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OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.
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Objective:To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1(LncRNA NEAT1)and miR-27a-3p in serum and cerebro-spinal fluid of patients with Alzheimer disease(AD).Methods:Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered,according to the clinical dementia rating scale score,they were grouped into mild group(≤ 1 point,n=41)and moderate-to-severe group(＞1 point,n=25).Another 66 cases of serum and cerebrospinal fluid sam-ples from outpatient physical examination personnel were regarded as the control group.The general infor-mation on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1(BACE1),β-amyloid(Aβ)40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scores;Pearson method was per-formed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio(SUVR)and cerebrospinal fluid miR-27a-3p,NEAT1,BACE1,Aβ42 and Aβ40 levels.Results:The MMSE score[21(17,25),9(7,11)vs.27(21,34)],MoCA score[17(12,21),10(7,13)vs.27(21,31)],serum miR-27a-3p level(0.55±0.13,0.46±0.06 vs.0.97± 0.22),cerebrospinal fluid miR-27a-3p(0.48±0.10,0.35±0.10 vs.1.03±0.31),Aβ42 levels[(303.55±36.77)ng/L,(231.45±34.14)ng/L vs.(499.99±53.63)ng/L]and Aβ42/Aβ40 ra-tio(0.030±0.008,0.022±0.007 vs.0.048±0.010)of AD patients in mild group and moderate-to-severe group were all lower than those in the control group,and the moderate-to-severe group were lower than the mild group(all P＜0.05);the serum NEAT1 level(2.31±0.64,3.13±0.76 vs.1.05± 0.20),SUVR(1.50±0.29,1.76±0.52 vs.0.74±0.15),and cerebrospinal fluid NEAT1(3.51± 1.24,4.30±1.65 vs.1.01±0.23)and B ACE 1 levels[(55.78±5.98)μg/L,(72.32±16.08)μg/L vs.(21.39±3.73)μg/L]were higher than those in the control group,and the moderate-to-se-vere group were higher than the mild group(all P＜0.05).Serum NEAT1 level in AD patients was posi-tively correlated with SUVR,cerebrospinal fluid NEAT1 and BACE1(r=0.350,0.606,0.341,P＜0.05),and negatively correlated with MMSE score and MoCA score(r=-0.473,-0.482,all P＜0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level,MMSE score and MoCA score(r=0.695,0.424,0.412,all P＜0.05),and negatively correlated with SUVR and cerebrospinal fluid BACE1 level(r=-0.521,-0.447,all P＜0.05).Conclusion:The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are con-sistent,the level of NEAT1 is increased,and the level of miR-27a-3p is decreased.The levels of the two are negatively correlated,which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.
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Objective To investigate the effects of puerarin on myocardial ischemia-reperfusion injury and its mecha-nism.Methods Molecular docking and dynamics simulation were utilized to predict the binding potential of puerarin and SIRT1.A myocardial ischemia-reperfusion model was established in SD rats by ligating the anterior descending branch of the left coronary artery.The protective effect of puerarin on myocardial injury was observed,and the therapeutic effect of puerarin was compared after inhibition of SIRT1 expression.The infarct volume was detected using 2,3,5-triphenyltetrazolium chloride(TTC)staining.The apoptosis rate and SIRT1 expression of cardiomyocytes were detected by using TUNEL combined with im-munofluorescence.Transmission electron microscope was used to observe the myocardial ultrastructure.Western blot was per-formed to detect the expression of ferroptosis-related proteins.Results Molecular docking studies confirmed the formation of stable complexes between puerarin and SIRT1.Puerarin treatment significantly increased myocardial ischemia-reperfusion injury through upregulation of SIRT1,SLC7A11 and GPX4 expression,and downregulation of IREB2 expression in rats.The protec-tive effect of puerarin on myocardium was abolished once SIRT1 protein expression was inhibited.Conclusion Molecular doc-king and molecular dynamics simulation techniques can accurately predict the interaction of puerarin,and the main target SIRT1.Puerarin inhibits ferroptosis by activating SIRT1 pathway,thereby alleviating myocardial ischemia-reperfusion injury.
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Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.
