Objective To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

Objective:To investigate the effects of Jianpi Rougan Xifeng Decoction on the behaviors and the Ca 2+ -CaM-CaMK Ⅱ signaling pathway in the striatum of rats with tic disorder models. Methods:Seventy-two SPF-grade SD male rats were randomly divided into blank group, model group, tiapride group (15.93 mg/kg, intragastric administration), low-dose (4.32 g/kg, intragastric administration), medium-dose (8.64 g/kg, intragastric administration) and high-dose (17.28 g/kg, intragastric administration) Jianpi Rougan Xifeng Decoction groups, with 12 rats in each group. Rats in the blank group and model group were gavaged with 0.5 mg/kg of distilled water while rats in other 4 groups were gavaged with corresponding drugs, all rats were gavaged once a day for 28 days.The evaluations of motor behavior and stereotyped behavior were conducted using the Kadasah scoring method and the Diamond scoring method. Calcium content in the striatum was detected using a calcium assay kit. Immunohistochemical analysis was employed to detect the expression of dopamine transporter (DAT) and inositol 1, 4, 5-triphosphate (IP3) in the striatum of rats. Western blot was used to assess the expression of calmodulin (CaM) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the striatum. RT-PCR was utilized to detect the expression of CaM and CaMK Ⅱ mRNA in the striatum. All data were processed using SPSS 26.0 software, and comparisons among multiple groups were performed using one-way ANOVA and Kruskal-Wallis test.Results:(1) After four weeks of pharmacological intervention, statistically significant differences were observed in the locomotor activity scores and stereotyped scores among the six groups of rats ( H=41.20, 44.24, both P<0.01). Specifically, the locomotor activity scores(3.00(3.00, 3.25), 1.00(0.75, 1.25), 1.00(0.75, 2.00), 1.00(0, 1.00)) and stereotyped scores(3.00(3.00, 4.00), 1.00(0.75, 2.00), 2.00(0.75, 2.00), 1.00(0, 1.25)) in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups were significantly lower than those in the model group (all P<0.01). (2) Results from the calcium assay kit revealed statistically significant differences in striatal calcium content among the six groups of rats ( F=146.67, P<0.01). The calcium content in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups was significantly lower than that in the model group (all P<0.01). Additionally, the calcium content in the medium-dose ((0.40±0.02)mmol/g) and high-dose ((0.30±0.03)mmol/g) Jianpi Rougan Xifeng Decoction groups was lower than that in the low-dose group ((0.48±0.02)mmol/g) (both P<0.01). (3) Immunohistochemical results showed that there were statistically significant differences in the mean optical density values of DAT and IP3 in the striatum among the six groups of rats ( F=25.57, 154.98, both P<0.01). The IP3 mean optical density in the tiapride group and the Jianpi Rougan Xifeng Decoction groups with medium and high doses exhibited lower values compared to the model group (all P<0.05), whereas the DAT mean optical density displayed higher values in these groups compared to the model group (all P<0.05). The low-dose Jianpi Rougan Xifeng Decoction group also exhibited a lower optical density value of IP3 compared to the model group( P<0.05). The optical density values of IP3 (2.68±0.21, 2.40±0.22) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than that in the low-dose group (4.27±0.23) (both P<0.01). (4) Western blot results indicated that there were statistically significant differences in the protein expression levels of CaM and CaMK Ⅱ in the striatum among the six groups of rats ( F=233.03, 118.60, both P<0.01). The protein expression levels of CaM and CaMK Ⅱ in the tiapride group and the low-dose, medium-dose, and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the model group (all P<0.01). The protein expression levels of CaM (1.02±0.06, 0.84±0.02) and CaMK Ⅱ (0.48±0.03, 0.40±0.02) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the low-dose group (1.21±0.03, 0.57±0.02)) (all P<0.05). Additionally, the protein expression level of CaM in the high-dose Jianpi Rougan Xifeng Decoction group was lower than that in the medium-dose group( P<0.05).(5) The RT-PCR results indicated significant variations in the mRNA expression levels of CaM and CaMK Ⅱ within the striatum across the six groups rats ( F=30.54, 20.78, both P<0.01). The mRNA expression levels of CaM and CaMK Ⅱ in the tiapride group and the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the model group (both P<0.05). The mRNA expression levels of CaMK Ⅱ (1.38±0.17) in the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the low-dose group (1.99±0.27) ( P<0.01). Conclusion:Jianpi Rougan Xifeng Decoction can improve locomotor activity and stereotyped behavior in rats with tic disorder model. The mechanism may be through inhibiting the Ca 2+ -CaM-CaMK Ⅱ signaling pathway and regulating the expression of DAT and IP3, thereby modulating the release and recovery of dopamine and reducing the occurrence of tic symptoms.

