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Objective:To evaluate the effect of Salvianolic acid B (Sal B) on the inflammatory responses of vascular smooth muscle cells (VSMCs) in septic mice and the role of circACTA2.Methods:In vivo experiment Eighty-one healthy male C57BL/6 mice, aged 6-8 weeks, were divided into 3 groups ( n=27 each) by a random number table method: sham operation group, sepsis group and Sal B group. Sepsis model was developed by cecal ligation and puncture. After sucessful preparation of the model, Sal B 7 mg/kg/d was intraperitoneally injected once a day for 2 consecutive days in Sal B group. Twenty mice in each group were randomly selected to measure systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and whole blood lactic acid (Lac) and to record the survival within 7 days after developing the model. Seven mice in each group were randomly selected at 48 h after developing the model, and the arterial vascular tissues were collected for determination of the expression of interleukin-1beta (IL-1β) (by immunofluorescence staining), expression of IL-1β, tumor necrosis factor-alpha (TNF-α) and IL-6 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction, respectively), and expression of circACTA2 (by quantitative real-time polymerase chain reaction). Cell experiment Mouse VSMCs were cultured and divided into 6 groups ( n=3 each) by a random number table method: control group (C group), lipopolysaccharide (LPS) group, Sal B group, si-circACTA2+ C group, si-circACTA2+ LPS group, and si-circACTA2+ Sal B group. The cells were incubated for 24 h with LPS (final concentration 1 μg/ml) in LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) in Sal B group. VSMCs were transfected with si-circACTA2 only in si-circACTA2+ C group. At 24 h after transfection of si-circACTA2 into VSMCs, the cells were incubated with LPS (final concentration 1 μg/ml) in si-circACTA2+ LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) for 24 h in si-circACTA2+ Sal B group. The expression of IL-1β, TNF-α and IL-6 protein and mRNA was detected using Western blot and quantitative real-time polymerase chain reaction, and the expression of circACTA2 was determined by the quantitative real-time polymerase chain reaction. Results:In vivo experiment Compared with sham operation group, SBP, DBP and MAP were significantly decreased, the concentrations of whole blood Lac were increased, 7-day survival rate was decreased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was up-regulated, circACTA2 expression was down-regulated ( P<0.05), and the fluorescence of IL-1β was enhanced in sepsis group. Compared with sepsis group, SBP, DBP and MAP were significantly increased, whole blood Lac concentrations were decreased, 7-day survival rate was increased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was down-regulated, the expression of circACTA2 was up-regulated ( P<0.05), and the fluorescence of IL-1β was weakened in Sal B group. Cell experiment Compared with group C, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated, and the expression of circACTA2 was down-regulated in LPS group ( P<0.05). Compared with LPS group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly down-regulated, and the expression of circACTA2 was up-regulated in Sal B group ( P<0.05). Compared with si-circACTA2+ C group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated in si-circACTA2+ LPS group ( P<0.05). There were no significant differences in the expression of IL-1β, TNF-α and IL-6 protein and mRNA between si-circACTA2+ LPS group and si-circACTA2+ Sal B group ( P>0.05). Conclusions:Sal B can reduce the inflammatory responses of VSMCs, and the mechanism may be related to promoting the expression of circACTA2 in septic mice.
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BACKGROUND: Posterior interosseous nerve (PIN) entrapment syndrome is one of the causes of weakness and pain of the arm muscles, which is prone to missed diagnosis and misdiagnosis in clinic practice. This paper reports a case of PIN entrapment syndrome, with PIN injury indicated by electrophysiology. Musculoskeletal ultrasound was applied to identify that the entrapment point was located at the inlet of the Frohse arch and the outlet of the supinator muscle. Treatment with ultrasound-guided nerve hydrodissection was performed on the entrapment point, which significantly improved the symptoms. Ultrasound-guided nerve hydrodissection is an effective therapeutic method for PIN entrapment syndrome. CASE SUMMARY: A male patient, 35 years old, worked as an automobile mechanic. He felt slightly weak extension activity of his right fingers 2 years ago but sought no treatment. Later, the symptoms gradually became aggravated and led to finger drop, particularly severe in the right middle finger, accompanied by supination weakness of the right forearm. Neural electrophysiological examination showed that the patient had partial PIN injury of the right radius. Musculoskeletal ultrasound examination indicated PIN entrapment at the inlet of the Frohse arch and the outlet of the supinator muscle. Therefore, PIN entrapment syndrome was diagnosed. After treatment with ultrasound-guided nerve hydrodissection around the entrapment point, the dorsiflexion weakness of the right hand was significantly improved compared with before treatment. CONCLUSION: Ultrasound-guided hydrodissection is efficacious for PIN entrapment syndrome, with high clinical value and great application prospects.
