OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

[摘 要] 目的：探讨lncRNA核内富集丰富转录本1（NEAT1）调控miR-1287-5p/DNA损伤诱导转录本4（DDIT4）轴对卵巢癌SKOV3细胞增殖、凋亡和侵袭的影响及其机制。方法：收集2023年6月至2024年6月期间湖北医药学院附属随州医院手术切除的27例卵巢癌患者的癌及癌旁组织标本，以及正常人卵巢上皮细胞IOSE80和卵巢癌细胞系SKOV3、CAOV3和A2780，RT-qPCR检测卵巢癌组织与细胞中lncRNA NEAT1、miR-1287-5p及DDIT4 mRNA表达。将SKOV3细胞分为Ctrl组、si-NC组、si-NEAT1组、si-NEAT1 + anti-miR-NC组、si-NEAT1 + anti-miR-1287-5p组、si-NEAT1 + vector组、si-NEAT1 + OE-DDIT4组。CCK-8法、克隆形成实验、流式细胞术、Transwell实验分别检测各组细胞增殖、凋亡及侵袭能力，WB法检测细胞中DDIT4、细胞周期蛋白D1（cyclin D1）、p53、迁移侵袭增强子1（MIEN1）蛋白水平。双萤光素酶报告基因验证lncRNA NEAT1与miR-1287-5p/DDIT4靶向结合关系，RNA pull-down实验、RNA免疫沉淀实验分别验证lncRNA NEAT1与miR-1287-5p、miR-1287-5p与DDIT4的靶向结合关系。另设pcDNA组（转染空载体pcDNA3.1）和pc-NEAT1 组（转染pcDNA-NEAT1）以验证NEAT1过表达效应。结果：卵巢癌组织中lncRNA NEAT1、DDIT4 mRNA表达水平显著高于癌旁组织（P < 0.05），而miR-1287-5p表达显著低于癌旁组织（P < 0.05）。敲低lncRNA NEAT1后，与Ctrl组和si-NC组相比，si-NEAT1组lncRNA NEAT1表达、DDIT4 mRNA表达均显著降低（均P < 0.05），miR-1287-5p 表达显著升高（P < 0.05）；而过表达lncRNA NEAT1则下调miR-1287-5p表达并上调DDIT4表达，呈现与敲低实验相反的调控效应；敲低lncRNA NEAT1后，克隆形成数、细胞增殖活性、细胞侵袭数均显著降低（均P < 0.05），细胞凋亡率显著升高（P < 0.05）；DDIT4、cyclin D1、MIEN1蛋白表达均显著降低（均P < 0.05），p53蛋白表达显著升高（P < 0.05）。进一步实验证实，anti-miR-1287-5p或OE-DDIT4均可减弱si-NEAT1对SKOV3细胞增殖和侵袭的抑制作用，同时减弱其对细胞凋亡的促进作用。lncRNA NEAT1靶向调控miR-1287-5p/DDIT4。结论：lncRNA NEAT1通过靶向调控miR-1287-5p/DDIT4轴促进SKOV3细胞增殖和侵袭，抑制细胞凋亡。

ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.

In recent years, hybrid brain-computer interfaces (BCIs) have gained significant attention due to their demonstrated advantages in increasing the number of targets and enhancing robustness of the systems. However, Existing studies usually construct BCI systems using intense auditory stimulation and strong central visual stimulation, which lead to poor user experience and indicate a need for improving system comfort. Studies have proved that the use of peripheral visual stimulation and lower intensity of auditory stimulation can effectively boost the user's comfort. Therefore, this study used high-frequency peripheral visual stimulation and 40-dB weak auditory stimulation to elicit steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) signals, building a high-comfort hybrid BCI based on weak audio-visual evoked responses. This system coded 40 targets via 20 high-frequency visual stimulation frequencies and two auditory stimulation frequencies, improving the coding efficiency of BCI systems. Results showed that the hybrid system's averaged classification accuracy was (78.00 ± 12.18) %, and the information transfer rate (ITR) could reached 27.47 bits/min. This study offers new ideas for the design of hybrid BCI paradigm based on imperceptible stimulation.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Acoustic Stimulation ; Photic Stimulation ; Electroencephalography ; Evoked Potentials, Auditory/physiology* ; Adult

