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 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 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.

At present,precise radiotherapy has been widely used through the development with many years,but the existing technique still is limited by the limitation of tolerance dose of normal tissues,which cannot achieve the optimal goal of treating tumor.Flash radiotherapy(Flash-RT)is one kind of radiotherapy technique that uses the beam with ultra-high dose rate(UHDR)to conduct irradiation,which can furthest treat tumors while significantly reduce radiation injury of normal tissues.But until now,the biological mechanism,key physical parameters and triggering mechanism of Flash-RT are still unclear,and its principle and clinical translational application are still in the stage of research.This review clarified the technological advance and clinical translational application of Flash-RT research through summarized the relevant research of Flash-RT.

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 investigate the regulatory role of mesenchymal stem cells(MSCs)on radiation-induced lung injury in mice by the ferroptosis pathway.Methods:The mice were divided into normal control group,MSCs-treated group(MSCs group),single irradiation group(IR group)and IR combined with MSCs group(IR+MSCs group)according to random number table method before irradiation.A mouse model of radiation-induced lung injury was constructed using whole thorax irradiation with cobalt 60(60Co)(20Gy each time),and TNF-α and IL-6 levels of mouse were detected by enzyme-linked immunosorbent assay(ELISA).The injury of lung tissue in mice was assessed using hematoxylin eosin(HE)staining and Masson staining.Western Blot was used to examine the expression levels of ferroptosis-related proteins in lung tissue,including nuclear factor erythroid NF-E2 related factor 2(Nrf2),4-Hydroxynonenal(4-HNE)and glutathione peroxidase 4(GPX4).The expression level of prostaglandin-endoperoxide synthase 2 Gene(PTGS2)in the lung tissue of mice was detected by using quantitative polymerase chain reaction(qPCR),and the level of reactive oxygen species(ROS)in the lung tissue of mice was detected after radiation by using dihydroethidium(DHE),and the level of malondialdehyde(MDA)content in the lung tissue was detected after radiation.And then,the level of oxidative damage in the lung tissue of mice was assessed.Results:Elisa results showed the serum TNF-α and IL-6 levels in mice after irradiation in IR group were significantly higher than those in normal control group(F=53.60,10.65,P＜0.05),respectively.The HE and MSCs staining of pathological analysis showed that MSCs treatment could significantly relieve both early radiation-induced pneumonitis and advanced pulmonary fibrosis.After radiation,the 4-HNE expression level was upregulation and the Nrf2 expression level was downregulation in the lung tissues of mice,whereas MSCs were able to significantly reduce the 4-HNE expression and upregulate the Nrf2 expression.The mRNA expression level and MDA content of the ferroptosis gene PTGS2 were significantly increased,which were significantly higher than those of normal control group,while MSCs were able to significantly reduce its expression,and the differences were statistically significant(F=105.8,7.693,P＜0.05).Conclusion:MSCs is able to relieve significantly ionizing radiation-induced ferroptosis of lung epithelial cells,thereby relieve radiation-induced lung injury.

Objective:To investigate clinical efficacy of nail removal in combination with periungual dermis-fat flap tamponade in the treatment of bilateral severe curved ingrown nails.Methods:A retrospective analysis was conducted on clinical data collected from 7 patients with bilateral severe curved ingrown nails visiting the hospital between January 2018 and January 2020. There were 3 males and 4 females, aged 25-49 years (average: 35 years) . All patients were treated with nail removal in combination with periungual dermis-fat flap tamponade at outpatient clinics.Results:All the 7 patients experienced primary healing of incisions without infections, and achieved pain relief 1-2 weeks after surgery. During the follow-up of 12 to 24 months, new nail plates grew back without curling deformity, no erythematous swelling occurred in the nail grooves, and no recurrence of paronychia was observed. All patients were satisfied with the clinical efficacy.Conclusion:Nail removal in combination with periungual dermis-fat flap tamponade is effective for the treatment of bilateral severe curved ingrown nails.