Objective:To analysis the current utilization of nuclear medicine diagnosis and treatment equipments in Gansu province, evaluate the fairness of its distribution and provide a theoretical basis for government decision-making and the allocation of nuclear medicine diagnosis and treatment resources.Methods:In May 2023, Basic data were collected through questionnaires from the "Occupational Radiation Disease Monitoring" and "Radiation Protection Monitoring in Medical and Health Institutions" projects undertaken by Gansu Provincial Center for Disease Control and Prevention.The Gini coefficient and Theil index were calculated using STATA SE software to evaluate the equity of clinical nuclear medicine diagnosis and treatment resource allocation. Simultaneously, personal dose monitoring was conducted for nuclear medicine personnel. The fairness of clinical nuclear medicine diagnosis and treatment resource allocation was evaluated using the Gini coefficient and Theil index.Results:As of December 31, 2023, a total of 12 medical institutions in Gansu Province engaged in nuclear medicine diagnosis and treatment, employing 137 nuclear medicine radiation workers. Throughout the province, there were a total of 3 PET/CT scanners, 13 SPECT scanners and 3 medical cyclotrons available. In addition, 33712 nuclear medicine diagnostic procedures and 9365 various types of nuclear medicine treatments were administered over the year, resulting in a diagnostic frequency of 1.35 procedures per thousand population and a treatment frequency of 0.37 procedures per thousand population. The Gini coefficients for nuclear medicine personnel, equipment and diagnostic and treatment applications calculated per capita were 0.50, 0.53 and 0.61, respectively. The corresponding Theil indices were 0.0672, 0.0669 and 0.1277. In 2023, the average annual effective dose from external exposure for nuclear medicine workers was 0.37 mSv per person, while the average annual effective dose from internal exposure to thyroid 131I for nuclear medicine workers was 1.41 mSv. Conclusion:The distribution of nuclear medicine health resources and applications in Gansu Province is uneven. Greater emphasis should be placed on strengthening the adjustment of nuclear medicine resource allocation between regions, continuously promoting coordinated development within regions, and improving dose monitoring for nuclear medicine personnel.

Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.

Objective:To evaluate the effects of nasal endoscopy in curettage of large mandibular cyst.Methods:20 cases of large mandibular cyst admitted to Xianyang Hosptial of Yan'an University from January 2022 to December 2023 were included.The curet-tage of mandibular cyst was performed under general anesthesia through intraoral incision by nasal endoscopy-assisted illumination and enlargement of the lesion area during the operation.The application effects were evaluated from the aspects of surgical incision length,nerve injury and cyst recurrence.Results:During operation,the surgical filed of view was clear and the operation was suc-ceeded in all cases.There was no complication in and after the nasal endoscopy-assisted curettage,no cyst recurrence was observed during 1-year follow-up.Conclusion:Nasal endoscopy-assisted curettage of large mandibular cyst is effective and safe.

