OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective To explore the value of diffusion kurtosis imaging(DKI)in the diagnosis of Parkinson's disease with mild cognitive impairment(PD-MCI)patients.Methods A total of 18 patients with Parkinson's disease cognitive normal(PDN),22 patients with PD-MCI,and 24 healthy controls(HC)were prospectively included.All participants underwent DKI,and regions of interest(ROI)were selected in the substantia nigra,red nucleus,striatum,and posterior cingulate gyrus for post-processing.The diagnostic efficacy of DKI parameters on PD patients' cognitive status was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the PDN group,the PD-MCI group had a longer disease duration and a higher H-Y stage.Compared with the HC group,the PD-MCI group showed significantly lower mean kurtosis(MK),radial kurtosis(RK),axial kurtosis(AK),and fractional anisotropy(FA)values in the substantia nigra and posterior cingulate gyrus.In the PDN group,FA and MK values in the substantia nigra were significantly decreased,while FA values in the striatum and posterior cingulate gyrus were significantly increased(P＜0.05).Compared with the PDN group,the PD-MCI group showed significantly decreased DKI parameter values in the substantia nigra and posterior cingulate gyrus,and significantly decreased RK,AK,and FA values in the striatum(P＜0.05).The FA values of striatum,posterior cingulate gyrus and joint predictors were the most effective in the diagnosis of PD-MCI and the area under the curve(AUC)were 0.826,0.853 and 0.960,respectively.Conclusion DKI can detect microstructural changes in PD patients.Microstructural alterations in the striatum and posterior cingulate gyrus have an impact on early cognitive function changes in PD patients.FA demonstrate high sensitivity and specificity in the diagnosis of PD-MCI,and the combined diagnostic efficacy across multiple regions is even higher.

Objective:To systematically evaluate the influencing factors of retinal re-detachment after the first silicone oil removal.Methods:Chinese databases (CNKI, CBM, VIP, Wanfang) and English databases (PubMed, Cochrane, Embase, Web of science) were searched to retrieve the factors affecting the retinal re-detachment after the first pars plana vitrectomy (PPV) combined with silicone oil removal from the inception of the databases to August 20, 2023.The quality of literature was evaluated according to the Newcastle-Ottawa Scale (NOS).The influencing factors related to the retinal re-detachment after the first silicone oil removal were extracted from the literature, and the influencing factors mentioned in <3 literatures were excluded.RevMan5.3 software was used for quantitative and comprehensive analysis.Results:A total of 14 articles were included, including 3 393 eyes, with 498 eyes in the recurrent group, and 2 895 eyes in the non-recurrent group.The results of meta-analysis showed that high myopia (odds ratio [ OR]=1.40, 95% confidence interval [ CI]: 1.08-1.81), giant retinal hole( OR=2.36, 95% CI: 1.63-3.41), vitreous residue ( OR=130.02, 95% CI: 66.03-256.02), intraocular lens status before PPV ( OR=1.86, 95% CI: 1.26-2.75) were the risk factors for retinal re-detachment after silicone oil removal.Rhegmatogenous retinal detachment ( OR=0.68, 95% CI: 0.50-0.92), PPV combined with external scleral compression ( OR=0.63, 95% CI: 0.45-0.88) and fundus laser photocoagulation 2-4 weeks before silicone oil removal ( OR=0.25, 95% CI: 0.13-0.49) were protective factors for retinal detachment after silicone oil removal.The results of sensitivity analysis showed that there was no significant change in the analysis results after changing the analysis model.There was no publication bias among the included studies. Conclusions:High myopia, giant retinal detachment, vitreous residue and intraocular lens status before PPV increased the risk of retinal re-detachment after the first silicone oil removal, Rhegmatogenous retinal detachment, PPV combined with external scleral pressure and fundus laser photocoagulation 2-4 weeks before silicone oil removal may be protective factors.

