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【Objective】 To compare the desalination effects of five desalination methods and their effects on the components for human coagulation factor Ⅷ(FⅧ), and provide reference for selection of protein desalination methods. 【Methods】 Sephadex G-25 Medium gel, Fractogel EMD BioSEC gel, ultrafiltration, room temperature dialysis and 4℃ dialysis were used to desalt human FⅧ. The desalination effect was evaluated by the removal rate of Na +, citrate ion and glycine. FⅧ protein recovery, FⅧ activity (FⅧ∶C), VWF antigen (VWF∶Ag), VWF activity(VWF∶Ac), VWF polymers and SDS-PAGE analysis before and after desalination were compared to evaluate the effect of desalination on FⅧ components. 【Results】 In terms of desalination effect, the removal rate of Na+ was the lowest in ultrafiltration desalination, while that of Fractogel EMD BioSEC gel was the highest [(97.90±0.06) % vs (99.82±0.07) %]. Except that there was no statistical significance between Sephadex G-25 Medium gel desalination and Fractogel EMD BioSEC gel desalination (P=0.90), the removal rates of the other four methods were statistically significant. The removal rate of glycine was the lowest in ultrafiltration desalination, wihle that of Fractogel EMD BioSEC gel desalination was the highest [(95.78±0.42) % vs (99.81±0.08) %]. Significant difference in glycine removal was noticed in ultrafiltration desalination, but not among the other four desalination methods. There was no significant difference in the removal rate of citrate ions among the five methods (P=0.85). For the effect of FⅧ components, FⅧ∶C, VWF∶Ag, VWF∶Ac and protein recovery rates of ultrafiltration desalination were the highest, with (18.34±1.99) IU/mL, (11.81±0.33) IU/mL, (12.26±0.58) IU/mL and (97.13±1.37) %, respectively. There was no significant change in VWF∶Ac/VWF∶Ag before and after desalination by the five methods. SDS-PAGE and VWF polymer analysis showed that different desalination methods had no significant impact on protein composition. 【Conclusion】 Although different desalination methods had no significant effect on the composition of FⅧ protein, the desalination effect was different. Moreover, different desalination methods had significant effects on protein recovery, FⅧ∶C, VWF∶Ag and VWF∶Ac. The selection of desalination methods should be more considered during protein processing,
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@#We reported a 32 years female patient in whom lung metastasis from breast cancer was presented as solitary pulmonary pure ground-glass opacity (GGO) lesion. The patient received rational preoperative examinations and surgery though the preoperative diagnosis was not accurate. Because of different therapy strategies and purposes, it is crucial to make distinction of atypical metastases from primary cancers. Thus, for patients with a history of malignancy, possible metastasis should be taken into consideration if new GGO was found on the CT. Besides this, the follow-up interval of CT should be shortened appropriately, preoperative examinations and surgical procedures should be made according to the suggestions of multidisciplinary team.
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With the deepening reform of ideological and political education, Medical Parasitology teaching needs to update the teaching concept, change the teaching ideas, as well as keep trying to combine ideological and political education with the curriculum content closely. In addition to teaching students’ basic knowledge and practical skills, teachers are needed to cultivate their moral literacy and political awareness through course teaching, so as to provide the basis for students’ subsequent adaptations to social environments and jobs. Currently, the study of ideological and political education in Medical Parasitology teaching is still in the exploratory stage. Therefore, colleges and universities need to carry out effective construction of ideological and political education in Medical Parasitology teaching, in order to achieve good teaching outcomes and provide insights into ideological and political education in teaching.
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@#The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.
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Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.
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Objective:To determine the potency of epidural ropivacaine in inhibiting breakthrough pain in primiparae undergoing labor analgesia with programmed intermittent epidural bolus (PIEB).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ primiparae of full-termpregnancy, with a singleton fetus in vertex presentation, aged ≥18 yr, with body mass index < 30 kg/m 2, presenting with breakthrough pain during labor analgesia with PIEB, were enrolled in this study. Ropivacaine 10 ml was epidurally administered, and the concentration was determined by up-and-down sequential allocation. The initial concentration was set at 0.15% in the first patient in each group. Each time the concentration increased/decreased in the next patient depending on whether the patients showed breakthrough pain relief, and the ratio between the two successive doses was 0.9. The criterion of breakthrough pain relief was defined as numerical rating scale score < 4 points within 30 min after epidural injection of ropivacaine. The median effective concentration (EC 50) and 95% confidence interval of ropivacaine in inhibiting breakthrough pain were calculated by Dixon-Massey′s method. Results:Twenty-six patients were finally included in this study.The EC 50 (95% confidence interval)of ropivacaine in inhibiting breakthrough pain was 0.102% (0.088%-0.117%). Conclusions:The EC 50(95% confidence interval) of epidurally administered ropivacaine 10 ml is 0.102%(0.088%-0.117%) when used for inhibiting breakthrough pain during labor analgesia with PIEB in primiparae.