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

Objective:To explore the characteristics of blood lipid profile and its correlation with clinical features and cytokines in patients with active systemic sclerosis (SSc).Methods:In this study, from January 2018 to March 2023, a total of 102 SSc patients visited the Second Hospital of Shanxi Medical University and the First Hospital of Shanxi Medical University were enrolled, among which 57 cases were localized skin type, 25 cases were diffuse skin type, 20 cases were overlap syndrome. At the same time, 89 gender and age-matched health check-up subjects in the Second Hospital of Shanxi Medical University were selected as the healthy control group. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were compared between the two groups. According to the blood lipid level, they were grouped into normal blood lipid group and abnormal group, TG elevated group and normal group, HDL-C decreased group and normal group. The association between various lipid groups and organ involvement, modified Rodnan skin score (mRSS), laboratory examination and cytokines were analyzed. Continuous data were analyzed using t-test or Mann-Whitney U test, count data were tested with chi-square test, and Spearman correlation analysis was used for correlation analysis. Results:The level of TG [1.31 (1.04, 1.77) mmol/L vs. 1.05 (0.79, 1.35) mmol/L] and LDL-C [(2.33±0.69)mmol/L vs. (2.12±0.64) mmol/L] in active SSc patients were higher than that in HCs, and the level of TC [(4.27±1.11)mmol/L vs. (4.85±0.98)mmol/L] was lower than that in HCs ( Z=3.821, P<0.001; t=2.171, P=0.031; t=-3.791, P<0.001). Fifty-six (54.9%) SSc patients had dyslipidemia, the incidence of the TG increase and the HDL-C reduction was significantly higher. ESR, mRSS score and renal involvement in the dyslipidemia group were higher than that in normal blood lipid group. mRSS score and the incidence of cardiac and renal involvement were higher in the TG elevated group than that in normal group. TG was positively correlated with the mRSS scores ( r=0.321, P=0.001). The incidence of ESR increase and cardiac involvement was higher in HDL-C decreased group than that in normal group, while anti-Scl-70 positive rate was lower. HDL-C was negatively correlated with the ESR ( r=-0.411, P<0.001). In active SSc patients, levels of IL-2[2.78(2.04, 4.96)pg/ml], IL-6[14.71(7.74,28.38)pg/ml], IL-17[10.73(4.38, 26.62)pg/ml], and IFN-γ[5.40(3.11, 10.45)pg/ml] in the dyslipidemia group were higher than those in normal blood lipid group [IL-2:1.73(0.96, 3.75)pg/ml, Z=2.452, P=0.014; IL-6:6.78(4.38, 9.17)pg/ml, Z=3.726, P<0.001; IL-17:4.46(2.98, 12.53)pg/ml, Z=2.176, P=0.030;IFN-γ:3.76(2.20, 4.87)pg/ml, Z=2.960, P=0.003]. TG was positively associated with IL-2( r=0.358, P=0.002), IL-6( r=0.324, P=0.006), IL-10( r=0.270, P=0.024), IL-17( r=0.279, P=0.019), and IFN-γ( r=0.297, P=0.012)in patients with active SSc. HDL-C was negatively associated with levels of IL-2( r=-0.292, P=0.014), IL-6( r=-0.348, P=0.003), IL-10 ( r=-0.261, P=0.029)and TNF-α( r=-0.251, P=0.036). Conclusion:The incidence of dyslipidemia is higher in active SSc patients than that in HCs, the main manifestations are increased TG and LDL-C and decreased TC and HDL-C. Active SSc patients with dyslipidemia have higher levels of ESR and inflammatory cytokines, higher incidence of cardiac and renal involvement, and relatively severe skin fibrosis, which suggest that abnormal lipid metabolism plays an important role in the development of active SSc and organ involvement.

Objective:To learn about the distribution characteristics of marmot in Qinghai-Tibet Plateau Himalayan marmot plague foci, and to study the spatial-temporal patterns and variation characteristics of Himalayan marmot density in the Yarlung Zangbo River, Lhasa River and Nyangqu River Region. Methods:The density survey data of Himalayan marmot from 2001 to 2019 in the Qinghai-Tibet Plateau were collected from the Tibet Autonomous Region Center for Disease Control and Prevention, and the habitat characteristic data of Himalayan marmot were collected from the database of the Resource and Environmental Science Data Platform of Chinese Academy of Sciences and other relevant institutions. Based on the density survey data of Himalayan marmot and its habitat characteristics, five regression models were constructed. The best regression model was selected by comparing the accuracy indicators [root-mean-square error ( RMSE), coefficient of determination ( R 2), mean absolute error ( MAE), and mean bias error ( MBE)]. The habitat characteristics of Himalayan marmot at the basin scale from 2001 to 2019 were included in the best regression model to analyze the spatial-temporal pattern of the density of Himalayan marmot, and the hotspot analysis was used to analyze the aggregation pattern of the density of Himalayan marmot. Results:In the constructed regression models, the random forest regression model had high accuracy, with RMSE of 0.05, R 2 of 0.65, MAE of 0.02, and MBE of 0.01. Among the characteristics of various habitats, the contribution of average temperature was the highest, at 0.85. The prediction results of the random forest regression model showed that the density distribution of Himalayan marmot at the basin scale was basically similar in different years, and the overall spatial distribution characteristics were "high in the north, low in the south" and "high in the east and west, low in the middle". The northwest of Xietongmen County, the northeast of Maizhokunggar County, and the north of Namling County were hotspot area. Conclusions:The distribution of Himalayan marmot in the Yarlung Zangbo River, Lhasa River and Nyangqu River Region has obvious spatial aggregation, and the high-density aggregation areas of Himalayan marmot in different years are basically similar. It is necessary to continue to monitor the density of Himalayan marmot and strengthen the prevention and control of plague.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.