Objective To observe the effects of Bushen Zhuyun Prescription on regulating mitochondrial function and endometrial angiogenesis;To explore its mechanism of improving endometrial receptivity.Methods The mouse model of controlled ovarian hyperstimulation(COH)was established,and the mice were randomly divided into normal group,model group,and Bushen group,with 20 mice in each group.Bushen group received Bushen Zhuyun Prescription for gavage for 11 d,and the normal group and model group received normal saline for gavage.The number of embryo implantation was counted,the endometrial morphology was observed by HE staining,α-smooth muscle actin(α-SMA)expression was observed by immunofluorescence staining.Human endometrial microvascular endothelial cells(HEMECs)were cultured in vitro,they were divided into control group,VEGFA group,Bushen group and VEGFA + Bushen group,and were intervened with VEGFA and/or Bushen Zhuyun Prescription medicated serum.The activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ,the content of ATP,the expression of PCNA and Caspase-3 were detected.Results Animal experiment showed that,compared with the normal group,the number of embryo implantation in model group significantly decreased(P<0.05),α-SMA protein expression in endometrial tissue significantly decreased(P<0.05);compared with the model group,the number of embryo implantation in Bushen group significantly increased(P<0.05),α-SMA protein expression in endometrial tissue significantly increased(P<0.05).Cell experiment showed that,Bushen Zhuyun Prescription medicated serum could increase the activity of mitochondrial respiratory chain complexes Ⅰ-Ⅳ and ATP content in HEMECs,promote PCNA protein expression,and inhibit Caspase-3 protein expression(P<0.05,P<0.01).Conclusion Bushen Zhuyun Prescription can promote endometrial angiogenesis through improving mitochondrial function.

Objective:To search for potential synergistic drugs that can enhance the inhibitory effect of lenvatinib on the proliferation of hepatocellular carcinoma cells by compound screening and explore the underlying molecular mechanisms.Methods:The impact of lenvatinib on the proliferation of Huh7 cells was detected using CCK-8 assay and long-term cell proliferation assays.The potential synergistic drugs for lenvatinib in Huh7 cells was screened using an FDA-approved compound library.Subsequently,the inhibitory effect of lenvatinib combined with zinc pyrithione on the proliferation of Huh7 cells was assessed using CCK-8 assay and long-term cell proliferation assay.Furthermore,RNA-sequencing was utilized to investigate the changes in gene expression profiles following the combined action of zinc pyrithione and lenvatinib,exploring the potential molecular mechanisms.The impact of combination therapy on signaling pathways was investigated through Gene Set Enrichment Analysis(GSEA)and Gene Ontology Analysis(GO).Results:Lenvatinib exerts dose-dependent inhibition on the proliferation of Huh7 in vitro(IC50 value=0.190 μmol/L).Screening of compound libraries identified zinc pyrithione as a compound that synergistically promotes the inhibition of Huh7 cell proliferation by lenvatinib.This result was further validated through CCK-8 assay(P<0.05)and long-term cell proliferation experiments.Compared to treatment with lenvatinib alone,the combination treatment of zinc pyrithione and lenvatinib upregulated signaling pathways related to oxidative stress response,apoptosis,and cellular responses to copper ions in Huh7 cells,with Gene Set Enrichment Analysis(GSEA)showing significant enrichment of the oxidative phosphorylation pathway.Conclusion:Lenvatinib can inhibit the proliferation of Huh7 cells in vitro,while Zinc Pyrithione can synergize with lenvatinib to exert a more significant inhibitory effect on the Huh7 cells.The molecular mechanism of this synergistic effect may involve generation of a large amount of reactive oxygen species(ROS)to induce apoptosis of liver cancer cells through oxidative stress response,as well as promoting the death of hepatocellular carcinoma cells by disrupting copper homeostasis.