Objective:To investigate the effects of Jianpi Rougan Xifeng Decoction on the behaviors and the Ca 2+ -CaM-CaMK Ⅱ signaling pathway in the striatum of rats with tic disorder models. Methods:Seventy-two SPF-grade SD male rats were randomly divided into blank group, model group, tiapride group (15.93 mg/kg, intragastric administration), low-dose (4.32 g/kg, intragastric administration), medium-dose (8.64 g/kg, intragastric administration) and high-dose (17.28 g/kg, intragastric administration) Jianpi Rougan Xifeng Decoction groups, with 12 rats in each group. Rats in the blank group and model group were gavaged with 0.5 mg/kg of distilled water while rats in other 4 groups were gavaged with corresponding drugs, all rats were gavaged once a day for 28 days.The evaluations of motor behavior and stereotyped behavior were conducted using the Kadasah scoring method and the Diamond scoring method. Calcium content in the striatum was detected using a calcium assay kit. Immunohistochemical analysis was employed to detect the expression of dopamine transporter (DAT) and inositol 1, 4, 5-triphosphate (IP3) in the striatum of rats. Western blot was used to assess the expression of calmodulin (CaM) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the striatum. RT-PCR was utilized to detect the expression of CaM and CaMK Ⅱ mRNA in the striatum. All data were processed using SPSS 26.0 software, and comparisons among multiple groups were performed using one-way ANOVA and Kruskal-Wallis test.Results:(1) After four weeks of pharmacological intervention, statistically significant differences were observed in the locomotor activity scores and stereotyped scores among the six groups of rats ( H=41.20, 44.24, both P<0.01). Specifically, the locomotor activity scores(3.00(3.00, 3.25), 1.00(0.75, 1.25), 1.00(0.75, 2.00), 1.00(0, 1.00)) and stereotyped scores(3.00(3.00, 4.00), 1.00(0.75, 2.00), 2.00(0.75, 2.00), 1.00(0, 1.25)) in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups were significantly lower than those in the model group (all P<0.01). (2) Results from the calcium assay kit revealed statistically significant differences in striatal calcium content among the six groups of rats ( F=146.67, P<0.01). The calcium content in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups was significantly lower than that in the model group (all P<0.01). Additionally, the calcium content in the medium-dose ((0.40±0.02)mmol/g) and high-dose ((0.30±0.03)mmol/g) Jianpi Rougan Xifeng Decoction groups was lower than that in the low-dose group ((0.48±0.02)mmol/g) (both P<0.01). (3) Immunohistochemical results showed that there were statistically significant differences in the mean optical density values of DAT and IP3 in the striatum among the six groups of rats ( F=25.57, 154.98, both P<0.01). The IP3 mean optical density in the tiapride group and the Jianpi Rougan Xifeng Decoction groups with medium and high doses exhibited lower values compared to the model group (all P<0.05), whereas the DAT mean optical density displayed higher values in these groups compared to the model group (all P<0.05). The low-dose Jianpi Rougan Xifeng Decoction group also exhibited a lower optical density value of IP3 compared to the model group( P<0.05). The optical density values of IP3 (2.68±0.21, 2.40±0.22) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than that in the low-dose group (4.27±0.23) (both P<0.01). (4) Western blot results indicated that there were statistically significant differences in the protein expression levels of CaM and CaMK Ⅱ in the striatum among the six groups of rats ( F=233.03, 118.60, both P<0.01). The protein expression levels of CaM and CaMK Ⅱ in the tiapride group and the low-dose, medium-dose, and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the model group (all P<0.01). The protein expression levels of CaM (1.02±0.06, 0.84±0.02) and CaMK Ⅱ (0.48±0.03, 0.40±0.02) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the low-dose group (1.21±0.03, 0.57±0.02)) (all P<0.05). Additionally, the protein expression level of CaM in the high-dose Jianpi Rougan Xifeng Decoction group was lower than that in the medium-dose group( P<0.05).(5) The RT-PCR results indicated significant variations in the mRNA expression levels of CaM and CaMK Ⅱ within the striatum across the six groups rats ( F=30.54, 20.78, both P<0.01). The mRNA expression levels of CaM and CaMK Ⅱ in the tiapride group and the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the model group (both P<0.05). The mRNA expression levels of CaMK Ⅱ (1.38±0.17) in the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the low-dose group (1.99±0.27) ( P<0.01). Conclusion:Jianpi Rougan Xifeng Decoction can improve locomotor activity and stereotyped behavior in rats with tic disorder model. The mechanism may be through inhibiting the Ca 2+ -CaM-CaMK Ⅱ signaling pathway and regulating the expression of DAT and IP3, thereby modulating the release and recovery of dopamine and reducing the occurrence of tic symptoms.

Objective:To investigate the molecular characteristics of low-risk acute myeloid leukemia(AML)at recurrence,and analyze the factors affecting retreatment efficacy and prognosis.Methods:A retrospective analysis was conducted on the clinical and laboratory data of 31 patients with newly diagnosed low-risk AML who relapsed during consolidation treatment or follow-up after treatment in our hospital from April 2017 to January 2023.Gene mutations before and after relapse were compared,retreatment efficacy following relapse was evaluated,and univariate and multivariate analyses were performed to identify factors influencing treatment efficacy and prognosis.Results:Gene sequencing results after relapse showed that the most common newly acquired mutation was FLT3-ITD,while RAS mutation detected at initial diagnosis were predisposed to loss of expression during relapse.The median overall survival(OS)after relapse for the entire cohort was 349(170-528)days,with non-hematopoietic stem cell transplantation(HSCT)group and HSCT group demonstrating median survival times of 210(106-314)days and not reached,respectively(P=0.001).Multivariate analysis revealed that age ≥60 years was a significant risk factor for achieving remission after retreatment in initially diagnosed low-risk AML patients who experienced relapse(OR=18.222,95％CI:1.188-279.597,P=0.037).Additionally,DNMT3A mutation was identified as an independent risk factor for OS(HR=13.165,95％CI:2.018-85.877,P=0.007),while HSCT post-relapse demonstrated significant survival benefits(HR=0.133,95％CI:0.025-0.698,P=0.017)and served as an independent protective factor for OS.Conclusion:Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD.Age ≥ 60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival,respectively,while HSCT significantly improved patient outcomes.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.