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Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.
Subject(s)
Humans , Female , Germ-Line Mutation , Core Binding Factor Alpha 2 Subunit/genetics , Pedigree , Blood Platelet Disorders/complications , Leukemia, Myeloid, Acute/geneticsABSTRACT
This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.
Subject(s)
Animals , Mice , Biological Products , Chromatography, High Pressure Liquid , Coleoptera , Cyclooxygenase 2 , Diarrhea/drug therapy , Antineoplastic AgentsABSTRACT
OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Retrospective Studies , Leukemia/pathology , Hematopoietic Stem Cell Transplantation , Prognosis , Myeloproliferative Disorders , Skin Neoplasms/pathology , Acute Disease , Dendritic CellsABSTRACT
Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.
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OBJECTIVE@#To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed.@*RESULTS@#Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×108/kg, and CD34+ cell count was (3.57-4.65)×106/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS).@*CONCLUSIONS@#BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.
Subject(s)
Female , Humans , Male , Adult , Middle Aged , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Acute Disease , Graft vs Host Disease/prevention & control , Myeloproliferative Disorders , Leukemia, Myeloid, Acute/pathology , Dendritic CellsABSTRACT
ObjectiveTo observe the clinical effect of Mahuang Xixin Fuzitang combined with acupuncture and moxibustion in the treatment of localized scleroderma. MethodA total of 95 patients with localized scleroderma treated in Wuhan No. 1 Hospital from September 2019 to October 2021 were assigned into a control group (47 patients) and an observation group (48 patients) by random number table method. The control group was treated with Centella triterpenes tablets and heparin sodium cream, and the observation group was additionally treated with Mahuang Xixin Fuzitang combined with acupuncture and moxibustion. Both groups were treated for 8 weeks, and the clinical effect was compared between groups. The traditional Chinese medicine(TCM) syndrome score (local skin sclerosis, loss of skin texture, darkening of skin pigment, scaly dry skin, etc.), serum levels of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-alpha (TNF-α), erythrocyte sedimentation rate (ESR), and eosinophil count (EO) were compared between before and after treatment as well as between groups. Additionally, the adverse reactions were recorded. ResultThe observation group had higher total effective rate than the control group [95.83% (46/48) vs. 82.98% (39/47), χ2=4.166 4, P<0.05]. Before treatment, the TCM syndrome score, sIL-2R, TNF-α, ESR, and EO showed no significant differences between the two groups. The 8 weeks of treatment improved the TCM syndrome score, sIL-2R, TNF-α, ESR, and EO. Moreover, the observation group was superior to the control group in these indicators (P<0.05). During the treatment, the observation group showed 1 case of abnormal liver function and 1 case of nausea and vomiting, and the control group had 1 case of nausea and vomiting, 1 case of abnormal renal function, and 1 case of abnormal liver function. The total adverse reactions of the observation group (4.17%) and the control group (6.38%) had no significant difference (χ2=0.233 9, P=0.062 86). ConclusionMahuang Xixin Fuzitang combined with acupuncture and moxibustion is safe and effective in the treatment of localized scleroderma.
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ObjectiveTo observe the clinical effect of Mahuang Xixin Fuzitang combined with acupuncture and moxibustion in the treatment of localized scleroderma. MethodA total of 95 patients with localized scleroderma treated in Wuhan No. 1 Hospital from September 2019 to October 2021 were assigned into a control group (47 patients) and an observation group (48 patients) by random number table method. The control group was treated with Centella triterpenes tablets and heparin sodium cream, and the observation group was additionally treated with Mahuang Xixin Fuzitang combined with acupuncture and moxibustion. Both groups were treated for 8 weeks, and the clinical effect was compared between groups. The traditional Chinese medicine(TCM) syndrome score (local skin sclerosis, loss of skin texture, darkening of skin pigment, scaly dry skin, etc.), serum levels of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-alpha (TNF-α), erythrocyte sedimentation rate (ESR), and eosinophil count (EO) were compared between before and after treatment as well as between groups. Additionally, the adverse reactions were recorded. ResultThe observation group had higher total effective rate than the control group [95.83% (46/48) vs. 82.98% (39/47), χ2=4.166 4, P<0.05]. Before treatment, the TCM syndrome score, sIL-2R, TNF-α, ESR, and EO showed no significant differences between the two groups. The 8 weeks of treatment improved the TCM syndrome score, sIL-2R, TNF-α, ESR, and EO. Moreover, the observation group was superior to the control group in these indicators (P<0.05). During the treatment, the observation group showed 1 case of abnormal liver function and 1 case of nausea and vomiting, and the control group had 1 case of nausea and vomiting, 1 case of abnormal renal function, and 1 case of abnormal liver function. The total adverse reactions of the observation group (4.17%) and the control group (6.38%) had no significant difference (χ2=0.233 9, P=0.062 86). ConclusionMahuang Xixin Fuzitang combined with acupuncture and moxibustion is safe and effective in the treatment of localized scleroderma.