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Objective To explore the mechanism and management of acute kidney injury induced by the interaction be-tween voriconazole and nifedipine.Methods A patient with acute kidney injury was treated with nifedipine controlled-release tablets and voriconazole tablets at the same time.Pharmacists analyzed drug interactions and drug characteristics during diagnosis and treatment and proposed treatment recommendations,discontinued suspected drugs(cefotaxime and voriconazole),and deter-mined subsequent treatment based on the analysis results.Results The doctor accepted the advice and the patient gradually re-covered from acute kidney injury.Conclusion Drug-drug interactions,especially those based on the interaction of liver drug enzyme CYP450,should be paid attention to in clinical diagnosis and treatment,to improve efficacy and reduce adverse reactions.
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Objective:To investigate the correlation between gender, age, blood collection time, season and changes in cTnT concentration.Methods:In this study, 3548 patients (non-cardiovascular diseases) in Zhongshan Hospital of Fudan University were selected from 1 January to 31 December 2019. The basic data of the patients were collected, including gender, age, time of blood collection, medical history, clinical diagnosis, and results of cTnT testing. 1 840 males and 1 708 females were finally enrolled, with an age distribution of 65 (53, 75) years. The distribution of the data was assessed using the Kolmogorov-Smirnov (K-S) test, where non-normally distributed data were expressed as M( Q1, Q3). The Mann-Whitney U-test was used to compare cTnT concentrations between men and women, and to analyse the influence of gender on cTnT results. The Kruskal-Wallis test was used to compare cTnT levels between gender groups, to analyse the correlation between different times of blood collection, seasons, and other factors and cTnT concentrations. Result:cTnT concentrations increased with age in both males and females over the age of 60 years. cTnT levels were highest in individuals over the age of 90 years (0.028 ng/ml in males and 0.018 ng/ml in females). cTnT levels were higher in males (0.012 ng/ml) than in females (0.009 ng/ml) in all age groups ( H=6.340, P<0.01). The concentrations of cTnT varied at different time points of blood collection. In both males and females, cTnT concentrations reached a maximum at 8:00 and 13:00 (0.013 ng/ml and 0.012 ng/ml, respectively). Analysis of the physiological effect of season on cTnT secretion showed that cTnT levels were generally higher in spring and winter(0.012 ng/ml) than in summer and autumn(0.010 ng/ml). Conclusions:cTnT concentration is influenced by gender, age, time of blood collection and season. When analysing cTnT results in clinical practice, the gender and age of the individual should be taken into account, as well as the time point of blood collection and seasonal factors.
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【Objective】 To explore the correlation between body mass index (BMI) and lipid indexes with prostate volume in patients with benign prostatic hyperplasia (BPH) so as to provide reference for the clinical prevention of this disease. 【Methods】 Clinical data of 578 patients admitted to the Department of Urology of Chinese PLA General Hospital during Jan.2014 and Dec.2022 were collected.The patients underwent initial prostate puncture biopsy or prostatectomy and BPH was confirmed pathologically.The patients’ age, time of onset of the disease, BMI, past medical history and biochemical indexes were analyzed.According to the total prostate volume (TPV) grading, the patients were divided into TPV>75 mL and TPV≤75 mL groups.The general data of the two groups were compared, and predictors of TPV were determined with linear regression analysis.The samples were stratified with BMI to observe the differences in the effects of apolipoprotein B (ApoB) on TPV. 【Results】 There were 215 cases in the TPV>75 mL group and 363 cases in the TPV≤75 mL group.The levels of BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) were higher in the TPV>75 mL group (P0.05), and ApoB predicted prostate volume growth in overweight and obese BPH population respectively (β=26.411, P=0.011; β=47.602, P=0.017). 【Conclusion】 Age, ApoB and BMI can be used as predictors of volume growth in BPH patients, which can help further research on the pathogenesis and progression of BPH.
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ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.
