Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.

Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

Objective To explore the mediating effect of triglyceride-glucose(TyG)index on the risk of proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods 734 patients with T2DM who underwent routine physical examination in Quyang Road Community Health Service Center,Shanghai from March 2023 to May 2023 were enrolled.The results of basic information,biochemical indicators,abdominal ultrasound and other results were collected.All patients were divided into the normal group,microproteinuria group,and massiveproteinuria group,and stratification analyses were underwent according to glycated hemoglobin(HbA1c),body mass index(BMI),TyG index,and presence or absence of non-alcoholic fatty liver disease(NAFLD).Factors affecting proteinuria in T2DM patients were analyzed.Multivariate logistic regression was used to analyze the impact of TyG index and NAFLD on proteinuria in type 2 diabetes population.Regression coefficient sequential test was used to analyze whether TyG mediates NAFLD associated proteinuria.Results There were statistically significant differences in age,BMI,urinary creatinine,HbA1c,TyG index,etc.among the normal group,microproteinuria group,and massiveproteinuria group(all P＜0.05);there was no statistically significant difference in gender among the three groups.Multivariate logistic regression analysis showed that taking the HbA1c＜7％and BMI＜24 kg/m2 group as a reference,the patients with HbA1c≥7％and BMI≥24 kg/m2 had the highest risk of proteinuria(P=0.022),followed by the HbA1c≥7％and BMI＜24 kg/m2 group(P=0.039).Taking the TyG index(7.65-8.69)as a reference,the risk of proteinuria in the(9.45-11.90)group was 3.321 times(P＜0.001).The mediation effect analysis showed that the TyG mediated NAFLD associated proteinuria(P＜0.001),with the mediation effect accounting for 55.70％of the total effect.Conclusion TyG index may be an independent risk factor for proteinuria in patients with T2DM,and the prevalence of proteinuria is high in patients with poor control in HbA1c and excessive BMI,and TyG may partially mediate the risk of proteinuria in patients with T2DM.

Objective:To analyze the activation of primary somatosensory cortex(S1)neurons in post-traumatic stress disorder(PTSD)mice after tactile stimulation of whiskers and the changes of S1 cortical neurons in PTSD mice.Methods:Using the neuron cytoskeleton-associated protein(Arc)labeling strategy and immunofluorescence staining technique,the Arc of S1 cortical neurons in PTSD mice and control mice after whisker stimulation was marked and ob-served.By analyzing the difference in the spatial expression position of Arc labeled neurons and the number of positive cells,the activation level of S1 cortical neurons in the two groups was compared and analyzed.The pyramidal neurons of S1 cortex were labeled by sparse virus labeling method,and the number of dendrites and the morphology and number distribution of dendritic spines were compared between the two groups.Results:After whisker stimulation,it was found that Arc positive neurons were distributed from shallow layer to deep layer of S1,and more densely distributed in layersⅡ/Ⅲ and V.Compared with the control group,the number of positive neurons in different layers of the PTSD group was significantly increased.The results of cell morphology and structure analysis showed that,compared with the control group,the density of dendritic spines in layer Ⅱ/Ⅲ of mice with PTSD increased,and the number of mushroom dendrit-ic spines increased,while the number of filamentous pseudopod dendritic spines decreased.The number of dendritic spines of Si V layer mushroom type and slender type was higher,but the total number of dendritic spines was not sig-nificantly different.Conclusion:After whisker stimulation in PTSD mice,S1 neurons were over-activated,and the structure and morphology of neurons changed significantly.