摘要
Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Subject(s)
Humans , Adult , Retrospective Studies , Neoplasm Recurrence, Local , Hematologic Neoplasms/therapy , Busulfan/therapeutic use , Graft vs Host Disease/prevention & control , Chronic Disease , Unrelated Donors , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Transplantation Conditioning摘要
Objective:To observe the effect of α-lipoic acid(ALA) on the intracerebroventricular injection(icv) of streptozotocin(STZ)-induced spatial learning memory impairments in rats and the underlying molecular mechanisms.Methods:Forty-five male SD rats were assigned into 3 groups, control group, icv-STZ group and icv-STZ+ ALA group, 15 rats each. STZ was dissolved in artificial cerebrospinal fluid then injected into the lateral ventricles of the rat by using stereotaxic device. ALA was administrated by gavage after STZ injection. The spatial learning memory was examined by using Morris water maze test after 4 weeks of treatment. Immunohistochemistry was performed to detect the number of microglia and astrocytes, electron microscopy was applied to detect mitochondrial integrity, Western blotting was used to detect the protein expression levels, and the changes of lipid peroxidation and redox system were examined by kit.Results:Spatial learning memory was impaired in rats after 4 weeks of STZ injection, and ALA treatment ameliorated STZ-induced cognitive dysfunction in rats. Iron concentration, lipid peroxidation, neuroinflammation, Tau hyperphosphorylated were enhanced markedly after STZ injection, along with and the activation of MAPK and GSK-3β, which were ameliorated by ALA. Further examination revealed that STZ activated the JAK2/STAT3 pathway and transcriptionally inhibited the expression of peroxidase GPX. Inhibition of STAT3 activity can block STZ-induced downregulation of GPX4 and Tau hyperphosphorylation.Conclusion:ALA ameliorated STZ-induced spatial learning memory impairments in rats via deactivation of JAK2/STAT3 pathway, restored GPX4 protein level, resulting in chelating iron, improving mitochondrial function, balancing the redox system, ameliorating Tau hyperphosphorylation and neuroinflammation.
摘要
This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.
Subject(s)
Animals , Humans , Rats , Glucocorticoids/pharmacology , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic/metabolism , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism摘要
Objective:To establish a model of cervical spondylosis of vertebral artery type (CSA) in rats by mixed modeling method, and observe the intervention effect of Panlongqi tablet (PLQT) on CSA rats. Method:SD rats were divided into a normal control group, a model group, low- (0.16 g·kg<sup>-1</sup>), medium- (0.32 g·kg<sup>-1</sup>), and high-dose (0.64 g·kg<sup>-1</sup>) PLQT groups, and a Jingfukang granule (JFK, 1.35 g·kg<sup>-1</sup>) group. The rats were treated correspondingly 24 hours after modeling for eight weeks, and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay, vertebral artery flow volume by multi-mode high-frequency sound wave for small animals, and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography (Micro CT). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of endothelin-1 (ET-1), nitric oxide (NO), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI). Result:Compared with the normal control group, the model group showed decreased limb movement, vertebral artery flow volume, and microcirculatory blood flow in the pia mater, and increased imaging of the cervical spine and score (<italic>P</italic><0.05,<italic>P</italic><0.01). PLQT could dose-dependently improve the motor function, increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater, and reduce the degree and score of imaging of the cervical spine in CSA rats(<italic>P</italic><0.05,<italic>P</italic><0.01). The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group, while such changes were reversed by PLQT treatment(<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:PLQT can enhance the limb movement, promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater, improve the degree of imaging of the cervical spine, regulate the vasomotor function, and improve the coagulation and fibrinolysis system of CSA rats, which shows good potential for the treatment of CSA.