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Objective:To evaluate the efficacy of goal-directed analgesia/sedation for improvement in the preoperative management of the patients with aortic dissection.Methods:One hundred and ten patients of either sex, aged≥18 yr, diagnosed with arterial dissection by aortic CTA in our hospital, were divided into 2 groups ( n=55 each) using a random number table method: conventional group and goal-directed analgesia/sedation group. Routine preoperative management was performed in both groups. Fentanyl 0.13 μg/min was intravenously infused, and the infusion rate of fentanyl was adjusted to maintain the numerical rating scale (NRS) score at 0-3 at rest in conventional group. Midazolam 0.02 mg·kg -1·h -1 and fentanyl 0.13 μg/min were intravenously infused, and the infusion rates of midazolam and fentanyl were adjusted to maintain Richmond agitation-sedation score at -2 to 0 and NRS score at rest 0-3 in goal-directed analgesia/sedation group. Nicardipine was intravenously injected and the administration rate was adjusted to maintain systolic blood pressure at 100-120 mmHg, and metoprolol was taken orally to maintain the heart rate 60-70 beats/min. The time to reach the target blood pressure and consumption of fentanyl and nicardipine within 24 h were recorded, and the occurrence of drug-related adverse reactions during analgesia and sedation and perioperative death were recorded. Results:Compared with conventional group, the time to reach the target blood pressure was significantly shortened, and the consumption of fentanyl and nicardipine within 24 h was decreased in goal-directed analgesia/sedation group ( P<0.05). No adverse reactions or perioperative death was observed in two groups. Conclusions:Goal-directed analgesia/sedation (Richmond Agitation-Sedation Scale score -2-0, NRS score at rest 0-3) is helpful in controlling blood pressure and heart rate, thus improving the quality of preoperative management of patients with aortic dissection.
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The purpose of this study was to identify the potential diagnostic biomarkers in hepatocellular carcinoma (HCC) by machine learning (ML) and to explore the significance of immune cell infiltration in HCC. From GEO datasets, the microarray datasets of HCC patients were obtained and downloaded. Differentially expressed genes (DEGs) were screened from five datasets of GSE57957, GSE84402, GSE112790, GSE113996, and GSE121248, totalling 125 normal liver tissues and 326 HCC tissues. In order to find the diagnostic indicators of HCC, the LASSO regression and the SVM-RFE algorithms were utilized. The prognostic value of VIPR1 was analyzed. Finally, the difference of immune cell infiltration between HCC tissues and normal liver tissues was evaluated by CIBERSORT algorithm. In this study, a total of 232 DEGs were identified in 125 normal liver tissues and 326 HCC tissues. 11 diagnostic markers were identified by LASSO regression and SVM-RFE algorithms. FCN2, ECM1, VIRP1, IGFALS, and ASPG genes with AUC>0.85 were regarded as candidate biomarkers with high diagnostic value, and the above results were verified in GSE36376. Survival analyses showed that VIPR1 and IGFALS were significantly correlated with the OS, while ASPG, ECM1, and FCN2 had no statistical significance with the OS. Multivariate assays indicated that VIPR1 gene could be used as an independent prognostic factor for HCC, while FCN2, ECM1, IGFALS, and ASPG could not be used as independent prognostic factors for HCC. Immune cell infiltration analyses showed that the expression of VIPR1 in HCC was positively correlated with the levels of several immune cells. Overall, VIPR1 gene can be used as a diagnostic feature marker of HCC and may be a potential target for the diagnosis and treatment of liver cancer in the future.
