OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

Objective:To evaluate the feasibility and clinical effectiveness of placing a nasointestinal ileus tube (NTI) during extensive adhesive bowel obstruction (ABO) surgery.Methods:A retrospective analysis was performed for the clinical and follow-up data of 60 patients with extensive ABO admitted to the Department of General Surgery of Daxing District Hospital of Capital Medical University from April 2019 to April 2021, of which 30 patients underwent intraoperative NIT intraintestinal alignment (observation group) and 30 patients who did not undergo NIT intraintestinal alignment (control group) during the same period. There were 12 males and 18 females in the observation group. There were 16 males and 14 females in the control group. The operation time, gastrointestinal function recovery time, discharge time, total effective rate and postoperative complication rate were compared between the two groups, and the quantitative data of the recurrence rate of intestinal obstruction at 24 months after surgery were expressed as mean ± standard deviation ( ± s), and the t-test was used for comparison between groups. Numerological data were presented as cases (percentage) [ n (%)], and chi-square tests were used for comparison between groups. Results:All patients were successfully completed the surgery and discharged from the hospital. There was no statistically significant difference in total effective rate between the control group and the observation group( χ2=3.16, P=0.237). The surgical time in the observation group was slightly longer than that in the control group [(110.6±4.6) min vs (94.3±2.5) min, t=17.27, P=0.001]. The recovery time of gastrointestinal function and hospitalization time in the observation group were shorter than those in the control group[(8.13±1.00) d vs (8.70±0.70) d, t=2.53, P=0.014; (12.83±1.57) d vs (13.67±1.03) d, t=0.03, P=0.018]. The incidence of postoperative complications was lower than that in the control group (10% vs 30%, P=0.028), and the difference was statistically significant. Conclusion:Intraoperative application of NIT is safe and effective, and can significantly reduce the recurrence rate of postoperative intestinal obstruction.

BACKGROUND:Oxidative stress plays a critical role in intervertebral disc degeneration.As a reducing material with good biocompatibility,black phosphorus quantum dots have the potential to resist oxidative stress and retard intervertebral disc degeneration.OBJECTIVE:To evaluate the effect of black phosphorus quantum dots on scavenging reactive oxygen species in the microenvironment of an intervertebral disc through in vivo and in vitro experiments,and further explore the role of black phosphorus quantum dots in Nrf2/ARE pathway and intervertebral disc inflammation.METHODS:Black phosphorus quantum dots were prepared by a liquid exfoliation technique.(1)In vitro experiment:The nucleus pulposus cells of SD rats were isolated and extracted,and the passages 2-4 nucleus pulposus cells were cocultured with different solutions,including F12-DMEM medium(blank group),black phosphorus quantum dot solution,hydrogen peroxide solution,hydrogen peroxide+black phosphorus quantum dot solution,hydrogen peroxide+black phosphorus quantum dot+Nrf2 specific inhibitor ML385 solution.Cell live/dead staining and intracellular reactive oxygen species,mitochondrial membrane potential and western blot assay were performed respectively.(2)In vivo experiment:Thirty SD rats were randomly divided into sham operation,puncture and puncture + black phosphorus groups,with 10 rats in each group.A Co7-10 intervertebral disc degeneration model was established using intervertebral disc puncture in the puncture group and the puncture+black phosphorus group.Black phosphorus quantum dot solution was injected in the intervertebral disc after a puncture in the puncture+black phosphorus group.The intervertebral disc tissue imaging and histological staining were evaluated at 4 and 8 weeks after surgery.RESULTS AND CONCLUSION:(1)In vitro experiment:Live/dead staining revealed that the black phosphorus quantum dots had good biocompatibility,were non-toxic to cells,and had a protective effect on nucleus pulposus cells under oxidative stress.Intracellular reactive oxygen species and JC-1 fluorescent probes showed that black phosphorus quantum dots could regulate the reduction of mitochondrial membrane potential caused by oxidative stress in nucleus pulposus cells and protected cells from hydrogen peroxidation-induced intracellular oxidative stress.Western blot analysis showed that compared with the blank group,the protein expressions of Nrf2,heme oxygenase 1,quinone oxidoreductase and type Ⅱ collagen were decreased in the hydrogen peroxide group(P<0.05),while the protein expressions of tumor necrosis factor α,interleukin 1β,matrix metalloproteinase 13 and p65 were increased(P<0.05).The addition of black phosphorus quantum dots could reverse the inhibitory effect of hydrogen peroxide on the Nrf2 pathway and reduce the inflammatory response caused by oxidative stress,but NrF2-specific inhibitors could cancel this effect.(2)In vivo experiment:X-ray and MRI demonstrated that at 4 and 8 weeks after surgery,the intervertebral disc height and water content of nucleus pulposus in the puncture group were lower than those in the sham operation group(P<0.05),and the intervertebral disc height and water content of nucleus pulposus in the puncture+black phosphorus group were higher than those in the puncture group(P<0.05).Histological staining exhibited that the degree of intervertebral disc degeneration in the puncture+black phosphorus group was less than that in the puncture group,and the expression of heme oxygenase 1 protein was higher than that in the puncture+black phosphorus group.(3)Our results have indicated that black phosphorus quantum dots can exert an antioxidant effect and delay intervertebral disc degeneration by regulating Nrf2/ARE pathway.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Transient receptor potential vanilloid-1(TRPV1) channel is a non-selective ligand-gated cationic channel with multiple activation mechanisms in the transient receptor potential subfamily. In recent years, a large number of studies have found that TRPV1 plays an important role in the field of cardiovascular diseases such as hypertension and atherosclerosis. With the in-depth study of traditional Chinese medicine, it has been found that Chinese medicine monomers and their active components can activate or inhibit TRPV1 channels, which has certain potential in the study of cardiovascular diseases. In this paper, the role of TRPV1 channel in cardiovascular diseases and the research progress of traditional Chinese medicine prevention and treatment of cardiovascular diseases based on TRPV1 channel are reviewed, in order to provide new ideas for prevention and treatment of cardiovascular system diseases.

