Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective: To explore the core features of trait aggression in children and adolescents, so as to provide a theoretical basis for behavioral interventions targeting the central psychological characteristics of aggression in children and adolescents. Methods: From March to May 2020, a simple random convenience sampling method was employed to recruit 39 165 students from grades 4 to 12 in Sichuan, Chongqing, Guizhou, and Shandong. Data were collected via online questionnaires, with all participants completing the Chinese Version of the Aggression Questionnaire. Psychometric network analysis was utilized for data processing. Results: Trait aggression among Chinese children and adolescents was at a moderately low level. The core nodes of the network structure included physical aggression [if someone intentionally causes trouble for me, I will hit them severely (AGG6); if someone hits me, I will retaliate (AGG11)] and self aggression [When I am very irritable, I think of hurting myself (AGG5); when I am in a bad mood, I engage in behaviors that harm my health, such as overeating (AGG25)]. Across grade levels, core nodes primarily originated from the anger dimension [When I m angry, I feel like a powder magazine that could explode at any moment (AGG13); I can t control my temper (AGG18); I am prone to getting angry when I see things that are not pleasing to the eye (AGG23); I will get angry for no reason (AGG27)]. Except for grades 7 and 9, core nodes in other grades included the verbal aggression dimension [I am prone to arguments with people (AGG22)]. Before grade 8, core nodes incorporated the self aggression dimension (AGG 5, AGG 25); after grade 8, core nodes included the physical aggression dimension [AGG 6, AGG 11, I fight slightly more than others (AGG16), and if people around me make things difficult for me to a certain extent, I will fight with them (AGG26)]. No statistically significant differences were found in the trait aggression network structures across grades, genders, or within gender comparisons of different grades. Conclusion These findings broaden our understanding of aggression in children and adolescents, suggesting that behavioral interventions can effectively reduce aggressive behaviors in this population.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To evaluate the long-term clinical efficacy and the influence on anal function of surgery combined with ustekinumab (UST) in active Crohn's disease (CD) patients with perianal fistula.Methods:A retrospective cohort study was conducted. Clinical data of active CD patients with perianal fistula undergoing surgery combined with UST at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from August 2020 to December 2022 were collected. The primary endpoints were clinical healing rate, Wexner score, and anorectal manometry values at week 52 of treatment. Secondary endpoints included the Crohn's disease activity index (CDAI), perianal Crohn's disease activity index (PDAI), laboratory indicators [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) ], endoscopic remission rate, Van Assche score, and radiographic healing rate at week 52 of treatment.Results:A total of 28 patients were included, with 22 males (78.6%) and 6 females (21.4%) ; age (25.2 ± 7.7) (16.0-52.0) years. There was 1 patient (3.6%) of simple anal fistula. There were 27 patients (96.4%) of complex anal fistulas, including 12 of high intersphincteric type, 15 of high transsphincteric type, in which 15 with branched tracts (or ≥2 fistula tracts). The pre-treatment CDAI was 187.0 (156.0, 245.0), and the PDAI was 10.0 (9.0, 12.0). Among the 28 patients, 23 (82.1%) underwent fistulotomy, 1 (3.6%) underwent transanal opening of intersphincteric space (TROPIS), and 4 (14.3%) underwent video-assisted anal fistula treatment (VAAFT) combined with fistula-tract laser closure (FiLaC). All the patients received UST treatment postoperatively, without concurrent use of immunosuppressants or corticosteroid therapy. At week 52 of treatment, 28 (100%) patients achieved clinical healing. Compared to pre-treatment, Wexner score of patients at week 52 of treatment was significantly lower [0 (0, 0) vs. 1.0 (0, 3.0), P < 0.001], maximum anal sphincter pressure increased [ (137.6±40.9) mmHg vs. (105.1±29.2) mmHg, P < 0.001], maximum anal sphincter contraction time extended [9.0 (5.0, 15.0) s vs. 4.0 (2.0, 6.0) s, P < 0.001], and there was no significant decrease in anal resting pressure ( P > 0.05). Compared to pre-treatment, CDAI, PDAI, Van Assche scores, and simple endoscopic score for Crohn's disease (SES-CD) of patients at week 52 of treatment all significantly decreased (all P < 0.001), and CRP, ESR, and FC all decreased (all P < 0.05), with statistically significant differences. The radiographic healing rate at week 52 of treatment was 75.0% (21/28), and the radiographic remission rate was 92.9% (26/28). The endoscopic remission rate was 57.1% (16/28), and the endoscopic response rate was 82.1% (23/28) . Conclusion:The long-term clinical healing rate of active CD patients with perianal fistula receiving surgery combined with UST is high, and the anal function can be improved significantly.

