ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

Objective To identify specific behaviors detrimental to language development in parent-child inter-actions among Mandarin-speaking infants and toddlers with language delays,and to provide a foundation for develo-ping parent-involved early intervention programs that enhance language acquisition.Methods A qualitative research design was used,employing interaction analysis and categorical analysis methods.Observations from 30 parent-child interaction videos involving children with delayed language development were analyzed to identify common detrimen-tal behaviors(coding).The validity of the qualitative findings was tested by analyzing 108 parent-child where low-quality parental interactions were identified and provided with five rounds of constructive feedback.Results Two major categories of detrimental behaviors with three aspects and a total of 10 issues were identified:5 issues related to parental interaction skills,3 issues related to mutual influences between parent and child,and 2 issues related to the interaction environment.After 5 rounds of feedback,detrimental behaviors in the 108 parent-child pairs im-proved significantly,with 8 behaviors met the 80％stability standard.Conclusion The study identified and catego-rized behaviors in parent-child interactions that hinder language development in children with language delays.Video-based behavior analysis and feedback can enhance parental interaction skills and create a conductive environ-ment for early language development.

Objective:To evaluate the prognosis of Hall technique and traditional performed metal crown (PMC) restoration technique, and to follow up the occlusal changes before and after treatment with Hall technique, providing references for the promotion of Hall technique.Methods:Children who visited the Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University from May 2021 to December 2022 were screened according to the inclusion and exclusion criteria. The therapeutic effects of the two groups were followed up at three time points: 1, 2 and 3 months after operation. The observation results were divided into three outcomes: success (crown in place, no symptoms of pulpitis or periapical periodontitis, no obvious abnormality in occlusion, no need for further treatment), partial failure (crown falling off or crown broken, tooth defect can be repaired, reversible pulpitis) and complete failure (irreversible pulpitis or periapical periodontitis, crown falling off and tooth defect irreparable), and statistical analysis was made. At the same time, the Hall technique group was followed up at five time points as before operation, immediately after operation, 2 weeks after operation, 4 weeks after operation and 8 weeks after operation respectively, in which the occlusion was analyzed by Dental Prescale Ⅱ system. The vertical dimension of occlusion (VDO), overbite and coverage, and canine relationship were recorded and compared. Three-dimensional finite element method was used to model and analyze the stress of the teeth treated with traditional PMC treatment and Hall technique, and the differences between them were compared.Results:Finally, 21 children were included in the Hall technique group, including 12 boys and 9 girls, with age of (5.0±1.4) years. Meanwhile, 22 children including 15 boys and 7 girls were in the traditional PMC group, with age of (5.1±1.3) years. There were 0 cases of complete failure and 0 cases of partial failure both in the Hall technique group and in the traditional PMC group within 1 month. There were 0 cases of complete failure and 1 case of partial failure in the Hall technique group, while 0 cases of complete failure and 0 cases of partial failure in the traditional PMC group within 2 months after operation. Hall technique group failed completely in 1 case and partially in 1 case, while the traditional pre-crown group failed completely in 0 cases and partially in 0 cases 3 months after operation. There was no significant difference in the incidence of primary index/complete failure and secondary index/partial failure between Hall technique group and traditional PMC group (all P>0.05). The occlusal area and occlusal force of children treated with Hall technique decreased immediately after operation compared with those before operation, but gradually recovered to the preoperative level at 2, 4 and 8 weeks after operation. To elaborate, the occlusal area decreased significantly from (14.79±3.55) mm 2 before operation to (10.15±3.17) mm 2 immediately after operation ( P=0.001), and recovered to (15.58±3.39) mm 2 at 8 weeks after operation ( P>0.05 compared with pre-operation). The occlusal force decreased significantly from (436.94±109.59) N before operation to (292.70±96.05) N immediately after operation ( P=0.001), and recovered to (441.86±104.31) N at 8 weeks after operation ( P>0.05 compared with pre-operation). Overbite decreased significantly from (2.54±1.05) mm before operation to (1.80±0.94) mm immediately after operation ( P=0.044) and then recovered to (2.35±1.02) mm ( P>0.05 compared with pre-operation). The coverage changed from (2.41±0.66) mm before operation to (2.27±0.61) mm immediately after operation ( P>0.05) and then recovered to (2.48±0.62) mm ( P>0.05 compared with pre-operation). The canine relationship was (3.12±0.54) mm before operation, and decreased significantly immediately after operation (2.17±0.89) mm ( P=0.001), and recovered to (3.05±0.61) mm after 8 weeks ( P>0.05 compared with pre-operation). In the three-dimensional finite element analysis, the maximum stress of all parts of the affected tooth increased immediately after Hall technique treatment, but with occlusal adjustment, the maximum stress of all parts of the affected tooth decreased, which was similar to that of the traditional metal pre-crown group. The vertical load and oblique load of pre-crown decreased from 180.11 and 496.16 MPa to 108.05 and 297.69 MPa, respectively. The vertical load and oblique load of enamel decreased from 94.83 and 255.94 MPa to 57.21 and 156.44 MPa, respectively. The vertical load and oblique load of dentin decreased from 55.19 and 124.77 MPa to 33.19 and 74.59 MPa, respectively. Conclusions:During the experimental observation period, there is no obvious difference between Hall technique and traditional PMC treatment technology in terms of post-treatment occlusion and clinical prognosis, which supports clinical application.