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Objective:To explore the impact of donor cold ischemia time(CIT)on early recovery after liver transplantation(LT).Methods:From January 2016 to December 2020, the relevant clinical data were retrospectively reviewed for 456 LT recipients.According to the value of CIT of donor liver, they were assigned into two groups of CIT >5 h and CIT≤5 h. T, Mann-Whitney U or Chi square test was employed for statistical processing.Intraoperative findings and liver function(LF)parameters of two groups were compared, including operative duration, intraoperative volume of hemorrhage, erythrocyte transfusion and anhepatic phase.LF parameters included alanine aminotransferase(ALT), aspartate aminotransferase(AST)and total bilirubin(TB)within Day 1-7 post-LT.Postoperative recovery was evaluated by postoperative stay of intensive care unit(ICU), normalization time of liver function recovery, length of postoperative hospitalization and incidence of postoperative complications.Results:Among them, 407(89.3%)patients underwent classic orthotopic LT.Median CIT of donor liver was 309 min.In CIT≤5 h and CIT >5 h groups, operative duration was[(446.3+ 76.8)vs.(526.0+ 98.1)min], anhepatic phase time[(51.9+ 13.3)vs.(62.6+ 18.9)min]and intraoperative volume of erythrocyte transfusion[(7.3+ 5.8)vs.(10.0+ 6.87)U]. And the differences were statistically significant( P<0.001, 0.001 & 0.001). Postoperative hospitalization stay was longer[(29.1±15.9)vs.(27.1±13.0)]day.And the incidence of postoperative complications was higher in CIT >5 h group[22.7%(54/238)vs.12.4%(27/218)]. And the difference was statistically significant( P=0.045 & 0.004). As compared with CIT≤5 h group, ALT, AST & TB spiked in CIT >5 h group at Day 1 post-operation and the differences were statistically significant( P=0.002, P<0.001, P=0.001). In CIT >5 h group, ALT rose at Day 2/5/6/7 post-LT( P=0.026, 0.026, 0.015 & 0.011), AST jumped from Days 2-6( P=0.002, 0.004, 0.035, 0.029 and 0.019)and TB increased from Days 2-7 post-LT and the differences were statistically significant( P=0.003, 0.014, 0.030, 0.039, 0.027 & 0.009). LF recovered at CIT≤5 h and CIT>5 h group[(10.0±3.2)vs.(10.7±3.3)day]. There were significantly statistical differences( P=0.044). Conclusions:Non-conducive to patient recovery, prolonged cold ischemic time aggravates early LF injury post-LT.
