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.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective To assess the clinical efficacy of intravitreal anti-vascular endothelial growth factor(VEGF)agents plus panretinal photocoagulation(PRP)for treating young and middle-aged patients with proliferative diabetic reti-nopathy(PDR).Methods A retrospective case study was conducted on young and middle-aged PDR patients presenting to the Ophthalmology Department of Shaanxi Provincial People's Hospital between January 1,2021 and October 1,2024.The patients were divided into three groups according to Chinese Clinical Guidelines for Diabetic Retinopathy(2022):se-vere non-proliferative diabetic retinopathy(NPDR),early proliferative diabetic retinopathy(E-PDR)and fibrous prolifera-tive diabetic retinopathy(F-PDR).A total of 53 patients(94 eyes)were included in this study,and the mean age was(41.66±10.24)year old.There were 17 cases(31 eyes)in the NPDR group,18 cases(33 eyes)in the E-PDR group,and 18 cases(30 eyes)in the F-PDR group.All the patients were treated with the intravitreal injection of anti-VEGF agents(0.5 mg ranibizumab)about 3.5 mm from the sclerocorneal limbus at the inferior temporal sector,once a month,for three consecutive months.Routine PRP treatment was given 1 week after the first injection.Best-corrected visual acuity[BCVA(logMAR)],intraocular pressure,slit-lamp,slit-lamp fundus,optos fundus photography and OCT examinations were per-formed.The central macular thickness(CMT),average macular thickness(AMT),and the incidence of diabetic vitreous hemorrhage and emerging epiretinal membrane were recorded 1 month and 3 months after the first injection.Results Pa-tients in the F-PDR group were younger than those in NPDR and E-PDR groups(all P＜0.05).The BCVA values of eyes in all the three groups increased to varying degrees after 3 months of treatment,compared with those before treatment(all P＜0.05).The eyes in the F-PDR group had poorer vision than those in NPDR and E-PDR groups after 3 months of treat-ment(all P＜0.05).CMT and AMT decreased in all groups after 3 months of treatment,compared with those before treat-ment(all P＜0.05).No significant difference was found in CMT and AMT among the three groups at the same period(all P＞0.05).Eyes in the F-PDR group had higher risk of diabetic vitreous hemorrhage and emerging epiretinal membrane than those in NPDR and E-PDR groups 3 months after treatment(all P＜0.05).Conclusion Intravitreal anti-VEGF therapy combined with PRP can effectively slow the progression of PDR and improve vision acuity in young and middle-aged pa-tients.PDR patients with fibrovascular proliferation are at higher risk of diabetic vitreous hemorrhage and emerging epireti-nal membrane during the treatment with intravitreal anti-VEGF therapy plus PRP.These patients need a close follow-up,and vitrectomy should be performed in a timely manner to relieve vitreous traction when necessary.

Objective:To investigate the diagnosis，therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed，and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome，10 males and 11 females，aged 5 days to 10 years old. Compared with the adult-type group，the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05)，a high concomitant rate of intracardiac malformations (100% vs. 40%， P=0.002)，a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg， P=0.016]，a high incidence of pulmonary hypertension(91.0% vs. 50.0%， P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0， P=0.034)，prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h， P=0.007]，and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d， P<0.001]. Eleven cases underwent surgical treatment only，and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%，and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective To assess the clinical efficacy of intravitreal anti-vascular endothelial growth factor(VEGF)agents plus panretinal photocoagulation(PRP)for treating young and middle-aged patients with proliferative diabetic reti-nopathy(PDR).Methods A retrospective case study was conducted on young and middle-aged PDR patients presenting to the Ophthalmology Department of Shaanxi Provincial People's Hospital between January 1,2021 and October 1,2024.The patients were divided into three groups according to Chinese Clinical Guidelines for Diabetic Retinopathy(2022):se-vere non-proliferative diabetic retinopathy(NPDR),early proliferative diabetic retinopathy(E-PDR)and fibrous prolifera-tive diabetic retinopathy(F-PDR).A total of 53 patients(94 eyes)were included in this study,and the mean age was(41.66±10.24)year old.There were 17 cases(31 eyes)in the NPDR group,18 cases(33 eyes)in the E-PDR group,and 18 cases(30 eyes)in the F-PDR group.All the patients were treated with the intravitreal injection of anti-VEGF agents(0.5 mg ranibizumab)about 3.5 mm from the sclerocorneal limbus at the inferior temporal sector,once a month,for three consecutive months.Routine PRP treatment was given 1 week after the first injection.Best-corrected visual acuity[BCVA(logMAR)],intraocular pressure,slit-lamp,slit-lamp fundus,optos fundus photography and OCT examinations were per-formed.The central macular thickness(CMT),average macular thickness(AMT),and the incidence of diabetic vitreous hemorrhage and emerging epiretinal membrane were recorded 1 month and 3 months after the first injection.Results Pa-tients in the F-PDR group were younger than those in NPDR and E-PDR groups(all P＜0.05).The BCVA values of eyes in all the three groups increased to varying degrees after 3 months of treatment,compared with those before treatment(all P＜0.05).The eyes in the F-PDR group had poorer vision than those in NPDR and E-PDR groups after 3 months of treat-ment(all P＜0.05).CMT and AMT decreased in all groups after 3 months of treatment,compared with those before treat-ment(all P＜0.05).No significant difference was found in CMT and AMT among the three groups at the same period(all P＞0.05).Eyes in the F-PDR group had higher risk of diabetic vitreous hemorrhage and emerging epiretinal membrane than those in NPDR and E-PDR groups 3 months after treatment(all P＜0.05).Conclusion Intravitreal anti-VEGF therapy combined with PRP can effectively slow the progression of PDR and improve vision acuity in young and middle-aged pa-tients.PDR patients with fibrovascular proliferation are at higher risk of diabetic vitreous hemorrhage and emerging epireti-nal membrane during the treatment with intravitreal anti-VEGF therapy plus PRP.These patients need a close follow-up,and vitrectomy should be performed in a timely manner to relieve vitreous traction when necessary.

