Drug Repurposing of Clinically Approved Drugs to Target Epithelial-mesenchymal Transition Using Molecular Docking Approach

@#Introduction: Epithelial-mesenchymal transition (EMT) is a process of epithelial transformation into mesenchymal cells. It is also a process that contributes to the progression of fibrosis and cancer metastasis. Transforming growth factor-beta (TGF-β), as a potent inducer of EMT, has therefore became a potential therapeutic target. However, clinical developments of TGF-β inhibitors have been un-successful due to safety risks. Hence, drug repurposing of existing safe-to-use drugs could over-come this issue. Methods: In this study, the TGF-β receptor type 1 (ALK5) was selected as the target protein. Molecular docking was performed using known ALK5 inhibitors as positive controls. Clinical drugs with similar binding affinity and amino acid interaction were selected for in vitro experimental validation. Results: ALK5 inhibitor demonstrated binding affinities ranging from -11.2 to -9.5 kcal/mol. Analysis of amino acid interaction revealed that Val219, Ala230, Lys232, and Leu340 amino acid residues are crucial for binding. Subsequent screening of clinically approved drugs against ALK5 showed top five potential drugs (ergotamine, telmisartan, saquinavir, indinavir, and nelfinavir). The selected drugs were tested in TGF-β1-induced normal human bronchial epithelial cell line, BEAS-2B. Western blot analysis showed that the drugs did not exhibit inhibitory effects on the downregulation of epithelial proteins (E-cadherin) and upregulation of mesenchymal proteins (vimentin and α-smooth muscle actin). Conclusion: Based on these experimental outcome, it is postulated that the results from molecular docking were false positives. The tested drugs in this study could serve as negative controls in future screening against ALK5 protein.

Therapeutic mechanism of emodin for treatment of rheumatoid arthritis: a network pharmacology-based analysis / 南方医科大学学报

OBJECTIVE@#To investigate the therapeutic mechanism of emodin in the treatment of rheumatoid arthritis (RA) using a network pharmacology-based method and validate this mechanism in a fibroblast-like synovial cell line.@*METHODS@#The PubChem, Targetnet, SwissTargetPrediction, Genecards, OMIM, and DisGeNET databases were searched to obtain emodin targets and RA-related genes. A protein-protein interaction (PPI) network was constructed, and GO and KEGG pathway enrichment analyses were carried out to analyze the intersection genes. AutoDock4.2.6 software was used to simulate molecular docking between emodin and its candidate targets. In a cultured fibroblast-like synovial cell line (MH7A), the effects of different concentrations of emodin on proliferation of tumor necrosis factor-α (TNF-α)-induced cells were investigated using CCK-8 assay, cell scratch experiment and flow cytometry; the changes in the expressions of nuclear factor-κB (NF-κB) pathway proteins were detected using Western blotting, and the mRNA expressions of the hub genes were examined with RT-qPCR.@*RESULTS@#We identified 32 intersection genes of emodin and RA, and the key targets including CAPS3, ESR1, and MAPK14 involved mainly the NF-κB signaling pathway. Cell scratch experiment and flow cytometry demonstrated a strong inhibitory effect of emodin on MH7A cell proliferation. Treatment with TNF-α significantly increased the cellular expressions of the NF-κB pathway proteins, which were obviously lowered by treatment with 80 μmol/L emodin. The results of RT-qPCR showed that TNF-α treatment obviously up-regulated the expressions of the hub genes COX2 and P38MAPK, and emodin treatment significantly down-regulated the expressions of MAPK and PTGS2 and up-regulated the expression of CASP3.@*CONCLUSION@#The therapeutic effect of emodin on RA is mediated mainly through regulation of cell proliferation, apoptosis, and the NF-κB pathway.

Estimating the basic reproduction number of COVID-19 in Wuhan, China / 中华流行病学杂志

Objective@#The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number (R0) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention.@*Method@#The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R0.@*Result@#Among the four methods, the EG method fitted the data best. The estimated R0 was 3.49 (95% CI: 3.42-3.58) by using EG method. The R0 was estimated to be 2.95 (95%CI: 2.86-3.03) after taking control measures.@*Conclusion@#In the early stage of the epidemic, it is appropriate to estimate R0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.

