RESUMO
Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.
Assuntos
Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Estudos Prospectivos , Anticorpos Monoclonais/uso terapêutico , Imunoterapia/efeitos adversosRESUMO
OBJECTIVE@#To investigate herpes zoster reactivation induced by arsenic in patients with acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 212 patients with APL treated in the Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from 2008 to 2019 were retrospectively analyzed to observe the activation of varicella zoster virus induced by arsenic. Kaplan-Meier analysis, chi-square test, and boxplot were used to analyze and describe the cumulative dose of arsenic and the time from the beginning of arsenic treatment to the occurrence of herpes zoster.@*RESULTS@#Excluding early death cases and early automatic discharge cases, 17 cases developed herpes zoster reactivation in 175 patients with APL treated with arsenic, and the cumulative median dose of arsenic was 6.2(2-12) mg/kg. Precise risk of reactivation of herpes zoster with 10 months in APL patients treated by arsenic was 9.7%.@*CONCLUSION@#Arsenic treatment can induce high reactivation rate of herpes zoster virus.
Assuntos
Humanos , Arsênio , Herpes Zoster/epidemiologia , Herpesvirus Humano 3 , Leucemia Promielocítica Aguda/tratamento farmacológico , Estudos RetrospectivosRESUMO
Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas , Quimiorradioterapia , Neoplasias Hipofaríngeas/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ObjectiveTo explore the molecular mechanism of Yishen Tongluo prescription in inhibiting the apoptosis of glomerular podocytes in rats with membranous nephropathy (MN) based on the miR-514a-5p/tumor necrosis factor superfamily member 15 (TNFSF15) signaling pathway. MethodEighty SD rats were pre-immunized and injected with cationized bovine serum albumin (C-BSA) into the tail vein for inducing MN, and the successfully modeled MN rats were randomly divided into the model group, high-, middle-, and low-dose (26.44, 13.22, 6.61 g·kg-1) Yishen Tongluo prescription groups, and benazepril (10 mg·kg-1) group, with 10 rats in each group, and another 20 healthy rats were classified into the normal group. Rats in each group were gavaged with the corresponding drugs, once a day, for four successive weeks. After the administration, the 24-hour urine total protein (UTP) level, serum total cholesterol (TC), triglyceride (TG), albumin (ALB), creatinine (SCr), and urea nitrogen (BUN) levels were measured. The miR-514a-5p and TNFSF15 mRNA expression levels in the rat kidney tissue were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the expression levels of podocyte marker proteins Nephrin, Podocin, Podocalyxin, Synaptopodin, TNFSF15, and podocyte apoptosis-related proteins B lymphocytoma-2 (Bcl-2)-related X protein (Bax), Bcl-2-associated death promoter (BAD) protein, and B-cell lymphoma-extra large (Bcl-XL) by immunohistochemistry (IHC). Western blot was used to detect the expression levels of TNFSF15, Bax, BAD, Bcl-2, and BCL-XL in the rat kidney tissue. The apoptosis rate of rat kidney tissue was measured using the in situ end labeling method (Tunnel). ResultCompared with the normal group, the level of miR-514a-5p in the kidney tissue was significantly reduced (P<0.05), and the TNFSF15 mRNA expression was significantly increased (P<0.05). The expression levels of podocyte marker proteins Nephrin, Podocin, Podocalyxin, and Synaptopodin were down-regulated (P<0.05). The protein expression levels of TNFSF15, Bax, and BAD were increased (P<0.05), whereas the Bcl-2 and Bcl-XL protein expression levels were decreased (P<0.05). The number of apoptotic cells diminished significantly (P<0.05). Compared with the model group, the level of miR-514a-5p in the kidney tissue was significantly increased (P<0.05), while the level of TNFSF15 mRNA was significantly decreased (P<0.05). The expression levels of podocyte marker proteins Nephrin, Podocin, podocalyxin, and Synaptopodin were up-regulated (P<0.05), whereas the TNFSF15, Bax, and BAD protein expression levels were down-regulated (P<0.05). Bcl-2 and Bcl-XL protein expression levels rose (P<0.05). The number of apoptotic cells significantly decreased (P<0.05). ConclusionYishen Tongluo prescription reduces the apoptosis of rat kidney podocytes and alleviates the kidney injury of MN rats through the miR-514a-5p/TNFSF15 signaling pathway.
