Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective To compare the efficacy,acceptability and safety of a low-volume magnisium sodicum potassium sulfate oral sulfate solution(OSS)with polyethylene glycol(PEG)electrolytes powder in bowel preparation for colonoscopy.Methods A prospective,single-blinded and single-center cohort study was conducted.The ambulatory and hospitalized 1 037 patients who underwent colonoscopy from April 2023 to January 2024 were enrolled.Participants were divided into OSS group(639 cases)and PEG group(398 cases),according to the bowel cleansing drugs taken orally.After propensity score matching(PSM),each group included 385 cases.The success rate of bowel preparation,scores of Boston bowel preparation scale(BBPS),medication taste,patients'satisfaction and the occurrence of adverse events were compared.Results The success rate of bowel preparation in the OSS group was 96.4％(371/385),higher than the 91.7％(353/385)in the PEG group,and the difference was statistically significant(P＜0.05).The total and segmented BBPS scores of the OSS group were higher than those of the PEG group,the differences were statistically significant(P＜0.05).The medication taste and patients satisfaction of the OSS group were significantly better than those of the PEG group,the differences were statistically significant(P＜0.05).There was no statistically significant difference in incidence of adverse reactions between the two groups(P=0.800).Conclusion Compared to PEG,OSS has a better intestinal cleaning effect,medication taste,and patients satisfaction.In addition,OSS has security that is not inferior to PEG.

Objective To compare the efficacy,acceptability and safety of a low-volume magnisium sodicum potassium sulfate oral sulfate solution(OSS)with polyethylene glycol(PEG)electrolytes powder in bowel preparation for colonoscopy.Methods A prospective,single-blinded and single-center cohort study was conducted.The ambulatory and hospitalized 1 037 patients who underwent colonoscopy from April 2023 to January 2024 were enrolled.Participants were divided into OSS group(639 cases)and PEG group(398 cases),according to the bowel cleansing drugs taken orally.After propensity score matching(PSM),each group included 385 cases.The success rate of bowel preparation,scores of Boston bowel preparation scale(BBPS),medication taste,patients'satisfaction and the occurrence of adverse events were compared.Results The success rate of bowel preparation in the OSS group was 96.4％(371/385),higher than the 91.7％(353/385)in the PEG group,and the difference was statistically significant(P＜0.05).The total and segmented BBPS scores of the OSS group were higher than those of the PEG group,the differences were statistically significant(P＜0.05).The medication taste and patients satisfaction of the OSS group were significantly better than those of the PEG group,the differences were statistically significant(P＜0.05).There was no statistically significant difference in incidence of adverse reactions between the two groups(P=0.800).Conclusion Compared to PEG,OSS has a better intestinal cleaning effect,medication taste,and patients satisfaction.In addition,OSS has security that is not inferior to PEG.

ABATRACT OBJECTIVE To utilize the pharmacophore model-molecular docking combined with the virtual screening strategy of free energy calculation and the chemical bioinformatics method of traditional Chinese medicine in cell biology experiments to investigate the components of Guiqi Baizhu prescription that target phosphatidylinositol 3-kinase(PI3K) and inhibit the proliferation of uveal melanoma(UM) cells. METHODS The pharmacophore model of PI3K inhibitor was constructed, and the compounds of Guiqi Baizhu prescription were virtual screened. The components that fit the pharmacophore model were calculated by molecular docking and binding free energy, and the potential inhibitory components were selected for biological experimental evaluation. The effects of potential inhibitory components on UM cell proliferation were detected by CCK-8 and clonal formation assay. Flow cytometry was used to detect the cell cycle and apoptosis of UM cells. The mitochondrial membrane potential of UM cells was detected using JC-10 staining. The expressions of PI3K and downstream pathway proteins were detected by Western blotting.RESULTS The pharmacophore model included 2 hydrogen bond receptors, 2 aromatic ring centers, and exclusion volumes. The results of the CCK-8 experiment showed that quercetin, tangerine, and nobiletin at concentrations of 10, 20, 40, 80 μmol·L−1, and cyrtin at concentrations of 20, 40, 80 μmol·L−1, were able to inhibit the proliferation of UM cells. The clonal formation experiment showed that quercetin, tangerine, nobiletin, and morusin, at different concentrations, could significantly inhibit the clonal proliferation of UM cells. Flow cytometry showed that UM cells were arrested in the G0/G1 phase by tangeretin and quercetin, while UM cells were arrested in the G2/M phase by nobiletin and morusin. The results of JC-10 staining showed that quercetin, nobiletin, tangeretin, and morusin could reduce the mitochondrial membrane potential of UM cells. Western blotting results showed that 4 compounds could target PI3K, but their downstream pathways were different.CONCLUSION Based on the method of chemical bioinformatics in traditional Chinese medicine, this study explores the material basis for the inhibition of UM cell proliferation by the Guiqi Baizhu prescription. It also provides insights for the modern development of traditional Chinese medicine prescription.

