Objective To investigate the effect of microplastic(MPs)exposure on learning and memory in mice,and its mechanism by observing the protein expression of brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)/N-methyl-D-aspartate receptor subtype 2B(NR2B)signaling pathway and neurogenesis.Methods Forty male C57BL/6 mice were randomly divided into control group(Ctrl)and microplastics exposure group(MPs).Mice in MPs group were treated with 0.3 mg/(kg·d)microplastics,administered by gavage at a volume of 200 μl for 30 consecutive days.Morris water maze test was used to evaluate the spatial learning and memory ability of mice.Western blotting was used to detect the protein levels of BDNF,TrkB and NR2B in hippocampus of mice.Immunofluorescent staining was used to observe the number of doublecortin(DCX)and neuronal nuclei antigen(NeuN)positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.Results Compared with the control group,the ability of learning and memory decreased significantly in MPs group mice(P＜0.01).The expression levels of BDNF,TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group(P＜0.05).The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group(P＜0.01).Conclusion MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/pathology* ; Exons ; Humans ; Janus Kinase 2/genetics* ; Middle Aged ; Mutation ; Mutation, Missense ; Polycythemia Vera/genetics* ; Young Adult

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Stroke/drug therapy*

Background: In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism. Methods: The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student’s t test, and comparisons among multiple samples were performed by oneway analysis of variance and a Bonferroni post hoc test. Results: The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286 ± 0.017 vs. 3.211 ± 0.034, t= 11.540, P < 0.0001) and cell lines (P < 0.01 in all BC cell lines). Besides, we also indicated that over-expression of miR-139-5p reduced the proliferation of ECV-304 (P = 0.001) and T24 cells (P = 0.005). Moreover, miR-139-5p over-expression weakened the invasion (P = 0.001) and migration (P = 0.001) of ECV-304 cells. Furthermore, the relative luciferase activity of CX43-wild type construct was distinctly lessened by up-regulation of miR-139-5p (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.916 ± 0.063 vs. 0.356 ± 0.048, t = 7.085, P = 0.002), nevertheless the activity of CX43-mutant type construct was untouched (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.918 ± 0.057 vs. 0.878 ± 0.039, t= 0.577, P = 0.595). Finally, the rescue assay revealed that CX43 deletion enhanced the depressor effect of miR-139-5p on ECV-304 cell proliferation (P < 0.01), invasion (P = 0.028), and migration (P = 0.014). Conclusion MiR-139-5p, as a tumor-suppressor, repressed cell proliferation, invasion, and migration in BC, which might be achieved by regulating CX43.

·AIM: To investigate the relationship between the thickness of choroid and the development of idiopathic macular epiretinal membrane (IMEM). ·METHODS: A retrospective analysis on 48 cases (48 eyes) of idiopathic macular epiretinal membrane patients (the IMEM group) was taken in our hospital from January 2014 to December 2016, and 50 right eyes in 50 healthy persons with physical examination were selected the control group, comparison on subfoveal choroidal thickness (SFCT) levels of sicked eyes, normal eyes in IMEM group and the control group were made, postoperative SFCT level change of sicked eyes in IMEM patients and normal eyes were investigated via follow-up, and analysis on correlation between postoperative choroidal thickness and the best corrected visual acuity was taken. ·RESULTS: The SFCT of sicked eyes in IMEM group 362.22±40.75μm was significantly lower than that of the contralateral eyes (410.56 ± 38.45μ m) and the right eyes of the control group (420.73±39.63μ m), and data of the contralateral eyes was lower than right eyes of the control group, distinct difference was shown between groups(P<0.05). The IMEM group's SFCT of sicked eyes and normal eyes at postoperative 1wk had no significant difference with that before operation (P>0.05), and at postoperative 1mo,SFCT of sicked eyes and normal eyes evidently increased, showing sharp difference compared with that before operation (P<0. 05). After that, the SFCT value stabilized, but there was no obvious difference between the sicked eyes and healthy eyes at postoperatively 1mo (P>0.05). The numbers of patients whose postoperative BCVA ≥ 0. 5 with different preoperative SFCT values had statistically significant differences (P<0.05), and those with BCVA ≥0.5 of SFCT values> 380μ m were significantly higher than those with <320μ m and 320μ m-380μ m groups. Fisher exact probability analysis showed that the differences were significant. Pearson analysis showed that there was a positive correlation between the postoperative choroid thickness and the best corrected visual acuity of IMEM group (r=0.629,P<0.05). · CONCLUSION: Choroidal thinning may be an important cause of IMEM, and preoperative choroidal thickness also has an influential effect on postoperative visual recovery.