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Phylogenetically distant coronaviruses have evolved to use ACE2 as their common receptors, including NL63 and many Severe acute respiratory syndrome (SARS) coronavirus-related viruses. We recently reported two Middle East respiratory syndrome coronavirus (MERS-CoV) closely related bat merbecoviruses, NeoCoV and PDF-2180, use Angiotensin-converting enzyme 2 (ACE2) for entry. However, their host range and cross-species transmissibility remain unknown. Here, we characterized their species-specific receptor preference by testing ACE2 orthologs from 49 bats and 53 non-bat mammals. Both viruses exhibited broad receptor recognition spectra and are unable to use ACE2 orthologs from 24 species, mainly Yinpterochiropteran bats. Comparative analyses of bat ACE2 orthologs underscored four crucial host range determinants, all confirmed by subsequent functional assays in human and bat cells. Among them, residue 305, participating in a critical interaction, plays a crucial role in host tropism determination. NeoCoV-T510F, a mutation that enhances human ACE2 recognition, further expanded the potential host range via tighter interaction with an evolutionary conserved hydrophobic pocket. Our results elucidated the molecular basis for the species-specific ACE2 usage of MERS-related viruses across mammals and shed light on their zoonotic risks.
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Pseudorabies virus (PRV) is an alpha herpesvirus found in many wild and domestic animals, and causes neurological diseases in humans. Several cases of PRV-induced human encephalitis accompanied with severe visual impairment have been reported. There is currently no effective treatment for severe visual impairment caused by PRV. We report a case of PRV encephalitis with severe visual impairment. The diagnosis and treatment experience of this patient is summarized to improve the awareness of clinicians. We present a 42-year-old man with PRV infection who was admitted due to intermittent fever for 5 days and unconsciousness for 1 day. He subsequently developed severe visual impairment during hospital stay. Empirical antiviral treatment with ganciclovir and sodium foscarnet was started on the day of admission and continued for > 50 days, which had significant treatment effect. Eye complications caused by PRV infection have been frequently reported in patients with PRV encephalitis. In this patient, based on the patient's condition, antiviral therapy was initiated on admission day, and according to the results of the next-generation sequencing of the cerebrospinal fluid, the duration of antiviral therapy was prolonged, which improved treatment efficacy and alleviated neurological symptoms and eye vision damage. To the best of our knowledge, this is the first report that describes partial restoration of acute vision loss associated with PRV infection after aggressive treatment. Our experience suggests that although prompt treatment cannot prevent the acute vision loss associated with PRV infection, timely anti-viral and anti-inflammatory treatment can alleviate ocular complications.
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Neuroinflammation occurs early in Alzheimer's disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aß clearance and disruption of synaptic connection. CEBPß, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPß-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPß facilitated the interaction of CEBPß with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1ß, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced ß-amyloid (Aß) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPß with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aß secretion by inhibiting the CEBPß-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEßCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEßCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.
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Enfermedad de Alzheimer , Abietanos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Cognición , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Interleucina-6 , Ratones , Ratones Transgénicos , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Presenilina-1 , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors1-4. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic5. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.
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Objective:To observe the clinical effect of internal administration of Traditional Chinese Medicine (TCM) and external application of hot election bag combined with acupuncture on urinary retention after stroke with kidney qi deficiency type.Methods:A total of 106 patients admitted to Chengde Hospital of Traditional Chinese Medicine from January 2017 to December 2020 who met the inclusion criteria were randomly divided into 2 groups according to the random number table method, with 53 in each group. The control group was treated with conventional western medicine therapy and bladder function training, while the observation group was treated with TCM, acupuncture and external application on the basis of the control group. Both groups were treated for 28 days. Before and after treatment, TCM syndrome scores were performed, and the maximum urinary capacity and residual urine volume were recorded by abdominal B-ultrasound to evaluate the bladder function of the patients. The improvement time of urinary pain, first urination time, catheter indwelling time, length of hospital stay and adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 96.2% (51/53) in the observation group and 84.9% (45/53) in the control group, and the difference between the two groups was statistically significant ( χ2=3.98, P=0.046). The residual urine volume of the observation group after treatment [(54.23±6.23) ml vs. (91.24±11.25) ml, t=20.95] was significantly lower than that of the control group ( P<0.01), and the maximum urinary bladder volume [(366.23±30.23) ml vs. (259.63±26.23) ml, t=19.39] was significantly higher than that of the control group ( P<0.01). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=13.25, P<0.01), and the bladder function score of the observation group was significantly lower than that of the control group ( t=13.53, P<0.01). The improvement time of urinary pain, first urination time, catheter indwelling time and hospital stay in the observation group were significantly lower than those in the control group ( t=5.73, 17.91, 6.76, 9.67, all Ps <0.01). No adverse reactions occurred in the two groups during treatment. Conclusion:The combination of TCM, hot compress therapy and acupuncture plus routine therapy can treat the patients with urinary retention after stroke and kidney qi deficiency type with good bladder function, improved symptoms and fast recovery and safety.
