ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Objective To prepare an advanced irrigation device equipped with a specialized nozzle designed to access the pericoronal blind sac of impacted wisdom teeth,and evaluate its efficacy in plaque removal.Methods 3D-printer was utilized to develop pericoronal models simulating mandibular wisdom teeth with high vertical impaction and varying soft tissue coverage(0%,25%,50%,and 75%,respectively)and personalized pericoronal irrigator.The obtained pericoronal models were randomly divided into 3 groups,treated with personalized precision pericoronal flushing,routine flushing and brushing,respectively,and,under a pressures of 45 psi or 75 psi(1 psi=6 894.76 Pa),were performed to clean the test surfaces of plaque-biofilm-obstructed wisdom teeth,respectively.Images of the tooth surfaces were analyzed before and after cleaning,and the cleaning rate was calculated using Python software.Results For wisdom teeth with 50%and 75%pericoronal soft tissue coverage,at a pressure of 45 psi,the precision pericoronal flushing group demonstrated significantly higher cleaning rate when compared to the brushing and routine flushing groups(P<0.05).At 0%and 25%pericoronal soft tissue coverage,the precision pericoronal flushing and brushing groups exhibited significantly higher cleaning rates than the routine flushing group(P<0.05).Furthermore,at 75 psi,the precision pericoronal flushing group achieved a significantly higher cleaning rate across all 4 levels of pericoronal soft tissue coverage than both the routine flushing and brushing groups(P<0.05).Notably,the precision pericoronal flushing group at 75 psi obtained significantly higher cleaning rate than at 45 psi across 0%,25%,and 50%pericoronal soft tissue coverage(P<0.05).Conclusion The precision pericoronal irrigation device demonstrates significantly superior cleaning efficacy for vertically impacted mandibular third molars compared to conventional irrigation devices and manual tooth brushing.It is an effective device for preventing and treating pericoronitis.

Objective To investigate the effect of gender on prognosis after transcatheter patent foramen ovale(PFO)closure in patients with cerebral infarction or transient ischemic attack.Methods A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack(TIA)who underwent PFO closure at our hospital between January 2013 and December 2023.The patients were grouped by gender,and related data were collected,including age,comorbidities,Risk of Paradoxical Embolism(RoPE)score,laboratory results,findings of transthoracic/transesophageal echocardiography(TTE/TEE),and post-procedural complications,such as device-related thrombosis(DRT),recurrent stroke,bleeding,and atrial fibrillation(AF).Results A total of 112 patients were enrolled,including 59 males and 53 females,at a mean age of 42.47±12.35 years.The females had significantly higher preoperative RoPE score than the males(6.6±1.4 vs 6.0±1.5,P=0.046),and a statistical difference was observed in the distribution of infarction sites between them(Chi-square=10.25,P=0.006),indicating that the males were prone to posterior circulation infarction.Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females(9.3±2.4 mm vs 7.6±2.0 mm,P<0.001).During a median follow-up of 4 years,the male group had 1 case of myocardial infarction,1 cerebral hemorrhage,1 paroxysmal AF,2 gingival bleeding episodes,and 1 skin ecchymosis.In the female group,1 case experienced pulmonary embolism,1 paroxysmal atrial fibrillation,3 gingival bleeding episodes,2 skin ecchymoses,2 recurrent cerebral infarctions,and 2 recurrent TIAs.There was no statistical difference in overall adverse events between gender(P=0.291).Although the females had higher rates of recurrent cerebral infarction and TIA,this difference lacked statistical significance(P=0.222).Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors,such as RoPE score,age,hypertension,coronary heart disease,and other factors,gender was not an independent predictor of composite endpoint events after surgery.Conclusion Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA.However,females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaneous embedding combined with repetitive transcranial magnetic stimulation(rTMS)in the treatment of post-stroke dysphagia.Methods A total of 120 cases of patients with post-stroke dysphagia admitted to the 908th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China from February 2022 to February 2024 were randomly divided into the observation group and the control group according to random number table method,with 60 cases in each group.Both groups of patients were given conventional symptomatic supportive treatment,such as trophic nerve,improving circulation,etc.,and the control group was given high-frequency rTMS treatment,while the observation group was treated with thumb-tack needling for subcutaneous embedding therapy on the basis of the treatment in the control group.The course of treatment covered four weeks continuously.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in scores of traditional Chinese medicine(TCM)syndrome,Functional Oral Intake Scale(FOIS)and Standardized Swallowing Assessment(SSA),as well as levels of serum total protein(TP),serum albumin(ALB),and hemoglobin(Hb)before and after treatment were observed in the patients of the two groups.The changes in swallowing wave amplitude and swallowing duration before and after treatment were compared between the two groups of patients.Results(1)During the study,there were none in the observation group and eight cases in the control group were failed to follow-up.Finally,64 cases in the observation group and 56 cases in the control group were included in the efficacy statistics.(2)The total effective rate was 92.19%(59/64)in the observation group and 76.79%(43/56)in the control group,and the efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(3)After treatment,the TCM syndrome scores of the patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with statistically significant differences(P<0.05).(4)After treatment,the FOIS score and SSA score of the patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the swallowing wave amplitude and swallowing duration of patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(6)After treatment,the TP,ALB and Hb levels of patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with statistically significant differences(P<0.05).Conclusion Thumb-tack needling for subcutaneous embedding combined with rTMS in the treatment of post-stroke dysphagia can significantly shorten the patients'swallowing duration and enlarge the swallowing wave amplitude,thus improving their swallowing function and improving their quality of life.

Objective: The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying. Methods: A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender. Results: The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01). Conclusions ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.