Objective:To explore the regulatory effect of glutathione S-transferase P1(GSTP1) on the radiosensitivity of mouse Lewis lung cancer (LLC) cells.Methods:GSTP1-shRNA lentivirus and negative control lentivirus were used to respectively infect the LLC cells, and stable transgenic strains were selected. Real-time PCR and Western blot were conducted to quantitatively measure the expression levels of GSTP1 mRNA and protein in the LLC cells to verify the knockdown effect. The cell counting kit-8(CCK-8) assay was used to detect cell viability after irradiation. The colony formation assay was utilized to assess the cell proliferation ability after irradiation. Flow cytometry was performed to assess the level of cell apoptosis after irradiation. The tumor-bearing mice were established and irradiated to detect the changes in the tumor volume after irradiation. TUNEL staining was employed to detect the level of tumor apoptosis after irradiation. Immunofluorescence was used to detect the number of CD 4+ CD 8+ T cells in the tumor after irradiation. Results:Real-time PCR and Western blot showed that after shRNA lentivirus interference, the expression levels of GSTP1 mRNA and protein were significantly down-regulated. Down-regulation of GSTP1 reduced cell viability and proliferation, and increased the rate of cell apoptosis after irradiation. The tumor volume of the tumor-bearing mice after irradiation in the GSTP1 knockdown group was significantly smaller than that in the NC group, whereas the tumor apoptosis rate was significantly higher and the number of infiltrating CD 4+ CD 8+ T cells in the tumor was remarkably higher compared with those in the control group. Conclusion:Knockdown of GSTP1 can significantly increase the radiosensitivity of LLC cells and enhance the infiltration of lymphocytes in tumor tissues.

ObjectiveTo investigate the protective effect of tanshinone I (T-I) on hepatic ischemia-reperfusion injury (HIRI) in mice. MethodsA total of 36 C57BL/6J mice were randomly divided into sham-operation group, ischemia-reperfusion (IR) group, IR+T-I (5 mg/kg) group, IR+T-I (10 mg/kg) group, IR+T-I (20 mg/kg) group, and IR+T-I (40 mg/kg) group, with 6 mice in each group. Each group was given intraperitoneal injection. The mice in the sham-operation group and the IR group were injected with an equal volume of the solvent olive oil; the mice in the IR+T-I groups were administered once a day for 7 consecutive days, a model of 70% HIRI was established at 2 hours after the last administration, and serum and liver samples were collected after 6 hours of reperfusion. Related kits were used to measure the serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the content of superoxide dismutase (SOD), malondialdehyde (MDA), caspase-3, and reduced glutathione (GSH) in liver tissue; HE staining was used to observe liver histopathology; the TUNEL method was used to measure the level of hepatocyte apoptosis; immunohistochemistry was used to measure the protein expression of caspase-3 and heme oxygenase-1 (HO-1). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the IR group, the IR+T-I (20mg/kg) group had significant reductions in the serum levels of ALT (192.48±23.67 U/L vs 336.90±41.52 U/L, P＜0.01) and AST (123.19±9.16 U/L vs 206.90±18.81 U/L, P＜0.01), and thus 20 mg/kg was determined as the optimal concentration. Compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in MDA (1.34±0.21 μmol/mg vs 3.48±0.95 μmol/mg, P＜0.05) and caspase-3 (0.69±0.97 μmol/mg vs 1.04±0.35 μmol/mg, P＜0.05) and significant increases in SOD (274.47±30.53 U/mg vs 160.29±27.37 U/mg, P＜0.05) and GSH (2.12±0.27 μmol/mg vs 1.03±0.42 μmol/mg, P＜0.05). HE staining showed that the IR group had disordered structure of hepatic lobules and focal or extensive degeneration and necrosis of hepatocytes; compared with the IR group, the IR+T-I (20 mg/kg) group had a reduction in the area of hepatocyte necrosis and a basically complete structure of the liver. Immunohistochemistry showed that compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in the number of apoptotic hepatocytes and the protein expression of caspase-3 and a significant increase in the protein expression of HO-1. ConclusionT-I exerts a protective effect against HIRI in mice by inhibiting liver oxidative stress response and hepatocyte apoptosis.

The segmentation of organs at risk is an important part of radiotherapy. The current method of manual segmentation depends on the knowledge and experience of physicians, which is very time-consuming and difficult to ensure the accuracy, consistency and repeatability. Therefore, a deep convolutional neural network (DCNN) is proposed for the automatic and accurate segmentation of head and neck organs at risk. The data of 496 patients with nasopharyngeal carcinoma were reviewed. Among them, 376 cases were randomly selected for training set, 60 cases for validation set and 60 cases for test set. Using the three-dimensional (3D) U-NET DCNN, combined with two loss functions of Dice Loss and Generalized Dice Loss, the automatic segmentation neural network model for the head and neck organs at risk was trained. The evaluation parameters are Dice similarity coefficient and Jaccard distance. The average Dice Similarity coefficient of the 19 organs at risk was 0.91, and the Jaccard distance was 0.15. The results demonstrate that 3D U-NET DCNN combined with Dice Loss function can be better applied to automatic segmentation of head and neck organs at risk.