摘要
Objective:To observe the effect of Tongluo Shenggu capsule (TLSGC) on glucocorticoid-induced vascular endothelial cell functional damage, and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate (MPS, 0.04 g·L<sup>-1</sup>) and/or vascular endothelial growth factor (VEGF, 20 μg·L<sup>-1</sup>), and were treated with TLSGC(12.5, 25, 50 μg·L<sup>-1</sup>) continuously for 5 days to observe the number, length and area of microvascular ring buds.In addition, human umbilical vein endothelial cells (HUVEC) induced by VEGF(20 μg·L<sup>-1</sup>) were added into MPS(0.04 g·L<sup>-1</sup>) and TLSGC (12.5, 25, 50 μg·L<sup>-1</sup>) were added. Then, Transwell migration, Transwell invasion and lumen formation experiments were used to detect the migration, invasion and lumen formation ability of HUVEC, respectively. The content of nitric oxide(NO) in the cell supernatant was detected by nitrate reductase method, the content of endothelin 1(ET-1) in the cell supernatant was detected by dry powder method. Moreover, the protein contents of vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-regulated kinase (ERK), phospho-extracellular signal-regulated kinase (p-ERK), mitogen extracellular kinase1(MEK) and phosphorylated mitogen extracellular kinase1(p-MEK) in the cells were determined by Western blot. Result:Compared with the normal group, MPS could significantly inhibit the number, length and area of VEGF-induced rat thoracic aortic ring microvessels, HUVEC cell migration, invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2, p-MEK and p-ERK in HUVEC(<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, TLSGC could dose-dependently increase the number, length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels, promote MPS-induced abnormally decreased HUVEC cell migration, invasion and lumen formation ability. It could increase the protein contents of NO, VEGFR2, p-MEK and p-ERK in HUVEC, and reduce abnormally increased ET-1 content(<italic>P</italic><0.05<italic>,P</italic><0.01). Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid, and the mechanism may be related to the activation of MEK/ERK signaling pathway.
摘要
Objective::To prepare 15 batches of Banxia Xiexintang substance benchmark and lyophilized powder from different places, and the lyophilized powder was analyzed by ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) in order to investigate the advantages of DESI-MSI in quality control of famous classical formulas. Method::Taking Banxia Xiexintang as the research model, fingerprints of the substance benchmark and lyophilized powder were established by UHPLC-DAD, and the content of index components and the yield of dry extract were also investigated. Meanwhile, as the research carrier, the lyophilized powder corresponding to Banxia Xiexintang was dissolved in methanol and dotted on qualitative filter paper with 5 μL quantitative capillary, and fixed it on the slide to make samples. The samples were analyzed on a DESI-MSI system in positive and negative ion mode with methanol-formic acid (1 000∶1, flow rate of 3 μL·min-1) as spray solvent, N2 as spray gas (pressure of 0.5 MPa). The scanning range was 100-1 200 Da, the spatial resolution was 300 μm, the spray voltage was 3 kV, the sampling cone voltage was ±40 V, incidence angle of sprayer was 60 degree, its collection angle was 10 degree, the ion source temperature was 120 ℃. Result::DESI-MSI could not only detect the index components of liquiritin, baicalin and wogonoside, as well as the common peaks of liquiritin apioside, berberine and glycyrrhizic acid, but also analyzed them semi-quantitatively, the analysis results were basically consistent with UHPLC-DAD. At the same time, DESI-MSI could detect 16 other components from Glycyrrhizae Radix et Rhizoma, Coptidis Rhizoma, Scutellariae Radix, Jujubae Fructus and Ginseng Radix et Rhizoma, such as licoricesaponin G2, palmatine, coptisine, rutin and ginsenoside Rg1, and present their relative content visually. The qualitative analysis ability of DESI-MSI was much better than UHPLC-DAD. Conclusion::DESI-MSI can be used as the quality control method for substance benchmark and lyophilized powder and dispensing granules of famous classical formulas with advantages of high sensitivity, strong analytical ability, no complex sample processing, qualitative and relative content analysis of complex samples without reference substance.
摘要
Shaoyao Gancaotang, first seen in Treatise on Febrile and Miscellaneous Diseases, is composed of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle in equal proportion.It has the functions of preserving Yin to nourish blood, harmonizing liver and spleen, relieving spasm and pain.This formula is applied in leg and foot spasm and abdominal pain caused by blood deficiency, body fluid consuming and the unmoistened muscles and veins.It has been highly praised and used by medical experts throughout the ages and has extended its application scope.Modern pharmacological studies have shown that Shaoyao Gancaotang has significant effects in antispasmodic, analgesic, antitussive and other areas, and is used to treat spastic diseases, painful diseases, inflammatory diseases and so on.This paper will systematically elaborate the historical evolution, compatibility analysis, pharmacological and pharmacodynamic studies, modern clinical application of Shaoyao Gancaotang, in order to provide theoretical basis and reference for the development of this famous classical formula.
