Objective The aim of this study is to examine the Chinese version of Visual Prostate Symptom Score(CVPSS)and the International Prostate Symptom Score(IPSS)in the assessment of lower urinary tract symptoms in BPH pa-tients.Methods By using convenient sampling,inpatients in the urology department of a tertiary grade A hospital in Shanghai were selected as the survey subjects from March 2023 to March 2024.The lower urinary tract symptoms of the patients were eval-uated using the self-designed general information questionnaire.And the CVPSS and IPSS with their urine flow rate were meas-ured.A comparative analysis was conducted from aspects such as internal consistency,correlation of item scores,completion time of the scale,and assistance rate.Results A total of 246 patients with BPH were recruited.The total score and life quality score were 13.93±3.55 and 4.23±1.02 by CVPSS.And the total score and life quality by IPSS was 18.33±7.55 and 4.36±1.02,respectively.The Cronbach's α coefficient were 0.761 and 0.787,respectively.The time taken on CVPSS was less than that on IPSS(P＜0.01).And the rate of needing assistance was 23.58％for CVPSS,which was significantly lower than that(65.24％)for IPSS.Conclusion CVPSS is significantly correlated with the corresponding items and total scores of IPSS,as well as the quality of life.Moreover,it takes less time and can be used as a simple and effective self-assessment tool for lower urinary tract symptoms in elderly BPH patients with lower education levels.It reduces the burden of medical staffs as well.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Objective To investigate the effect of Ching Shum Pills(CSP)for alleviating non-alcoholic fatty liver disease(NAFLD)and the underlying mechanism.Methods In a mouse model of NAFLD,the therapeutic effect of CSP was evaluated by measuring serum glucose,lipid profiles(TC,TG,LDL-C,HDL-C),and hepatic function markers.Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP,HERB,SwissTargetPrediction,GeneCards,OMIM,and DisGeNET.Protein-protein interaction(PPI)networks,Gene Ontology(GO),and KEGG pathway analyses were conducted.Molecular docking(AutoDock Vina)was used to assess the compound-target binding affinities.Quantitative real-time PCR(qRT-PCR)was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models.Results In the mouse model of NAFLD,treatment with CSP significantly reduced body weight gain and serum TG levels of the mice,and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation.Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP,which target TNF,AKT1,IL6,TP53,and ALB.Docking simulations suggested strong binding between the two core compounds and their target proteins.The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53,Cpt1,and Ppara expressions in mice,which was effectively reversed by CSP treatment.Conclusion CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function.The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.

OBJECTIVES: To investigate the effect of Ching Shum Pills (CSP) for alleviating non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. METHODS: In a mouse model of NAFLD, the therapeutic effect of CSP was evaluated by measuring serum glucose, lipid profiles (TC, TG, LDL-C, HDL-C), and hepatic function markers. Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP, HERB, SwissTargetPrediction, GeneCards, OMIM, and DisGeNET. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were conducted. Molecular docking (AutoDock Vina) was used to assess the compound-target binding affinities. Quantitative real-time PCR (qRT-PCR) was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models. RESULTS: In the mouse model of NAFLD, treatment with CSP significantly reduced body weight gain and serum TG levels of the mice, and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation. Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP, which target TNF, AKT1, IL6, TP53, and ALB. Docking simulations suggested strong binding between the two core compounds and their target proteins. The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53, Cpt1, and Ppara expressions in mice, which was effectively reversed by CSP treatment. CONCLUSIONS CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function. The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Lipid Metabolism/drug effects* ; Molecular Docking Simulation ; Disease Models, Animal ; Liver/metabolism* ; Male ; Lipid Metabolism Disorders/drug therapy* ; PPAR alpha/metabolism* ; Mice, Inbred C57BL ; Network Pharmacology