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Objective To investigate the role and mechanism of action of Scabiosa atropurea in inhibiting the proliferation of hepatic stellate cells using cell experiment. Methods A total of 20 Wistar rats were randomly divided into control group and administration group, with 10 rats in each group. The rats in the control group were given normal saline by gavage, and those in the administration group were given Scabiosa atropurea by gavage to prepare drug-containing serum. HSC-T6 cells were incubated with the serum from the control group (10%) or the low-, middle-, and high-dose serum containing Scabiosa atropurea (10%, 15%, and 20%, respectively). MTT assay was used to observe the effect of different drug concentrations on cells in different periods of time; flow cytometry was used to measure cell apoptosis; qRT-PCR and Western blot were used to measure the mRNA and protein expression levels of fibrosis markers (α-SMA, collagen Ⅰ) and PI3K/Akt signaling pathway-related factors in hepatic stellate cells (HSCs). A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t - test was used for further comparison between two groups. Results Compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had a significant reduction in the OD value of cells (all P < 0.05) and a significant increase in the overall apoptosis rate of cells (all P < 0.05). The results of qRT-PCR showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the mRNA expression levels of α-SMA, collagen Ⅰ, PI3K, and Akt and a significant increase in the mRNA expression level of PTEN (all P < 0.05); Western blot showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the protein expression levels of α-SMA, collagen Ⅰ, PI3K, Akt, and p-Akt and a significant increase in the protein expression level of PTEN (all P < 0.05). Conclusion The Mongolian medicine Scabiosa atropurea can inhibit the proliferation of HSC-T6 cells and promote their apoptosis, possibly by regulating fibrosis markers and the PI3K/Akt signaling pathway to exert an anti-liver fibrosis effect.
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Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.
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Objective:To analyze the interaction between obesity and diabetes, obesity and central obesity, central obesity and diabetes on hypertension.Methods:A questionnaire survey on 7 622 residents of Han Chinese ethnicity, aged 35-75 years, of Liangzhou district of Wuwei city were performed using multi-stage random sampling method in September to December 2018. Relative excess risk due to interaction, attributable proportion, synergy index, and 95% CI of the three were used to evaluate the additive interaction. Logistic regression analysis was used to analyze the multiplicative interaction. Results:Among the 7 622 residents, hypertension was detected in 3 212 residents, with a crude prevalence rate of 42.14% and a standardized incidence of 33.81%. There was a significant difference in incidence of hypertension between residents of different sexes, between residents at different ages, between obese residents and normal weight residents, between residents who had central obesity and those who had no central obesity, between residents who smoked and those who did not, between residents of different family economic situations, between residents who had different occupations, and between residents who had diabetes and those who had no diabetes (all P < 0.05). Getting primary, middle, and high school education was a protective factor against hypertension, while obesity, central obesity, diabetes, male gender, age greater than 45 years were the risk factors for hypertension. Multivariate logistic regression analysis showed that there was no additive interaction between obesity and diabetes, obesity and central obesity, central obesity and diabetes on hypertension. There was a multiplicative interaction between obesity and central obesity on hypertension ( P = 0.031, 95% CI: 0.53-0.97) and the interaction was antagonistic, but there were no multiplicative interaction between obesity and diabetes, central obesity and diabetes on hypertension. Conclusion:There was a negative multiplicative interaction between obesity and central obesity on hypertension.
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Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.
