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RNA methylation is a common epigenetic post-transcriptional modification with various patterns,such as N1-methyladenosine(m1A),5-methylcytidine(m5C)and N6-methyladenosine(m6A).RNA methylation can perform specific biological functions in corresponding targets,dynamical and reversible,thus bridging exogenous environmental factors and different disease outcomes.Exogenous chemicals can induce oxidative stress,inflammation,autophagy and cell cycle disorders,which are reg-ulated by specific RNA methylation modifications and bring about epigenetic toxic effects.These altera-tions act as new key molecular events during cellular senescence and the development of aging and age-related disorders.The correlation between RNA methylation and cell senescence will provide a new line of thought for prevention of and interventions in aging.
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【Objective】 To explore the distribution of serological markers related to samples whose serological test results were inconsistent with HBV DNA test results among voluntary blood donors in Xi′an. 【Methods】 A total of 71 HBsAg ELISA positive and NAT non-reactive (ELISA+ /NAT-)blood samples were collected from Shaanxi Blood Center from November 1, 2022 to April 30, 2023. The serological markers of hepatitis B were detected by electrochemiluminescence method, and the HBV S region and C region gene fragments were amplified by nested-PCR. 【Results】 The positive rate of nested-PCR in double ELISA+ /NAT- group(n=30) was statistically higher than that of ELISA+ /NAT- group(n=41)(60% vs 24.4%, P<0.05). Donors in double ELISA+ /NAT- group were all first-time blood donors, with the positive rate of anti-HBc in serum of 100%, and the serological pattern was mainly positive for items 1, 4 and 5 items(80%). Among the ELISA+ /NAT- group, 31.7% were repeat blood donors, with the positive rate of anti-HBc in serum of only 19.51%, and the serological patterns were mainly single anti-HBs positive (43.90%) and all negative (36.58%). 【Conclusion】 There are false positives in the test results of ELISA+ /NAT- group, which leads to unnecessary blood discarding. Meanwhile, the samples with negative NAT may have low levels of HBV DNA, which may lead to missed detection. It is suggested that multiple systems and methods should be applied to trace the blood donors who are HBsAg positive and NAT non-reactive, so as to improve the accuracy of HBV screening of blood donors and reduce blood waste.
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Objective:To observe any effect of using a lower limb exoskeleton robot during ankle rehabilitation training on the walking ability of stroke survivors.Methods:Forty-five persons with cerebral apoplexy were randomly divided into a control group, a robot group and a combination group, each of 15. In addition to routine rehabilitation training 5 days a week for 3 weeks, the robot group additionally trained for 10 minutes assisted by a lower limb exoskeleton. The combined group joined that training and additionally undertook 10 minutes of ankle rehabilitation training. Before and after the experiment all of the participants were evaluated using the Fugl-Meyer lower extremity scale (FMA-LE), the Holden functional walking scale (FAC), and for walking speed and step frequency.Results:After treatment, significant improvement was observed in the average FMA-LE score, FAC grade, walking speed and step frequency in all 3 groups. The robot group′s average FMA-LE score, walking speed and step frequency were then significantly better than those of the control group ( P<0.05). Moreover, the average FMA-LE score, step speed and step frequency of the combined group after treatment were (22.67±1.63) min, (0.65±0.05) m/s and (80.80±4.28) steps /min, respectively, significantly better than the other two groups ( P<0.05). Conclusion:Using an exoskeleton robot combined with ankle rehabilitation training can significantly improve the walking of stroke survivors.
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Environmental pollution is closely linked to the occurrence and development of cancer. Chemical carcinogens are the most important environmental factors causing cancer in humans. Among them, persistent organic pollutants (POPs) are characterized by their widespread distribution, persistence, and bioaccumulation. Research on the carcinogenic effects of POPs has received considerable attention in recent years. This article reviewed the internal exposure, association with cancer risk, and potential carcinogenic mechanisms of five typical classes of POPs in the environment, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants (BFRs), and short-chain chlorinated paraffins (SCCPs). These five types of POPs have distinct carcinogenic mechanisms, including interfering with cell proliferation cycle, altering epigenetic inheritance, promoting oxidative stress, altering energy metabolism, and affecting immune function. The development of cancer is the result of interaction between intrinsic genetic factors and external environmental factors. In addition to focusing on how environmental POPs affect the genetic material of organisms, it is also important to consider their effects on the tumor microenvironment, including tumor immunity and angiogenesis. Understanding these effects is crucial for guiding future efforts in pollution control and precision medicine in cancer treatment.