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Objective To analyze the effect of HIV/AIDS patients receiving antiretroviral therapy (ART) for the first time in Jiangyin, and to provide a reference for further improvement of Jiangyin's AIDS antiretroviral treatment. Methods The historical cards and related information in the treatment management database of Jiangyin City's cases who received ART for the first time from 2005 to 2019 were collected and statistically analyzed. The changes in viral load and CD4+ T lymphocytes (CD4 cells) before and after treatment were compared. Results Among 652 patients receiving ART, 507 cases (77.76%) were successful in virological treatment. The median natural change rate of annual average CD4 cell count was 90.8 cells/μL/year (χ2=37.915, P2=10.713, P<0.05; H =10.394, P<0.05) and different baseline CD4 count layers. The results showed that age and baseline CD4 value were the influencing factors of treatment effect. Conclusion Age and baseline CD4 value can affect the effect of ART treatment. The older the age and the lower the baseline CD4 value, the worse the virological efficacy and the recovery effect of CD4 cells. It is suggested that the infected patients should be involved in ART in time, which is conducive to shorten the time of initial treatment and further improve the effect of antiviral treatment.
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Objective:To investigate the clinicopathological features, treatment programs and prognosis of patients with primary diffuse large B-cell lymphoma (DLBCL) in cavernous sinus.Methods:The clinical data of a patient with primary DLBCL in cavernous sinus who were admitted to Wuhan No.1 Hospital in December 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 63-year-old female who underwent resection of the cavernous sinus lesion, and the pathological diagnosis was DLBCL. The patient received 6 courses of R-CHOP regimen chemotherapy, lumbar puncture + intrathecal injection of chemotherapy drugs, and twice additional rituximab immunochemotherapy, and no tumor cells were found in the results of liquid-based thin layer cytology for cerebrospinal fluid exfoliated cells; twice magnetic resonance imaging (MRI) re-examination after the operation showed no recurrence and adjacent metastasis of the tumor. The patient's symptoms were significantly improved without residual neurological sequelae.Conclusions:Primary DLBCL in cavernous sinus is rare in clinical practice, early diagnosis is crucial for the prognosis of patients, and different protein expression may indicate the prognosis. Biopsy, complete resection of the tumor under the premise of preserving important anatomical structures and functions, and standardized chemotherapy combined with intrathecal injection local chemotherapy can effectively prolong the survival time of patients and improve the quality of life.
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OBJECTIVE@#To investigate the safety and efficacy of a new proteasome inhibitor Ixazomib followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of POEMS syndrome.@*METHODS@#The clinical manifestations, diagnosis and treatment process and follow-up results of 4 patients with POEMS syndrome who were treated with Ixazomib-based regimen combined with AHSCT in Wuhan No.1 Hospital from February 2018 to July 2020 were analyzed retrospectively. All patients were male, aged from 37-54 years old, with varying degrees of peripheral neuropathy, organ enlargement (liver, spleen or lymph nodes), circulatory overload (peripheral edema and/or pleural effusion), osteosclerosis, endocrine diseases (thyroid, gonads, etc.), skin changes (pigmentation, hemangioma, white nails, etc.), M protein, papilledema and other clinical manifestations and characteristics at the time of initial treatment. Two patients were pathologically diagnosed as hyaline vascular Castleman disease by lymph node biopsy. Three patients underwent lumbar puncture examinations and all showed elevated cerebrospinal fluid protein. All patients received at least 2 cycles of sequential AHSCT after induction chemotherapy based on ixazomib. The follow-up time was 10-28 months, and the median follow-up time was 16 months.@*RESULTS@#All cases survived. The complications were controllable during the treatment. Moreover, the clinical symptoms related to the disease were improved to a certain extent after the treatment. The levels of vascular endothelial growth factor (VEGF) showed a gradual decline.@*CONCLUSION@#Ixazomib combined with AHSCT is safe and effective in the treatment of POEMS syndrome.