RESUMO
Objective:To observe the effects of Yishen Tongluo prescription (YTP) on autophagy-related proteins in rats with membranous nephropathy (MN) and explore its possible molecular mechanism in protecting the kidney. Method:Twenty of 80 Sprague-Dawley (SD) rats were randomly selected as the normal control, and the rest rats were pre-immunized and injected with cationized bovine serum albumin (C-BSA) through the tail vein to induce MN. The SD rats that were successfully modeled were randomized into the model group, benazepril hydrochloride group (10 mg·kg<sup>-1</sup>), and low- (6.61g·kg<sup>-1</sup>), medium- (13.22 g·kg<sup>-1</sup>), and high-dose (26.44 g·kg<sup>-1</sup>) YTP groups, and administered with the corresponding drugs by gavage, once a day, for four consecutive weeks. Then the changes in such quantitative indicators as plasma albumin (ALB), triglyceride (TG), total cholesterol (TC), serum creatinine (SCr), blood urea nitrogen (BUN), and 24-hour urinary total protein (UTP) were detected, followed by hematoxylin and eosin (HE) staining, Masson's trichrome staining, and periodic Schiff-methenamine (PASM) staining for observing the pathological changes in kidney under the transmission electron microscope (TEM). The deposition of immunoglobulin G (IgG) and complement 3 (C3) in the glomerulus was detected by fluorescence immunoassay. The expression levels of autophagy marker proteins Beclin-1, microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and p62 were measured by immunohistochemistry (IHC), and those of related proteins in the adenosine monophosphate-activated protein kinase / mechanisic target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were determined by Western blot assy. Result:Compared with the normal group, the model group exhibited significantly increased UTP (<italic>P</italic><0.01) and serum TG and TC (<italic>P</italic><0.01), decreased ALB (<italic>P</italic><0.01), disordered glomerular structure, enlarged volume, thickened basement membrane, vacuolated renal tubules, excessively deposited collagen fibers and fuchsinophilic proteins, extensively fused podocyte foot processes, and diffusely deposited IgG and C3 in glomerular capillary loops. Besides, the expression levels of Beclin-1, LC3II, and phosphorylated AMPK (p-AMPK) decreased (<italic>P</italic><0.01), while those of p62, phosphorylated mTOR (p-mTOR), and phosphorylated ULK1 (p-ULK1) increased (<italic>P</italic><0.01). The comparison with the model group revealed that the TG, TC, and UTP levels in the low-, medium-, and high-dose YTP groups and the benazepril hydrochloride group were reduced to varying degrees (<italic>P</italic><0.05, <italic>P</italic><0.01), whereas the ALB level was increased (<italic>P</italic><0.01). There was no statistically significant difference in SCr or BUN level. The pathological damages were alleviated. The expression levels of Beclin-1, LC3Ⅱ, and p-AMPK were up-regulated (<italic>P</italic><0.05, <italic>P</italic><0.01), while those of p62, p-mTOR, and p-ULK1 were down-regulated (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:YTP protects the kidney of rats with MN possibly by regulating related proteins in the AMPK/mTOR/ULK1 signaling pathway and activating the autophagy.