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective:To investigate the effect of monocular form deprivation (MD) during the pre-critical period of visual development on the density and morphology of dendritic spines in mouse primary visual cortex (V1) neurons.Methods:Twenty SPF male C57BL/6J mice with eyes opened on postnatal day 14 (P14) were selected and divided into MD and control groups using a random number table, with 10 mice in each group.The MD group was fed to P18 after 4 days of MD in the right eye, and the control group was raised to P18 under the same feeding conditions.All mice were decapitated after cardiac perfusion, and the sections were stained with the cell membrane fluorescent probe 1, 1′-dioctadecyl-3, 3′, 3′-tetramethylindocarbocyanine perchlorate, and imaged by laser scanning confocal microscopy to observe and compare the differences in density and morphology of dendritic spines in bilateral V1 neurons between the control group and the MD group.This study was approved by the Animal Ethics Committee of Tianjin Medical University (No.TMUaMEC2022004).Results:The total density of dendritic spines in the V1 area on the left side of the control group, the right side of the control group, the left side of the MD group, and the right side of the MD group were (7.57±0.25), (7.42±0.25), (6.54±0.18), and (7.51±0.29)spines/10 μm, respectively, with a statistically significant overall difference ( F=3.818, P<0.05).The total density of dendritic spines in the left V1 area of mice in the MD group was significantly lower than that in the left side of the control group and the right side of the MD group, and the differences were statistically significant (both P<0.05).There was a significant difference in the proportion of the four types of dendritic spines in V1 neurons on both sides between the two groups ( χ2=26.295, P=0.002).There was a significant difference in the proportion of the four types of dendritic spines between the left V1 of the MD group and the left and right V1 of the control group (both P<0.008 3).There was a significant difference in the filopodia-type dendritic spine density in bilateral V1 neurons between the two groups ( F=3.253, P<0.05).Compared with the left V1 area of the control group, the density of filopodia-type dendritic spines in the left V1 area of the MD group decreased significantly, with a statistical significance ( P<0.05).There was no significant difference in the density of thin-type, mushroom-type, and stubby-type dendritic spines in bilateral V1 area neurons between the two groups ( F=1.760, 2.618, 1.749; all P>0.05). Conclusions:MD during the pre-critical period of visual development can cause a decrease in the total density of dendritic spines and significant changes in the compositional proportions in the V1 contralateral to the deprived eye, and is mainly manifested by a decrease in the number of filopodia, suggesting that abnormal visual experience can cause plastic changes in the number and structure of synapses in the visual cortex during the pre-critical period of visual development.

Objective The aim of this study is to examine the Chinese version of Visual Prostate Symptom Score(CVPSS)and the International Prostate Symptom Score(IPSS)in the assessment of lower urinary tract symptoms in BPH pa-tients.Methods By using convenient sampling,inpatients in the urology department of a tertiary grade A hospital in Shanghai were selected as the survey subjects from March 2023 to March 2024.The lower urinary tract symptoms of the patients were eval-uated using the self-designed general information questionnaire.And the CVPSS and IPSS with their urine flow rate were meas-ured.A comparative analysis was conducted from aspects such as internal consistency,correlation of item scores,completion time of the scale,and assistance rate.Results A total of 246 patients with BPH were recruited.The total score and life quality score were 13.93±3.55 and 4.23±1.02 by CVPSS.And the total score and life quality by IPSS was 18.33±7.55 and 4.36±1.02,respectively.The Cronbach's α coefficient were 0.761 and 0.787,respectively.The time taken on CVPSS was less than that on IPSS(P＜0.01).And the rate of needing assistance was 23.58％for CVPSS,which was significantly lower than that(65.24％)for IPSS.Conclusion CVPSS is significantly correlated with the corresponding items and total scores of IPSS,as well as the quality of life.Moreover,it takes less time and can be used as a simple and effective self-assessment tool for lower urinary tract symptoms in elderly BPH patients with lower education levels.It reduces the burden of medical staffs as well.

Objective:To investigate the effect of monocular form deprivation (MD) during the pre-critical period of visual development on the density and morphology of dendritic spines in mouse primary visual cortex (V1) neurons.Methods:Twenty SPF male C57BL/6J mice with eyes opened on postnatal day 14 (P14) were selected and divided into MD and control groups using a random number table, with 10 mice in each group.The MD group was fed to P18 after 4 days of MD in the right eye, and the control group was raised to P18 under the same feeding conditions.All mice were decapitated after cardiac perfusion, and the sections were stained with the cell membrane fluorescent probe 1, 1′-dioctadecyl-3, 3′, 3′-tetramethylindocarbocyanine perchlorate, and imaged by laser scanning confocal microscopy to observe and compare the differences in density and morphology of dendritic spines in bilateral V1 neurons between the control group and the MD group.This study was approved by the Animal Ethics Committee of Tianjin Medical University (No.TMUaMEC2022004).Results:The total density of dendritic spines in the V1 area on the left side of the control group, the right side of the control group, the left side of the MD group, and the right side of the MD group were (7.57±0.25), (7.42±0.25), (6.54±0.18), and (7.51±0.29)spines/10 μm, respectively, with a statistically significant overall difference ( F=3.818, P<0.05).The total density of dendritic spines in the left V1 area of mice in the MD group was significantly lower than that in the left side of the control group and the right side of the MD group, and the differences were statistically significant (both P<0.05).There was a significant difference in the proportion of the four types of dendritic spines in V1 neurons on both sides between the two groups ( χ2=26.295, P=0.002).There was a significant difference in the proportion of the four types of dendritic spines between the left V1 of the MD group and the left and right V1 of the control group (both P<0.008 3).There was a significant difference in the filopodia-type dendritic spine density in bilateral V1 neurons between the two groups ( F=3.253, P<0.05).Compared with the left V1 area of the control group, the density of filopodia-type dendritic spines in the left V1 area of the MD group decreased significantly, with a statistical significance ( P<0.05).There was no significant difference in the density of thin-type, mushroom-type, and stubby-type dendritic spines in bilateral V1 area neurons between the two groups ( F=1.760, 2.618, 1.749; all P>0.05). Conclusions:MD during the pre-critical period of visual development can cause a decrease in the total density of dendritic spines and significant changes in the compositional proportions in the V1 contralateral to the deprived eye, and is mainly manifested by a decrease in the number of filopodia, suggesting that abnormal visual experience can cause plastic changes in the number and structure of synapses in the visual cortex during the pre-critical period of visual development.

