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 analyze the expression of serum mannose binding lectin associated serine protease 1(MASP1)and protein kinase D2(PRKD2)in locally advanced cervical cancer(LACC)patients,and their relationship with the efficacy of neoadjuvant chemotherapy(NACT).Methods The clinical data of 98 LACC patients(LACC group)treated with NACT in the hospital from March 2019 to April 2021 were retrospective-ly selected,and they were divided into effective group(n=76)and ineffective group(n=22)according to the efficacy.Fifty patients with early cervical cancer diagnosed and treated in the same period were selected as the early cervical cancer group,and 50 female health examination subjects were selected as the healthy control group.Enzyme-linked immunosorbent assay was applied to detect serum levels of MASP1 and PRKD2.Logis-tic regression analysis was applied to analyze the influencing factors of NACT efficacy.The evaluation value of serum MASP1 and PRKD2 on the efficacy of NACT were analyzed by the receiver operating characteristic curve.Results The serum levels of MASP1 and PRKD2 in the LACC group were higher than those in the ear-ly cervical cancer group and the control group,and the differences were statistically significant(P＜0.05).The serum levels of MASP1 and PRKD2 in LACC group were correlated with International Federation of Gy-necology and Obstetrics(FIGO)stage and pathological grade,and the serum levels of MASP1 and PRKD2 in patients with FIGO stage Ⅲ and pathological grade G3 were higher(P＜0.05).FIGO stage Ⅲ proportion,se-rum MASP1 and serum PRKD2 levels in NACT ineffective group were higher than those in effective group(P＜0.05).FIGO stage Ⅲ,serum MASP1 and serum PRKD2 were independent risk factors for NACT efficacy in LACC patients(P＜0.05).The area under the curve of serum MASP1 and PRKD2 combined to evaluate the efficacy of NACT was 0.883(95％CI:0.828-0.935),which was larger than 0.802(95％CI:0.761-0.846)and 0.825(95％CI:0.764-0.852)predicted by the single index,and the difference were statistically significant(Z=4.111,5.012,both P＜0.001).Conclusion Level of serum MASP1 and PRKD2 in LACC pa-tients are increase,which are independent risk factors affecting the efficacy of NACT.Combined detection of MASP1 and PRKD2 has high predictive value for NACT efficacy.

Objective To explore the efficacy of carotid color Doppler ultrasonography(CDU)combined with transcranial color Doppler ultra sonography(TCCD)in the diagnosis of carotid artery stenosis in elderly patients with acute cerebral infarction(ACI).Methods The clinical data of 306 elderly patients with suspected ACI who were admitted to the Second Affiliated Hospital of Air Force Medical University,and received CDU and TCCD from May 2021 to May 2023 were retrospectively analyzed.The result of digital subtraction angiography(DSA)was taken as the gold standard.The patients were assigned to cerebral infarction group or non-cerebral infarction group according to the gold standard.CDU parameters(peak systolic velocity[PSV]and end diastolic velocity[EDV]of the common carotid artery])and TCCD parameters(resistance index[RI]and pulsatility index[PI]of posterior cerebral artery[PCA])were compared between the two groups.According to the degree of carotid artery stenosis,ACI patients were assigned to mild stenosis subgroup,moderate stenosis subgroup or severe stenosis subgroup.CDU parameters(PSV,EDV)and TCCD parameters(RI,PI)were compared among subgroups.The efficacy of related parameters in the diagnosis of ACI and the degree of carotid artery stenosis was evaluated by receiver operating characteristic(ROC)curve.Results There were 155 patients(50.65%)in the cerebral infarction group and 151 patients(49.35%)in the non-cerebral infarction group.The cerebral infarction group had higher EDV,PSV and RI and lower PI than the non-cerebral infarction group(P＜0.05).The areas under curve(AUC)values of ROC curves of EDV,PSV,RI,PI and their combination in the diagnosis of ACI were 0.577,0.563,0.644,0.643 and 0.726(P＜0.05).The levels of EDV,PSV and RI in the subgroups were as follows:severe stenosis subgroup＞moderate stenosis subgroup＞mild stenosis subgroup,and the change trend of PI was shown as mild stenosis subgroup＞moderate stenosis subgroup＞severe stenosis subgroup(P＜0.05).The AUC values of ROC curves of EDV,PSV,RI,PI and their combination in evaluating the degree of carotid artery stenosis in ACI patients were 0.767,0.802,0.845,0.846 and 0.952(P＜0.05).Conclusion Carotid CDU combined with TCCD can effectively diagnose ACI and carotid artery stenosis,and has high application value for the evaluation of carotid artery stenosis in elderly ACI patients.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.