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Objective:To explore intrinsic mechanisms underlying the inhibitory effect of resveratrol on neovascularization in cutaneous squamous cell carcinoma from the perspective of ubiquitin/ubiquitin-like protein modification balance.Methods:The human cutaneous squamous cell carcinoma cell line A431 was used as the research object. Cultured A431 cells at exponential growth phase were divided into 3 groups (control group, 50 μmol/L resveratrol group, and 100 μmol/L resveratrol group) to be cultured with mediums containing 0, 50, and 100 μmol/L resveratrol, respectively. Cell proliferation activity was assessed by the 3- (4,5) -dimethylthiazol (-z-y1) -2,5-di-phenytetrazoliumromide (MTT) assay after 48-hour culture; the vasculogenic mimicry formation assay was performed to evaluate the vasculogenic mimicry formation ability of A431 cells after 12-hour treatment with resveratrol; Western blot analysis was conducted to detect the relative protein expression levels of ubiquitin, small ubiquitin-related modifier-1 (SUMO1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor receptor (VEGFR) in different groups after 48-hour treatment with resveratrol. Then, 24 8-week-old BALB/c male thymectomized mice were randomly and equally divided into 3 groups to be subcutaneously inoculated with A431 cells in the inguinal region, followed by intraperitoneal injections of 1 mg/kg or 2 mg/kg resveratrol (1 mg/kg or 2 mg/kg resveratrol group), or the same volume of physiological sodium chloride solutions (control group) ; the intraperitoneal injections were done once every 3 days in all groups; all the above mice were sacrificed on the 21st day, and the tumors were resected and weighed. Immunohistochemistry assay was performed to determine the CD31 expression in tumor tissues. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference (LSD) - t test was used for multiple comparisons. Results:The proliferation rate of A431 cells significantly differed among the control group, 50 μmol/L resveratrol group, and 100 μmol/L resveratrol group ( F = 17.75, P = 0.017), and was significantly lower in the 50 μmol/L resveratrol group (66.53% ± 5.09%) and the 100 μmol/L resveratrol group (35.88% ± 4.28%) than in the control group (100%, LSD- t = 21.17, 29.04, P = 0.011, 0.004, respectively) ; the total length of vessel wall-like structures formed by A431 cells significantly differed among the 3 groups ( F = 21.37, P = 0.004), and was significantly lower in the 50 μmol/L resveratrol group (102.73 ± 11.36 μm) and the 100 μmol/L resveratrol group (37.83 ± 4.19 μm) than in the control group (185.26 ± 8.02 μm, both P < 0.05) ; the relative protein expression levels of ubiquitin, SUMO1, HIF-1α, and VEGFR also significantly differed among the 3 groups, the ubiquitin protein expression was significantly higher in the 50 μmol/L resveratrol group (2.09 ± 0.13) and the 100 μmol/L resveratrol group (3.53 ± 0.16) than in the control group (0.68 ± 0.11, both P < 0.05), while the protein expression of SUMO1, HIF-1α, and VEGFR was significantly lower in the 50 μmol/L resveratrol group (1.87 ± 0.13, 0.81 ± 0.06, 0.73 ± 0.09, respectively) and the 100 μmol/L resveratrol group (1.02 ± 0.11, 0.45 ± 0.06, 0.39 ± 0.05, respectively) than in the control group (3.10 ± 0.11, 0.97 ± 0.08, 0.98 ± 0.07, respectively, all P < 0.05). In the mice experiment, the weight of subcutaneous tumors and the proportion of CD31-positive cells in tumor tissues significantly differed among the control group, 1 mg/kg resveratrol group, and 2 mg/kg resveratrol group (weight: 3.29 ± 0.57 g, 2.91 ± 0.49 g, 2.55 ± 0.52 g; proportion: 76.24% ± 5.51%, 39.45% ± 5.48%, 12.07% ± 3.54%; F = 14.33, 15.34, P = 0.019, 0.021, respectively), and were significantly lower in the 1 mg/kg resveratrol group and 2 mg/kg resveratrol group than in the control group (all P < 0.05) . Conclusion:Resveratrol could inhibit tumor growth and neovascularization in tumor tissues, which were possibly associated with the inhibitory effect of resveratrol on neovascularization in cutaneous squamous cell carcinoma by suppressing the SUMOylation of HIF-1α protein via ubiquitin/ubiquitin-like protein modification pathways.
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【Objective】 To investigate the role and mechanism of dapagliflozin (Dapa), a sodium glucose co-transporter 2 inhibitor, in acute liver injury. 【Methods】 Eight-week-old C57BL6/J mice were given a single intraperitoneal injection of CCl4 to induce acute liver injury. The mice were preventively given 5 mg/kg Dapa by gavage 24 h and 2 h before CCl4 injection, while those in the control group were given an equal volume of solvent gavage. After 24 h, the mice were anesthetized and sacrificed. H&E staining, plasma biochemistry, RT-qPCR, and Western blotting were used to detect the severity of liver injury and the expressions of macrophage-related genes. 【Results】 In the CCl4 group, hepatic infiltration of inflammatory cells increased, and liver and renal functions significantly deteriorated, which was further aggravated by Dapa. CCl4 could promote the expressions of M1 macrophages and fibrosis-related genes in the liver, but reduce those of M2 and antioxidant-related genes, and the latter was further inhibited by Dapa. In addition, the protein expression of arginase 1 decreased and that of SGLT2 increased after Dapa intervention, while NF-κB pathway did not change significantly, suggesting that Dapa might directly affect the energy metabolism homeostasis in the liver and aggravate acute liver injury induced by CCl4. 【Conclusion】 Dapa can exacerbate hepatic and renal damage in acute stage of liver injury, inhibit macrophages M2 polarization, and aggravate oxidative stress and inflammatory injury induced by CCl4.
