May 2024), who were stratified as <32 gestational weeks ( n=47) and ≥32 gestational weeks ( n=78). All underwent LUS, chest X-ray, and blood gas analysis within 2 h of admission. The lung ultrasound score (LUSsc) quantified impaired lung volume percentage (graded: A=normal, B=coalescent B-lines, C=dense B-lines/focal consolidation, D=lobar consolidation). Aeration heterogeneity was measured by coefficient of variation (CV, within-patient) and Gini-Simpson index (between-patients), while oxygenation was assessed by arterial oxygen partial pressure/inhaled oxygen concentration (P/F). Group comparisons, including basic information, lung aeration, and lung aeration heterogeneity, used two independent sample t-tests, Mann-Whitney U tests, Chi square tests, or Wilcoxon tests; partial correlation analyzed aeration-oxygenation relationships. Results:(1) Analysis of impaired lung volume percentage revealed similar distribution patterns between groups, with the <32-week cohort ( n=47, 564 lung segments) showing proportions of 15.6% (88/564), 14.9% (84/564), 35.5% (200/564), and 34.0% (192/564) for graded patterns A through D, respectively, while the ≥32-week cohort ( n=78, 936 segments) demonstrated corresponding proportions of 15.7% (147/936), 16.3% (153/936), 31.7% (297/936), and 36.2% (339/936), with no statistically significant difference between groups ( Z=－0.24, P=0.812). (2) Within-patient heterogeneity analysis revealed no significant CV difference between <32-week group and ≥32-week group [0.33 (0.20-0.84) vs. 0.43 (0.21-0.73), Z=－0.99, P=0.321]. (3) Between-patient heterogeneity was significantly higher in the ≥32-week group, as reflected by the Gini-Simpson index [0.12 (0.09-0.14) vs. 0.09 (0.06-0.14), Z=－1.99, P=0.046], with heterogeneous aeration predominantly located in non-gravity-dependent regions—specifically the left upper lung in the <32-week group and anterior lungs in the ≥32-week group. (4) Correlation analyses demonstrated significantly inverse relationships between CV and LUSsc in <32-week and ≥32-week groups ( r=－0.912, P<0.001; r=－0.886, P<0.001), while the ≥32-week group additionally showed positive CV-P/F correlation ( r=0.373, P=0.001) and inverse LUSsc-P/F association ( r=－0.287, P=0.013). Conclusions:LUS effectively evaluates aeration and its heterogeneity in early NRDS. Infants ≥32 weeks exhibit greater between-patient heterogeneity, with ventilation parameters correlating significantly with oxygenation status.

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.