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This article analyzed the specific path of iron overload affecting EMT "blood countercurrent cell survival/adhesion/invasion/angiogenesis ectopic lesions" from the three aspects of mediating NF-κB and inflammatory reaction, stimulation of abnormal activation of macrophages, and induction of oxidative stress injury; introduced the theoretical connotation of the pathogenesis of "cold coagulation and blood stasis", and briefly described the progress of the pathogenesis of EMT from the perspective of "blood out of menstruation - injury caused by cold pathogenic factors - cold coagulation and blood stasis - long-term accumulation syndrome"; based on the mutual confirmation of "menstruation countercurrent - iron overload microenvironment - cell survival/adhesion/invasion/angiogenesis - ectopic focus" and "blood out of menstruation - cold pathogen injury - cold coagulation and blood stasis - chronic accumulation syndrome", it was believed that starting from iron overload could tap the scientific connotation and microscopic materials of the pathogenesis of "cold coagulation and blood stasis" in EMT, so as to provide new directions and theoretical references for the research of the pathogenesis of EMT and the mechanism of drugs.
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Objective:To explore the independent risk factors of in-hospital cardiac arrest (IHCA) in critically ill patients and construct a nomogram model to predict the risk of IHCA based on the identified risk factors.Methods:Patients who were admitted to the intensive care units (ICUs) from 2008 to 2019 were retrospectively enrolled from the Medical Information Mart for Intensive Care -Ⅳ database. The patients were excluded if they (1) were younger than 18 years old, (2) had repeated ICU admission records, or (3) had an ICU stay shorter than 24 h. The patients were randomly divided into the training and internal validation cohorts (7 : 3). Univariate and multivariate logistic regression models were used to identify independent risk factors of IHCA, and a nomogram was constructed based on these independent risk factors. Calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the nomogram model. Finally, the nomogram was externally validated using the emergency ICU collaborative research database.Results:A total of 41,951 critically ill patients were enrolled (training cohort, n=29 366; internal validation cohort, n=12 585). Multivariate analysis showed that myocardial infarction, pulmonary heart disease, cardiogenic shock, respiratory failure, acute kidney injury, respiratory rate, glucose, hematocrit, sodium, anion gap, vasoactive drug use, and invasive mechanical ventilation were independent risk factors of IHCA. Based on the above risk factors, a nomogram for predicting IHCA was constructed. The area under the ROC curve (AUC) of the nomogram was 0.817 (95% CI: 0.785–0.847). The calibration curve showed that the predicted and actual probabilities of the nomogram were consistent. Moreover, DCA showed that the nomogram had clinical benefits for predicting IHCA. In the internal validation cohort, the nomogram had a similar predictive value of IHCA (AUC=0.807, 95% CI: 0.760–0.862). In an external validation cohort of 87,626 critically ill patients, the nomogram had stable ability for predicting IHCA (AUC=0.804, 95% CI: 0.786–0.822). In addition, the nomogram also had predictive value for in-hospital mortality (AUC=0.818, 95% CI: 0.802-0.834). Conclusions:The nomogram is constructed based on identified independent risk factors, which has good predictive value for IHCA. Moreover, the performance of the nomogram in the external validation cohort is robust. The study findings may help clinicians to assess the risk of IHCA in critically ill patients.
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【Objective】 To explore the population characteristics, the reasons for deferral and the changing trend of unqualified rate of blood test of voluntary blood donors in Xi′an, so as to provide a data support for recruiting low-risk regular blood donors, reducing unqualified rate, improving blood safety and blood quality. 【Methods】 The age, gender, occupation, education and unqualified blood test of voluntary blood donors in Xi′an area from 2012 to 2021 were classified and analyzed retrospectively. 【Results】 The number of voluntary blood donors in Xi′an increased year by year from 2012 to 2021, while the overall unqualified rate of blood test kept decreasing, with an overall unqualified rate at 2.36%, which was at a middle level in China. There were more male blood donors than female donors, and the highest proportion of blood donors in terms of age, occupation and education was between 21-30 years old group (40.19%), other occupation group(21.75%), and undergraduate and above group (32.61%) respectively. The total unqualified rate was ALT (0.68%)>HBsAg (0.55%) > anti -HCV (0.48%) > anti -TP (0.43%) > anti -HIV (0.17%). The unqualified rate of blood donors aged 31 to 40 was the highest. With the increase of academic qualifications, the unqualified rate generally showed a gradual downward trend. The unqualified rate of soldiers, teachers, civil servants and medical workers was low, while the unqualified rates of various items of students were high. There were seasonal differences in the total number of blood donors, the total unqualified rate and the unqualified rate of each item (except anti -HIV). 【Conclusion】 The voluntary blood donors are mainly males, aged 21 to 30, with other occupations and with bachelor degree or above. Regular voluntary blood donation teams in this area should be established among soldiers, teachers, civil servants, medical workers and highly educated groups, and more attention should be paid to health consultation for workers, farmers and students before blood donation.