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Objective:To observe the relationship between different serum sodium ion levels and hospital death in patients with chronic heart failure.Methods:The clinical data of patients hospitalized with heart failure from January 2013 to December 2018 in Shengjing Hospital of China Medical University were continuously collected, and a retrospective cohort study database was established. The study collected clinical data of 10 488 patients. Use SPSS 26.0 software to establish a database and perform statistical analysis. The patients were divided into 6 groups by different blood sodium levels, the heart failure indicators and hospital deaths among the groups were compared, the lowest death rate group (141 - 145 mmol/L) was as a reference, and univariate Logistic analysis of different blood sodium levels were performed to clarify the risk of in-hospital death from heart failure with different blood sodium levels. GraphPad Prism 5 software was used to draw Kaplan-Meier curve and analyzed the cumulative survival rate during hospitalization.Results:In 10 488 patients, there were 417 cases occurred in-hospital deaths. The range of serum sodium at admission was 108.0 - 168.0 mmol/L, and the normal reference range was 135 - 145 mmol/L. The patients were divided into 6 groups according to the blood sodium level at the time of admission: group A (<130 mmol/L), group B(130 - 135 mmol/L), group C (136 - 140 mmol/L), group D (141 - 145 mmol/L), group E (146 - 150 mmol/L), group F(≥151 mmol/L), the hospital mortality of different blood sodium groups were 14.5%, 8.6%, 3.6%, 2.4%, 5.1% and 33.3% respectively. Took the lowest in-hospital mortality group D group as a reference, 6 groups with different serum sodium were included in a single factor binary Logistic regression analysis, the results showed that increased or decreased serum sodium may increase the risk of death in the hospital for patients with heart failure. Kaplan-Meier survival analysis showed that the accumulate survival rate among the 6 groups was statistically significant ( P<0.05). Conclusions:Patients with abnormal blood sodium at admission have a higher risk of death in the hospital during the hospital stay. The in-hospital mortality rate of patients with serum sodium ions ranging from 141 to 145 mmol/L is the lowest. With the increase or decrease in serum sodium, the in-hospital mortality rate increases with the increase or decrease in serum sodium. The blood sodium level and the mortality of patients with heart failure show a "U" shape. Curve relationship. Abnormal blood sodium on admission is an independent predictor of in-hospital mortality in inpatients with heart failure.
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Objective:To investigate the influence of hypomagnesemia on the prognosis of patients with severe sepsis.Methods:A retrospective study was conducted. The clinical data of 207 septic patients admitted to the department of critical care medicine of the First Affiliated Hospital of University of Science and Technology of China from January 1, 2016 to December 21, 2020 were analyzed, including gender, age and laboratory indicators within 24 hours after sepsis diagnosis [procalcitonin (PCT), C-reactive protein (CRP), blood lactic acid (Lac), pH value and blood magnesium, calcium, chlorine and phosphorus levels]. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score and 28-day prognosis were collected. The patients were divided into survival group and non-survival group according to the prognosis, and the clinical data and laboratory indexes were compared between the two groups. Pearson correlation test was used to analyze the correlation between clinical indicators. Multivariate Logistic regression analysis was used to screen the risk factors affecting the prognosis. The receiver operator characteristic curve (ROC curve) was drawn, and the area under ROC curve (AUC) was calculated to evaluate the potential prognostic indicators.Results:Among the 207 septic patients, 102 survived and 105 died on the 28th day, and the 28-day mortality was 50.72%. There were no significant differences in gender, age, CRP, pH value, blood chlorine or blood phosphorus levels between the two groups. The blood magnesium and blood calcium levels in the non-survival group were significantly lower than those in the survival group [blood magnesium (mmol/L): 0.68±0.14 vs. 0.80±0.12, blood calcium (mmol/L): 1.93±0.21 vs. 2.01±0.20, both P < 0.01], and PCT, Lac, APACHE Ⅱ score and SOFA score were significantly higher than those in the survival group [PCT (mg/L): 8.32 (1.64, 55.01) vs. 3.55 (0.97, 12.31), Lac (mmol/L): 2.90 (1.70, 4.30) vs. 2.10 (1.03, 3.89), APACHE Ⅱ score: 21.24±6.40 vs. 17.42±7.02, SOFA score: 9.14±3.55 vs. 6.91±3.31, all P < 0.01]. Among