Subject(s)
Adult , Humans , Male , Middle Aged , Boron Compounds , Glycine/analogs & derivatives , Hematopoietic Stem Cell Transplantation , POEMS Syndrome/therapy , Retrospective Studies , Transplantation, Autologous , Vascular Endothelial Growth Factor AABSTRACT
The pathogenesis of metabolic syndrome (MS) includes insulin resistance (IR), central obesity, chronic low-grade inflammation, oxidative stress, endoplasmic reticulum stress, elevated free fatty acid levels, intestinal flora imbalance, renin angiotensin system abnormality, and autophagy activity deficiency, etc. Most researchers believe that IR plays a central role in the pathogenesis of MS, and abdominal obesity is an important initial factor of MS. According to the incidence and clinical characteristics, MS is classified as "obesity" "pidan" " abdominal fullness " and other diseases. It is said that the pathogenesis of MS is related to the deficiency of spleen and kidney, the formation of phlegm, turbidity, blood stasis and other pathological products, which damage the body's functions of qi, blood, yin and yang. Traditional Chinese medicine (TCM) has unique advantages in treating MS based on the holistic view and syndrome differentiation concept. It has multi-level, multi-target and multi-channel treatment characteristics. It can intervene insulin signal transduction, regulate adipocyte factor secretion level, relieve oxidative stress and endoplasmic reticulum stress response, regulate intestinal flora and renin angiotensin system, reduce free fatty acid level and regulation Autophagy and other ways to improve chronic low-grade inflammation and IR status, and then comprehensive prevention and treatment of MS and its complications. However, the following problems still exist:lack of high-quality randomized controlled clinical research and large sample real-world research, clinical unified diagnosis and treatment standard has not yet formed, lack of genetic animal model in basic research, relatively single signal pathway and target of experimental research, and difficulty in timely formation of clinical transformation of scientific research achievements. Therefore, we should make full use of modern scientific and technological means to carry out systematic and standardized multicenter, large sample, high-quality randomized controlled trials or real-world research, we should prepare perfect animal models, focus on the crosstalk relationship between multiple related cell signaling pathways, and actively explore the potential relationship between signaling pathways and prescription compatibility, so as to actively promote basic scientific research achievements Clinical practice may be the key research direction in the prevention and treatment of MS in TCM.
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Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.
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@#Objective To analyze the correlation between the gray value of epicardial fat and the prognosis of patients with atrial fibrillation (AF) treated by thoracoscopic radiofrequency ablation. Methods The clinical data of 97 patients, including 75 males and 22 females with an average age of 57.8±9.4 years, who underwent thoracoscopic radiofrequency ablation in Fuwai Hospital from 2017 to 2018 were analyzed retrospectively. The left atrial fat volume and average gray scale were calculated by left atrial enhanced CT. According to the average gray scale of left atrial fat tissue, the patients were divided into three groups: a high gray scale group, a medium gray scale group and a low gray scale group. The patients were followed up at 3, 6 and 12 months after operation. The end point of follow-up was the recovery rate of sinus rhythm. Survival analysis was used to analyze the correlation between CT features of epicardial fat enhancement and prognosis. Results After adjustment of body mass index, body surface area, gender and left atrial end diastolic diameter, regression analysis showed that the fat gray of left atrial enhanced CT was correlated with the type of AF (OR=0.30, 95%CI 0.12-0.79, P=0.014). Cox regression analysis showed that the fat gray value of left atrial CT predicted the recurrence of AF after thoracoscopic radiofrequency ablation (OR=0.92, 95%CI 0.85-0.99). The Kaplan-Meier curve showed significant difference in the long-term recurrence rate of AF among the three groups (P=0.011). The lower left atrial fat enhanced CT gray scale was, the higher long-term recurrence rate of AF was. Conclusion The gray value of left atrial fat enhanced CT can effectively predict the recurrence of AF after radiofrequency ablation in thoracoscopic surgery.