RESUMO
Objective To explore the effect of microRNA( miR) -193a on the apoptosis of mouse podocytes in diabetic nephropathy (DN) and its mechanism. Methods The DN model was replicated by culturing podocytes with high glucose in vitro and intraperitoneal injection of streptozocin (STZ) in mice in vivo. The cells or 60 mice were randomly divided into normal control (NC) group, model control group, and miR-NC inhibitor group, miR-193a inhibitor group, miR-NC mimic group and miR-193a mimic group. Flow cytometry, immunohistochemistry, TUNEL, Real-time PCR, Western blotting were used to examine the apoptosis of DN mice and mouse podocytes. Results The expression of Nephrin and Podocin in podocytes was weakened in DN mice and renal podocytes induced by high glucose, the apoptotic rate increased significantly, miR-193a was highly expressed, the levels of cleaved-Caspase-3 and Bax protein increased significantly, the level of Bcl-2 protein decreased significantly, and miR-193a inhibitor could improve this process. Wilms' tumor gene 1 ( WT1 ) mRNA and protein expression levels were significantly reduced in DN mice and podocytes cultured with high glucose. WT1 protein expression increased significantly after miR-193a inhibitor intervention, and WT1 protein expression was significantly reduced after miR-193a mimic transfection. Up-regulating WT1 could reduce the effect of miR- 193a on the apoptosis of mouse podocytes induced by high glucose. The dual luciferase reporter experiment confirmed the targeting relationship between miR-193a and WT1. Conclusion MiR-193a down-regulates the expression of WT1 and promotes apoptosis of DN podocytes.
RESUMO
This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever ( 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.
Assuntos
Criança , Feminino , Humanos , Masculino , Betacoronavirus , Fisiologia , Estudos de Casos e Controles , Infecções por Coronavirus , Sangue , Epidemiologia , Alergia e Imunologia , Virologia , Influenza Humana , Sangue , Epidemiologia , Alergia e Imunologia , Pandemias , Pneumonia Viral , Sangue , Epidemiologia , Alergia e Imunologia , VirologiaRESUMO
Objective::To established fingerprint of Acanthopanacix Cortex by UPLC method, in order to provide reference for quality control and evaluation. Method::UPLC method was performed on Waters BEH C18 (2.1 mm×100 mm, 1.7 μm), with acetonitrile-0.1% glacial acetic acid as the mobile phase for gradient elution.The detection wavelength was 282 nm, the flow rate was 0.3 mL·min-1, the column temperature was 25 ℃, and the injection volume was 2 μL.With syringin as reference substance, the fingerprint of 20 batches Acanthopanacix Cortex were analyzed under the same chromatographic conditions.The Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Media (version 2012) was used to analyze the similarity of 20 batches of Acanthopanacix Cortex, and the SPSS 21.0 was applied for cluster analysis. Result::The UPLC fingerprint of the Acanthopanacix Cortex was established.The similarity results showed that the 7 batches of the 20 batches of Acanthopanacix Cortex was less than 0.800, and the remaining medicinal materials were similar within the range from 0.800 to 0.924.Besides, 12 common fingerprint peaks were calibrated and 4 components were identified, namely protocatechuic acid (peak 1), chlorogenic acid (peak 3), syringin (peak 4), and 4-methoxysalicylaldehyde (peak 12). The clustering results showed that the 20 batches of Acanthopanacix Cortex were divided into four groups.Among these batches, S1, S3, S9, S13 and S20 were clustered into one category, S11 was a category, S14 was a category, and the remaining samples belonged to a category. Conclusion::With a good precision, repeatability and stability, short analysis time as well as superior specificity, the method will provide a scientific basis to evaluate and control the quality of Acanthopanacix Cortex.