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[Objective]To investigate the relationship between platelet activation and traditional Chinese medicine(TCM)syndrome distribution in patients with diabetic peripheral neuropathy(DPN).[Methods]A total of 188 DPN patients admitted to our hospital from February 2020 to December 2022 were collected.The TCM syndrome type usesd the index cluster analysis to draw the cluster diagram.The correspondence between TCM syndrome type and lesion degree was analyzed by simple correspondence analysis,and shown on the two-dimensional plan.It compared the general clinical data,platelet parameters and platelet activation of different TCM syndrome types,so as to explore the relationship between platelet activation and the distribution of TCM syndrome types.[Results]The syndrome types summarized in different positions of the cluster map were different.Among them,D-point interception could be divided into five syndrome types:Qi deficiency syndrome,Yin deficiency syndrome,Yang deficiency syndrome,stagnation of blood stasis syndrome and phlegm-dampness blocking collaterals syndrome.Among the 188 DPN patients,phlegm-dampness blocking collaterals syndrome was found in 18 cases(9.57％),stagnation of blood stasis syndrome in 53 cases(28.19％),Yang deficiency syndrome in 28 cases(14.89％),Yin deficiency syndrome in 39 cases(20.74％),and Qi deficiency syndrome in 50 cases(26.60％).The grade of DPN lesion was grade Ⅰ in 56 cases(29.79％),grade Ⅱ in 76 cases(40.43％),and grade Ⅲ in 56 cases(29.79％).The syndrome of phlegm-dampness blocking collaterals and stagnation of blood stasis in the middle of the two-dimensional projection map did not deviate to a certain grade of DPN lesion degree;Yang deficiency syndrome inclined to grade Ⅲ,Yin deficiency syndrome to grade Ⅱ,and Qi deficiency syndrome to grade Ⅰ.Compared with Qi deficiency syndrome,platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW),granular membrane protein-140(GMP-140),platelet activating factor(PAF)and E26 transformation specific-l(ETS-l)in patients with Yin deficiency syndrome and Yang deficiency syndrome were significantly higher(P＜0.05),and PLT,MPV,PDW,GMP-140,PAF and ETS-1 in patients with Yang deficiency syndrome were higher than those of Yin deficiency syndrome(P＜0.05).[Conclusion]DPN can be routinely divided into five basic syndrome types:Qi deficiency,Yin deficiency,Yang deficiency,stagnation of blood stasis and phlegm-dampness blocking collaterals.With the development of DPN,TCM syndromes are transformed from Qi deficiency to Yin deficiency to Yang deficiency,while blood stasis and phlegm-dampness blocking collaterals are accompanied by various stages of DPN patients.In the progress of DPN,platelet activation may be involved in the transformation of TCM syndrome types.
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External treatment of Traditional Chinese Medicine (TCM) is a common treatment for lumbar disc herniation, which mainly includes fumigation and washing of TCM, and hot ironing therapy. It can cooperate with oral administration of TCM, Tuina, acupuncture and other therapies to play a synergistic effect and enhance the efficacy. External application of TCM in the treatment of lumbar intervertebral disc herniation is effective with long duration, easy-operated and safe It has showed curative effect in alleviating clinical symptoms and improving lumbar function. Its mechanism mainly includes regulating nerve inflammatory reaction, improving hemorheology and exerting analgesic effect.
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Objective:To evaluate the clinical efficacy of modified Qiwei Baizhu Powder combined with conventional therapy in the treatment of type 2 diabetes mellitus (T2DM) with abnormal lipid metabolism.Methods:A total of 96 patients with T2DM and abnormal lipid metabolism from March 2018 to March 2021 in Anhui Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria were divided into 2 groups according to the random number table method, with 48 in each group. The control group was treated with conventional western medicine, while the observation group was treated with modified Qiwei Baizhu Powder and treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were performed before and after treatment. Fasting blood glucose (FPG) and 2 hPG were detected by glucose oxidase method, HbA1c was detected by HPLC, TC, TG, HDL-C and LDL-C were detected by cholesterol peroxidase method, glycerophosphate oxidase method, direct inhibition method and direct surfactant clearance method. Adverse events during treatment were recorded and clinical efficacy was evaluated.Results:The total effective rate was 93.8% (45/48) in the observation group and 79.2% (38/48) in the control group, with a statistically significant difference between the two groups ( χ2=4.36, P=0.037). After treatment, the scores of dry mouth, fatigue, anorexia, dizziness, tongue, pulse and total scores in the observation group were significantly lower than those in the control group ( t values were 3.58, 3.17, 3.24, 3.59, 3.58, 2.76 and 8.44, respectively, all Ps<0.05); the levels of FPG, 2 hPG and HbA1c in the observation group were significantly lower than those in the control group ( t values were 3.37, 2.05 and 3.73 respectively, all Ps<0.05). After treatment, the levels of TC [(4.30±0.85) mmol/L vs. (4.78±0.94) mmol/L, t=2.62], TG [(3.00±0.37) mmol/L vs. (3.19±0.54) mmol/L, t=2.01], LDL-C [(2.60±0.71) mmol/L vs. (2.95±0.44) mmol/L, t=2.90] were significantly lower than those in the control group ( P<0.05). After treatment, the HDL-C [(2.07±0.63) mmol/L vs. (1.82±0.55) mmol/L, t=2.01] level was significantly higher than that of the control group ( P<0.05). Conclusion:Modified Qiwei Baizhu Powder combined with conventional therapy can improve blood glucose and blood lipid levels in T2DM patients with abnormal lipid metabolism, relieve clinical symptoms and improve curative effect.