Objective:To search for potential synergistic drugs that can enhance the inhibitory effect of lenvatinib on the proliferation of hepatocellular carcinoma cells by compound screening and explore the underlying molecular mechanisms.Methods:The impact of lenvatinib on the proliferation of Huh7 cells was detected using CCK-8 assay and long-term cell proliferation assays.The potential synergistic drugs for lenvatinib in Huh7 cells was screened using an FDA-approved compound library.Subsequently,the inhibitory effect of lenvatinib combined with zinc pyrithione on the proliferation of Huh7 cells was assessed using CCK-8 assay and long-term cell proliferation assay.Furthermore,RNA-sequencing was utilized to investigate the changes in gene expression profiles following the combined action of zinc pyrithione and lenvatinib,exploring the potential molecular mechanisms.The impact of combination therapy on signaling pathways was investigated through Gene Set Enrichment Analysis(GSEA)and Gene Ontology Analysis(GO).Results:Lenvatinib exerts dose-dependent inhibition on the proliferation of Huh7 in vitro(IC50 value=0.190 μmol/L).Screening of compound libraries identified zinc pyrithione as a compound that synergistically promotes the inhibition of Huh7 cell proliferation by lenvatinib.This result was further validated through CCK-8 assay(P<0.05)and long-term cell proliferation experiments.Compared to treatment with lenvatinib alone,the combination treatment of zinc pyrithione and lenvatinib upregulated signaling pathways related to oxidative stress response,apoptosis,and cellular responses to copper ions in Huh7 cells,with Gene Set Enrichment Analysis(GSEA)showing significant enrichment of the oxidative phosphorylation pathway.Conclusion:Lenvatinib can inhibit the proliferation of Huh7 cells in vitro,while Zinc Pyrithione can synergize with lenvatinib to exert a more significant inhibitory effect on the Huh7 cells.The molecular mechanism of this synergistic effect may involve generation of a large amount of reactive oxygen species(ROS)to induce apoptosis of liver cancer cells through oxidative stress response,as well as promoting the death of hepatocellular carcinoma cells by disrupting copper homeostasis.

Objective:To explore the influencing factors for pulmonary complications of patients with Parkinson's disease (PD) after deep brain stimulation (DBS), and to construct a nomogram model for predicting pulmonary complications after DBS.Methods:Two hundred and seventy-two patients with PD accepted DBS, admitted to our hospital from March 2015 to December 2019, were chosen in our study; they were divided into pulmonary complication group ( n=56) and non-pulmonary complication group ( n=216). The clinical data of patients from the two groups were compared retrospectively. Multivariate Logistic regression was used to analyze the risk factors for pulmonary complications of patients with PD after DBS, and a nomogram model was established to predict the risk of pulmonary complications; receiver operating characteristic (ROC) curve was used to analyze the prediction performance of the model. Results:As compared with non-pulmonary complication group, the pulmonary complication group had significantly higher percentages of patients with history of pulmonary disease, preoperative albumin<35 g/L, preoperative forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)<60%, operation time≥180 min, and age≥70 years, and significantly lower Parkinson's disease sleep scale (PDSS) scores, unified Parkinson's disease rating scale Ⅲ (UPDRS Ⅲ) scores, and preoperative albumin level, and statistically longer postoperative hospital stays ( P<0.05). Multivariate Logistic regression analysis results showed that history of pulmonary disease ( OR=4.230, 95%CI: 2.035-8.207), preoperative albumin<35 g/L ( OR=6.159, 95%CI: 2.570-5.091), preoperative FEV1/FVC<60% ( OR=31.771, 95%CI: 6.702-66.412), operation time≥180 min ( OR=3.550, 95%CI: 2.261-10.065), age≥70 years ( OR=3.714, 95%CI: 1.451-4.827), and PDSS scores ( OR=1.017, 95%CI: 1.351-13.880) were the independent risk factors for pulmonary complications of patients with PD after DBS. Nomogram model established by using the above indicators showed that area under the curve for predicting pulmonary complications of patients with PD after DBS was 0.841 ( 95%CI: 0.774-0.904, P=0.000), with sensitivity of 84.03% and specificity of 75.06%. Conclusion:PD patients with history of pulmonary disease, preoperative albumin<35 g/L, preoperative FEV1/FVC<60%, operation time≥180 min, age≥70 years, and low PDSS scores are trend to have pulmonary complications after DBS; the nomogram model based on the above variables is highly effective in predicting the risk of postoperative pulmonary complications.