RESUMO
The ginseng endophytic bacteria F1 is a potential biocontrol agent for ginseng bacterial soft rot. In this paper,the chemotactic response of ginseng endophytic bacteria F1 on 8 kinds of sugar and amino acids was detected by capillary method to explore its biocontrol mechanism. The chemotactic response of F1 strain to 4 kinds of better chemotaxis substances such as glucose,glycine,L-rhamnoseand L-glutamic acid under parameters( concentration,time,temperature and pH) was studied. The results showed that under the same experimental conditions( incubation temperature 25 ℃,incubation time 60 min,chemotaxis concentration 1 mg·L~(-1)),ginseng endophytic bacteria F1 showed different degrees of response to the eight substances tested. The phenomenon of positive chemotaxis of the measured sugars and amino acids was obvious,and the chemotactic response to total ginsenosides was low. The degree of chemotaxis response is positively correlated with the chemotaxis index within a certain range of parameters,but as the temperature,p H,time,concentration and other factors continue to increase,the chemotaxis effect decreases,and F1 optimizes the chemotaxis of the four substances. The parameters are as follows: glucose: 25 ℃,10 mg·L~(-1),45 min,pH 7; glycine: 30 ℃,10 mg·L~(-1),75 min,pH7; L-rhamnose: 30 ℃,1 mg·L~(-1),30 min,pH 6; L-glutamic acid: 25 ℃,0. 1 mg·L~(-1),45 min,pH 8. The chemotactic response is more sensitive to low concentrations of chemotactic substances.
Assuntos
Aminoácidos/farmacologia , Bactérias/efeitos dos fármacos , Quimiotaxia , Endófitos/fisiologia , Ginsenosídeos/farmacologia , Panax/química , Exsudatos de Plantas/farmacologia , Açúcares/farmacologiaRESUMO
<p><b>OBJECTIVE</b>To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO.</p><p><b>METHODS</b>The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve.</p><p><b>RESULTS</b>Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg.</p><p><b>CONCLUSION</b>The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.</p>
Assuntos
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio , Arsenicais , Leucemia Promielocítica Aguda , Óxidos , Recidiva , Estudos Retrospectivos , TretinoínaRESUMO
This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles (LCAPNs), which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel (PTX) loaded lipid coated calcium phosphate nanoparticles (PTX-LCAPNs) were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line (Huh-7). The results suggested that the mean diameter of the spherical LCAPNs was 124.73±6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration (IC50) values of PTX compared with calcium phosphate nanoparticles loaded with PTX (PTX-CAPNs), demonstrating a stronger cancer cell lethality.
RESUMO
This study aims to synthesize new phospholipids, 1,3-dipalmaminophospholipid(Pad-PC-Pad), and prepare shear-stress sensitive liposomes(SSSL). 1H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching(ACQ)characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.
RESUMO
<p><b>BACKGROUND</b>Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease (KD). This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD.</p><p><b>METHODS</b>Lactobacillus casei cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally (i.p.) to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin (IVIG) treatment group was i.p. injected with IVIG (2 g/kg), while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 (high-resolution small animal ultrasound [Vevo770 pattern; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]) which were measured and analyzed with Vevo770 software.</p><p><b>RESULTS</b>Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group (0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ± 0.05 mm; 0.34 ± 0.04 mm) was significantly larger than those of IVIG treatment group (0.22 ± 0.02 mm; 0.28 ± 0.03 mm; 0.26 ± 0.03 mm; 0.27 ± 0.05 mm; 0.26 ± 0.03 mm; all P < 0.01) and the normal control group (0.21 ± 0.02 mm; 0.22 ± 0.03 mm; 0.22 ± 0.02 mm; 0.23 ± 0.02 mm; 0.27 ± 0.04 mm; all P< 0.01) on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac function among the groups on days 0, 7, 14, 28, and 56 (all P > 0.05).</p><p><b>CONCLUSIONS</b>Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.</p>
RESUMO
Plate assay and spore germination method were used to study the chemotaxis response of Alternaria panax to arginine, glutamic acid, aspartic acid and threonine. The result showed that the optimum temperature of A. panax chemotaxis response to four amino acids were all 25 ℃. And chemotaxis responses of A. panax were different under conditions of different concentration and pH value. The chemotaxin reached to the highest under the condition of 2 mg•L⁻¹ and pH value was 7 for arginine, glutamic acid and threonine while 20 mg•L⁻¹ and pH value was 6 for aspartic acid . The data of chemotactic migration index (CMI) were 1.24, 1.38, 1.27, 1.31 and chemotactic growth rates(CGR) were 0.451 0, 0.353 0, 0.381 3, 0.228 8 and spores germination rates(SGR) were 57.33%,63%,56.67%,58% and the dry weight of mycelial (DWM) were 372.9, 348.5, 314.4, 390.2 mg•L⁻¹ respectively. It indicated that the low and middle concentration of amino acid had significant promoting effect on chemotaxis response of A. panax. As important substances generated in ginseng root, amino acids exhibited an efficient chemotactic effect on A. panax, and some even show inhibition effect under high concentration.