Objective:To systematically evaluate the influencing factors of retinal re-detachment after the first silicone oil removal.Methods:Chinese databases (CNKI, CBM, VIP, Wanfang) and English databases (PubMed, Cochrane, Embase, Web of science) were searched to retrieve the factors affecting the retinal re-detachment after the first pars plana vitrectomy (PPV) combined with silicone oil removal from the inception of the databases to August 20, 2023.The quality of literature was evaluated according to the Newcastle-Ottawa Scale (NOS).The influencing factors related to the retinal re-detachment after the first silicone oil removal were extracted from the literature, and the influencing factors mentioned in <3 literatures were excluded.RevMan5.3 software was used for quantitative and comprehensive analysis.Results:A total of 14 articles were included, including 3 393 eyes, with 498 eyes in the recurrent group, and 2 895 eyes in the non-recurrent group.The results of meta-analysis showed that high myopia (odds ratio [ OR]=1.40, 95% confidence interval [ CI]: 1.08-1.81), giant retinal hole( OR=2.36, 95% CI: 1.63-3.41), vitreous residue ( OR=130.02, 95% CI: 66.03-256.02), intraocular lens status before PPV ( OR=1.86, 95% CI: 1.26-2.75) were the risk factors for retinal re-detachment after silicone oil removal.Rhegmatogenous retinal detachment ( OR=0.68, 95% CI: 0.50-0.92), PPV combined with external scleral compression ( OR=0.63, 95% CI: 0.45-0.88) and fundus laser photocoagulation 2-4 weeks before silicone oil removal ( OR=0.25, 95% CI: 0.13-0.49) were protective factors for retinal detachment after silicone oil removal.The results of sensitivity analysis showed that there was no significant change in the analysis results after changing the analysis model.There was no publication bias among the included studies. Conclusions:High myopia, giant retinal detachment, vitreous residue and intraocular lens status before PPV increased the risk of retinal re-detachment after the first silicone oil removal, Rhegmatogenous retinal detachment, PPV combined with external scleral pressure and fundus laser photocoagulation 2-4 weeks before silicone oil removal may be protective factors.

Objective To explore the value of diffusion kurtosis imaging(DKI)in the diagnosis of Parkinson's disease with mild cognitive impairment(PD-MCI)patients.Methods A total of 18 patients with Parkinson's disease cognitive normal(PDN),22 patients with PD-MCI,and 24 healthy controls(HC)were prospectively included.All participants underwent DKI,and regions of interest(ROI)were selected in the substantia nigra,red nucleus,striatum,and posterior cingulate gyrus for post-processing.The diagnostic efficacy of DKI parameters on PD patients' cognitive status was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the PDN group,the PD-MCI group had a longer disease duration and a higher H-Y stage.Compared with the HC group,the PD-MCI group showed significantly lower mean kurtosis(MK),radial kurtosis(RK),axial kurtosis(AK),and fractional anisotropy(FA)values in the substantia nigra and posterior cingulate gyrus.In the PDN group,FA and MK values in the substantia nigra were significantly decreased,while FA values in the striatum and posterior cingulate gyrus were significantly increased(P＜0.05).Compared with the PDN group,the PD-MCI group showed significantly decreased DKI parameter values in the substantia nigra and posterior cingulate gyrus,and significantly decreased RK,AK,and FA values in the striatum(P＜0.05).The FA values of striatum,posterior cingulate gyrus and joint predictors were the most effective in the diagnosis of PD-MCI and the area under the curve(AUC)were 0.826,0.853 and 0.960,respectively.Conclusion DKI can detect microstructural changes in PD patients.Microstructural alterations in the striatum and posterior cingulate gyrus have an impact on early cognitive function changes in PD patients.FA demonstrate high sensitivity and specificity in the diagnosis of PD-MCI,and the combined diagnostic efficacy across multiple regions is even higher.

