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。

Objective Exploring alterations in regional homogeneity(ReHo)in the brain of adolescents with depression and suicide attempts.Methods Adolescent patients with depression were included.Those with at least one suicide attempt within one year were classified as the suicide attempt group(32 cases),and those without suicide attempts within one year were classified as the non-suicide attempt group(33 cases).Additionally,a healthy control group(31 individuals)was included.All subjects underwent resting-state functional magnetic resonance imaging(fMRI)scans,and the ReHo values were calculated.The severity of depressive symptoms and the suicide risk were evaluated using the patient health questionnaire-9(PHQ-9)and the mini-international neuropsychiatric interview(MINI)suicide scale,respectively.The ReHo values were compared across groups,and the correlations between ReHo values in distinct brain regions and the PHQ-9 and the MINI suicide scales were analyzed.Results Compared with the healthy control group,the ReHo values in the right and left thalamus,right and left precentral gyrus were decreased in the suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected),while the ReHo value in the right superior temporal gyrus was increased(voxel level P<0.001,cluster level P<0.05,GRF corrected).Compared with the healthy control group,the ReHo values in the right midbrain and the right thalamus were decreased in the non-suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected),while the ReHo values in the left middle frontal gyrus,right middle frontal gyrus,and right superior frontal gyrus were increased(voxel level P<0.001,cluster level P<0.05,GRF corrected).Compared with the non-suicide attempt group,the ReHo values in the right medial and paracingulate gyrus were decreased in the suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected).ReHo values in the right superior temporal gyrus of the suicide attempt group showed a positive correlation with PHQ-9 scores(r=0.407,P=0.026).Conclusion Reduced ReHo values in the right medial and paracingulate gyrus at rest in the group with suicide attempt depression may be a potential neural mechanism for suicide in adolescent depressed patients.

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 investigate the neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill(RNSP)on 6-hydroxydopamine(6-OHDA)induced Parkinson's disease model rats and its related mechanism.Methods Totally 48 male SD rats were randomly divided into control group,model group,model plus low-dose RNSP group(90 mg/kg),model plus medium-dose RNSP group(180 mg/kg),model plus high-dose RNSP group(360 mg/kg),and model plus madopar group(50 mg/kg),with 8 rats in per group.Except for the control group,the other rats were treated with 6-OHDA single injection into the striatum to establish the PD model.Each group was given intragastric administration after modeling and the control group and model group were given an equal volume of saline once a day for 4 weeks.The rats were subjected to apomorphine-induced rotation,experiments at the 2nd and 4th week after the completion of modeling,and the open field experiment was conducted the next day after the last rotation experiment to observe the animal behavior.After the behavioral experiment,the rats were stained with tyrosine hydroxylase(TH)in the substantia nigra pars compacta by immunohistochemical method and the positive neurons were counted.The protein levels of Bcl-2,BAX,Caspase-3 in substantia nigra and P38,P-P38,ERK,P-ERK,JNK,P-JNK in the striatum were detected by Western blotting.Results Compared with the control group,the rotation frequency and percentage of rotating rats in the model group increased significantly at the 2nd and 4th weeks after modeling;the open field active distance,average speed and times of crossing the grid were significantly decreased;and the rest time was significantly increased.While the number of TH positive neurons in the substantia nigra was significantly decreased,the BAX and Caspase-3 protein levels were increased significantly,Bcl-2 was decreased significantly,the ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly increased in PD group.Compared with the model group,the rotation frequency and percentage of rotating rats in the low-,medium-and high-dose groups of RNSP had no significant changes after 2 weeks of administration,the rotation frequency in the high-dose group and percentage of rotating rats in the low-and medium-dose RNSP groups significantly decreased after 4 weeks of administration.The open field active distance,average speed,and times of crossing the grid were significantly increased;the rest time was significantly decreased.The number of TH positive neurons in the substantia nigra was significantly increased,the Bax and Caspase-3 protein levels were decreased significantly while the Bcl-2 was significantly increased.The ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly decreased.Conclusion Tibetan medicine RNSP can improve the motor ability and reduce the loss of DA neurons in PD rats,and its mechanism may be related to inhibiting P38/JNK/ERK signaling pathway and reducing the apoptosis of midbrain neurons.

Objective Exploring alterations in regional homogeneity(ReHo)in the brain of adolescents with depression and suicide attempts.Methods Adolescent patients with depression were included.Those with at least one suicide attempt within one year were classified as the suicide attempt group(32 cases),and those without suicide attempts within one year were classified as the non-suicide attempt group(33 cases).Additionally,a healthy control group(31 individuals)was included.All subjects underwent resting-state functional magnetic resonance imaging(fMRI)scans,and the ReHo values were calculated.The severity of depressive symptoms and the suicide risk were evaluated using the patient health questionnaire-9(PHQ-9)and the mini-international neuropsychiatric interview(MINI)suicide scale,respectively.The ReHo values were compared across groups,and the correlations between ReHo values in distinct brain regions and the PHQ-9 and the MINI suicide scales were analyzed.Results Compared with the healthy control group,the ReHo values in the right and left thalamus,right and left precentral gyrus were decreased in the suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected),while the ReHo value in the right superior temporal gyrus was increased(voxel level P<0.001,cluster level P<0.05,GRF corrected).Compared with the healthy control group,the ReHo values in the right midbrain and the right thalamus were decreased in the non-suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected),while the ReHo values in the left middle frontal gyrus,right middle frontal gyrus,and right superior frontal gyrus were increased(voxel level P<0.001,cluster level P<0.05,GRF corrected).Compared with the non-suicide attempt group,the ReHo values in the right medial and paracingulate gyrus were decreased in the suicide attempt group(voxel level P<0.001,cluster level P<0.05,GRF corrected).ReHo values in the right superior temporal gyrus of the suicide attempt group showed a positive correlation with PHQ-9 scores(r=0.407,P=0.026).Conclusion Reduced ReHo values in the right medial and paracingulate gyrus at rest in the group with suicide attempt depression may be a potential neural mechanism for suicide in adolescent depressed patients.

Objective To explore the predictive value of ultra-sound(US)combined with multi-sequence MRI in a clinical-deep learning radiomics nomogram(DLRN)for the short-term efficacy of neoadjuvant chemotherapy(NAC)in patients with triple-negative breast cancer(TNBC).Methods A total of 122 TNBC patients from five hospitals were retrospectively analyzed,and divided into training group(72 cases)and validation group(50 cases).The clinical and pathological data,NAC regimens,and imaging data were collected.The lesions and its surrounding 10-unit voxels from US and MRI images were retained as the region of interest(ROI).Pyradiomics software and a ResNet152 convolutional neural network(CNN)framework were used to extract radiomics and deep learning features to construct a clinical-DLRN with outcome dimension fusion.The receiver operating characteristic(ROC)curve and calibration curve were plotted,and five-fold cross-validation decision curve were used to verify the model's clinical effec-tiveness.Results The clinical-DLRN constructed by US combined with multi-sequence MRI showed that area under the curve(AUC)was 0.967[95％confidence interval(CI)0.782-0.967]and accuracy(ACC)was 0.900,respectively.The five-fold cross-validation decision curve showed good generalization,with the highest clinical net benefit between risk thresholds of 0.72 and 0.96.Conclusion The clinical-DLRN integrating US and multi-sequence MRI has the best efficacy in predicting the short-term efficacy of NAC in TNBC patients,which offering potential guidance for personalized TNBC treatment.

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 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.