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Objective:To evaluate the effectiveness of the information management system on the clinical application of special-grade antimicrobial.Methods:Using the established knowledge database, a computer program was designed and developed, which was embedded in the electronic medical record to intervene the clinical use of the special-grade antimicrobial since 2015. The basic information of all discharged patients from the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to December 2020 were extracted from the HIS system, including the medical orders for antibiotics and the drug storehouse dispensing data.The trend analysis was carried out on the changes of the use rates and antibiotic use density (AUD) of the special-grade antimicrobials in the whole hospital and intensive care units (ICU). The data were processed and analyzed using SPSS 24.0.Results:From 2013 to 2015, except for meropenem and amphotericin B, the usage rate of all special-grade antimicrobials in the whole hospital showed an upward trend ( P<0.05). The proportion of special-grade antimicrobials used in the hospital increased year by year ( χ2=7 804.081, P<0.01). The total usage rate of special-grade antimicrobials in ICU showed an upward trend year by year ( χ2=67.028, P<0.01). Since the implementation of the special-grade antimicrobial information management system in 2015, the total use rate of special-grade antimicrobials in the hospital, the use rate of various antibiotics except linezolid, amphotericin B and posaconazole, and the proportion of special-grade antimicrobials used in the hospital have all shown a downward trend year by year ( P<0.01). The total usage rate and total AUD of special-grade antimicrobials in ICU showed a decreasing trend year by year ( χ2=343.514, P<0.01, β=-0.963, P=0.002). Conclusion:The information management system for special-grade antimicrobial can effectively reduce the utilization rate and AUD of most special-grade antibiotics in hospitalized patients including ICU, and has a good clinical application value in antimicrobial stewardship.
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ObjectiveTo develop a quantitative analysis of multi-components by single marker （QAMS） for determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills， and to provide a method for improving the national standard of the pills. MethodHigh performance liquid chromatography （HPLC） was developed for simultaneous determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills and the methodology validation was carried out. The chromatographic separation was performed on a Nucleosil 100-5 C18 column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile -0.1% potassium dihydrogen phosphate aqueous solution （pH adjusted to 3.2 with phosphoric acid） （48∶52）， and the flow rate was 0.6 mL·min-1， the detection wavelength was set at 296 nm and the column temperature was 35 ℃. Taking cinobufagin as the internal standard， the relative correction factors （RCFs） of bufalin and resibufogenin were calculated， and the key influencing factors of RCFs were investigated. Relative retention time was used for the chromatographic peak location of the analyte， combining with the on-line ultraviolet spectroscopy and accurate relative molecular weight obtained by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF/MS）. The external standard method was used to verify the contents of three components obtained by QAMS. ResultQAMS was established for the determination of bufalin， cinobufagin and resibufogenin in the samples， and RCFs of cinobufagin to bufalin and resibufogenin were 0.922 and 1.01， respectively. The total content of the three marker compounds in 11 batches of Shexiang Baoxin pills was 33.7-36.0 µg per pill. There was no significant difference between the quantitative results of QAMS and external standard method. ConclusionThe established method can be used for the quality control of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills. It is suggested that bufalin should be considered as one of three marker compounds， and the sum of bufalin， cinobufagin and resibufogenin should be used for the content limit of this preparation.
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Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.
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Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.
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Objective:To evaluate the effectiveness of antimicrobial stewardship based on self-developed antibiotic clinical decision support system (aCDSS) in the inpatients at a tertiary hospital for consecutive 6 years, and to provide reference for rational use and antimicrobial stewardship.Methods:aCDSS was self-designed based on information technology and applied in clinical use in our hospital from 2015. Data of inpatient information and antibacterial use from January 2015 to December 2020 were collected from HIS and aCDSS. A retrospective study was conducted in all inpatients on the utilization rate and antibiotic use density.Results:Since 2015, with the comprehensive implementation of antimicrobial stewardship based on the aCDSS,there was a significant decline on the annual rate of antibiotic usage from 44.18% in 2015 to 38.70% in 2020, as well as on the usage rate of extended-spectrum antimicrobial agents including carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors, tigecycline, broad-spectrum cephalosporins, fluoroquinolones, as well as glycopeptide and antifungal drugs. Compared with 2015, the usage of carbapenems, tigecycline and broad-spectrum β-lactam/β-lactamase inhibitors was declined nearly 50% in 2020, and the density of carbapenems and tigecycline were decreased by 29.6% and 7.1%, respectively in 2020. On the other side, the utilization rate and use density of narrow-spectrum cephalosporins continued to increase by year, the use density of narrow-spectrum cephalosporins accounting for 28.2% of all antibiotics in 2020.Conclusions:With the comprehensive implementation of aCDSS, the utilization rate and density of broad-spectrum and high-priced antibacterial drugs in our hospital have decreased continuously to decline in the past 6 years, while the proportion of narrow-spectrum antimicrobials has increased year by year, indicating that the structure of antimicrobial use has been continuously optimized and that antimicrobial stewardship based on the information technology have achieved remarkable results.