Objective:To detect pathogenic mutation in a Chinese family affected with isolated bilateral microtia.Methods:During 2022 June to December, one Chinese Han family with non-syndromic bilateral microtia was recruited at the First Hospital of Shanxi Medical University. The clinical data and peripheral blood samples were collected from the family members. Whole genome sequencing (WGS) was performed in the proband to screen all candidate variants. Quantitative PCR was applied to identify the candidate copy number variation (CNV) among the proband, the unaffected wife and the affected son to demonstrate the association between candidate variant and phenotype.Results:The patients in the family had non-syndromic bilateral concha-type microtia. WGS detected the duplication in the intergenic region of HMX1 and CPZ gene in the proband, which involved the evolutionarily conserved region (ECR). Both the proband and his affected son carried the CNV, while his unaffected wife did not have this variation.Conclusion:Duplications involving the long range HMX1 enhancer ECR are associated with the bilateral concha-type microtia in this family.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Objective:To detect pathogenic mutation in a Chinese family affected with isolated bilateral microtia.Methods:During 2022 June to December, one Chinese Han family with non-syndromic bilateral microtia was recruited at the First Hospital of Shanxi Medical University. The clinical data and peripheral blood samples were collected from the family members. Whole genome sequencing (WGS) was performed in the proband to screen all candidate variants. Quantitative PCR was applied to identify the candidate copy number variation (CNV) among the proband, the unaffected wife and the affected son to demonstrate the association between candidate variant and phenotype.Results:The patients in the family had non-syndromic bilateral concha-type microtia. WGS detected the duplication in the intergenic region of HMX1 and CPZ gene in the proband, which involved the evolutionarily conserved region (ECR). Both the proband and his affected son carried the CNV, while his unaffected wife did not have this variation.Conclusion:Duplications involving the long range HMX1 enhancer ECR are associated with the bilateral concha-type microtia in this family.

Objective To investigate the effect of thalidomide combined with infliximab (IFX) in treatment of refractory inflammatory bowel disease (IBD) and its effects on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group, with 60 cases in each group. The two groups were given conventional treatment (mesalazine), the control group was given IFX, and the experimental group was given IFX combined with thalidomide, continuous treatment for two months. The efficacy, intestinal flora disturbance rate, adverse reactions, Crohn's disease activity index (CDAI), Lewis score, serum IGF-1, TGF-β1 levels and nutritional status indexes[albumin (ALB), transferrin (Tf)]before and after treatment for 1 month and 2 months of the two groups were compared. Results The total effective rate of the experimental group was significantly higher than that of the control group (P < 0.05). After one month and two months of treatment, CDAI and Lewis scores of the experimental group were significantly lower than those of the control group (P < 0.05); the serum levels of IGF-1, TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group (P < 0.05). The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group (P < 0.05). There was no significant difference in the incidence of oral and nasal mucosa dryness, throat discomfort, nausea and vomiting between two groups (P>0.05). Conclusion In the treatment of refractory IBD patients, thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels, effectively relieve clinical manifestations, inhibit inflammatory activities, and improve nutritional status and intestinal flora disorders of patients, and it has high safety.

【Objective】 To analyze the characteristics and mobility of the overlapping population of voluntary blood donation and plasmapheresis donation, so as to provide a scientific basis for the formulation of recruitment and retention strategies for blood donation and plasmapheresis donation, and to further propose a scientific reference for the decision-making of blood banks and plasmapheresis station management in China. 【Methods】 The basic information of blood donors and plasmapheresis donors in two counties in Guangyuan, Sichuan Province, which carried out whole blood collection and plasmapheresis collection from the establishment of the station to July 31, 2021 was statistically compared and analzed using the chi-square test and Post hoc testing test. 【Results】 As of July 31, 2021, a total of 50 658 people participated in blood donation and 63 375 people participated in plasmapheresis donation in Jiange County and Cangxi County, with a total overlap of 6 189 people. In the two regions, 16 458 (35.2%) people aged 40 to 50, and 35 558 people (56.1%) were over 50 years old. Among the overlapping population, 2 496 (40.3%) were 40 to 50 years old, accounted for the largest proportion, and 3 146 (50.8%) were males. Significant differences were noticed in age (P<0.001) and gender (P<0.001). There was a shift in dontion in 5 183, including 2 072 people from plasma to blood and 3 111 people from blood to plasma, among which 2 671 (51.5%) were men and 3 632 (70.1%) were over 50 years old, with significant differences in gender (P<0.05) and age (P<0.001). 【Conclusion】 There were a small number of donors donating both blood and plasma in Jiange and Cangxi, and men aged 40 to 50 were the majority, and people over 50 years old were more likely to shift the donation goals. The vast majority of donors have a single and fixed donation goal (blood or plasma), and are not easy to change.