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Objective:To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on lipopolysaccharide(LPS)-induced inflammatory response of NLRP3 inflammasome in BV2 microglial cells.Methods:BV2 microglial cells were routinely cultured.CCK-8 assay was used to detect the effect of different concentrations(0.5,1,1.5,2 g/L)LBP on cell activity.Cells were di-vided into three groups:control group,LPS group and LBP+LPS group.Effect of LBP on LPS-induced cell activity was detected by CCK-8 method;RT-qPCR and immunofluorescence assay were used to detect NLRP3,ASC,Caspase-1,IL-18 and IL-1β expressions.Western blot was used to detect expressions of NLRP3,ASC,Caspase-1,TLR4,MyD88,NF-κB p65,IL-18,IL-1β and TNF-α pro-teins.Results:CCK-8 assay showed that 1 g/L LBP was the most applicable.Compared with control group,cell viability in LPS group was decreased;RT-qPCR,immunofluorescence and Western blot results showed that fluorescence intensity,mRNA and protein expres-sions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β were increased in LPS group.Western blot results showed that TLR4,MyD88,NF-κB p65 and TNF-α protein expressions were increased in LPS group.After LBP treatment,cell viability was increased;expres-sions of NLRP3,ASC,Caspase-1,NF-κB p65,TLR4,MyD88,IL-18,IL-1β and TNF-α were decreased.Conclusion:LBP may in-hibit LPS-induced NLRP3 inflammatory vesicles in BV2 cells via TLR4/MyD88/NF-κB signaling pathway.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

Objective To identify specific behaviors detrimental to language development in parent-child inter-actions among Mandarin-speaking infants and toddlers with language delays,and to provide a foundation for develo-ping parent-involved early intervention programs that enhance language acquisition.Methods A qualitative research design was used,employing interaction analysis and categorical analysis methods.Observations from 30 parent-child interaction videos involving children with delayed language development were analyzed to identify common detrimen-tal behaviors(coding).The validity of the qualitative findings was tested by analyzing 108 parent-child where low-quality parental interactions were identified and provided with five rounds of constructive feedback.Results Two major categories of detrimental behaviors with three aspects and a total of 10 issues were identified:5 issues related to parental interaction skills,3 issues related to mutual influences between parent and child,and 2 issues related to the interaction environment.After 5 rounds of feedback,detrimental behaviors in the 108 parent-child pairs im-proved significantly,with 8 behaviors met the 80％stability standard.Conclusion The study identified and catego-rized behaviors in parent-child interactions that hinder language development in children with language delays.Video-based behavior analysis and feedback can enhance parental interaction skills and create a conductive environ-ment for early language development.

Objective:To study the correlation between hair fluorine level and hypertension of permanent residents in high altitude areas of Tibet Autonomous Region (Tibet).Methods:A random cluster sampling method was used to select 5 villages in the high altitude areas of Tibet from June to August 2021 and June to August 2022, respectively, and questionnaire survey, physical examination, and biochemical indicator testing were conducted on permanent Tibetan residents in the above mentioned villages. At the same time, hair samples were collected, the hair fluorine level was determined by ion selective electrode method, and the correlation between various indicators and hair fluorine level and hypertension was analyzed.Results:A total of 227 individuals were included, with hair fluorine level of (15.06 ± 0.16) mg/kg. Correlation analysis showed that there was no correlation between the study subjects' systolic blood pressure, diastolic blood pressure, body mass index, pulse, neck circumference, chest circumference, uric acid level and hair fluorine level ( P > 0.05). Abdominal circumference, hip circumference, and hemoglobin level were positively correlated with hair fluorine level ( r = 0.23, 0.14, 0.29, P < 0.05), while blood glucose level and finger pulse oxygen were negatively correlated with hair fluorine level ( r = - 0.23, - 0.24, P < 0.001). Binary logistic regression analysis showed that age ( OR = 1.04, 95% CI: 1.01 - 1.06), chest circumference ( OR = 1.10, 95% CI: 1.01 - 1.20), and hair fluorine level ( OR = 1.22, 95% CI: 1.02 - 1.46) had an impact on hypertension ( P < 0.05). Conclusion:There is a certain correlation between hair fluoride level and hypertension in the population of high altitude areas in Tibet.