Estimating the basic reproduction number of COVID-19 in Wuhan, China / 中华流行病学杂志

Objective The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number ( R 0 ) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R 0 . Result Among the four methods, the EG method fitted the data best. The estimated R 0 was 3.49 (95% CI : 3.42-3.58) by using EG method. The R 0 was estimated to be 2.95 (95% CI : 2.86-3.03) after taking control measures. Conclusion In the early stage of the epidemic, it is appropriate to estimate R 0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.

Prevention effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou: a dynamic model of infectious disease / 中华流行病学杂志

Objective@#To evaluate the effect of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou, during 2010-2017, using a dynamic compartmental model.@*Methods@#A dynamic compartmental model was developed to describe the HIV situation among MSM in Guangzhou. This model was parameterized on data from published literature or surveillance programs from the Guangzhou CDC. The Matlab 7.0 software was used for coding and analysis on collected data. HIV prevalence was analyzed among MSM under the status quo data and estimated the impact by the "Internet Plus" AIDS prevention services project.@*Results@#HIV prevalence would have increased to 22.75% in 2017, and the total number of new HIV infections would have been 11 038, from 2010 to 2017, using the data status quo. Under the Guangzhou "Internet Plus" AIDS prevention services project, the prevalence of HIV among MSM from 2010 to 2017 was estimated to be 8.44%, 9.68%, 10.65%, 11.34%, 11.73%, 11.83%, 11.71% and 11.43% in Guangzhou, which were similar to the surveillance data. The total number of new infections in the past 8 years under the "Internet Plus" scenario was estimated to be 4 009. The "Internet Plus" program would have prevented 7 029 (63.68%) new infections during 2010-2017 as compared to the number, status quo.@*Conclusions@#The fitting result of dynamic compartmental model seemed more reasonable, which was applicable to predict HIV epidemic among MSM in Guangzhou, suggesting that the increase of HIV prevalence had been curbed since the "Internet Plus" project which was launched in 2010, and the "Interner Plus-based AIDS Comprehensive Prevention Service System" had achieved the purpose as planned, epidemiologically.

Evaluation of root-knot nematode disease control and plant growth promotion potential of biofertilizer Ning shield on Trichosanthes kirilowii in the field

Abstract Biofertilizer Ning shield was composed of different strains of plant growth promotion bacteria. In this study, the plant growth promotion and root-knot nematode disease control potential on Trichosanthes kirilowii in the field were evaluated. The application of Ning shield significantly reduced the diseases severity caused by Meloidogyne incognita, the biocontrol efficacy could reached up to 51.08%. Ning shield could also promote the growth of T. kirilowii in the field by increasing seedling emergence, height and the root weight. The results showed that the Ning shield could enhance the production yield up to 36.26%. Ning shield could also promote the plant growth by increasing the contents of available nitrogen, phosphorus, potassium and organic matter, and increasing the contents of leaf chlorophyll and carotenoid pigment. Moreover, Ning shield could efficiently enhance the medicinal compositions of Trichosanthes, referring to the polysaccharides and trichosanthin. Therefore, Ning shield is a promising biofertilizer, which can offer beneficial effects to T. kirilowii growers, including the plant growth promotion, the biological control of root-knot disease and enhancement of the yield and the medicinal quality.

Impact of the 90-90-90 goal and pre-exposure prophylaxis on HIV transmission and elimination in men who have sex with men in China: A mathematical modeling study / 中华流行病学杂志

Objective To establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037.Methods A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China.The model was parameterized using data from the literature available.We used MATLAB 7.0 software for data simulation and graphics rendering.We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM.Results Under the current policy,the number of new HIV infections would reach 770 000,the infection rate would reach 11.1％ and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years.Under the 90％-90％-90％ goal,440 000 new infections (57.7％) would be reduced,the HIV infection rate would decline to 5.7％ and the incidence rate would decline to 0.24/100 person years in the next 20 years,but it is still unlikely to achieve the goal of HIV elimination.With 100％ PrEP compliance,the required PrEP coverage rates for achieving HIV elimination in the next 10,15 and 20 years would be 65％,32％ and 19％,respectively.Conclusion It is necessary to strengthen the comprehensive intervention in MSM,continue to expand HIV testing and treatment,and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.