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Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
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Objective:To study the clinical characteristics and death risk factors of the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020.Methods:The clinical data were retrospectively analyzed of the 894 patients with fall-related injuries who had been admitted to Department of Trauma Center, The First People's Hospital of Kashgar Prefecture, Xinjiang Uygur Autonomous Region from January 2019 to December 2020. Recorded were the patient's gender, age, location of fall, month of fall, fall height, major injury site, injury severity score (ISS) and Glasgow score (GCS). The clinical characteristics and death risk factors of the fall patients were analyzed.Results:Of the 894 patients, 72.3%(646/894) were male and 86.9%(777/894) fell from a height from 1 to 6 meters. Their ages ranged mainly from 15 to 59 years old (74.3%, 664/894). Home was the most frequent site for falls (60.2%, 538/894) and the patients who fell in summer months (from June to August) were the most (32.3%, 289/894). Twenty-one patients (2.3%, 21/894) died. There were significant differences in the major injury site, blood transfusion, ISS score and GCS score between the dead and survival patients ( P<0.05). The multivariate logistic regression analysis showed that the injury to the head, face and neck [ OR=10.936, 95% CI: 1.177 to 101.627, P=0.035] and GCS score ≤12 [ OR=5.640, 95% CI: 2.658 to 11.968, P< 0.001] were the death risk factors for the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020. Conclusions:In the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020, males aged from 15 to 59 years old were the high-risk group of falls. Months with a high incidence of falls were from June to August. The fall patients with injuries to the head, face and neck and with a GCS score of ≤12 were at a high risk of death.
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【Objective】 To establish a new method for the determination of fibrinogen content in cryoprecipitated antihemophilic factor. 【Methods】 Fibrinogen (Fib) could bind with sheep anti-human fibrinogen (anti-Fib) specifically and further form antigen-antibody complex. When the Fib was present in the solution, the fluorescence of fluorescein isothiocyanate (FITC) labeled on the anti-Fib (FITC-anti-Fib) was quenched due to the formation of immune complex. The fluorescence quenching degree of FITC-anti-Fib was positively correlated with Fib concentration (cFib) in a certain concentration range. 【Results】 The linear relationship between fluorescence quenching degree [(I0-I)/I0] of FITC-anti-Fib and ln(cFib) was (I0-I)/I0=15.53ln(cFib)+ 80.79 (R2=0.99) when the cFib was in the range of (0.007 8-0.560 0) g/L. The recovery of Fib was (96.77-102.43) %. When the method was applied to determine Fib at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.31%, 0.56%, and 0.49%, respectively, and the inter-day variation coefficients were 3.81%, 3.06%, and 4.13%, respectively. There was no significant difference between the results measured by fluorescence quenching method and coagulation method (t=-0.075, P>0.05). 【Conclusion】 In this work, a new fluorescence method for the determination of Fib in cryoprecipitated antihemophilic factor was successfully established based on the specific combination of fib and FITC-anti-Fib. The method is simple and rapid. The obtained results were accurate and reliable by using this method to determine Fib.