the 207 patients, 96 patients had normal blood magnesium level (0.75-1.25 mmol/L) and 111 patients had hypomagnesemia (< 0.75 mmol/L). The 28-day mortality of septic patients in the hypomagnesemia group was significantly higher than that in the normal magnesium group [61.26% (68/111) vs. 38.54% (37/96), P < 0.01]. Pearson correlation analysis showed that the blood magnesium level of sepsis patients was negatively correlated with PCT ( r = -0.173, P < 0.05), and it was positively correlated with APACHE Ⅱ score ( r = 0.159, P < 0.05), but it had no correlation with CRP or SOFA score ( r values were -0.029 and 0.091, both P > 0.05). Logistic regression analysis showed that serum magnesium, APACHE Ⅱ score and SOFA score were independent risk factors for 28-day death in patients with sepsis [serum magnesium: odds ratio ( OR) < 0.001, 95% confidence interval (95% CI) was 0.000-0.002, P < 0.001; APACHE Ⅱ score: OR = 1.092, 95% CI was 1.022-1.168, P = 0.010; SOFA score: OR = 1.168, 95% CI was 1.026-1.330, P = 0.019]. ROC curve analysis showed that blood magnesium and APACHE Ⅱ score had a certain predictive value for 28-day mortality in patients with severe sepsis [AUC (95% CI) was 0.723 (0.655-0.791) and 0.680 (0.607-0.754), respectively]. When the blood magnesium threshold was 0.64 mmol/L, the sensitivity was 41.0% and the specificity was 93.1%. When APACHE Ⅱ score threshold was 16.50, the sensitivity was 78.1% and the specificity was 55.9% indicating that the specificity of serum magnesium was higher than that of APACHE Ⅱ score. Conclusions:Severe septic patients complicated with hypomagnesemia have a poor prognosis. Serum magnesium level can be used as a prognostic indicator for severe septic patients.
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Acute intermittent porphyria(AIP) is a rare inherited metabolic disease that can cause severe and fatal acute attacks. This article shares the treatment and management of a severe AIP patient. It is proposed that (1) avoiding incentives is essential; (2) emotional problems easily overlooked should be paid attention; (3) long-term follow-up and patient education can improve the prognosis. The patient underwent renal biopsy during the remission period. We found a red-brown-yellow-white refractive index crystal under a polarized light microscope that had not been reported in the previous literature, which was speculated to be a porphyrin crystal.
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BACKGROUND: Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM: To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS: ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS: Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC50) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo. CONCLUSION: We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.
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Nanopartículas , Neoplasias Gástricas , Óxido de Zinc , Animales , Apoptosis , Autofagia , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Resistencia a Antineoplásicos , Ratones , Ratones Desnudos , Neoplasias Gástricas/tratamiento farmacológico , Óxido de Zinc/farmacologíaRESUMEN
Objective:To investigate the value of serum urea nitrogen on in-hospital death in patients with heart failure.Methods:The clinical data of 9 459 patients with heart failure from January 2013 to December 2018 in Shengjing Hospital of China Medical University were retrospectively analyzed. Among them, 296 cases died in hospital (death group) and 9 163 cases survived (survival group). The clinical data of patients were collected, including general condition, disease history, physical examination, laboratory indicators and relevant physical examination, etc. Correlation was finished with Pearson correlation analysis. Multivariate Logistic regression analysis was used to determine independent risk factors for in-hospital death in patients with heart failure. Receiver operating characteristic (ROC) curve was used to determine the optimal predictive threshold of urea nitrogen for in-hospital death.Results:The in-hospital mortality in patients with heart failure was 3.1% (296/9 459). There were statistical differences in age, hypertension rate, diabetes rate, a history of atrial fibrillation rate, smoking history rate, hemoglobin, albumin, glycosylated hemoglobin, urea nitrogen, creatinine, uric acid, serum potassium, serum sodium, troponin I, N terminal brain natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) between death group and survival group ( P<0.01 or <0.05), and there were no statistical difference in gender composition, coronary heart disease rate, platelet, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) between 2 groups ( P>0.05). Pearson correlation analysis result showed that the urea nitrogen was