Objective:To evaluate the effects of different volumes of ropivacaine for iliopsoas muscle plane block on quadriceps strength in patients undergoing hip arthroplasty.Methods:In this prospective study, 75 patients of either sex, aged 40-80 yr, with a body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing elective hip arthroplasty from June to December 2023 at Baoding First Central Hospital, were randomized into 3 groups ( n=25 each) by using a computer-generated randomization sequence: ropivacaine 5 ml group (group Ⅰ), ropivacaine 10 ml group (group Ⅱ), and ropivacaine 15 ml group (group Ⅲ). Before induction of anesthesia, iliopsoas muscle plane block was performed with 0.5% ropivacaine 5, 10 and 15 ml in Ⅰ, Ⅱ and Ⅲ groups, respectively. The lateral femoral cutaneous nerve block was carried out using 0.5% ropivacaine 5 ml in all the three groups. The quadriceps muscle strength and status of quadriceps motor block in the affected limb were assessed on admission to postanesthesia care unit (PACU) and at 2, 4, 6, 24 and 48 h after surgery. The consumption of dezocine, score for patient′s satisfaction with analgesia, and occurrence of complications were recorded. Results:Compared with group Ⅰ, the quadriceps muscle strength scores were significantly decreased on admission to PACU and at 2, 4 and 6 h postoperatively in group Ⅲ, the rate of quadriceps motor block was significantly increased on admission to PACU in group Ⅱ, and the rate of quadriceps motor block was significantly increased on admission to PACU and at 2 and 4 h postoperatively in group Ⅲ ( P<0.05), and the consumption of dezocine was significantly decreased in group Ⅱ and group Ⅲ ( P<0.05). Conclusions:The recommended volume of ropivacaine for iliopsoas plane block is 10 ml in patients undergoing hip arthroplasty.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

Objective To explore the efficacy of ozone gas bath on necrotizing fasciitis after debride-ment.Methods Fifty patients with necrotizing fasciitis who underwent debridement in the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from January 2020 to July 2024 were selected and divided into control group(25 cases)and observation group(25 cases)according to random number table method.The control group was given routine dressing change(normal saline,povidone iodine,hydrogen per-oxide,metronidazole sodium chloride injection),and the observation group was treated with ozone gas bath.The clinical efficacy,pain scores,laboratory indicators,postoperative complications,and total hospital days of the two groups were compared before and after treatment.Results Compared with the control group,the ob-servation group had a higher total effective rate(92.0%vs.68.0%),lower numerical rating scale for pain(NRS)scores at 1 week postoperatively,2 weeks postoperatively,and before discharge,as well as lower levels of WBC,C reactive protein(CRP),and procalcitonin(PCT),and a lower total incidence of complications(52.0%vs.80.0%).The hospital stay was shorter[(22.40±2.06)d vs.(29.28±2.28)d)],with statistical-ly significant differences(P<0.05).Conclusion Ozone gas bath can reduce postoperative pain and promote recovery in necrotizing fasciitis after debridement.

Objective To investigate the protective effects of mitochondrial preconditioning in pericytes(PC)against pulmonary vascular leakage in septic rats.Methods ① 128 specific-pathogen-free SD rats(equal gender,200±20 g)were randomized into:Sham group(postoperative tail vein injection of 0.5 mL saline),Sepsis(Sep)group(CLP+saline),PC group(CLP+untreated PC:106 cells/rat),and Mito-PC group(CLP+PC preconditioned with 2 μg mitochondria/104 cells for 12 h).Assessments included:PC lung colonization(flow cytometry),pulmonary barrier function(Evans blue assay),lung histopathology(HE staining),serum organ injury markers[cTnT(cardiac),urea/creatinine(renal)],and inflammatory cytokines(TNF-α,IL-6).② MSC-derived mitochondria were validated by electron microscopy/flow cytometry;primary retinal PCs from weaned SD rats were purity-verified(confocal microscopy).In vitro groups:Control(PC),Mito-PC,PC+H2O2(0.5 μmol/L,4 h),and Mito-PC+H2O2.Antioxidant capacity was assessed via pentose phosphate pathway(PPP)activity,NADPH levels,G6PD activity,and NADP+/NADPH ratio.Results① Compared with Sham,Sep group showed significant increase in pulmonary leakage(Evans blue P<0.05),severe lung injury,elevated serum markers(TNF-α,IL-6,cTnT,urea,creatinine all P<0.05),0％72 h survival.PC group showed partial improvement(P<0.05).Mito-PC group demonstrated significant reduction in vascular leakage(P<0.05 vs PC group),improved histopathology and organ function(P<0.05),attenuated inflammation(P<0.05),higher 72 h survival rate(P<0.05).② Mitochondrial preconditioning significantly enhanced PPP activation and NADPH-mediated antioxidative capacity,Mito-PC+H2O2 vs PC+H2O2 showed improved cell viability(P<0.05),Mito-PC vs PC showed increased G6PD activity(P<0.05),decreased NADP+/NADPH ratio(P<0.05).Conclusion Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.