Objective:To explore the effects of Zishui Qinggan Decoction on the PTEN-induced putative kinase protein 1 (PINK1)/Parkin and cyclic GMP-AMP (cGAS)/ stimulator of interferon genes (STING) signaling pathways; To reveal the anti-inflammatory mechanism of Zishui Qinggan Decoction in treating depression.Methods:Totally 60 rats were randomly divided into control group, model group, and Zishui Qinggan Decoction low-, medium-, and high-dosage groups using a random number table method ( n=12 in each group) . All rats except for the rats in control group were prepared with CUMS induced depression models. The rats in the Zishui Qinggan Decoction low-, medium-, and high-dosage groups were orally administered with 12, 24, and 48 g/kg of Zishui Qinggan Decoction for gavage, respectively. The control group and model group were orally administered with distilled water of equal volume for gavage, once a day for 4 weeks. Forced swimming test (FST), the open field test (OFT) and the sucrose preference test (SPT) were used to detect behavioral changes in rats in each group. Hematoxylin eosin (HE) staining was used to observe the cell structure of the medial prefrontal cortex. The levels of IL-1 β, IL-6, TNF-α and Interferon-γ (IFN-γ) were detected using ELISA. Western blot was used to detect the expressions of Pink1, Parkin, cGAS and STING. Results:Behavioral testing results showed that, compared with the model group, the incubation period for rats in Zishui Qinggan Decoction low-, medium-, and high-dosage groups to enter the first immobility state in FST was significantly prolonged ( P<0.05), and the immobility time was significantly shortened ( P<0.05); the time spent in the central area was significantly increased ( P<0.05), and the incubation period for entering the central area was significantly shortened in ( P<0.05); the percentage of sugar water consumption significantly increased in ( P<0.05). HE staining revealed that the aggregation of prefrontal cortex nuclei decreased, the number of neurons increased, and the distribution of neurons was uniform in Zishui Qinggan Decoction low-, medium-, and high-dosage groups. Compared with the model group, the levels of IL-1β, IL-6, TNF-α and IFN-γ in the Zishui Qinggan Decoction groups significantly decreased ( P<0.05). The protein expressions of PINK1 and Parkin in the prefrontal cortex in Zishui Qinggan Decoction groups significantly increased ( P<0.05), while the protein expression levels of cGAS and STING significantly decreased ( P<0.05). Conclusion:Zishui Qinggan Decoction can significantly improve the depressive behavior, neuronal damage, and neuroinflammatory response in CUMS rats. Its mechanism may be related to up-regulating the PINK1/Parkin signaling pathway and inhibiting the cGAS/STING signaling pathway.

OBJECTIVE：To investigate the protective effects of drug-contained serum of Xiaoxuming decoction （XXM）on astrocyte of oxygen and glucose deprivation model rats ，and to explore its mechanisms. METHODS ：The astrocytes of rats were randomly divided into control group ，model group and XXM low-dose ，middle-dose，high-dose groups. The cells in the control group were not treated ；after 2.5 h of OGD ，model group and XXM low-dose ，middle-dose，high-dose groups were reoxygenated for 0，3，6，12 h in 0（i.e. the model group was not added with drugs ），2.5％，5％，10％ of XXM ，respectively. The content of lactate dehydrogenase （LDH）was detected by colorimetry. The reactive oxygen species （ROS）level was detected by fluorescence probe method ，and the expression of Manganese superoxide dismutase （MnSOD）was determined by immunofluorescence double staining method in control group ，model group and XXM high-dose group after 12 h of reoxygenation following OGD. RESULTS ： The content of LDH in the control group was always kept at a low level ；LDH content in the model group gradually increased from （110.99±17.06）U/L to （436.64±55.29）U/L after 0-12 h of reoxygenation following OGD ，which was significantly higher than that in the control group （P＜0.05）. Compared with model group at the same time point after reoxygenation following OGD ，the contents of LDH in the cells of XXM low-dose ，medium-dose and high-dose groups were decreased to different extents ，and showed a time-and dose-dependent trend. The contents of LDH in XXM groups at 6 and 12 h after reoxygenation following OGD were significantly lower than that of the model group （P＜0.05）. At 12 h after reoxygenation following OGD ，the levels of ROS in model group were significantly higher than control group ， while the level of MnSOD was significantly lower than control group（P＜0.05）. The level of ROS in XXM high-dose group hospital.sh.cn was significantly lower than model group ，while the level of MnSOD was significantly higher than model group （P＜0.05）.. CONCLUSIONS：XXM can protect astrocyte by up-regulating sh.cn levels of MnSOD ，scavenging excessive oxygen free radicals ， to relieve the OGD induced astrocytic injury ，with protective effect.