positively correlated with age, coronary heart disease, hypertension, diabetes, glycosylated hemoglobin, creatinine, uric acid, serum potassium, troponin I, NT-proBNP, LVEDV and LVESV ( r = 0.130, 0.024, 0.053, 0.128, 0.033, 0.739, 0.468, 0.377, 0.065, 0.432, 0.084 and 0.101; P<0.01 or <0.05); and the urea nitrogen was negatively correlated with gender, history of atrial fibrillation, hemoglobin, platelet, albumin, total cholesterol, LDL-C, serum sodium and LVEF ( r = -0.033, -0.063, -0.272, -0.077, -0.188, -0.070, -0.071, -0.199 and -0.113, P<0.01); and there were no correlation between urea nitrogen and smoking history or triglyceride ( P>0.05). Multivariate Logistic regression analysis result showed that age, hypertension, albumin, urea nitrogen, troponin I and NT-proBNP were independent risk factors for in-hospital death in patients with heart failure ( OR = 1.018, 0.613, 0.924, 1.082, 1.340 and 1.005; 95% CI 1.002 to 1.033, 0.427 to 0.881, 0.889 to 0.961, 1.040 to 1.126, 1.111 to 1.617 and 1.003 to 1.007; P<0.05 or <0.01). ROC curve analysis result showed that the area under the curve (AUC) of urea nitrogen for prediction of in-hospital death in patients with heart failure was 0.737 (95% CI 0.728 to 0.748), and the optimal threshold value was 11.41 mmol/L, with a sensitivity of 60.16% and a specificity of 77.01%; the AUC of NT-proBNP for prediction of in-hospital death in patients with heart failure was 0.726 (95% CI 0.712 to 0.740), and there was no statistical difference in the AUC between urea nitrogen and NT-proBNP ( Z=1.055, P=0.291). Conclusions:Elevated urea nitrogen level is independently associated with an increase in in-hospital mortality in patients with heart failure, and the optimal threshold for predicting in-hospital death is 11.41 mmol/L.
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Objective:To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment.Methods:The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed.Results:A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3±2.1, 2.2±1.0 and 1.4±0.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2±17.6 vs. 39.3±15.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (μmol·s -1·L -1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. Conclusions:The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.
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Objective:To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR) in classification of patients with coronavirus disease 2019 (COVID-19).Methods:A retrospective analysis was performed on 72 patients with COVID-19 admitted to the critical ward of Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan from February to March in 2020. The patients were divided into two groups: moderate type (non-severe group) and severe/critical type (severe group). The results of white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), interleukin-6 (IL-6) and D-dimer were collected at the 2nd day after admission from the two groups, and the NLR was calculated. The diagnostic value of WBC, NEU, LYM, IL-6, D-dimer and NLR on COVID-19 classification was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 72 COVID-19 patients were enrolled, among whom 52 were moderate, 17 were severe, and 3 were critical. The most common clinical manifestations of patients were fever (70.8%), cough (36.1%), chest tightness and breathlessness (37.5%), diarrhea (15.3%), fatigue (15.3%), vomiting and nausea (11.1%), occasionally accompanied by acute dyspnea (2.8%), and only one patient had no clinical symptom (1.4%). The levels of WBC, NEU, IL-6, D-dimer and NLR in the severe group were significantly higher than those in the non-severe group [WBC (×10 9/L): 7.81±3.65 vs. 5.34±1.69, NEU (×10 9/L): 5.83±3.13 vs. 3.24±1.53, IL-6 (ng/L): 133.63 (71.09, 249.61) vs. 28.05 (6.41, 101.24), D-dimer (mg/L): 0.86 (0.31, 2.56) vs. 0.33 (0.20, 0.71), NLR: 6.14±4.75 vs. 2.66±1.93, all P < 0.05], and the level of LYM was significantly lower than that in the non-severe group (×10 9/L: 1.09±0.56 vs. 1.49±0.74, P < 0.05). The results of ROC curve analysis showed that the areas under ROC curve (AUC) of WBC, NEU, LYM, IL-6, D-dimer and NLR for COVID-19 classification were 0.790 [95% confidence interval (95% CI) was 0.684-0.897), 0.869 (95% CI was 0.789-0.949), 0.719 (95% CI was 0.592-0.847), 0.790 (95% CI was 0.682-0.898), 0.676 (95% CI was 0.526-0.827), and 0.888 (95% CI was 0.814-0.963) respectively. The AUC of NLR was the highest, which was of high diagnostic value; when the optimum cut-off value of NLR was 3.00, the sensitivity was 100%, and the specificity was 73.1%. Conclusion:NLR can be used as a biomarker to predict classification of COVID-19 patients independently, which can provide a theoretical basis for the classification management of COVID-19 patients.