摘要
Objective:To observe the analgesic effect of Panlongqi tablet(PLQT) on rats with chronic inflammatory pain, and to explore mechanism of the action preliminarily from the perspective of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)and mitogen-activated protein kinase(MAPKs) signaling pathways. Method:Rats were induced to establish model of chronic inflammatory pain by complete Freund adjuvant(CFA), which was divided into normal group, model group, the PLQT 0.16,0.32,0.64 g·kg-1 group, and the ibuprofen 0.05 g·kg-1 group(also positive group), give the medicine once a day by gavage. Standard Von Frey fiber was used to evaluated the mechanical pain threshold, acetone was used to stimulated rats inflammatory foot to get the cold-induced response score, with the mechanical pain threshold and cold-induced response score to be observed at 1, 2, 3, 4 and 6 h before and after administration on day 1, and at 4 h after administration on day 3-7. The content of PGE2, IL-1, TNF-α in serum, inflammatory foot and 4-5 lumbar spinal cord was detected by enzyme-linked immunosorbent assay(ELISA). The protein level of MAPKs (p-p38, p-ERK, p-JNK) in lumbar spinal cord 4-5 was detected by Western blot. The expression of NF-κB p65 in the lumbar spinal cord was detected by IFA. Result:Model group had lower mechanical pain threshold and higher cold-induced response score than these in normal group(P<0.01), while the mechanical pain threshold and cold-induce response score of the model rats were dose-dependent better regulated after administration of PLQT 0.16, 0.32, 0.64 g·kg-1·d-1(P<0.05,P<0.01), these effect lasted 6 h, of which PLQT groups get the most significant effect on 4 h, however the effect of IBP was similar to that of PLQT medium dose group. In addition, PLQT reduced the abnormal increase of PGE2, IL-1 and TNF-α contents in serum, inflammatory foot and spinal cord of rats in model group, decreased the protein phosphorylation levels of ERK and JNK in spinal cord, and decreased the protein expression of NF-κB p65, that was significant in the PLQT high-dose group(P<0.01). Conclusion:PLQT had significant analgesic effect on chronic inflammatory pain model rats, which may be related to the inhibition of NF-κB and MAPKs signaling pathways in spinal cord.
摘要
Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
摘要
The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.
Subject(s)
Animals , Female , Male , Rats , Apoptosis , China , Drugs, Chinese Herbal/pharmacology , Glycosides/pharmacology , Oxidative Stress , Random Allocation , Signal Transduction , Tablets , Tripterygium/chemistry摘要
To systematically evaluate the adverse drug reaction(ADR) of Tripterygium Glycosides Tablets(TGT) in the treatment of rheumatoid arthritis(RA). Four Chinese databases(CNKI, VIP, WanFang, SinoMed) and three English databases(Cochrane Library, EMbase, PubMed), from the time of database establishing to August 2019, were systematically retrieved to collect literature on the treatment of all types of RA with TG. Screening literature and extracting data according to inclusion and exclusion criteria. All studies were assessed by using internationally recognized methodological quality assessment tools or reporting quality evaluation criteria, with data being extracted and Meta-analyzed. There were 79 studies included, randomized controlled trials(RCT) containing TGT in the treatment group, non-randomized controlled trials(non-RCT), case series, case reports, and RCT containing TGT only in the control group were covered. There were in the control group; 765 ADR of 2 214 patients in 30 RCT(treatment group given TGT), 11 non-RCT and 7 case reports. The results of Meta-analysis of these 48 literatures showed that the overall incidence of ADRs was 0.23(95%CI[0.22,0.24]); ADR mainly occured in the reproductive, gastrointestinal, skin and accessories, blood, hepatobiliary system damage and the incidence of ADR in systems mentioned about respectively were 0.14(95%CI[0.12,0.17]),0.07(95%CI[0.06,0.08]),0.06(95%CI[0.04,0.07]),0.04(95%CI[0.03,0.05]),0.04(95%CI[0.03,0.05]). Further subgroup analysis results showed that the incidence of total ADR, especially the gastrointestinal, reproductive and cutaneous ADR of patients with treatment alone was higher than that in those paients with MTX or MTX+LEF therapy; The incidence of ADR, especially the gastrointestinal ADR, was also positively correlated with daily dose and course of treatment, while the incidence of different systems ADR was also correlated with different drug manufacturers, for instance, damage on the female reproductive system occurs most frequently in Hunan manufacture TGT administration, same as the damage on skin and accessories induced by TGT from Jiangsu manufacture. Above all, The clinical treatment of TGT for RA will cause multi-system ADR, with the highest incidence in the reproductive system, followed by the gastrointestinal system, which is closely related to the way of medication(monotherapy), daily dose, course of medication and drug manufacturer. Therefore, it is recommended that, in the treatment of RA, using TGT in combination, low dose or short-course medication, take measures to protect the reproductive system, stomach and liver, and paying attention to the drug manufacturer as well response of patients during administration should be valued to avoid ADRs to the maximum possibility.
