Objective:To explore the effects of peripheral nerve injury(PNI)on neuropathic pain(NP)and memo-ry function in mice,as well as the activation of neurons in the paraventricular nucleus(PVT)of the thalamus,so as to provide a basis for studying the relationship between NP and memory impairment.Methods:Twenty one 8-week-old male C57 BL/6J mice were randomly divided into sham group and experimental group,and the routine spared nerve inju-ry(SNI)was constructed in the mice of experimental group.The pain behavior and memory impairment of mice after SNI were evaluated with hot plate and eight-arm maze behavioral tests.Pearson correlation analysis was performed to an-alyze the correlation between pain behavior and memory impairment.The c-FOS expression in PVT was detected with immuno-staining.Results:Compared with the sham group,the heat pain threshold of mice in the experimental group was significantly reduced(P＜0.001).The results of the eight-arm maze test showed that the total rest time was signifi-cantly increased(P＜0.001),and the working memory error was increased from 1 to 4 days after SNI(P＜0.01).Correlation analysis indicated that early working memory errors were negatively correlated with heat pain threshold after SNI(P＜0.001).The immunofluorescence revealed that the number of c-FOS positive cells in PVT increased signifi-cantly(P＜0.001).Conclusion:SNI can cause abnormal pain behavior and memory impairment in mice,and cause neuronal activation in PVT.This study provides a basis for neurons in PVT to participate in the regulation of memory impairment in the context of NP.

Objective:To explore the effects of peripheral nerve injury(PNI)on neuropathic pain(NP)and memo-ry function in mice,as well as the activation of neurons in the paraventricular nucleus(PVT)of the thalamus,so as to provide a basis for studying the relationship between NP and memory impairment.Methods:Twenty one 8-week-old male C57 BL/6J mice were randomly divided into sham group and experimental group,and the routine spared nerve inju-ry(SNI)was constructed in the mice of experimental group.The pain behavior and memory impairment of mice after SNI were evaluated with hot plate and eight-arm maze behavioral tests.Pearson correlation analysis was performed to an-alyze the correlation between pain behavior and memory impairment.The c-FOS expression in PVT was detected with immuno-staining.Results:Compared with the sham group,the heat pain threshold of mice in the experimental group was significantly reduced(P＜0.001).The results of the eight-arm maze test showed that the total rest time was signifi-cantly increased(P＜0.001),and the working memory error was increased from 1 to 4 days after SNI(P＜0.01).Correlation analysis indicated that early working memory errors were negatively correlated with heat pain threshold after SNI(P＜0.001).The immunofluorescence revealed that the number of c-FOS positive cells in PVT increased signifi-cantly(P＜0.001).Conclusion:SNI can cause abnormal pain behavior and memory impairment in mice,and cause neuronal activation in PVT.This study provides a basis for neurons in PVT to participate in the regulation of memory impairment in the context of NP.

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Objective:To study the changes in visual function and its mechanism in mice with acute hepatic enceph-alopathy(AHE)model.Method:Twelve male mice were divided into experimental and control groups,with six mice in each.A mouse model of AHE was created using TAA,and serum ALT,AST,and ammonia levels were measured using ELISA and colorimetric assays.Behavioral tests,including open-field and elevated cross maze experiments,were conducted,and neurological function scores were evaluated.HE staining was used to evaluate visual function scores in mice.Behavioural tests were conducted to assess neurological function scores.HE staining was used for pathological examination of the liver and retina.Visual electrophysiology was used to test visual function in both eyes.Retrograde tracer adeno-associated virus was used to label the ventrolateral thalamic nucleus(VL)of thalamus in c-Fos-CreERT2 mice.Results:Compared to the control group,the AHE mice had abnormal liver function and neurological changes.The HE results showed liver tissue damage.The retinal tissues were not significantly different from the control group.The visual electrophysiological results showed changes in visual function in both eyes of the AHE mice.The retrograde tracer virus injections revealed no significant difference in VL activation between the AHE model and the control group.In the AHE model,VL nucleus accumbens neurons primarily received input from ipsilateral visual cortical neurons.Conclusion:The visual deficits in AHE mice caused by TAA were primarily functional rather than organic changes,and were associated with the activation of the visual cortex-to-VL pathway.