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OBJECTIVE：To ex plore the effects of solamargine on the growth and apoptosis of human hepatocarcinoma cells HepG2 and its underlying mechanism. METHODS ：The effects of 0（blank group ）-12 μmol/L solamargine treatment of 24，48 h on survival rate of HepG 2 cells were investigated. The effects of 0（blank group ），6 μmol/L solamargine treatment of 10 days on cell clone formation were also investigated. The effects of 0（blank group ），4，6，8 μmol/L solamargine for 24 h on the apoptotic rate of cells，mRNA expression of Bcl- 2，Bax and caspase- 3， protein expression of Bcl- 2 and cleaved caspase- 3 as well as ratio of p-AMPKα to AMPKα were all tested. The effects of AMPK inhibitor as compound C on the protein expression of AMPKα and Bcl- 2 in cells were investigated after treated with 6 μmol/L solamargine for 24 h. RESULTS ：Compared with 020-39318678。E-mail：wujingjing6028@gzucm.edu.cn blank group ，1-12 μ mol/L solamargine for 24，48 h could significantly decrease the survival rates of cells （P＜0.05）in a concentration-dependent manner ；IC50 of them were 8.310 and 7.996 μmol/L，respectively；the rate of cell clone formation was decreased significantly after treated with 6 μmol/L solamargine for 10 days（P＜0.05）. The apoptotic rate of HepG 2 cells，mRNA expression of Bax and caspase- 3，protein expression of cleaved caspase-3（except for 8 μmol/L）as well as ratio of p-AMPKα to AMPKα（except for 8 μmol/L）were all increased significantly after treated with 6，8 μmol/L solamargine（P＜0.05）；mRNA and protein expression of Bcl- 2 were decreased significantly （P＜ 0.05）；the changes of some indexes were in a concentration-dependent manner. The compound C could inhibit protein expression of AMPKα，and reverse the inhibitory effect of solamargine on Bcl- 2 protein. CONCLUSIONS ：Solamargine can inhibit the proliferation of HepG 2 cells and induce apoptosis ，the mechanism of which may be associated with activating AMPK signaling pathway.
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Objective:To explore the predictive value of computed tomography (CT) texture analysis for the recurrence in children with acute pancreatitis (AP).Methods:The clinical diagnostic test was conducted. The clinical data of 56 children with primary AP who were admitted to Wuhan Fourth Hospital from January 2016 to January 2018 were collected. There were 13 males and 43 females, aged from 3.5 to 13.0 years, with a median age of 5.5 years. Based on follow-up in other hospitals, 20 children with recurrence of AP were allocated into recurrence group, and 36 children without recurrence were allocated into non-recurrence group. All the 56 children underwent abdomen plain and enhanced CT scan within 24 hours after first admission. Observation indicators: (1) comparison of clinicopathological features between two groups of children with AP. (2) comparison of CT texture parameters between two groups of children with AP. (3) diagnostic efficacy of clinical features and CT texture parameters. Follow-up using outpatient reexamination and telephone interview was conducted to detect recurrence of AP up to February 2020. The duration of follow-up required more than or equal to 24 months. The Shapiro Wilk test was used to analyze normality of measurement data. Measurement data with normal distribution were repre-sented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M (range) or M ( P25, P75), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Clinical parameters and CT texture parameters with statistical differences were multivariate analyzed using the Logistic regression model. Receiver operating characteristic curve (ROC) analysis was used to evaluate the predictive efficacy of parameters for recurrence of AP. Results:(1) Comparison of clinicopatholo-gical features between two groups of children with AP: cases with or without complications were 14 and 6 for the recurrence group, versus 7 and 29 for the non-recurrence group, showing a significant difference between the two groups ( χ2=14.021, P<0.05). Cases with minimal, moderately severe or severe disease (severity of disease) were 2, 5, 13 for the recurrence group, versus 19, 11, 6 for the non-recurrence group, showing a significant difference between the two groups ( Z=5.414, P<0.05). (2) Comparison of CT texture parameters between two groups of children with AP: the energy value in the arterial phase on CT examination was 0.186(0.174,0.206)for the recurrence group and 0.413(0.405,0.425) for the non-recurrence group, showing a significant difference between the two groups ( Z=9.413, P<0.05). The energy value and entropy value in the venous phase on CT examination were 0.084(0.078,0.092) and 0.961(0.210,1.720) for the recurrence group, versus 0.135(0.124,0.156) and 0.372(0.210,0.535) for the non-recurrence group, showing significant differences between the two groups ( Z=4.763, 7.243, P<0.05). (3) Diagnostic efficacy of clinical parameters and CT texture parameters: results of multivariate analysis showed the complications, severity of disease, energy value in the arterial phase on CT examination were related factors for recurrence in children with AP, energy value and entropy value in the venous phase on CT examination were related factor for recurrence in children with AP ( odds ratio=0.874, 0.765, 0.837, 0.902, 0.813, 95% confidence interval as 0.802?0.985, 0.581?0.914, 0.753?0.897, 0.862?0.948, 0.765?0.873, P<0.05). Results of ROC analysis showed that that areas under curve (AUC) of complications, severity of disease in the clinical parameters were 0.734 and 0.832, the AUC of single CT texture parameter was 0.811?0.867, the AUC of clinico-pathological parameters combined with CT texture parameters was 0.882. Conclusion:CT texture analysis can early and non-invasively predict the recurrence of AP in children, and the combination of clinicopathological parameters with CT texture parameter has a better predictive efficacy.