Subject(s)
Humans , Arthritis, Rheumatoid/drug therapy , Drugs, Chinese Herbal/therapeutic use , Glycosides/therapeutic use , Non-Randomized Controlled Trials as Topic , Randomized Controlled Trials as Topic , Tablets , Tripterygium/chemistry摘要
BACKGROUND@#Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.@*METHODS@#We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.@*RESULTS@#Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.@*CONCLUSION@#A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Betacoronavirus , Genetics , Coronavirus Infections , Diagnostic Imaging , Therapeutics , Virology , Pandemics , Pneumonia, Viral , Diagnostic Imaging , Therapeutics , Virology , Tomography, X-Ray , Treatment Outcome摘要
Objective: To investigate the antidepressant effect of Chaigui Granules on the symptoms associated with depression. Methods: The chronic mild unpredictable stress (CUMS) model was used to simulate mild to moderate depression. The effects of Chaigui Granules on rats in Morris water maze test, the elevated plus maze test and the gastrointestinal function test were investigated. Results: In all doses of Chaigui Granules, the latency of platform exploration in Morris experiment was significantly reduced (P < 0.05) and the number of times entering the platform was increased (P < 0.05). The ratio of open-arms time and the frequency of open-arms entries in the elevated plus maze experiment were also increased (P < 0.05, P < 0.01). The gastric residual rate was significantly reduced (P < 0.05) in the low and middle dose group, and the propulsion rate of intestinum tenue was increased (P < 0.05, P < 0.01) in all group. Conclusion: The results showed that Chaigui Granules obviously improved the decreased ability of learning and memory, anxiety, gastrointestinal dysfunction caused by CUMS model in rats, indicating that it can significantly improve the depressive symptoms and alleviate its associated symptoms.
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Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD), and insulin-resistance is commonly seen in patients with Hhcy. Liraglutide (Lir), a glucagon-like peptide that increases the secretion and sensitivity of insulin, has a neurotrophic or neuroprotective effect. However, it is not known whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy. By vena caudalis injection of homocysteine to produce the Hhcy model in rats, we found here that simultaneous administration of Lir for 2 weeks ameliorated the Hhcy-induced memory deficit, along with increased density of dendritic spines and up-regulation of synaptic proteins. Lir also attenuated the Hhcy-induced tau hyperphosphorylation and Aβ overproduction, and the molecular mechanisms involved the restoration of protein phosphatase-2A activity and inhibition of β- and γ-secretases. Phosphorylated insulin receptor substrate-1 also decreased after treatment with Lir. Our data reveal that Lir improves the Hhcy-induced AD-like spatial memory deficit and the mechanisms involve the modulation of insulin-resistance and the pathways generating abnormal tau and Aβ.