Objective Transient brain function inhibition is a common symptom after mild brain injury,but some patients show persistent post-concussional syndrome (PCS).The aims of this study are to assess functional and causal connectivity of attention and default mode network using resting-state functional MR imaging (fMRI) to investigate the abnormal connectivity and its significance in PCS patients.Methods Resting-state fMRI data were collected from 23 PCS patients with attention disorders,admitted to our hospital from November 2015 to October 2016 and 21 age-,gender,and education-matched healthy controls recruited at the same period.The fMRI data were analyzed by group independent component analysis (ICA) toolbox to attention networks and default mode network (DMN).The components of the selected networks were compared in PCS and healthy controls to explore the changes of functional connectivity (FC).Granger causality analysis (GCA) was performed by taking the above significant brain areas as regions of interest (ROIs) to calculate bivariate coefficient of each pair of ROIs.Comparisons were performed to find the significant different causal connectivity of the two groups.Results In attention networks,the FC value of left frontal eye field (FEF),bilateral intraparietal sulcus (IPS),bilateral ventral prefrontal cortex (vPFC) and bilateral temporo-parietal junction (TPJ) was decreased.In DMN,the FC value of bilateral medial prefrontal cortex (mPFC) was reduced and bilateral precuneus (PCUN) was enhanced.Correlating GCA value,it was increased significantly from left FEF to left PCUN and IPS,while it was reduced from left PCUN and IPS to left FEF;and it was decreased from left IPS to left vPFC and increased from left TPJ to left PCUN.Conclusion The attention networks are restrained in resting state,which may influence the attention function in PCS patients;and the causal connection is altered in the above ROIs,and these changes may be related to inhibition of activation of default network to compensate for the loss of attention function by antagonistic effects in PCS patients.

ObjectiveTo explore the changes of degree attribute values and its significance of post-concussion syndrome (PCS) patients with tinnitus by the brain network research method based on graph theory.Methods34 PCS patients were chosen,including 17 PCS patients with bilateral tinnitus (PCS tinnitus group) and 17 PCS patients without tinnitus (PCS non-tinnitus group).Meanwhile,17 healthy individuals with the matched age,gender and educational background were recruited as the control.Degree attribute values of PCS patients with tinnitus were figured out with the brain network research method based on graph theory.Results(1)The degree attribute values of PCS patients without tinnitus at left orbital middle frontal gyrus (3.13±1.07),left thalamus (2.51±1.03),left superior temporal gyrus (3.67±1.31),right anterior cingulate cortex (3.13±1.25),right posterior cingulate cortex (2.13±1.08) and right supramarginal gyrus (4.46±1.35) were reduced compared with the control group (4.41±1.47,3.71±1.08,5.27±2.13,5.51±0.67,5.63±2.16 and 5.64±1.30) (P<0.05).The degree attribute values of PCS patients without tinnitus at left posterior cingulate cortex (5.87±1.06) and left gyrus lingualis (4.67±1.48) increased compared with the control group (4.41±1.46,3.21±1.27) (P<0.05).(2) The degree attribute values of PCS patients with tinnitus at left posterior cingulate cortex (3.37±1.54),left parahippocampal gyrus (3.41±1.62),left amygdala (2.25±1.43),left angular gyrus (4.17±1.02),left superior temporal gyrus (3.25±1.02),right thalamus (2.35±1.34),right Heschl gyri (3.97±1.62),right superior temporal gyrus (3.26±1.22),right cuneus (3.18±1.32) and right lingular lobe (3.26±1.42) were decreased,compared with the control group (4.41±1.46,5.27±2.13,3.71±1.08,5.63±2.61,5.64±1.30,3.43±1.33,5.63±2.16,5.13±1.64,5.51±0.67,4.24±0.63) (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex (5.76±1.83),left MPFC (6.08±1.62) and right precuneus (6.08±1.06) were increased,compared with the control group (4.47±1.26,4.41±1.47,4.81±0.62) (P<0.05).(3)The degree attribute values of PCS patients with tinnitus at left MPFC,left amygdale,left parahippocampal gyrus,right Heschl gyri,right superior temporal gyrus,right cuneus and right lingular lobe were decreased,compared with PCS patients without tinnitus (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex and left insular lobe increased,compared with PCS patients without tinnitus (P<0.05).ConclusionsPCS patients with tinnitus present the alteration of degree attribute in related brain network structure.The alteration in degree attribute of relevant brain zones in auditory system,limbic system and default network system may be important factors which result in tinnitus of PCS patients.