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Lung is one of the most sensitive target organs of human beings under the shock waves. Due to its serious injury, rapid development and high mortality, blast lung injury has been a widely concerned research topic in the field of military medicine. In the normal physiological state, the body is in a dynamic balance between pro-inflammaton and anti-inflammation, oxidation and anti-oxidation, promoting apoptosis and inhibiting apoptosis. While blast lung injury breaks the balance and causes physiological, biochemical and pathological changes in the body, seriously leading to acute respiratory distress syndrome and multiple organ dysfunction syndrome, and eventually the mortality. So far, the researches on blast lung injury mainly involve damage model, pathogenesis, pathological changes, intervention treatment and so on, which has achieved great research findings. In the review, the authors summarize the progress of molecular mechanism for blast lung injury from the perspective of inflammatory reaction, oxidative stress, apoptosis and so on, which may promote the discovery of new targets for the diagnosis, treatment and rehabilitation intervention of blast lung injury.
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Objective:To investigate optimal antiplatelet therapy options based on the CYP2C19 genotype in elderly patients with acute coronary syndrome(ACS).Methods:Elderly patients with ACS admitted to our hospital from January 2018 to March 2019 were enrolled and received CyP2C19 gene testing.Patients with the intermediate metabolic genotype of CYP2C19 were randomly divided into two groups: the Ticagrelor group and the double-dose Clopidogrel group.After a one-year follow-up, the risk of bleeding and incidences of cardiovascular events in the two groups were analyzed.Results:468 elderly patients meeting the criteria, 214 had the intermediate metabolic genotype of CYP2C19, accounting for 45.7% of the total, and were randomly divided into the ticagrelor treatment group( n=107)and the double-dose Clopidogrel treatment group( n=107). There were significant differences between the Ticagrelor treatment group and the double-dose Clopidogrel treatment group in incidences of minor bleeding, massive hemorrhage, recurrent angina and recurrent acute myocardial infarction(11.2% vs.22.4%, 2.8% vs. 9.4 %, 4.7% vs.13.1%, 3.7% vs. 11.2%, P<0.05). The double-dose Clopidogrel group not only had a higher risk of cardiovascular events, but also a higher risk of bleeding. Conclusions:For elderly ACS patients with the intermediate metabolic genotype of CYP2C19, a standard dose of ticagrelor is recommended.
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Objective:To measure the skin color parameters of Chinese women with non-invasive instruments test, and to validate assessment scales (VAS) and image analysis. Skin tone index (STI) of Chinese women was created by PLS-VIP method, and then used to the overall evaluation of Chinese women skin color.Methods:The skin color scale by VAS, parameters measured by tristumulus colorimeter, narrow-band-simple reflectance meter and image analysis were administered at the cheek of 60 famle subjects. The correlations among all the parameters collected by the instruments and scales by VAS were investigated, and then the main impact factors of skin color grade were analyzed. The STI model was created by principal component analysis and further tested.Results:With b value exception, skin color score was significantly correlated with the instrument parameters. The absolute values of coefficients were from 0.6898 to 0.8648. Int, L, BS, MI and EI were the most important parameters which influenced the consumer＇s perception of skin visual color. The SWI=0.47*Int+ 0.47*L+ 0.43*BS-0.44MI-0.43EI was created by PLS-VIP. The coefficient between SWI and skin color scale was -0.834 ( P<0.0001). Conclusions:STI could be effectively and comprehensively representative of the degree of skin color change.