Objective To investigate the protective effects of Coptis chinensis decoction on the metabolic index and renal function of rats with fructose-induced metabolism syndrome (MS).Methods From 56 male Wistar rats,6 were randomly selected as normal control group,the other rats were daily fed with 10％ fructose water for 8 weeks to reproduce the MS model.Twenty-four rats were established successfully as MS model and randomly divided into 4 groups (6 each):model group,Coptis decoction group,tauroursodeoxycholic acid (TUDCA) group and berberine hydrochloride (BH) group.The body weight,visceral fat weight,fasting blood glucose (FBG),fasting insulin (FINS),insulin resistance index (HOMA-IR),cholesterol (TC),triglyceride (TG),systolic blood pressure (SBP),diastolic blood pressure (DBP),urinary N-acetyl-β-D-glucosidase (NAG),urine microalbumin (m-ALB),blood urea nitrogen (BUN) and serum creatinine (Scr) levels were compared between the groups,and the renal pathological changes were observed by light microscopy and electron microscopy.Results The levels of body weight,visceral fat weight,FINS,HOMA-IR,TC,TG,SBP,DBP and urinary NAG were obviously higher in the four MS model groups than in normal control group (P＜0.05),while the levels of m-ALB,BUN and Scr showed no significant difference (P＞0.05).After the intervention,the levels of body weight,visceral fat weight,FINS,HOMA-IR,TC,TG,SBP and DBP decreased significantly in Coptis decoction group than in model group (P＜0.05).Compared with BH group and TUDCA group,the levels of FINS and HOMA-IR decreased obviously in Coptis decoction group (P＜0.05),while the levels of body weight,TC,TG,SBP,DBP,urinary NAG,BUN and Scr showed no significant difference (P＞0.05).It was observed in model group by light microscopy and electron microscopy that the glomerular swelled obviously,the capillary basement membrane of glomerular and renal tubules thickened,mesangial region and interstitial substances hyperplasia,podocytes swelled markedly and most of fusion,the epithelial cells of renal tubules serious vacuolar degeneration,and a lot of secondary lysosomes formed,autophagy of organelles occurred,and most of endoplasmic reticulum and mitochondria disappeared.The kidney pathological damage reduced obviously after treatment of Coptis decoction,but no significant difference when compared with that in BH group and TUDCA group.Conclusions Coptis decoction may decrease the body weight,reduce the levels of blood lipid and blood pressure,and better improve the insulin resistance when compared with BH and TUDCA.In addition,Coptis decoction can also reduce the renal pathological damage,and has the protective function for kidney.

OBJECTIVETo investigate the relationship between a blood pressure variability (BPV)-based scoring system (BPVSS) and the target organ damage in patients with hypertension.

METHODSWe selected 95 consecutive inpatients with essential hypertension admitted between January and June, 2015 in the Department of Cardiology of Guangzhou General Hospital of Guangzhou Military Command. The BPV indices were analyzed for their correlation with the parameters of target organ damage (IVSd, LVPWd, baPWV_L/R, and IMT_L/R). The patients with a BPVSS of 3.9 or higher (control, 43 cases) and those with a lower BPVSS (observation group, 52 cases) were compared for differences in IVSd, LVPWd, baPWV_L/R, IMT_L/R and the proportion of carotid plaques.

RESULTSSimilar with the traditional BPV indices, BPVSS was negatively correlated with IMT_L/R (r=-0.278/-0.324, P<0.05). BPVSS was also negatively correlated with IVSd (r=-0.241), LVPWd (r=-0.223), and baPWV_L/R (r=-0.468/-0.373) (P<0.05). IVSd, LVPWd, baPWV_L/R and IMT_L/R were all significantly higher in the observation group than in the control group (t=2.307, 2.516, 3.250/2.790, and 2.372/3.425, respectively; P<0.05). The proportion of carotid plaques in the observation group was significantly higher than that in the control group (Χ(2)=27.833, P<0.001).

CONCLUSIONBPVSS indicates the severity of target organ damage in patients with hypertension. A greater BPV is correlated with a lower BPVSS score and more severe damages of the heart and blood vessels.

Objective To study the expressed dynamic change and roles of a disintegrin and metalloprotease 8 (ADAM8) during drug -induced liver injury induced by acetaminophen (AAP).Methods Mice were randomly divided into two groups:normal group and experimental group. The mice in experimental group were respectively drawn blood by remo -ving the eyeballs and serum was separated to detect the activity of aspar -tate aminotransferase (AST) and alanine aminotranferease (ALT) at 6, 24, 42 and 72 h after intraperitoneal injection with 550 mg? kg-1 AAP. The activity of serum AST and ALT in the mice of normal group was also detected.The expression of hepatic ADAM8 at protein and mRNA levels was detected by Western blot and RT -PCR in the mice of normal group and experimental group at different time points after AAP injection . Results Serum AST and ALT activity was first increased and then decreased after AAP injection in the mice.The expression of ADAM8 were significantly up -regulated (P <0.05) at 6 h, reached peak level at 24 h (P <0.05).Then gradually down -regulated and recovered near the normal level at 72 h after AAP injection.Conclusion ADAM8 were remarkably differently expressed during drug -induced liver injury induced by AAP, which may play an important role in promoting liver damage during drug -induced liver injury induced by AAP.