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OBJECTIVE: To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake. METHODS: With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model. RESULTS: Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in ß diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01). CONCLUSION: Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.
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Bifidobacterium/clasificación , Microbioma Gastrointestinal , Aprendizaje Automático , Prebióticos , Método Doble Ciego , Heces/microbiología , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
With the gradual promotion of the health care reform,improving the management level of public hospitals has become a key breakthrough.Hospital management should not only pay attention to the differences in the property,scale and region,but also pay attention to the differences among different groups within the hospital.Research shows that there are obvious differences between physicians and registered nurses management system,such as staffing,performance management,target management and talent management.The difference has a series of negative influence on relationship between physicians and nurses,so as to impede the efficient clinical work and harm hospital development.It can be changed by increasing the number of medical staff,establishing a scientific evaluation system and communication mechanism.
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<p><b>OBJECTIVE</b>To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake.</p><p><b>METHODS</b>With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model.</p><p><b>RESULTS</b>Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01).</p><p><b>CONCLUSION</b>Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.</p>
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Objective To investigate the clinical experience and associated factors of extracorporeal membrane oxygenation(ECMO)for adult patients with severe acute respiratory distress syndrome(ARDS).Methods The clinical data of 22 adult patients with severe ARDS,which met the criteria for ECMO,were retrospectively collected and analyzed.The ECMO team all receiving VV-ECMO treatment (Veno-venous extracorporeal membrane oxygenation),data collection including the patients,general data,blood gas analysis,hemodynamics,mechanical ventilation parameter before and after the ECMO treatment and the auxiliary complications,etc.The control group were 14 cases of patients with severe ARDS which receiving conventional treatment;We collected the same data as the research team.Results In the research,8 patients treated with VV-ECMO,There were 5 males and 3 females,with an average age of (46.3 ± 14.1)years.Compared with the factors at the same time point in the control group,those of the ECMO group,except MAP (t =-0.872,P =0.357),Respiratory rate (t =-1.670,P =0.357),Heart rate (t =-1.973,P =0.042),PH (t =-1.432,P =0.033),PaCO2 (t =-2.564,P =0.024),PO2 (t =-4.955,P < 0.001),PO2/FiO2 (t =-3.654,P < 0.01),PEEP (t =-1.382,P =0.031),Pplateau (t =-2.785,P < 0.01),Blood lactate (t =-2.564,P =0.024) were significantly improved after ECMO running 24 hours (all P < 0.05).And also the factors such as the length of ICU stay (t =-2.452,P =0.027),the times of mechanical ventilation (t =-1.478,P =0.038),number of organ failure(t =-1.963,P =0.047),the hospital mortality rates(t =-1.970,P =0.045) and treatment costs(t =-1.667,P =0.035) between the ECMO group and the control group were significantly different (P <0.05).In the end,we divided the ECMO group into survival group and death group,and compare the time of Mechanical Ventilation before ECMO(P =0.031) the total time of Mechanical Ventilation(P =0.038),the time of ECMO adjutant (P =0.047),the length of ICU stay (P =0.043) and the cost of treatment (P =0.037) between the two groups;and there were also statistically significant difference (P < 0.05).Conclusion ECMO can significantly improve the patients,oxygenation and respiratory physiology indexes which can not sustain under the conventional mechanical ventilation therapy and win the time for rest and repair of lung.Indexes such as age,time of mechanical ventilation before ECMO therapy,the primary cause of ARDS are the important factors influencing the efficacy of ECMO treatment in the patients with severe ARDS.