Parkinson's disease (PD) was the second most common neurodegenerative disorder after Alzheimer's disease. Incidence of PD was ascending year by year. The etiology of PD is poorly understood, involving aging, genetic and environmental factors. Recently, environmental compound had attracted more and more research interest. Studies and extrapolation from epidemiology, animal experiments and cell culture suggested that environmental compound had involved in the molecular mechanisms including mitochondrial dysfunction, oxidative stress, microglia activation,abnormal aggregation of α-synuclein and autophagy damage,which seemed to increase PD risk.

Parkinson's disease (PD) was the second most common neurodegenerative disorder after Alzheimer's disease. Incidence of PD was ascending year by year. The etiology of PD is poorly understood, involving aging, genetic and environmental factors. Recently, environmental compound had attracted more and more research interest. Studies and extrapolation from epidemiology, animal experiments and cell culture suggested that environmental compound had involved in the molecular mechanisms including mitochondrial dysfunction, oxidative stress, microglia activation,abnormal aggregation of α-synuclein and autophagy damage,which seemed to increase PD risk.

Objective To investigate the neuroprotective effect of Dengzhan Shengmai capsule (DZSM) in rat cerebral ischemia-reperfusion injury and to explore the mechanism. Methods Rats were divided into Sham group, MCAO group, DZSM group, carbenoxolone (CBX) group and DZSM + CBX group. Each group was assessed for neurological function , infarct volume and the expression of Caspase-3 48 h after reperfusion. Connexin 43 (Cx43) expression of MCAO group was detected 3, 12, 24, 48 h after reperfusion. Results There were lower neurological deficit scores , infarct volume and the expression of Caspase-3 in DZSM , CBX and DZSM + CBX group 48 h after reperfusion when compared with those in MCAO group (P < 0.05) but Cx43 expression level in each group increased after reperfusion at each time point (P < 0.05). Expression of Cx43 was lower in DZSM, CBX and DZSM + CBX group than that in MCAO group (P < 0.05). Lower expression of Cx43 was also seen in CBX and DZSM + CBX group when compared with that in DZSM group (P < 0.05). Conclusion DZSM capsule can improve neurological function , reduce infarct volume and inhibit the expression of Caspase-3. The mechanism may be related to its inhibition of Cx43 expression.

Background and purpose:In recent years, many studies have showed that elemene liposome is widely used in the treatment of digestive tract tumors, malignant pleural effusion and ascites. This study combined in vitro and in vivoexperiments to observe the inhibitory effect of elemene liposome on the growth of human gastric cancer and the HGC-27 cell line.Methods:In order to screen the optimum concentration of elemene liposome, machine vision automatic live cell observation analysis system (Cell-IQ) was applied to detect the best inhibitory effect on human gastric cancer cell line HGC-27, and the lfow cytometry was applied to further detect the apoptosis of HGC-27 treated with elemene liposome. The model of human gastric cancer peritoneal metastasis in nude mice was established to investigate the intervention of elemene liposome and cisplatin (DDP) on peritoneal cancer index (PCI). CD31 marker of tumor microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) in tumor tissues were investigated to explore the mechanism underlying the inhibitory effect on peritoneal metastasis of HGC-27 cells in nude mice.Results:Cell-IQ analysis showed that the inhibitory effect of elemene liposome on HGC-27 presented in a positive concentration-dependent manner, which could not be further enhanced when the concentration exceeded 100 μg/mL with the best reaction time between 4 and 19 hours. Flow cytometry showed that the early apoptosis rate was 45% in the elemene liposome group and only 0.019% in the control group. The early apoptosis rate was signiifcantly higher in treatment group than that in control group (P<0.05). PCI was signiifcantly lower in the group treated with elemene liposome plus DDP than that in control group (P<0.05) in the peritoneal metastasis of gastric cancer nude mice model. The expression of CD31-MVD and VEGF was not signiifcantly different between the treated and control groups (P>0.05).Conclusion:Elemene liposome can inhibit human gastric cancer cells at the optimal concentration of 100 μg/mL with the best reaction time between 4-19 hours. Elemene liposome has a clear preventive effect on peritoneal metastasis of human gastric cancer in nude mice. Induction of apoptosis in gastric cancer cells may be the main mechanism underlying the inhibitory effect of elemene liposome on human gastric cancer cells.