Impact of the 90-90-90 goal and pre-exposure prophylaxis on HIV transmission and elimination in men who have sex with men in China: A mathematical modeling study / 中华流行病学杂志

Objective To establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037.Methods A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China.The model was parameterized using data from the literature available.We used MATLAB 7.0 software for data simulation and graphics rendering.We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM.Results Under the current policy,the number of new HIV infections would reach 770 000,the infection rate would reach 11.1％ and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years.Under the 90％-90％-90％ goal,440 000 new infections (57.7％) would be reduced,the HIV infection rate would decline to 5.7％ and the incidence rate would decline to 0.24/100 person years in the next 20 years,but it is still unlikely to achieve the goal of HIV elimination.With 100％ PrEP compliance,the required PrEP coverage rates for achieving HIV elimination in the next 10,15 and 20 years would be 65％,32％ and 19％,respectively.Conclusion It is necessary to strengthen the comprehensive intervention in MSM,continue to expand HIV testing and treatment,and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.

The clinical significance of transcranial Doppler flow grade for patients with acute cerebral infarction combined with H type hypertension / 中国医学装备

Objective: To explore the clinical significance of transcranial Doppler flow grades for patients with acute cerebral infarction combined with H type hypertension. Methods: 92 patients with acute cerebral infarction combined with H type hypertension were divided into observation group, and 78 patients with acute cerebral infarction were divided into control group during the same period. The differences of the two groups were compared and researched. The correlation between transcranial Doppler flow grade of acute cerebral infarction combined with H type hypertension and the score of NIHSS was compared and analyzed. Results: As the results of transcranial Doppler flow grades, the ratio of the patients in 0 grade was 10.87% in observation group, and it was significantly higher than that of control group (1.28%) (x2=4.925, P<0.05). The ratio of the patients in 5 grade was 6.52% in observation group, and it was significantly lower than that of control group (21.79%) (x2=8.417, P<0.05). The blood flow velocities of systole and diastole of observation group were significantly lower than that of control group (t=3.645, t=5.251, P<0.05), respectively. The cerebral infarct size of observation group was significantly larger than that of control (t=4.405, P<0.05). The score of NIHSS of observation group was significantly higher than that of control group (t=2.688, P<0.05). The results of Pearson linear correlation analysis indicated that there was a significantly negative correlation between transcranial Doppler flow grades and NIHSS (r=-0.284, P<0.05). Conclusion: The transcranial Doppler flow grades can identify the order of severity for patients with acute cerebral infarction combined with H type hypertension.

Protection of Batroxobin Injection on super acute stage of thromboembolic cerebral stroke in rats / 药物评价研究

Objective To observe the effects of Batroxobin Injection on thromboembolic cerebral stroke by magnetic resonance imaging (MRI) and TTC staining.Methods Rat model ofthromboembolic stroke was prepared after the left middle cerebral artery was occluded by autologous blood clots,and 32 rats with successful operation were divided into four groups according to the degree of neurological deficit:model group,Batroxobin Injection low and high dose (0.3,1.0 BU/kg) group,and rt-PA (9 mg/kg) group,with eight rats in each group,and other eight rats in Sham group.Rats were administered 1 h after modeling by tail iv method.At 6 h after administration,neurological deficit score and MRIincluding SE-T2WI and DWI sequence scanning were measured.At 24 h after administration,the brain was cut for TTC staining to measure the infarct area,and blood FIB was measured.Results Compared with model group,Batroxobin Injection 0.3 BU/kg treatment for 24 h (P ＜ 0.05),1 BU/kg treatment for 6 and 24 h (P ＜ 0.05,0.01) could significntly improve the neurological function scores of rats.MRIresults showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the lesion range (P ＜ 0.05 and 0.01).Results of TTC stain showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the infarct size (P ＜ 0.05).Batroxobin Injection at doses of 0.3 and 1 BU/kg can significantly lower plasma FIB concentration (P ＜ 0.05,0.01,0.001) 6 and 24 h after administration.Conclusion Batroxobin Injection can improve the damaged neural function,reduce scope of lesions,decrease plasma fibrinogen,with protective effects for cerebral ischemia in rats.

