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 observe the clinical efficacy of modified painless suppurative moxibustion with wheat-grain sized moxa cones plus Western medication in treating cough variant asthma(CVA)due to wind-cold attacking the lung and its effects on pulmonary function,serum immunoglobulin(Ig)-E,hypersensitive C-reactive protein(hs-CRP),and interleukin(IL)-6.Methods:A total of 98 CVA patients were randomly divided into an observation group and a control group using the random number table method,with 49 cases in each group.The control group was treated with salmeterol xinafoate and fluticasone propionate powder for inhalation,and the observation group was treated with additional modified painless suppurative moxibustion with wheat-grain sized moxa cones.The treatment lasted for 8 weeks.The traditional Chinese medicine(TCM)symptom score of the patients in both groups was observed before treatment,after treatment,and at 1-month follow-up after treatment for its changes.The clinical efficacy after treatment and at 1-month follow-up was compared between the two groups.The pulmonary function[forced expiratory volume in the first second(FEV1),FEV1/forced vital capacity(FVC),and peak expiratory flow(PEF)]and serum IgE,hs-CRP,and IL-6 levels were compared between the two groups before and after treatment.The adverse reactions that occurred during the treatment in both groups were observed and recorded.Results:The total effective rate of the observation group after treatment and at follow-up was higher than that of the control group(P<0.05).The TCM symptom scores in both groups after treatment and at follow-up were lower compared to the baseline(P<0.05),and the scores in the observation group were lower than those in the control group(P<0.05).The FEV1,FEV1/FVC,and PEF after treatment in both groups were higher compared to the baseline(P<0.05),and the levels in the observation group were higher than those in the control group(P<0.05).The serum levels of IgE,IL-6,and hs-CRP after treatment in both groups were lower than the baseline(P<0.05),and the levels in the observation group were lower than those in the control group(P<0.05).There were no adverse reactions in either group during the course of the study.Conclusion:Modified painless suppurative moxibustion with wheat-grain sized moxa cones plus salmeterol xinafoate and fluticasone propionate powder for inhalation is effective in treating CVA due to wind-cold attacking the lung;it can relieve the clinical symptoms of the patients,improve their pulmonary function,and also reduce serum IgE,hs-CRP,and IL-6 levels.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

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 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 observe the clinical efficacy of modified painless suppurative moxibustion with wheat-grain sized moxa cones plus Western medication in treating cough variant asthma(CVA)due to wind-cold attacking the lung and its effects on pulmonary function,serum immunoglobulin(Ig)-E,hypersensitive C-reactive protein(hs-CRP),and interleukin(IL)-6.Methods:A total of 98 CVA patients were randomly divided into an observation group and a control group using the random number table method,with 49 cases in each group.The control group was treated with salmeterol xinafoate and fluticasone propionate powder for inhalation,and the observation group was treated with additional modified painless suppurative moxibustion with wheat-grain sized moxa cones.The treatment lasted for 8 weeks.The traditional Chinese medicine(TCM)symptom score of the patients in both groups was observed before treatment,after treatment,and at 1-month follow-up after treatment for its changes.The clinical efficacy after treatment and at 1-month follow-up was compared between the two groups.The pulmonary function[forced expiratory volume in the first second(FEV1),FEV1/forced vital capacity(FVC),and peak expiratory flow(PEF)]and serum IgE,hs-CRP,and IL-6 levels were compared between the two groups before and after treatment.The adverse reactions that occurred during the treatment in both groups were observed and recorded.Results:The total effective rate of the observation group after treatment and at follow-up was higher than that of the control group(P<0.05).The TCM symptom scores in both groups after treatment and at follow-up were lower compared to the baseline(P<0.05),and the scores in the observation group were lower than those in the control group(P<0.05).The FEV1,FEV1/FVC,and PEF after treatment in both groups were higher compared to the baseline(P<0.05),and the levels in the observation group were higher than those in the control group(P<0.05).The serum levels of IgE,IL-6,and hs-CRP after treatment in both groups were lower than the baseline(P<0.05),and the levels in the observation group were lower than those in the control group(P<0.05).There were no adverse reactions in either group during the course of the study.Conclusion:Modified painless suppurative moxibustion with wheat-grain sized moxa cones plus salmeterol xinafoate and fluticasone propionate powder for inhalation is effective in treating CVA due to wind-cold attacking the lung;it can relieve the clinical symptoms of the patients,improve their pulmonary function,and also reduce serum IgE,hs-CRP,and IL-6 levels.