[ ABSTRACT] AIM:To investigate the effect of triptolide on the inhibition of microglial activation in 1-methyl-4-phenyl pyridinium ( MPP+)-induced hemiparkinson disease rats.METHODS:The rat model of Parkinson disease was es-tablished by intranigral injection of MPP +.The rats were randomly divided into sham group, MPP+group, triptolide group and vehicle group.The survival of dopaminergic neurons was detected by the immunofluorescence of tyrosine hydroxylase ( TH) in the substantia nigra ( SN) .The activation of microglia was determined by immunofluorescence of OX-42 ( micro-glia marker) in the SN.The expression of chemokine receptor CX3CR1 in SN was measured by Western blotting.RE-SULTS:Intranigral injection of MPP+increased the fluorescence intensity of the microglial marker, and promoted DA neu-ron degenerative death.Immunohistological analysis showed that the OX-42 density was decreased (P<0.01) and tyrosine hydroxylase (TH) positive neurons were increased in the triptolide group (P<0.01).The expression of CX3CR1 was lower in triptolide group than that in model group (P<0.05).CONCLUSION:Triptolide may improve PA neurons func-tion in MPP+-induced rats through inhibiting CX3CR1 expression and microglial activation.

AIM:To investigate the integrative treatment of both coenzyme Q 10 ( CoQ10 ) and minocycline in the rats intranigrally intoxicated with 1-methyl-4-phenylpyridinium ( MPP+) .METHODS:The rat model of Parkinson disease ( PD) was established by intranigral microinjection of MPP +.The degree of microglial activation was measured by immuno-fluorescent density of OX-42 ( a microglia marker ) in the substantia nigra ( SN) .The number of viable dopaminergic neurons was determined by counting the tyrosine hydroxylase ( TH) positive neurons in the SN .The behavioral performances were re-vealed with the number of apomorphine-induced rotations , score of forelimb akinesia and vibrissae-elicited forelimb placing a-symmetry.RESULTS:Pretreatment with CoQ10 or intracerebroventricular (icv) posttreatment with minocycline alone pro-vided partial attenuation against MPP +-induced locomotor defects .Integrative therapy provided enhanced beneficial effects , and resulted in a significant attenuation of locomotor disability than any single therapy (all P<0.01).The results of immu-nohistological analysis showed that the TH positive neurons were maximally protected by integrative therapy compared with minocycline group and CoQ 10 group (P<0.01) .CONCLUSION:The integrative therapy of CoQ 10 combined with minocy-cline may offer additional therapeutic benefit to MPP +-induced hemiparkinson rat model .Such neuroprotective strategy of tar-geting different aspect of the neurodegenerative phenotypes may highlight a new therapeutic strategy for future management of PD.

To investigate the protective effects of Naoshuantong, a compound traditional Chinese herbal medicine, on the main components of neurovascular unit in rats with cerebral ischemia/reperfusion injury.

Objective To analyze nucleophosmin (NPM1) gene mutations in exon 12 in patients with acute myeloid leukemia (AML) and evaluate the clinical appliance of three methods which are frequently used for detecting gene mutation. Methods Genomic DNA from bone marrow of 54 AML patients was detected by PCR for NPM1 exon 12 and screened by PCR-capillary electrophoresis, denature high-performance liquid chromatography (DHPLC) and direct sequencing separately. FLT3-ITD (FMS-like tyrosine kinease internal tandem duplication) was detected by agarose gel electrophoresis and PCR-capillary electrophoresis. Results Seven AML sample harbored NPM1 gene mutations. Five of them were the most common mutation, known as type A (an insertion of a TCTG tetranucleotide at position 960 bp). One of them was type D (an insertion of a CCTG tetranuclectide at position 960 bp). The new variant was a deletion of a TGGCAGTG sequence at 958 bp and insertion of a GCCCGCGGTTTA sequence instead. The detection ratio of the three methods was all 100% and capillary electrophoresis was more rapid, reliable and easier than the other two methods. Moreover it could detect FLT3-ITD simultaneously. The resolving power of DHPLC was affected by many factors. The direct sequencing method was tedious and the heterozygous sequence might be misread. Conclusions There is a new mutation at position 958 bp with a 12-nucleotide insertion and substitution. PCR-capillary electrophoresis is convenient to screen NPM1 mutations of AML in clinical practice.