Tricuspid regurgitation associated with cardiac implantable electronic devices (CIED) constitutes a significant subset of secondary tricuspid regurgitation, characterized by a multifactorial etiology involving pacing lead-mediated mechanical interference and CIED-related systemic factors. The pathogenesis of CIED-related tricuspid regurgitation encompasses direct mechanical trauma or functional disruption of the tricuspid valve apparatus by pacing leads, pacing mode-induced hemodynamic alterations, and clinical risk factors such as permanent atrial fibrillation, apical pacing, and high right ventricular pacing burden. The natural progression and clinical outcomes of CIED-related tricuspid regurgitation parallel those of tricuspid regurgitation stemming from other etiologies. Advanced imaging modalities, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, enable precise diagnosis and longitudinal assessment of CIED-related tricuspid regurgitation. Management strategies emphasize multidisciplinary collaboration as well as integration of preventive approaches-such as refined lead implantation techniques and tailored pacing modalities-with therapeutic interventions ranging from pharmacotherapy to surgical valve repair or replacement. This article reviews the current understanding of CIED-related tricuspid regurgitation to provide a reference for clinical practice and research.
Tricuspid Valve Insufficiency/diagnosis* ; Humans ; Defibrillators, Implantable/adverse effects* ; Pacemaker, Artificial/adverse effects*

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To analyze the influencing factors of chronic liver failure in patients with primary hepatic carcinoma(PHC)before intervention,and to establish and evaluate a nomogram risk prediction model.Methods A retrospective analysis was conducted by collecting general data and clinical test data within 24 hours of admission for PHC patients.Univariate analysis and Lasso regression were used for variable selection,followed by multivariate logistic regression analysis to identify independent influencing factors for CLF before PHC intervention,leading to the establishment of a nomogram risk prediction model.The model was evaluated using the Hosmer-Lemeshow test,receiver operating characteristic(ROC)curve,calibration curve,clinical decision curve,and clinical impact curve.Result A total of 353 cases of PHC patients were collected,including 153 cases in the liver failure group and 200 cases in the non-liver failure group,with a prevalence rate of 43.3％.Variables selected by Lasso regression included gastrointestinal bleeding,prothrombin time(PT),albumin(ALB),total bilirubin(TBIL),and gamma glutamyl transferase(GGT).Multivariate logistic regression analysis showed that gastrointestinal bleeding(OR=13.549,95％CI:2.899～63.322,P=0.001),PT(OR=1.599,95％CI:1.282～1.995,P＜0.001),TBIL(OR=1.016,95％CI:1.006～1.025,P=0.002),and GGT(OR=1.002,95％CI:1.000～1.003,P=0.028)were independent risk factors for chronic liver failure prior to PHC intervention,leading to the establishment of a nomogram risk prediction model.The Hosmer Lemeshow test showed that the model had a good fit(x2=6.152,P＞0.05);the area under ROC was 0.902(0.869-0.934),with a sensitivity of 80.4％and a specificity of 87.5％.The calibration curve indicated that the model predicts chronic liver failure prior to PHC intervention with good consistency.Clinical decision curve analysis and clinical impact curve analysis showed that the model has good clinical utility within a certain threshold range.Conclusion Gastrointestinal bleeding,PT ≥16.05s,TBIL≥37.80 mmol/L,and GGT≥ 99.00 U/L are independent risk factors for the occurrence of chronic liver failure before PHC intervention.The established nomogram risk prediction model has certain clinical application value in predicting the risk of chronic liver failure before PHC intervention.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Objective: To construct a prediction model for preterm birth risk among pregnant women, so as to provide the reference for screening high-risk population and preventing preterm birth. Methods: Pregnant women who received antenatal examination and delivered at the Women's Hospital, School of Medicine, Zhejiang University from January 1 to December 31, 2019 were selected as the study subjects, among them, 80% were included in the modeling group, and 20% were included in the validation group. Demographic and clinical information were collected. A multivariable logistic regression model was used to analyze the predictive factors of preterm birth risk in the modeling group, and a preterm birth risk prediction model was established based on the OR values of predictive factors. The model was validated with the data from the validation group. The Youden index was used to determine the critical score for predicting preterm birth risk. The prediction performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 15 197 pregnant women were surveyed, including 12 131 pregnant women in the observation group and 3 066 pregnant women in the validation group. There was no statistically significant difference in age, education level and gravidity between the two groups of pregnant women (all P<0.05). Multivariable logistic regression analysis identified the number of pregnancies, education level, place of residence, hypertension, diabetes, history of preterm birth, twin-pregnancy, placenta praevia, and gestational hypertension as risk prediction factors for preterm birth risk among pregnant women. The risk score system for preterm birth was established as follows: >2 pregnancies (2 points), high school education or below (4 points), college degree or above (-4 points), rural residence (5 points), hypertension (7 points), diabetes (11 points), history of preterm birth (11 points), twin-pregnancy (28 points), placenta previa (19 points), and gestational hypertension (12 points). The total score of the preterm birth risk scoring system ranged from -4 to 99 points. When the critical score was 8 points, the Youden index was the highest at 0.480, with an area under the ROC curve of 0.749 (95%CI: 0.732-0.767), a sensitivity of 0.610, and a specificity of 0.886, indicating good prediction performance of the model. Conclusion The preterm birth risk prediction model established in this study based on demographic and clinical characteristics of pregnant women can effectively predict the risk of preterm birth among pregnant women.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Objective:To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy.Methods:A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors.Results:The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR=18.00, 95% CI 1.56-207.45, P=0.020) and bone marrow suppression ( OR=18.00, 95% CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions:PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Objective:To observe the effect of electroacupuncture(EA)combined with repetitive transcranial magnetic stimulation(rTMS)on limb dysfunction in ischemic stroke patients. Methods:A total of 63 stroke patients were divided into an observation group and a control group using the random number table method.Thirty-one patients in the control group were treated with routine Western medicine combined with rTMS;32 patients in the observation group were treated with EA in addition to the intervention in the control group.The duration of treatment was 3 months.The National Institutes of Health stroke scale(NIHSS),the Fugl-Meyer assessment(FMA),the modified Barthel index(MBI),and the motor evoked potential(MEP)latency of transcranial magnetic stimulation were observed before and after treatment in both groups. Results:Two cases withdrew from the observation group and 1 case withdrew from the control group.After treatment,the NIHSS score in both groups was lower than that before treatment,the FMA and MBI scores were higher than those before treatment,and the latency period of MEP was shorter than that before treatment,and the differences were statistically significant(P<0.05).After treatment,the NIHSS,FMA,and MBI scores and MEP latency period of the observation group improved more than those of the control group,and the differences between the groups were statistically significant(P<0.05). Conclusion:EA combined with rTMS can improve the motor function of limbs in ischemic stroke patients and improve their self-care ability.The mechanism may be related to increasing the excitability of the motor cortex and improving the electrophysiological function of the central nervous system.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.