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.

Objective:To analyze the hard tissue thickness in the crown of primary teeth by CBCT.Methods:The CBCT imaging data of 47 children were included,and the hard tissue thickness of primary teeth was measured by MIMICS software.SPSS 22.0 was used for data analysis.Results:The average thickness in the mesial surfaces was the smallest(P＜0.01),except for the libial surface of maxillary central incisor and the distal surface of mandibular first primary molar.In primary anteriors,the thickness in the same sur-face of maxillary teeth was greater than that of mandibular teeth significantly(P＜0.01)except for the libial surface of primary canine.In primary molars,the thickness of hard tissue in the same part of the distal and lingual side of the maxillary teeth was greater than that of the mandibular teeth(P＜0.01),and the thickness in the buccal side of maxillary teeth was lower than that of the mandibular teeth(P＜0.01).Conclusion:The distribution of hard tissue thickness of primary teeth in different position is different.

Objective:To assess the influence of extreme temperature events on the mortality risk of nervous system diseases in residents of Jiangsu Province and identify patients with nervous system diseases who are susceptible to extreme temperature events.Methods:Acase-crossover design was used to investigate the cumulative lagged effects of extreme temperature events on the mortality risk of nervous system disease in local residents by using the data on causes of death from nervous system diseases in Jiangsu from 2014 to 2020 with conditional logistic regression model. The final definition of extreme temperature events was established using Akaike information criterion. The heat wave was defined as 4 or more consecutive days with daily mean temperatures above the 92.5 th percentile of annual daily mean temperatures, and the cold spell was defined as 2 or more consecutive days with daily mean temperatures below the 10 th percentile of annual daily mean temperatures. Furthermore, stratified analyses was conducted to compare the effects of extreme temperature events on mortality risk in populations in different gender, age and marital status groups to identify susceptible populations to extreme temperature event. Results:Statistical results showed that the effect values of heat wave and cold spell on the mortality risk of nervous system diseases all peaked at the 7 th day of the cumulative lag, with OR of 1.60 (95% CI: 1.44-1.76) and 1.33 (95% CI: 1.13-1.56), respectively. Heat wave exposure increased mortality risk for individuals with Alzheimer's and Parkinson's diseases, while cold spell exposure increased the mortality risk for those with Alzheimer's disease. Stratified analyses showed that the mortality risk for nervous system disease and Alzheimer's disease was higher in partnerless population after heat wave exposure. Conclusions:Heat wave and cold spell were associated with increased mortality risks for nervous system disease, highlighting the need for improved early warning systems for extreme temperature event. In the context of heat wave, interventions to protect individuals with nervous system disease should prioritize partnerless population.

Objective To analyze the data of prostate cancer in Wuhan from 2010 to 2019, understand the characteristics and trends of incidence, mortality, and YLL, and provide decision-making basis for Wuhan's cancer prevention and control strategies. Methods Data on deaths and incident cases of prostate cancer in Wuhan from 2010 to 2019 and from 2013 to 2017, respectively, were collected from the Wuhan Death Monitoring System. Indicators such as incidence rate, mortality rate, and years of life lost due to premature death (YLL) of prostate cancer in Wuhan were calculated using Excel 2016 and Python. The Bayesian Age-Period-Cohort Model (BAPC) was used to predict the mortality rate of prostate cancer in Wuhan from 2020 to 2024. The trend changes were described using the annual average percentage change (AAPC). Results From 2010 to 2019, the incidence, mortality, and YLL rates of prostate cancer in Wuhan showed an overall increasing trend (AAPC >0, P <0.05). The standardized mortality and incidence rates in the central urban area were significantly higher than those in the outer urban area, and the age group of 85 and above had the highest incidence and mortality rates. The age group of 0-54 had the largest increase in incidence and mortality rates. From 2020 to 2024, prostate cancer in Wuhan is expected to continue to increase slightly (an increase of 0.94%). Conclusion The incidence, mortality, and YLL rates of prostate cancer in Wuhan are showing an overall increasing trend, and this trend may continue. The characteristics are higher in the central urban area than in the outer urban area, and higher in the older age group than in the younger age group. Targeted measures need to be taken, and screening for high-risk populations should be strengthened.