Objective:To investigate the value of CT radiomic model based on analysis of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer in differentiating stage T1-2 from stage T3-4 gastric cancer.Methods:This study was a case-control study. Totally 465 patients with gastric cancer treated in Affiliated People′s Hospital of Jiangsu University from December 2011 to December 2019 were retrospectively collected. According to postoperative pathology, they were divided into 2 groups, one with 150 cases of T1-2 tumors and another with 315 cases of T3-4 tumors. The cases were divided into a training set (326 cases) and a test set (139 cases) by stratified sampling method at 7∶3. There were 104 cases of T1-2 stage and 222 cases of T3-4 stage in the training set, 46 cases of T1-2 stage and 93 cases of T3-4 stage in the test set. The axial CT images in the venous phase during one week before surgery were selected to delineate the region of interest (ROI) at the primary lesion and the extramural gastric adipose tissue adjacent to the cancer areas. The radiomic features of the ROIs were extracted by Pyradiomics software. The least absolute shrinkage and selection operator was used to screen features related to T stage to establish the radiomic models of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer. Independent sample t test or χ2 test were used to compare the differences in clinical features between T1-2 and T3-4 patients in the training set, and the features with statistical significance were combined to establish a clinical model. Two radiomic signatures and clinical features were combined to construct a clinical-radiomics model and generate a nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of each model in differentiating stage T1-2 from stage T3-4 gastric cancer. The calibration curve was used to evaluate the consistency between the T stage predicted by the nomogram and the actual T stage of gastric cancer. And the decision curve analysis was used to evaluate the clinical net benefit of treatment guided by the nomogram and by the clinical model. Results:There were significant differences in CT-T stage and CT-N stage between T1-2 and T3-4 patients in the training set ( χ2=10.59, 15.92, P=0.014, 0.001) and the clinical model was established. After screening and dimensionality reduction, the 5 features from primary gastric cancer and the 6 features from the adipose tissue outside the gastric wall beside cancer established the radiomic models respectively. In the training set and the test set, the AUC values of the primary gastric cancer radiomic model were 0.864 (95% CI 0.820-0.908) and 0.836 (95% CI 0.762-0.910), and the adipose tissue outside the gastric wall beside cancer radiomic model were 0.782 (95% CI 0.731-0.833) and 0.784 (95% CI 0.702-0.866). The AUC values of the clinical model were 0.761 (95% CI 0.705-0.817) and 0.758 (95% CI 0.671-0.845), and the nomogram were 0.876 (95% CI 0.835-0.917) and 0.851 (95% CI 0.781-0.921). The calibration curve reflected that there was a high consistency between the T stage predicted by the nomogram and the actual T stage in the training set ( χ2=1.70, P=0.989). And the decision curve showed that at the risk threshold 0.01-0.74, a higher clinical net benefit could be obtained by using a nomogram to guide treatment. Conclusions:The CT radiomics features of primary gastric cancer lesions and the adipose tissue outside the gastric wall beside cancer can effectively distinguish T1-2 from T3-4 gastric cancer, and the combination of CT radiomic features and clinical features can further improve the prediction accuracy.

Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

Research on the mechanisms of depression is currently a focus of the field of neuroscience.The degeneration of brain plasticity(e.g.,decrease in volume,structural degradation,and functional disorder of the hippocampus,PFC,and CG)leads to depression.Exercise is an important means of improving the symptoms of depression.Current research confirms the importance of improving the volume,structure,and function of the hippocampus,PFC,and CG,in this process,but related research has focused solely on changes to the volume of certain brain regions or connectivity functions.Thus,we lack a comprehensive understanding of the antidepressant mechanisms that improve brain plasticity with exercise.Therefore,this study aimed to explore the roles of brain plasticity in the occurrence of depression and improvements to depression through exercise,promoting a more comprehensive understanding the role of brain plasticity in depression.We also provide new ideas for exercise intervention in depression.

Objective To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression of rats.Methods Seventy healthy male Wistar rats were randomly divided into seven groups,a Control group and sleep deprivation groups(24,48,72,96,120 and 144 hours).The sleep deprivation rat model was established by the modified multiplatform water environment sleep deprivation method.Spatial learning and memory were assessed by the Morris water maze.Anxiety was assessed by the open field test.The morphology and quantity of hippocampal neurons were observed by Nissl staining.Western blot and Real-time PCR were used to determine the expression of synaptophysin(SYN),post-synaptic density protein-95(PSD-95),and brain-derived neurotrophic factor(BDNF)in rats.Results Compared with the Control group,the numbers of standing and modification were significantly increased by prolongation of the sleep deprivation time(P＜0.05).The escape latency and path length were significantly increased in 120 and 144 h groups(P＜0.05),whereas the number of platform crossings and the percentage of the target quadrant time were significantly decreased(P＜0.01)and negatively correlated to the sleep deprivation time.The expression levels of BDNF,SYN,and PSD-95 were significantly decreased with the prolongation of sleep deprivation time(P＜0.01).Conclusions With the increase in sleep deprivation time,cognitive dysfunction and anxiety gradually deteriorated,which may be related to decreases in the expression of synaptic biomarkers.