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Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.
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【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.
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AIM: To study the distribution of CYP2C9∗3 and VKORC1-1639G>A gene polymorphism in Han population in Anhui province and their influence on the stable dose of warfarin. METHODS: The blood samples of 1 169 patients from 6 tertiary general hospitals in 5 areas of Anhui province from January 2020 to December 2021 were selected, the genotype of CYP2C9∗3 and VKORC1-1639G>A was detected by fluorescent staining in situ hybridization technique. RESULTS: The distribution of CYP2C9∗3 genotypes in 1 169 patients: the frequencies of AA, AC and CC genes were 90.16%, 9.24% and 0.60%, respectively; The distribution of VKORC1 genotype: the frequencies of AA, AG and GG genes were 84.26%, 14.71% and 1.03% respectively; There was no significant difference between the two genotypes in gender, age and regional distribution (P>0.05). The average daily warfarin dose of CYP2C9∗3 AA genotype in 755 patients with stable warfarin dose was (3.02±0.59) mg/d, which was significantly higher than patients with AC genotype and CC genotype; The average daily warfarin dose of patients with VKORC1-1639AA genotype was (2.72±0.40) mg/d, which was significantly lower than that of patients with AG genotype and GG genotype (P<0.05). And the difference was statistically significant (P<0.05); There are significant differences in gender, age and clinical diagnosis between patients with stable dose of warfarin and those without stable dose (P<0.05). CONCLUSION: CYP2C9 and VKORC1 genotypes are associated with the stable dose of warfarin. Clinical anticoagulation therapy guided by CYP2C9 and VKORC1 genotypes can provide guidance for individualized medication of warfarin.
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Objective:To explore the prognostic factors that may affect the postoperative survival of gastric cancer by analyzing patients with radical gastrectomy.Methods:The data of 525 patients with radical gastrectomy, including 387 male and 138 female with average age (62.5±10.7) years old (ranged from 16 to 89 years), were analyzed retrospectively in Anqing Municipal Hospital between October 2010 to July 2015. The relationship between 33 variables and prognosis was analyzed by a Cox proportionalhazards regression model, meanwhile ROC curve was established in order to explore the risk factor of postopertive survival.Results:The over survival(OS) rate of all patients was 89.3% at 1 year, 68.4% at 3 years and 59.6% at 5 years. The 5-year OS rate was 81.9% at stage Ⅰ, 71.4% at stage Ⅱ and 44.1% at stage Ⅲ. In the multivariate analysis that included these factors, preoperative comorbidity ( HR=1.595, P=0.001), hemoglobin( HR=1.377, P=0.017), CA199( HR=1.618, P=0.004), tumor distribution( HR=1.943, P=0.032), pT stage( HR=1.731, P=0.012), pN stage( HR=2.118, P=0.000), signet ring cell( HR=1.642, P=0.038)and intravascular tumor thrombus( HR=1.391, P=0.039) were independent risk factors associating with postopertive survival.According to ROC curve, the following area (AUC value) could predict survival after radical gastrectomy, including CA199 (AUC=0.568), hemoglobin(AUC=0.586), preoperative comorbidity(AUC=0.554), pT stage(AUC=0.636), pN stage(AUC=0.670)and intravascular tumor thrombus(AUC=0.626)( P<0.05). Conclusion:According to ROC curve analysis, preoperative comorbidity, anemia, CA199, pN stage, pT stage and intravascular tumor thrombus played an role in predicting long-term survival after radical resection of gastric cancer.
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Objective: To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods: The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein–protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results: The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion: This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.