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Objective:To analyze the mechanism of Qiwei Qinggan Powder in the treatment of hepatic fibrosis by animal experiment and network pharmacology.Methods:A total of 50 rats were randomly divided into blank group, model group and low, medium and high dose of Qiwei Qinggan Powder groups with 10 rats in each group. Except the blank group, other groups were gavaged with 50% carbon tetrachloride peanut oil solution to prepare liver fibrosis model. Rats of low, medium and high dose of Qiwei Qinggan Powder groups were gavaged with 135, 270 and 405 mg/kg Qiwei Qinggan Powder 0.5% CMC-Na solution once a day for 10 weeks. The contents of serum GPT and GOT were detected by Wright's method, the content of ALP was detected by visible light colorimetry method, and the liver structure was observed by HE staining and Masson staining. The mRNA and protein expressions of α-SMA and collagen Ⅰ were detected by Q-PCR and Western blot from hepatic stellate cells. Flow Cytometry was used to detect the effect of Qiwei Qinggan Powder on hepatic stellate cells apoptosis. By searching for Traditional Chinese Medicines Integrated Database, Traditional Chinese Medicine Systems Pharmacology Database as well as literature retrieval, the active chemical components and targets of Qiwei Qinggan Powder were obtained. The targets of hepatic fibrosis were obtainable through OMIM and PubMed. By using Cytoscape 3.7.2, the Medicine-active components-Gene-Disease network was constructed. Obtaining Protein-Protein Interaction Networks screens the central target by using STRING, and using R language to retrieve Bioconductor online GO function enrichment and KEGG pathway enrichment analysis were carried out on the platform.Results:Compared with the model group, the levels of GFT, GOT and ALP in high, medium and low dose groups were decreased ( P<0.01). Compared with the control group, the mRNA levels of α- SMA (0.24 ± 0.12, 0.25 ± 0.12, 0.41 ± 0.15 vs. 1.00 ± 0.00), collagenⅠ (0.64 ± 0.24, 0.33 ± 0.13, 0.28 ± 0.11 vs. 1.00 ± 0.00)was decreased ( P<0.05 or P<0.01) of serum containing low, medium and high dose groups of Qiwei Qinggan Powder, and α-SMA (0.03 ± 0.01, 0.01 ± 0.00, 0.01 ± 0.00 vs. 0.04 ± 0.00), collagenⅠ (0.08 ± 0.01, 0.10 ± 0.01, 0.13 ± 0.01 vs. 0.18 ± 0.01) mRNA levels was decreased of serum containing low, medium and high dose groups ( P<0.01). A total of 35 active components, 196 targets, 3 740 disease targets and 170 disease common targets were screened out. 159 items were obtained by GO enrichment analysis; 43 signal pathways were obtained by KEGG enrichment analysis. Conclusion:Qiwei Qinggan Powder can promote HSCs apoptosis and treat HF through multi-component, multi-target and multi-channel therapy.
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The delta checks are one of the patient-based quality control options to identify the errors and the significant changes in patients′ condition. Compared with the traditional internal quality control method, the delta checks have the characteristics of real-time monitoring, with no additional detecting cost, thus the delta checks are widely used in clinical laboratories. In addition, the delta checks are also useful in the auto-verification system to screen out the abnormal results for manual verification. This article reviewed the delta checks′ development history, parameters selection, application values in quality control and auto-verification.
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Objective@#To investigate the establishment of health care institutions and the staffing primary and secondary school health care in Shanghai, and to understand the capacity building needs of health care personnel.@*Methods@#A survey was conducted on all primary and secondary schools in Shanghai from April to August in 2020. The content of the questionnaire covers the establishment of health care institutions, the staffing of school health care centers and the capacity building need of health care personnel. Chi square test was used to compare the difference of the health care institutions setting and staffing by schools and areas.@*Results@#In 2020, there were 1 847 primary and secondary schools in Shanghai (including branches schools). About 51.4% of primary and secondary schools in Shanghai were equipped with school health care personnel in the ratio of the number of students at least 600∶1 , and the staffing compliance rate of urban schools (59.3%) was higher than that of suburban schools (47.3%)( χ 2=24.27, P <0.01). All school health care personnel believed that there are currently few opportunities for capacity buliding services from health facilities.@*Conclusion@#School health care institutions in Shanghai are well equipped, but the staffing shortage is substantial, with strong need for capacity building.