Objective:To investigate the diagnosis，therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed，and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome，10 males and 11 females，aged 5 days to 10 years old. Compared with the adult-type group，the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05)，a high concomitant rate of intracardiac malformations (100% vs. 40%， P=0.002)，a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg， P=0.016]，a high incidence of pulmonary hypertension(91.0% vs. 50.0%， P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0， P=0.034)，prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h， P=0.007]，and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d， P<0.001]. Eleven cases underwent surgical treatment only，and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%，and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.

Objective:To study the evolution of Traditional Chinese Medicine (TCM) syndromes of 171 cases of Kawasaki disease (KD) under the intervention of gamma globulin therapy based on factor analysis.Methods:A cross-sectional study. 171 cases of KD children hospitalized in the Department of Cardiology of Guangzhou Women's and Children's Medical Center from July 2019 to December 2020 were collected. All patients were treated with intravenous gamma globulin (2 g/kg) for 1 week. According to the results of the treatment with C-ball, 171 children with C-ball sensitive KD were selected to collect the four diagnostic data, and the representative syndromes of defensive level, qi level, yin level, and nutritive level were observed. Factor analysis was used to analyze the evolution of syndrome in 171 children with KD c-ball sensitivity.Results:The result of factor analysis showed that the KMO statistics of 171 children with c-ball sensitivity before treatment was 0.792, and Bartley test was significant ( P<0.01). 16 common factors were extracted, and 23 syndromes were screened, mainly including defensive level disorder, qi level disorder,nutritive level disorder,yin level disorder, heat stagnation and blood stasis syndrome. One week after treatment, the statistic of KMO test was 0.787, and Bartley test was significant ( P<0.01). 9 common factors were extracted, and 10 syndromes were screened, mainly including qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome. Conclusion:Before treatment, the TCM syndromes in KD C-cell sensitive children are mainly nutritive level disorder, defensive level disorder, qi level disorder yin level disorder, and heat stagnation and blood stasis syndrome; after treatment, the main TCM syndromes are mainly qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome.

Objective:To study the early outcomes of emergency operation employed with one of the prevalent surgical methods in neonates diagnosed as pulmonary atresia with intact ventricle septum(PA/IVS) and critical pulmonary stenosis(CPS), and to analyze the risk factors related to its early results.Methods:A retrospective analysis was conducted to collect the data of neonates suffered from PA/IVS and CPS from January 2016 to January 2020 in cardiothoracic surgery department at Shanghai Children′s Medical Center.According to their Z score, which reflects the development degree of right ventricle, the neonates received one of the relevant popular operations.Early outcomes were summarized and risk factors related to its early stage mortality were analyzed.Results:A total of 65 neonates were enrolled, including 27 CPS cases.They were operated on the basis of their respective Z scores, and also according to these data, the primary surgical procedure was chosen from the following methods: Blalock-Taussig(B-T) shunt, pulmonary valvulotomy and right ventricular outlet enlargement.Totally seven cases died, and mortality was 10.7%.Nine cases received re-operation in several following days because of severe hypoxemia and low cardiac output.All patients had mild improvement in oxygen saturation after operation and relied on large dose of inotropic agent.Multivariate Logistic regression analysis showed that B-T shunt and re-operation in early period were risk factors for death in neonates with PA/IVS and CPS.Conclusion:There is a higher mortality in neonates who received emergency operation for PA/IVS and CPS.Accurate assessment of the right ventricle development degree and selecting the corresponding appropriate surgical method is critical for the optimal result.B-T shunt and early stage re-operation are the risk factors for death in neonates with PA/IVS and CPS who received emergency operation.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.