Objective:To explore the effect and mechanism of naringenin (NAR) on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes mellitus (GDM) .Methods:10 normal pregnant rats were selected as the control group, and the GDM model was prepared. One-time tail iv streptozotocin (STZ, 35 mg/kg) was used to construct GDM model. The 50 rats successfully modeled were divided into model group, metformin group (Met group, 20 mg/kg), low NAR (NAR-L, 50 mg/kg), high (NAR-H, 100 mg/kg) dose groups and NAR+EX527 group (NAR 100 mg/kg+EX527 10 mg/kg), 10 rats per group. Rats in Met group and NAR low-dose and high-dose groups were given corresponding doses of drugs ig. Rats in NAR+EX527 group were given NAR ig and EX527 ip at the same time, once a day, for 28 consecutive days. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) in rats were detected, and the homeostasis model assessment for insulin resistance (HOMA-IR) was calculated; the levels of serum triglycerides (TG), cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were detected; the level of malondialdehyde (MDA) in pancreatic tissue and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected; the tissue lesions of pancreas and placenta were observed with HE staining; the expression of pancreatic tissue AMP-activated protein kinase (AMPK), p-AMPK, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1 α) proteins was detected with Western blotting method. Results:Compared with control, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the model group were significantly increased, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly reduced ( P<0.05), and the placenta and pancreas tissues showed obvious pathological damage; Compared with the model group, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the Met group and the NAR-L and NAR-H groups were significantly reduced, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly increased ( P<0.05), the placenta and pancreas tissues damage reduced; and on the basis of NAR intervention, the use of SIRT1 inhibitor EX527 could significantly reverse the protective effect of NAR on GDM rats. Conclusion:NAR may improve glucose and lipid metabolism disorder and oxidative stress response in GDM rats by activatin SIRT1/PGC-1 α pathway.

Objective:To explore the effect and mechanism of naringenin (NAR) on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes mellitus (GDM) .Methods:10 normal pregnant rats were selected as the control group, and the GDM model was prepared. One-time tail iv streptozotocin (STZ, 35 mg/kg) was used to construct GDM model. The 50 rats successfully modeled were divided into model group, metformin group (Met group, 20 mg/kg), low NAR (NAR-L, 50 mg/kg), high (NAR-H, 100 mg/kg) dose groups and NAR+EX527 group (NAR 100 mg/kg+EX527 10 mg/kg), 10 rats per group. Rats in Met group and NAR low-dose and high-dose groups were given corresponding doses of drugs ig. Rats in NAR+EX527 group were given NAR ig and EX527 ip at the same time, once a day, for 28 consecutive days. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) in rats were detected, and the homeostasis model assessment for insulin resistance (HOMA-IR) was calculated; the levels of serum triglycerides (TG), cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were detected; the level of malondialdehyde (MDA) in pancreatic tissue and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected; the tissue lesions of pancreas and placenta were observed with HE staining; the expression of pancreatic tissue AMP-activated protein kinase (AMPK), p-AMPK, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1 α) proteins was detected with Western blotting method. Results:Compared with control, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the model group were significantly increased, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly reduced ( P<0.05), and the placenta and pancreas tissues showed obvious pathological damage; Compared with the model group, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the Met group and the NAR-L and NAR-H groups were significantly reduced, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly increased ( P<0.05), the placenta and pancreas tissues damage reduced; and on the basis of NAR intervention, the use of SIRT1 inhibitor EX527 could significantly reverse the protective effect of NAR on GDM rats. Conclusion:NAR may improve glucose and lipid metabolism disorder and oxidative stress response in GDM rats by activatin SIRT1/PGC-1 α pathway.

Objective To determine the content of total flavonoids and luteolin from Pteris multifida Poir. Methods The content of total flavonoids was determined by gradient elution of macroporous resin D101 and ultraviolet spectrophotometry. The content of luteolin was determined by HPLC. The analysis was performed on a RP-C18 column(4.6 mm×250 mm, 5 μm) with aceconitrile-0.2% phosphoric acid (35:65) as the mobile phase at a flow rate of 1.0 ml/min, and 30 ℃ temperature. Results The detection of wave length was set at 349 nm. The content of luteolin was 0.015%, 0.019%, 0.016%, and the content of total flavonoids was 0.015%, 0.019%, 0.016%, respectively. Conclusions The method is suitable for the determination of flavonoids componets from Pteris multifida Poir.

This paper describes the role,method and experience,and working model of medical ethics in large-scale hospitals,and holds that the modern hospital management mode has transformed from scientific management to humanism-based management,whose essence is the transformation of managing concept,and the embody of management ethics and management culture.Important connotations and primary task including employing virtue in hospital management,obeying legal regulations in medical practice,and conducting humanistic medicine should be emphasized and concerned in hospital management.