Protection of Batroxobin Injection on super acute stage of thromboembolic cerebral stroke in rats / 药物评价研究

Objective To observe the effects of Batroxobin Injection on thromboembolic cerebral stroke by magnetic resonance imaging (MRI) and TTC staining.Methods Rat model ofthromboembolic stroke was prepared after the left middle cerebral artery was occluded by autologous blood clots,and 32 rats with successful operation were divided into four groups according to the degree of neurological deficit:model group,Batroxobin Injection low and high dose (0.3,1.0 BU/kg) group,and rt-PA (9 mg/kg) group,with eight rats in each group,and other eight rats in Sham group.Rats were administered 1 h after modeling by tail iv method.At 6 h after administration,neurological deficit score and MRIincluding SE-T2WI and DWI sequence scanning were measured.At 24 h after administration,the brain was cut for TTC staining to measure the infarct area,and blood FIB was measured.Results Compared with model group,Batroxobin Injection 0.3 BU/kg treatment for 24 h (P ＜ 0.05),1 BU/kg treatment for 6 and 24 h (P ＜ 0.05,0.01) could significntly improve the neurological function scores of rats.MRIresults showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the lesion range (P ＜ 0.05 and 0.01).Results of TTC stain showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the infarct size (P ＜ 0.05).Batroxobin Injection at doses of 0.3 and 1 BU/kg can significantly lower plasma FIB concentration (P ＜ 0.05,0.01,0.001) 6 and 24 h after administration.Conclusion Batroxobin Injection can improve the damaged neural function,reduce scope of lesions,decrease plasma fibrinogen,with protective effects for cerebral ischemia in rats.

Metallothinein 1E Enhances Glioma Invasion through Modulation Matrix Metalloproteinases-2 and 9 in U87MG Mouse Brain Tumor Model

Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.

Progress in anti-cancer research of American ginseng: with an example of colorectal cancer / 药学学报

Cancer is a group of various diseases, all of which involve unregulated cell growth. Many currently used chemotherapeutic drugs are derived from botanicals. Thus, searching botanical sources for novel oncology medications, including identifying the lead compounds and their derivatives for chemoprevention, is an essential step in advancing cancer therapeutics. This article mainly focuses on the data from our previous American ginseng anti-colon cancer studies. In addition to the potential role of American ginseng on cancer, the herb as an adjuvant for cancer treatment is presented, including describing the attenuation of adverse events induced by chemotherapeutic agents and increasing of quality of cancer patient life. Since heat-treated American ginseng and ginsenoside gut microbiome metabolites showed significant increases in cancer chemopreventive effects, active constituents of the steamed herb and their gut metabolites should be clearly identified, and the structure-activity relationship should be further explored. Data obtained from herbal medicine studies and clinical trials will help develop useful anticancer agents.

Effects of Xiongshao Decoction on immune liver fibrosis in rats / 中草药

Objective To research the effects of Xiongshao Decoction (XSD) on immune liver fibrosis in rats. Methods Eighty-four SD rats were randomly divided into normal control group, model group, Fuzheng Huayu (FZHY) Capsule group, XSD prevention group, XSD high-dose and low-dose groups (15.8 and 7.9 g/kg). The hepatic fibrosis model was induced by injecting porcine serum to the abdominal cavity of rats. To observe the effects of XSD on the serum hepatic function of rats: ALT, AST, ALB, and AJG, the serum marker of hepatic fibrosis: hyaluronic acid (HA), laminin (LN), procollagen III (PCIII), and collogen IV (CIV), and hepatic tissue pathomorphology as well. Results Compared with the model group, the levels of ALT, AST, HA, LN, and PCIII in every XSD treatment group were obviously decreased (P<0.05, 0.01), the levels of ALB and A/G were obviously increased (PO.01). The CIV level of serum in XSD prevention group was significantly decreased (P<0.05) and the degrees of hepatocyte degeneration and necrosis in all treatment groups were lower, with less liver fibrosis, especially those in XSD prevention group and high-dose group. Conclusion XSD could not only relieve the degree of liver cells damage of immune hepatic fibrosis in rats, improve hepatic function of them, and regulate the extracellular matrix metabolism, but also arrest the hepatic fibrosis or make it reversed.