Objective:To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods:Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results:A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes ( blaNDM-1, blaNDM-5, etc.) and virulence genes ( acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion:Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.

Objective To investigate the inhibitory effect of quercetin on Gastro entero pancreatic NEN(GEP-NEN).Methods Human pancreatic neuroendocrine tumor BON-1 cells were randomly divided into control group,quercetin group(80 μmol·L-1 quercetin),quercetin+si-NC group(transfected with si-NC+80 μmol·L-1 quercetin),quercetin+si-growth arrest-specific+ranscript 5(GAS5)group(transfected with si-GAS5+80 μmol·L-1 quercetin).Dual luciferase reporter gene assay was used to verify the targeted binding of GASS5 to miR-18b-5p;real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the mRNA expression levels of B-cell lymphoma-2(Bcl-2)and Bel-2 associated X protein(Bax);positive expression of GAS5 and miR-18b-5p in cells was detected by fluorescence in situ hybridization(FISH)assay.Results Dual luciferase reporter gene results showed that GAS5 was targeted to miR-18b-5p.The GAS5 expression levels of control group,quercetin group,quercetin+si-NC group and quercetin+si-GAS5 group were 1.00±0.13,1.72±0.19,1.78±0.14 and 1.16±0.11,respectively;the expression levels of miR-18b-5p were 1.00±0.15,0.67±0.08,0.72±0.06 and 0.95±0.11 respectively;Bax mRNA expression levels were 1.00±0.12,2.17±0.25,2.32±0.28 and 1.37±0.15,respectively;Bcl-2 mRNA expression levels were 1.00±0.15,0.41±0.05,0.37±0.06 and 1.21±0.13,respectively.The above indexes were significantly different between quercetin group and control group(all P＜0.05);the above indexes were significantly different between quercetin+si-NC group and quercetin+si-GAS5 group(all P＜0.05).Conclusion Quercetin may slow down the development of GEP-NEN by targeting GAS5/miR-18b-5p molecular axis to inhibit cell growth.

Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P＜0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P＜0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P＜0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P＜0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P＜0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P＜0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P＜0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P＜0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P＜0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P＜0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.