Objective:To study the changes in visual function and its mechanism in mice with acute hepatic enceph-alopathy(AHE)model.Method:Twelve male mice were divided into experimental and control groups,with six mice in each.A mouse model of AHE was created using TAA,and serum ALT,AST,and ammonia levels were measured using ELISA and colorimetric assays.Behavioral tests,including open-field and elevated cross maze experiments,were conducted,and neurological function scores were evaluated.HE staining was used to evaluate visual function scores in mice.Behavioural tests were conducted to assess neurological function scores.HE staining was used for pathological examination of the liver and retina.Visual electrophysiology was used to test visual function in both eyes.Retrograde tracer adeno-associated virus was used to label the ventrolateral thalamic nucleus(VL)of thalamus in c-Fos-CreERT2 mice.Results:Compared to the control group,the AHE mice had abnormal liver function and neurological changes.The HE results showed liver tissue damage.The retinal tissues were not significantly different from the control group.The visual electrophysiological results showed changes in visual function in both eyes of the AHE mice.The retrograde tracer virus injections revealed no significant difference in VL activation between the AHE model and the control group.In the AHE model,VL nucleus accumbens neurons primarily received input from ipsilateral visual cortical neurons.Conclusion:The visual deficits in AHE mice caused by TAA were primarily functional rather than organic changes,and were associated with the activation of the visual cortex-to-VL pathway.

OBJECTIVETo explore the optimal time of acupuncture intervention in the assisted reproduction.

METHODSOne hundred and twenty female mice and 60 male mice were collected. 20 female mice were selected in the natural period group and the rest 100 female mice were prepared as the model of controlled ovarian hyperstimulation (COH). The model mice were randomized into a COH group, a down-regulation group, a gonadotropins (Gn) start group, an injection of human chorionic gonadotropin (HCG) group and an embryo culture group, 20 mice in each one. The donor mice and receptor mice were subdivided in each group, 10 mice in each subgroup. One week before the experiment, vas deferens ligature was done in 30 male mice and the other 30 male mice did not receive ligature. In the down-regulation group, the Gn start group, the HCG injection group and the embryo culture group, electroacupuncture (EA) was applied to "Guanyuan" (CV 4), "Zhongji" (CV 3) and "Sanyinjiao" (SP 6) at the time points accordingly. EA stimulation was in the condition of continuous wave, 2 Hz and 1 mA. No inter-vention was given in the natural period group and the COH group. On the day of HCG injection, the donor mice and the non-ligatured male mice were put in the same cage of each group. The fertilized ovum was collected with the date of fertilization marked and was fostered in the incubator. At the ratio of 1:1, the receptor mice and ligatured mice were put in the same cage in each group. The vaginal plug was examined in the next morning. The pseudopregnancy was marked with the date of plug observed. In the 68th hour of embryo culture, the embryo of the donor was shifted to the receptor on the same day when the plug was observed. The clinical pregnancy rate and embryo imbed site number were observed. RT-PCR assay was adopted to determine the expression of insulin-like growth factor-1 (IGF-1) mRNA in endometrium.

RESULTSIn the COH group, the pregnancy rate, average imbed site number and endometrial IGF-1 mRNA expression were all significantly lower than those in the natural period group (all<0.01). After EA treatment, in the Gn group, the HCG injection group and the embryo culture group, the pregnancy rates were higher significantly than those in the COH group (<0.05,<0.01). In the HCG injection group, the average imbed site number and IGF-1 mRNA expression were increased apparently as compared with those in the COH group (both<0.01), better than those in the Gn group and the embryo culture group (all<0.01).

CONCLUSIONSIn the treatment with acupuncture combined with IVF-ET for infertility, the intervention of acupuncture on the day of HCG injection is the optimal time point. It increases the secretion of endometrial IGF-1 so as to improve the clinical pregnancy rate, the mean imbed site number and the embryo implantation.