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Phenylpropanoids are one of the major chemical constituents in Zanthoxylum species. They include simple phenylpropanoids, coumarins, and lignans and possess anti-tumor, anti-inflammatory, anti-platelet aggregation, anti-bacterial, anti-viral, insecticidal, and antifeedant activities. This review summarizes the chemical constituents and pharmacological activities from the Zanthoxylum plants in hopes of providing reference for the research and application of phenylpropanoids from this genus.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Coumarins/pharmacology , Lignans , Plant Extracts , ZanthoxylumABSTRACT
OBJECTIVE:To prepare Liguatrazine opthalmic liposome therm osensitive gel ,and to investigate its in vivo and in vitro characteristics. METHODS :The ammonium sulfate gradient method was used to prepare Liguatrazine liposomes. The preparation technology was optimized by using orthogonal test. Using poloxamer P 407 as gel matrix ,Liguatrazine liposomes were prepared into thermosensitive gel. A membraneless model was used to study the dissolution and in vitro drug release of the gel. The modified Franz diffusion cell was used to investigate corneal permeability and further determine corneal hydration value. The effects of the gel on the proliferation of human corneal epithelial cell HCE-T. HE staining and Draize test were used to investigate the stimulatory effects of the gel on corneal cells of the rabbit ,and the histological changes of the eyes were observed. RESULTS :The optimal preparation technology of Liguatrazine liposome was drug-lipid ratio of 1 ∶ 10(m/m),the ammonium sulfate concentration of 0.2 mol/L,phospholipid-cholesterol ratio of 4∶1(m/m),incubation temperature of 45 ℃. Then ligustrazine opthalmic liposome thermosensitive gel was prepared with 23% poloxamer P 407 as gel matrix. The gel had good gelatinization temperature. The in vitro drug release and dissolution showed zero-order kinetic characteristics ,and in vitro drug release of the gel was mainly related to dissolution (R2=0.993 4). The cumulative transcorneal permeability of the gel was 43.3% within 6 hours and corneal hydration value was 72.98%. Low and medium concentrations (1,5 mg/L)of Ligustrazine opthalmic liposome thermosensitive gel had no obvious proliferation toxicity to HCE-T cells ,but it showed cytotoxicity at high concentration (10 mg/L). The mean Draize eyeirritation score of the gel on rabbit cornea was within non-stimulation,and there was no abnormal change in rabbit (No.2018001) corneal histology. CONCLUSIONS : Prepared Ligustrazine opthalmic liposome thermosensitive gel has a suitable phase transition temperature ,good corneal permeability ,and low corneal irrit ation.
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Metabolic syndrome (MS) is a pathological condition characterized by central obesity, insulin resistance, hypertension, and hyperlipidemia. With the increase of poor dietary habits and lifestyles in modern society, especially the poor living habits of sedentariness and less movement, the prevalence of MS has increased year by year. According to relevant data, the number of MS patients worldwide will reach about 2.568 billion by 2040, which will seriously endanger human life and health. Huanglian Wendantang, as a famous traditional Chinese medicine prescription for clearing away heat and drying dampness, regulating Qi and resolving phlegm, and benefiting the stomach and gall, has been proved to have significant pharmacological effects in lowering blood fat, reducing blood sugar and resisting inflammation by modern pharmacological studies, and widely used in the treatment of metabolic diseases, cardiovascular diseases and other systemic diseases. In recent years, a large number of studies have proved that Huanglian Wendantang has a significant effect on MS. In terms of clinical efficacy, it could significantly improve the pathological state of obesity, dyslipidemia, abnormal glucose metabolism and hypertension in MS patients. Meanwhile, it could also interfere with the inflammatory state, prethrombotic state, abnormal vascular regulation and other potential risk factors in the body, with a high safety and fewer side effects. In terms of experimental study, it could enhance the insulin sensitivity, and improve the insulin resistance of MS animal models and cell models through interventions in insulin signal transduction, inflammatory response, and antioxidant stress. By retrieving PubMed, CNKI, Weipu, Wanfang and other databases, the author summarized the study reports of Huanglian Wendantang on MS in recent years in three aspects: theoretical study, clinical efficacy study and experimental mechanism study, in the expectation of provide some scientific references for in-depth study of the mechanism of Huanglian Wendantang in treating MS and the development and clinical promotion of the prescription.