Effect of different concentrations of bortezomib on the expression of ERK, JNK and P38 in daunorubicin-resistant K562 cells / 中国实验血液学杂志

The aim of this study was to investigate the effect of proteasome inhibitor bortezomib on the expression of ERK, JNK, and P38 in daunorubicin (DNR)-resistant K562 cells and its mechanism. MTT method was used to determine the drug-resistant K562 cells and the cellular toxicity of bortezomib; Western blot was used to detect the expression of protein ERK, JNK and P38 in K562 cells after treatment with 100 nmol/L DNR alone or combined with 1 nmol/L and 10 nmol/L bortezomib for 36 hours. Flow cytometry assay was used to detect the apoptosis rate in each group cells. The results indicated that the expression of ERK and P38 were significantly suppressed (p < 0.05) and the expression of JNK was significantly enhanced (p < 0.05) in the cells treated by DNR combined with bortezomib. It is concluded that bortezomib can decrease the expressions of protein ERK and P38 and enhance the expression of JNK, the bortezomib reverses the cellular drug-resistance and promote cell apoptosis through MAPK pathway.

Efficacy, side effects and blood concentration monitoring of high-dose methotrexate in treatment of 180 children with acute lymphoblastic leukemia / 中国实验血液学杂志

This study was purposed to investigate the effects of high-dose methotrexate (HD-MTX)-CF + VDT protocol on pediatric acute lymphoblastic leukemia (ALL) by means of retrospective analysis. MTX plasma concentration was dynamically detected and evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the time and dosage of calcium folinate (CF) or carry out the plasma exchange as occasion requires. Totally 180 cases of ALL were enrolled in this study, and received 380 administration of HD-MTX-CF + VDT protocol, including 122 patients with induction therapy as well as 58 cases during maintenance therapy, among which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as high risk. 2.0 g/m(2) MTX, 3.0 g/m(2) MTX, and 5.0 g/m(2) MTX were individually used according to low risk, middle risk or T immunohistochemical expression. The results indicated that 36.3% cases showed the side-effects of HD-MTX including mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal damage, fever, myelosuppression, cardiotoxicity, infection and allergic response. All of these side effects were reversible through treatment. The elimination delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration > 10 µmol/L at 24 hours, 50 cases > 1.0 µmol/L at 44 hours, the remaining 57 cases > 0.1 µmol/L at 68 hours. CF dosage was adjusted according to the concentration of MTX until it was less than 0.1 µmol/L. 1 case had renal interstitial inflammation and acute renal failure, but finally he was cured. No patients received plasma exchange or died. It is concluded that the extramedullary leukemia control protocol, in which MTX is main drug, is effective therapy for obtaining long-term remission and event-free survival rate in ALL patients, but the side effects and risks increase along with the increase of MTX dose. The metabolic level of HD-MTX has found to be obvious individual, so the dynamic monitoring of MTX concentration in plasma and administration of proper dosage of CF are important factors for HD-MTX protocol application in ALL patients.

Alleviating effects of dehydration under no hyperthermia on the immunomodulatory response to the polysaccharide fraction from fu-ling (Poria cocos) in male collegiate wrestlers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is well known that dehydration can impair bodily functions. To evaluate the impact of hydration status under ambient environmental temperature on the immune system, 25 male collegiate wrestlers were recruited to undergo an experimental dehydration program.</p><p><b>METHODS</b>Thirteen subjects had controlled diets with individual energy requirements to prevent body mass loss and restricted water intake to cause 4.52% dehydration; they formed the dehydrated group (DE). These subjects developed a urine specific gravity of about 1.030 in 84 hours. Twelve other subjects had no water restriction and maintained their total body weight comprised the euhydrated group (EU). Peripheral blood monocytes (PBMNC) were isolated after dehydration to perform immune response testing by being incubated with a polysaccharide fraction from fu-ling, Poria cocos (polysaccharide fraction from Poria cocos, PCPS, 1 - 30 £g/L), to prepare a conditioned medium termed conditioned medium of PBMNC stimulated by PCPS (PCPS-MNC-CM). More PCPS (25 µg/L) was needed in the DE group to prepare the PCPS-MNC-CM, which was assayed with a growth inhibitory curve for treated U973 cells.</p><p><b>RESULTS</b>The treated U937 cells, incubated together with PCPS-MNC-CM from the DE group, exhibited a much lower nitroblue tetrazolium (NBT) positive value of (63.7 ± 4.7)%. The concentration of interferon-gamma (IFN-γ), interleukin (IL)-1β and tumor necrosis factor (TNF)-α in PCPS-MNC-CM from subjects after dehydration was much lower than in the CM from the EU group.</p><p><b>CONCLUSION</b>The immune response to PCPS in the DE group was lower than in normally hydrated subjects.</p>