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Objective To investigate the electro-clinical features of epilepsy with eye closure sensitivity (ECS).Methods The electroencephalograph database was searched using ECS during half a year period from January to June 2017 in Xijing Hospital.The duration of the follow-up was one year.Results Fifty-one patients diagnosed as epilepsy with ECS were investigated.Patients were classified into four epilepsy syndromes:33 with eyelid myoclonia with absences (EMA);13 with juvenile myoclonia epilepsy (JME);two with epilepsy with generalized tonic-clonic seizure on awakening and three with idiopathic occipital lobe epilepsy (IOE).The duration of the epileptiform discharges (EDs) triggered by eye closure (ECL) lasted more than five seconds in four patients with EMA and one patient with IOE.The EDs triggered by ECL were more frequent (85.2± 11.4 vs 37.5± 12.6,t=12.399,P=0.000) and lasting longer ((4.3± 1.9) s vs (2.3±0.8) s,t=3.585,P=0.001) in EMA than in JME.Conclusions ECS is common in EMA.The frequency and duration of the EDs triggered by ECL are helpful for identifying EMA and JME.
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Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and NF-κB p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4⁺/CD8⁺ and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.
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Animals , Mice , Apoptosis , Boraginaceae , Carcinoma, Hepatocellular , Caspase 3 , Cytokines , Interleukin-10 , Interleukin-6 , Interleukins , Lamiaceae , STAT3 Transcription Factor , Therapeutic Uses , Tumor MicroenvironmentABSTRACT
Objective@#To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs).@*Methods@#The premature senescence was induced by 400 μmol/L H2O2 once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups.@*Results@#The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05).@*Conclusion@#During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.
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Objective To investigate the clinical manifestations and nerve electrophysiological abnormalities of the patients with multiple myeloma peripheral neuropathy (MMPN). Methods The clinical data of 35 patients with MMPN diagnosed in Shanxi Provincial People's Hospital from March 2010 to June 2018 were retrospectively analyzed. All patients received nerve electrophysiology examination, including nerve conductive velocity (NCV) and skin sympathetic response (SSR). Results The most common symptoms of peripheral nerve involvement for MMPN patients were sensory abnormalities (25 cases, 71%), including root pains (3 cases, 9%), pain ablation of the upper or lower limbs (18 cases, 51%), dyskinesia (15 cases, 43%), disappeared or reduced knee or ankle reflex (13 cases, 37%) and automatic sympathetic disorders (20 cases, 57%). Nerve electrophysiological tests showed 29 cases (83%) were involved in abnormal sensory nerve conduction velocity (SCV) or motor nerve conduction velocity (MCV), including 13 cases of upper limb abnormality in NCV, 5 cases of prolonged incubation in upper limb, and 10 cases of decreased amplitude;8 cases of lower limb abnormality in NCV, 6 cases of prolonged incubation in lower limb, and 4 cases of decreased amplitude. SSR test showed abnormalities were found in 17 patients (49%), including 8 cases of upper limb abnormality in SRR, 2 cases of prolonged incubation in upper limb, and 7 cases of decreased amplitude, 1 case of disappeared waveform; 6 cases of lower limb abnormality in SRR, 1 case of prolonged incubation in lower limb, and 4 cases of decreased amplitude, 2 cases of disappeared waveform; 3 cases of abnormal upper and lower limbs. Conclusions The most common peripheral nerve damages of MM are "sock and gloveˉlike" sensory ablation, accompanied with the involvement of automatic nerve damage. NCV is the major method to diagnose MMPN, and SSR plays an important role in the detection of sympathetic nerve damage of MMPN.
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Objective To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO2/PtcCO2) in the treatment of septic shock. Methods A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), the length of ICU stay and 28-day prognosis were collected; PtcCO2, PtcO2, PtcO2/PtcCO2 ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO2), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binaryLogistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients. Results A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHEⅡ score and PtcCO2 were higher and PtcO2/PtcCO2 ratio was lower in death group [APACHEⅡ:28.33±6.35 vs. 21.61±6.64, PtcCO2 (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO2/PtcCO2 ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO2/PtcCO2 ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO2/PtcCO2 ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L):3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO2 and ScvO2. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO2/PtcCO2 ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO2/PtcCO2 ratio at 6 hours of bundle therapy and APACHEⅡ score were risk factors of prognosis [PtcO2/PtcCO2 ratio: odds ratio (OR) = 7.876, P = 0.026; APACHEⅡscore: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO2/PtcCO2 ratio, APACHEⅡscore and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO2/PtcCO2 ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0％, and the specificity was 73.3％. In addition, the patients were divided into two groups according to whether the 6-hour PtcO2/PtcCO2 ratio was greater than 1.42. The results showed that: compared with the PtcO2/PtcCO2 < 1.42 group, the APACHEⅡ score in PtcO2/PtcCO2 ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower. Conclusions Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.