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Objective To discuss the application of 3D laser scanner and computer technology in restoration of the accident scene and reconstruction of the accident process, as well as identification of the driver-passenger relationship. Methods The scene of a traffic accident, the accident vehicle and the vehicle of the same type as accident vehicle were scanned using 3D laser scanner. The accident scene, traces and accident vehicle were integrated using computer technology to restore the accident scene, and the accident process was reconstructed and analyzed by combining the characteristics of the body injuries. Results By restoring the accident scene and reconstructing the accident process with 3D laser scanner, it was determined that Wu was in the driving seat at the time of the accident. Conclusion It is more objective and scientific to use 3D laser scanning technology to restore the accident scene, reconstruct the accident process and analyze the moving track of the driver and passengers in the vehicle. It will help to improve the accuracy of forensic identification of road traffic accidents.
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Accidents, Traffic , Computer SimulationABSTRACT
OBJECTIVE: To prepare puerarin microemulsion with phase Ⅰ metabolic regulation (R-PR-ME) and to study pharmacokinetic characteristics of rats in vivo. METHODS: R-PR-ME and Puerarin microemulsion without metabolic regulation (NR-PR-ME) were prepared by Shah method. Pseudo-ternary phase diagram was used to optimize microemulsion formula using drug loading amount as index. The particle size and PDI of microemulsion were characterized by using a laser particle size analyzer. Rats were used as animal models, and HPLC method was used to determine the blood concentration of puerarin before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600 min after intragastric administration of R-PR-ME, NR-PR-ME and puerarin suspension (PR-SP) at puerarin dosage of 120 mg/kg. The pharmacokinetic parameters were calculated by using DAS 2.0 software. SPSS 19.0 software was used for statistical analysis. The relative bioavailability of R-PR-ME was calculated with NR-PR-ME as reference preparation. RESULTS: The formula of R-PR-ME included that oleoyl polyoxyl-6 glyserides (oil phase)-polysorbate 20 (emulsifier)-glycerides (co-emulsifier) mass ratio of 2 ∶ 4 ∶ 4; drug-loading amount of 67.50 mg/g, particle size was (22.59±0.53) nm (n=3) and PDI was 0.182±0.017 (n=3). The formula of NR-PR-ME included that soybean oil (oil phase)-polysorbate 80 (emulsifier)- glycerol (co-emulsifier) mass ratio of 1 ∶ 4.5 ∶ 4.5, drug-loading amount of 61.32 mg/g, particle size of (15.45±1.06) nm(n=3) and PDI of 0.156±0.012 (n=3). Pharmacokinetic parameters of R-PR-ME, NR-PR-ME and PR-SP included that AUC0-600 min were (134.187±37.152), (65.145±18.762) and (49.623±12.143) μg·min/mL; cmax were (1.316±0.306), (1.082±0.294) and (0.425±0.106) μg/mL; MRT were (155.068±33.204), (100.264±27.683), (60.524±14.086) min; t1/2β were (365.880±101.250), (283.280±80.940), (80.063±21.189) min (n=6), respectively. Compared with PR-SP, AUC0-600 min, cmax, MRT and t1/2β of R-PR-ME and NR-PR-ME were increased significantly (P<0.05 or P<0.01). Compared with NR-PR-ME, AUC0-600 min, MRT and t1/2β of R-PR-ME were more higher (P<0.05). The relative bioavailability of of R-PR-ME was 205.98%. CONCLUSIONS: R-PR-ME is prepared successfully with high drug-loading amount, and can significantly increase the bioavailability of puerarin in rats, compared with PR-SP and NR-PR-ME.