Side effects of L-asparaginase during therapies for remission induction and maintenance in children with acute lymphocytic leukemia / 中国实验血液学杂志

This study was purposed to investigate the possible side effects of L-asparaginase (L-ASP) in the treatment of patients with acute lymphoblastic leukemia (ALL) and to explore the correlation of these side effects at different therapeutic stages by means of retrospective analysis, so as to reduce the incidence of side effects and improve the safety of chemotherapy and the long-term survival of patients. The probability and severity of side effects related to use of L-ASP in 38 cases of ALL during remission induction therapy (VDLDex regimen) and 40 cases of ALL during maintenance intensive therapy (VMLDex regimen) were compared. The results showed that allergic response, diabetes and drug-induced liver disease happened more frequently during maintenance therapy than during remission induction therapy, while defibrination, abnormal hemagglutinin, acute pancreatitis, hypoproteinemia, gastrointestinal reaction and infectious shock were observed more during remission induction therapy than those at maintenance therapy. In conclusion, the L-ASP showed some side effects especially for the patients during the remission induction therapy which should be paid enough attention. The regular and comprehensive monitoring can effectively reduce and avoid the side effects of L-ASP, to improve the safety of chemotherapy.

Effects of processing and extracting methods on active components in Radix Scutellariae by HPLC analysis / 中国中药杂志

<p><b>OBJECTIVE</b>To compare and analyze the effects of the contents of the active components in Radix Scutellariae by different processing and extracting methods.</p><p><b>METHOD</b>The raw and processed Radix Scutellariae were used, and the concentration of baicalin, wogonoside, baicalein, wogonin were determined by HPLC after five extracting techniques. HPLC method was performed on methanol-acetonitrile-water-acetic acid (18: 25: 57: 0.2) as the mobile phase at 30 C; The chromatographic column was Agilent Zorbax Extend-C18 (4.6 mm x 250 mm, 5 microm); The flow rate was 0.8 mL min(-1), and the detection wavelength was 275 nm.</p><p><b>RESULT</b>the ratios of baicalein and wogonin in raw material were 5.41%, 1.30% respectively by enzymatic extraction, which is higher than other extracting methods by raw material; The ratios of baicalin and wogonoside in raw material were 10.11% and 3.55% by ethanol of 60%, which is higher than other extracting methods; Different extracting methods have no evident effects on processed materials, enzymatic extraction is the best. The ratio of baicalin, wogonoside and baicalein, wogonin is 10.63%, 3.60% and 1.54%, 0.59%.</p><p><b>CONCLUSION</b>Different methods have evident extracting effects on the four active components with raw material, but have no evident effects with processed material. According to different active components most suitable extracting method should be adopted.</p>

Factors associated with retention in a community-based methadone maintenance treatment among drug users in Urumqi, Xinjiang Uigur Autonomous Region / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the factors associated with retention in a community-based methadone maintenance treatment(MMT) among drug users in Urumqi.</p><p><b>METHODS</b>With national MMT guideline( drift) for heroine addicted drug users, local heroine-dependent people were admitted to community-based MMT program affiliated to Xinjiang Uigur Autonomous Region Center for Mental Health. Data on outpatients' social-demo characteristics, baseline behaviors on drug use and daily stabilized dose of drugs were entered to MMT database.</p><p><b>RESULTS</b>Up to 10, Feb. , 2006,353 persons withdrew MMT treatment among 709 heroin dependant drug users. Between 11, Aug., 2005 and 10, Feb., 2006, with median duration as 77 days, cumulative drop-out rate of 90 days and 180 days after first dose of MMT were 73.8% among 455 and 99.4% among 355 drug users, respectively. The incidence of drop-outs was 29.8 per 100 person-month. The median length of stay (days) in MMT was 68.0 (95% CI: 59.0- 78.0). Correlates of retention were found as: Being Uigur(HR = 1.35;95% CI :1.09-1.67), duration of drug use (HR =0.74; 95% CI:0.55-0.99) and stabilized dose(HR = 0.60;95% CI: 0.48-0.74) was found in multiple Cox proportional hazard regression model.</p><p><b>CONCLUSION</b>Retention of MMT among drug users in Urumqi was low. Uigur people should be given individual counseling to help them increase the compliance rate. Within the ranges of clinic dosage, adjustment of the methadone dose on an individual base might serve as an appropriate approach to increase the effectiveness of the program.</p>