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Objective To investigate the changes in distribution and antimicrobial resistance of pathogens causing bloodstream infection in a hospital in 2012-2015.Methods Pathogenic bacteria isolated from blood culture in a hospital microbiology laboratory between January 2012 and December 2015 were collected and divided into 2012-2013 group and 2014-2015 group,distribution characteristics,constitute,and antimicrobial susceptibility of two groups were compared.Results Gram-negative bacteria were the main pathogens isolated during two periods,ac-counting for 54.96% and 54.66% respectively,there was no significant differences in pathogen distribution between two groups (P >0.05).Gram-positive cocci had a high sensitivity to vancomycin and linezolid,resistant rates were both 0;resistance rates of coagulase negative staphylococci to oxacillin were all >80%,resistance to penicillin was also >90%;Enterobacteriaceae was highly sensitive to imipenem and meropenem,but resistance strains had ap-peared;Acinetobacter baumannii was sensitive to minocycline during two periods,resistance rates were 35.90% and 34.55% respectively,resistance rates to other antimicrobial agents were also high (>75%).Conclusion The iso-lation rate of drug-resistant pathogenic strains causing bloodstream infection is high,monitoring on bacterial resistance is helpful for guiding rational use of antimicrobial agents in clinic.
摘要
Objective To investigate the changes in distribution and antimicrobial resistance of pathogens causing bloodstream infection in a hospital in 2012-2015.Methods Pathogenic bacteria isolated from blood culture in a hospital microbiology laboratory between January 2012 and December 2015 were collected and divided into 2012-2013 group and 2014-2015 group,distribution characteristics,constitute,and antimicrobial susceptibility of two groups were compared.Results Gram-negative bacteria were the main pathogens isolated during two periods,ac-counting for 54.96% and 54.66% respectively,there was no significant differences in pathogen distribution between two groups (P >0.05).Gram-positive cocci had a high sensitivity to vancomycin and linezolid,resistant rates were both 0;resistance rates of coagulase negative staphylococci to oxacillin were all >80%,resistance to penicillin was also >90%;Enterobacteriaceae was highly sensitive to imipenem and meropenem,but resistance strains had ap-peared;Acinetobacter baumannii was sensitive to minocycline during two periods,resistance rates were 35.90% and 34.55% respectively,resistance rates to other antimicrobial agents were also high (>75%).Conclusion The iso-lation rate of drug-resistant pathogenic strains causing bloodstream infection is high,monitoring on bacterial resistance is helpful for guiding rational use of antimicrobial agents in clinic.
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Objective:To prepare flupirtine maleate dry suspension and establish its quality control method. Methods: The dry suspension was prepared by a powder direct mixing method. With the sedimentation and redispersibility as the indices,the suspending effect of the hydrophilic polymers HPMC and CMC-Na was investigated. The optimal formula was obtained. The viscosity was deter-mined by a rotary viscometer. An HPLC fluorescence method was used to determine the content of main component. Results:The sedi-mentation ratio of flupirtine maleate dry suspension was 1 in 3h with good redispersibility and liquidity. The cumulative dissolution in 30min was above 80%. Conclusion:The quality of the prepared flupirtine maleate dry suspension is stable and controllable, and the production process is feasible, which provides basis for the research and development of new preparation of flupirtine maleate.
摘要
OBJECTIVE:To determine the contents of heavy metals in commercial Chinese crude drugs and to provide reference for the monitoring of heavy metals in the crude drugs.METHODS:UV spectrophotometry was established to determine the contents of heavy metals in 6 vegetable drugs(Panax quinquefolium,Panax ginseng,Lycium barbarum,Radix et Rhizoma Glycyrrhizae,Bulbus Fritillariae Cirrhosae and Salvia miltiorrhiza)and 2 animal-source drugs(Scolopendra subspinipes mutilans and Bombyx Batryticatus).RESULTS:The linear range of heavy metal plumbum(reference substance)was 0.01~0.50 ?g?mL-1(r=0.997 7),and the average recovery rate was 99.49%(RSD=1.41%).The contents of heavy metals in Panax quinquefolium,Panax ginseng,Lycium barbarum,Radix et Rhizoma Glycyrrhizae,Bulbus Fritillariae Cirrhosae,Salvia miltiorrhiza were 26.13,28.96,26.99,29.98,26.63 and 28.06 ?g?g-1 respectively,and the contents of Scolopendra subspinipes mutilans and Bombyx Batryticatus were on the high side(47.62 and 59.24 ?g?g-1 respectively).CONCLUSION:The method is easy,highly accurate,and it can be used for detection of heavy metals in Chinese crude drugs.