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM),SAP model group (SAP),and Chaihuang Qingyi Huoxue Granule (CH)group,with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5％ sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage,while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation,eight rats from each group were sacrificed to collect abdominal aortic blood,pancreatic and ileal tissues for analysis. Ascites,pancreatic and ileal tissues were observed. Serum amylase(AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points,the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels,pancreatic and ileal histopathological scores increased,and Claudin-1 protein expression in ileal tissue markedly decreased (all P<0.05). The differences in abundance of microbial community increased,while the evenness of community composition reduced. The microbial richness showed no significant change (P>0.05),but the microbial diversity decreased(P<0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 decreased,whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced,and the evenness of community composition increased. The microbial richness showed no significant change(P>0.05),but the microbial diversity increased (P<0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 increased,whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH,pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group(P<0.05). The differences in abundance of microbial community reduced,and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP,which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

Objective To investigate the intervention effect of Xuanfuhua decoction on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat, high-fructose, and high-cholesterol diet. Methods A total of 32 male C57/BL6J mice were randomly divided into normal group, model group, Xuanfuhua decoction group, and obeticholic acid group, with 8 mice in each group. Since week 24 of modeling using high-fat, high-fructose, and high-cholesterol diet, each group was given the corresponding drug for intervention at a dose of 14.19 g/kg by gavage for the Xuanfuhua decoction group and 10 mg/kg by gavage for the obeticholic acid group and a volume of 20 mL/kg for gavage, once a day for 6 consecutive weeks. HE staining, oil red O staining, Sirius Red staining, and Masson staining were used to observe the pathological changes, lipid deposition, and collagen deposition of liver tissue; related kits were used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and glucose, as well as the content of TG and hydroxyproline (Hyp) in liver tissue; quantitative real-time PCR was used to measure the expression of genes associated with lipid metabolism, inflammation, and fibrosis in liver tissue; immunohistochemical staining was used to observe the positive expression of F4/80 and α-SMA in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in body weight, liver wet weight, and serum levels of AST, ALT, TC, TG, LDL-C and glucose (all P < 0.01). HE staining showed hepatocyte steatosis, a large number of fat vacuoles, hepatocyte ballooning degeneration, and inflammatory cell infiltration in liver tissue of the mice in the model group, and the model group had a significant increase in NAFLD activity score (NAS) compared with the normal group ( P < 0.01). Oil red O staining showed the deposition of a large number of red lipid droplets with different sizes in hepatocytes of the mice in the model group, and compared with the normal group, the model group had significant increases in the area percentage of oil red O staining and the content of TG in the liver ( P < 0.01). Sirius Red staining and Masson staining showed significant collagen fiber hyperplasia in the perisinusoidal area, the central vein, and the portal area in the model group, and the model group had a significant increase in the content of Hyp in liver tissue compared with the normal group ( P < 0.05). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the serum levels of AST, ALT, TC, TG, LDL-C, and glucose (all P < 0.05), significant improvements in hepatic steatosis, inflammatory infiltration, lipid droplet deposition, and collagen fiber hyperplasia, and significant reductions in NAS score, area percentage of oil red O staining, and content of TG and Hyp in the liver (all P < 0.05). Compared with the normal group, the model group had significant increases in the mRNA expression levels of lipid metabolism-related genes (SREBP-1c, FASN, SCD-1, PPAR-γ, and CD36), inflammation-related genes (F4/80, TNF-α, CCL2, and CD11b), and the fibrosis-related gene α-SMA (all P < 0.05), and immunohistochemical staining showed significant increases in the positive expression of F4/80 and α-SMA ( P < 0.01). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the mRNA expression levels of SREBP-1c, FASN, SCD-1, PPAR-γ, CD36, F4/80, TNF-α, CCL2, CD11b, and α-SMA in liver tissue (all P < 0.05), and immunohistochemical staining showed significant reductions in the positive expression of F4/80 and α-SMA ( P < 0.01). Conclusion Xuanfuhua decoction has a good intervention effect on mice with NASH induced by high fat, high fructose, and high-cholesterol diet and can significantly inhibit hepatic lipid deposition, inflammatory response, and liver fibrosis.