ABSTRACT
Based on the fact that glycyrrhizic acid can form micelles in aqueous solution and play a role in solubilization, the optimal compatibility ratio between puerarin and glycyrrhizic acid was screened to prepare puerarin-glycyrrhizic acid dispersible tablets and investigate the dissolution of puerarin. The particle size, Zate potential and puerarin dissolution were compared among the micellar solutions with mass ratio of 7∶1, 6∶1, 5∶1, 4∶1, 3∶1 and 2∶1(puerarin to glycyrrhizic acid), and it was found that when the mass ratio of puerarin and glycyrrhizic acid was 5∶1, the micelle showed smallest particle size, uniform distribution, and largest puerarin dissolution, so mass ratio of 5∶1 was determined as the optimal condition. The formulation of puerarin-glycyrrhizic acid dispersible tablets was optimized by single factor and orthogonal test: puerarin 100.0 mg, glycyrrhizin 20.0 mg, polyvinylpolypyrrolidone 24.0 mg as disintegrating agent, microcrystalline cellulose 135.0 mg as stuffing bulking agent, hydroxypropyl methyl cellulose 18.0 mg as adhesive agent, magnesium stearate 2.7 mg as lubricant, and tablet weight of 300.0 mg. High-performance liquid chromatography(HPLC) method was used to determine the content of puerarin in dispersible tablets. Puerarin showed a good linear relationship(r=0.999 8) in the range of 15.5-248 g·L~(-1), with high precision(RSD<2.0%) and good repeatability(RSD<2.0%), and the recovery rate was 101.1%, RSD 0.89%. There was no significant difference in the quantity of puerarin in different batches of puerarin-glycyrrhizic acid dispersible tablets. When the artificial gastric juice was used as the dissolution medium, the dissolution of puerarin in puerarin-glycyrrhizic acid dispersible tablets could reach over 85% within 15 min. When phosphate buffer(pH 6.8) was used as the dissolution medium, the dissolution of puerarin in the puerarin-glycyrrhizic acid dispersible tablets had a faster dissolution rate in vitro, 99.8% in 30 min. Therefore, puerarin-glycyrrhizic acid dispersible tablets could improve the dissolution of puerarin in vitro due to the solubilization effect of glycyrrhizic acid.
Subject(s)
Glycyrrhizic Acid , Chemistry , Isoflavones , Chemistry , Solubility , TabletsABSTRACT
OBJECTIVE@#To explore the effect of the expression regulation of mitotic control protein DIS3 on the proliferation ability of 3 cell Lines of human myeloma.@*METHODS@#Human myeloma cell lines NCI-h929, RPMI 8226 and U266B1 were selected as study objects, and the over-expression vector of DIS3 gene and DIS3-siRNA were designed and constructed, respectively. The cell experiments were divided into 5 groups: control, DIS3 over-expression-empty vector, DIS3-siRNA negative control, DIS3 over-expression and DIS3-siRNA group. After culture for 24 h, 48 h and 72 h, the proliferation capacity of these three cell lines was measured by MTT assay. And cell samples were collected after culture for 72 h, the expression of proliferation cell nuclear antigen (PCNA) was detected by RT-qPCR and Western blot.@*RESULTS@#MTT assay results showed that the proliferation capacity of cells in DIS3 over-expression group was significantly reduced, as compared with the DIS3 over-expression-empty vector group at the same time point (24, 48 or 72 h) (P<0.05, P<0.01). Compared with DIS3-siRNA negative control group at the same time point (24, 48 or 72 h), the proliferation capacity of cells in the DIS3-siRNA group significantly increased (P<0.05, P<0.01). The results of RT-qPCR and Western blot showed that the mRNA and protein expression levels of PCNA in cells of DIS3 over-expression group were significantly reduced, as compared with DIS3 over-expression empty vector group (P<0.01). Compared with the DIS3-siRNA negative control group, the mRNA and protein expression of PCNA in the cells of DIS3-siRNA group very significantly increased (P<0.01).@*CONCLUSION@#Over expression of DIS3 can significantly reduce the proliferation ability of 3 cell lines of human myeloma, which may be closely related with reducing PCNA expression.