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Objective To discuss the role of clinical pharmacist in individualized treatment and pharmaceutical care for a patient with Pneumocystis jiroveci pneumonia after renal transplantation. Methods The clinical pharmacist participated in the pharmaceutical care for a patient with Pneumocystis jiroveci pneumonia after renal transplantation. the literature were reviewed and analyzed and the medication of anti-infective treatment plan was adjusted by Clinical pharmacist. The adverse reactions in the treatment process were discovered in time, and corresponding treatments were made. Results Clinical pharmacists assisted physicians to adjust the medication plan and the patient recovered well after the treatment. Conclusion Clinical pharmacists could assist doctors in discovering drug treatment-related problems by mastering relevant treatment guidelines, the effectiveness and safety characteristics of drugs, which could help to establish individualized treatment plans and improve the safety and effectiveness of patients' medication.
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Objective:To investigate the expression of four cancer stem cell (CSC) markers (EpCAM, CD133, CD90 and CD24) in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells (CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods:A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM, CD133, CD90 and CD24. The clinical data of patients were collected, including tumor size, tumor number, satellite lesions, vascular invasion, Edmondson stage, BCLC stage and liver cirrhosis, etc. The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results:The positive expression rates of EpCAM, CD133, CD90 and CD24 in hepatocellular carcinoma tissues were 66% (33/50), 18% (9/50), 60% (30/50) and 56% (28/50); the positive expression rates in CTC were 55% (16/29), 38% (11/29), 31% (9/29) and 59% (17/29). CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis ( P<0.05), while CD133 expression was negatively correlated with the 5-year survival rate of patients ( P<0.05). The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage ( P<0.05). The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression ( P<0.05); the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression ( P<0.05). The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepatocellular carcinoma tissue and negative in peripheral blood ( P<0.01). Conclusion:Different expression characteristics of four markers in cancer tissues and peripheral blood CTC might provide useful information about predicting prognosis of hepatocellular carcinoma. The expression of CD133 in tissues can be used as an important survival predictor of hepatocellular carcinoma patients. The differential expression of cancer markers in tissue samples and blood samples can provide more clinical prognostic information.
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Objective:To observe the expressions of c-Jun N-terminal kinase (JNK), matrix metalloproteinase-9 (MMP-9) and macrophage marker MAC387 in the blood vessels of rats with vertebrobasilar dolichoectasia (VBD), and to study the therapeutic effect and mechanism of rosuvastatin on VBD.Methods:Sixty male SD rats were randomly divided into sham-operated group, VBD model group and rosuvastatin intervention group ( n=20). Elastase at 0.3 uL (1.5 U/μL) was injected into the cisterna magna of rats in the latter two groups to establish VBD models; while same volume of saline solution was given to rats in the sham-operated group. Twenty-four h after model making, 5 mg/(kg.d) rosuvastatin (once/d, for 4 weeks) was administered intragastrically into rats in the rosuvastatin intervention group, and same volume of distilled water was administered intragastrically into rats in the other 2 groups. The degrees of extension and expansion of vertebrobasilar artery were measured and compared among the 3 groups. Western blotting was used to detect the expressions of JNK and MMP-9, and immunofluorescent staining was used to detect the MAC387 expression in the vertebrobasilar artery. Results:Fourteen rats in the VBD model group and rosuvastatin intervention group, respectively, had successful model making. As compared with the sham-operated group, the VBD model group and rosuvastatin intervention group had statistically increased basilar artery diameter and basilar artery tortuosity index ( P<0.05). The expressions of JNK, MMP-9 and MAC387 in the VBD model group and rosuvastatin intervention group were significantly increased as compared with those in the sham-operated group ( P<0.05); as compared with those in the VBD model group, the expressions of JNK, MMP-9 and MAC387 in the vertebrobasilar artery of rosuvastatin intervention group were significantly decreased ( P<0.05). Conclusion:Rosuvastatin can delay VBD progress, whose mechanism may be related to the inhibition of inflammatory response.