Objective To explore the functional imaging alteration of dorsal attention network (DAN) between heroin addicts and heroin abstainers and probe into its influence on attentional function.Methods Attention-related neuropsychological assessments were applied to evaluate the difference of attentional function between heroin addicts and heroin abstainers.With the functional magnetic resonance imaging (fMRI) data obtained from 17 heroin addicts and 15 heroin abstainers at resting state,we extracted the DANs of heroin withdrawal group and heroin dependence group respectively by using independent component analysis (ICA) and analysed the differences of intra-group and inter-group,then correlation analysis was performed among brain areas which have significant difference between groups and Stroop interference effect test.Results Compared with the heroin dependence group,there was a better result of attentional function in the heroin withdrawal group (P＜0.05),especially at the digit span test(backward) (P=0.0363),digit symbol test (writing) (P =0.0195),Stroop test C (reaction) (P =0.0379),Stroop test C (error) (P=0.0014) and Stroop interference effect test (P=0.0002).Neuroimaging findings demonstrated that there was a similar DAN in the heroin withdrawal group and heroin dependence group which mainly included the bilateral intraparietal suleus,postcentral gyrus and frontal eye field.Compared with the DAN of heroin addicts,significantly enhanced functional connectivity within the DAN of heroin abstainers was observed in the left superior parietal lobule (MIN:-24,-75,48),right inferior parietal lobule (MIN:39,-54,45) and left inferior parietal lobule (MIN:-33,-51,57).Significant negative correlations were observed between these brain areas and Stroop interference effect test in the heroin dependence group (r=-0.79,-0.69,-0.64,P＜0.01),but not in the heroin withdrawal group.Conclusions Heroin addiction can impair attentional function,compared with the DAN of heroin addicts,significantly enhanced functional connectivity in the left superior parietal lobule as well as bilateral inferior parietal lobule are observed in the heroin abstainers at resting state,which may be one of the neural mechanisms of attentional function improvement.

Objective To investigate the functional imaging alteration of default mode network (DMN) and its significance in heroin addicts by using the functional magnetic resonance imaging (fMRI) technology and independent component analysis (ICA).Methods Resting state fMRI data of 14 heroin addicts and 14 normal controls were analyzed by using ICA,and then the difference of functional connectivity in the DMN was acquired by analyzing the data of intra-group and inter-group respectively.Results Compared with the normal controls,heroin addicts showed decreased functional connectivity in the medial superior frontal gyrus (t =-2.61),anterior cingutate cortex (t =-3.32) and cuneus (tleft =-3.49,tright =-3.40); and increased functional connectivity in the posterior cingulate cortex (t =4.55),precuneus (tleft =4.31,tright =3.54) and angular gyrus (tleft =2.57,tright =6.39) in the DMN (all P ＜0.05).Conclusion The DMN of heroin addicts may have abnormal functional connectivity at resting state.

Objective To investigate the functional imaging alteration of default mode network (DMN) and its significance in heroin addicts by using the functional magnetic resonance imaging (fMRI) technology and independent component analysis (ICA).Methods Resting state fMRI data of 14 heroin addicts and 14 normal controls were analyzed by using ICA,and then the difference of functional connectivity in the DMN was acquired by analyzing the data of intra-group and inter-group respectively.Results Compared with the normal controls,heroin addicts showed decreased functional connectivity in the medial superior frontal gyrus (t =-2.61),anterior cingutate cortex (t =-3.32) and cuneus (tleft =-3.49,tright =-3.40); and increased functional connectivity in the posterior cingulate cortex (t =4.55),precuneus (tleft =4.31,tright =3.54) and angular gyrus (tleft =2.57,tright =6.39) in the DMN (all P ＜0.05).Conclusion The DMN of heroin addicts may have abnormal functional connectivity at resting state.

Objective To investigate the relationship between impulsive behaviors and the errorrelated negativity (ERN) component of event-related potentials of error processing in heroin addicts.Methods Using the paradigms for psychological experiment,the Iowa gambling task (IGT) was performed both in heroin addiction group (HA group,20 cases) and healthy control group (HC group,20 cases),and the inspection of electroencephalography was underwent in all subjects concurrently.Following the collection of data,the amplitude and latency of ERN were compared between the two groups,and then the relationship between the amplitude of ERN and the scores of Barratt Impulsiveness Scale (BIS-11) was analyzed separately.Results Decision-making course had no effect on the net score remarkably in HA group (F =1.21,P ＞0.05).Compared with HC group(64.3 ±8.4,73.8 ± 16.4),BIS score as well as the numbers of high frequency loss cards were significantly higher in HA group(75.2 ±7.6,105.5 ±22.2; t =-5.39,-9.24 ; P ＜ 0.05),while both the two groups had visible waveforms of ERN,and the amplitude was markedly lower in HA group(HA:(4.23 ±0.87) μV,HC:(6.11 ± 1.09) μV; t =5.96,P ＜0.05),but no statistical difference was found in latency of these two groups(HC:(102.1 ±28.2) ms,HA:(107.8 ±24.2) ms;t =-0.62,P =0.54),and the amplitude of the two groups was negatively associated with BIS score respectively in both two groups (HC:r =-0.66,HA:r =-0.78 ; both P ＜ 0.05).Conclusion The reduced capability of error processing maybe partly contribute to both addiction and relapse to heroin addict,and the ERN event-related potential could be regarded as an indicator of impulsive behaviors and the capability error processing.