RESUMO
<p><b>OBJECTIVE</b>To investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Through retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years.</p><p><b>RESULTS</b>There was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×10/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×10/L(P<0.05) and 91.5×10/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05).</p><p><b>CONCLUSION</b>The highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.</p>
RESUMO
Based on the typical characteristics of existing incentive and regulation in the pharmaceutical industry in China,the innovation incentive policy of the pharmaceutical industry can be divided into two types:incentive policy,and regulatory policy.This paper reviewed the research progress on the influence of price regulation policy,health insurance payment policy,centralized procurement regulation and incentive policy on the innovation of pharmaceutical industry.The present paper puts also forward the future research direction.Based on the literature review,it has been found that the futnre researches in this field should be based on the management practice situation in China,and make a breakthrough from the following three aspects-asymmetric information,comprehensive action mechanism from variable policy instruments,and introduction of new research paradigm.This research provides a theoretical reference for the research and decision-making of the innovation incentive policy in the pharmaceutical industry.
RESUMO
Based on the typical characteristics of existing incentive and regulation in the pharmaceutical industry in China,the innovation incentive policy of the pharmaceutical industry can be divided into two types:incentive policy,and regulatory policy.This paper reviewed the research progress on the influence of price regulation policy,health insurance payment policy,centralized procurement regulation and incentive policy on the innovation of pharmaceutical industry.The present paper puts also forward the future research direction.Based on the literature review,it has been found that the futnre researches in this field should be based on the management practice situation in China,and make a breakthrough from the following three aspects-asymmetric information,comprehensive action mechanism from variable policy instruments,and introduction of new research paradigm.This research provides a theoretical reference for the research and decision-making of the innovation incentive policy in the pharmaceutical industry.
RESUMO
Objective To investigate the clinical effect of sitagliptin combined with metformin in the treatment of sulfonylurea-deficient elderly patients with diabetes mellitus.Methods Sixty patients with diabetes mellitus were enrolled in our hospital from January 2013 to December 2016.The patients were divided into observation group(30 cases) and control group(30 cases) according to the random number method.The patients in the observation group were treated with sitagliptin and metformin.The patients in the control group were treated with gemcitabine, and the clinical treatment effect, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, fasting C peptide and postprandial 2hC peptide Level of statistical comparison.Results The clinical effect of the observation group was significantly higher than that of the control group.Before and after treatment, the fasting blood glucose, 2h postprandial blood glucose, glycosylated hemoglobin, fasting C peptide and postprandial 2hC peptide level were not significantly different After fasting blood glucose, 2h postprandial blood glucose and glycosylated hemoglobin levels were significantly lower than before treatment, after treatment of fasting C peptide and postprandial 2hC peptide levels were significantly higher than before treatment.Conclusion The clinical efficacy of serotretine combined with metformin in the treatment of elderly patients with diabetes mellitus is similar to that of Yuxing, and the combination is more convenient and more suitable for clinical treatment.It is worthy to be popularized and applied in clinical practice.
RESUMO
Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
Assuntos
Animais , Humanos , Camundongos , Linhagem Celular , Colistina , Farmacologia , Toxicidade , Escherichia coli , Infecções por Escherichia coli , Tratamento Farmacológico , Rim , Biologia Celular , Polietilenoglicóis , QuímicaRESUMO
The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.