Construction of a novel time-specific NLRP3 transgenic mouse model by Cre-LoxP system / 中国药理学通报

Aim To construct and identify a new time-specific NLRP3 point mutation transgenic mouse model by Cre-LoxP system. Methods Cre-LoxP system was used to generate NL-RP3

Establishment of animal model of Blau syndrome / 中国药理学通报

Aim To establish stable and reliable animal models of Blau syndrome (BS) in vivo. Methods C57BL/6J mice were intraperitoneally injected with muramyl dipeptide (MDP) or L18-MDP to induce systemic inflammatory model of BS. Meanwhile, positive drug etanercept (ETN) was set to investigate the response of the model to evaluate effectiveness. SD rats were intravitrealiy injected with MDP to establish BS-associated uveitis model. Serum levels of TNF-a, IL-6 and IL-8 were detected by enzyme linked immunosorbent assay (ELISA). Histopathologic al changes of rat eyeballs were detected by HE staining and the expressions of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in vitreous were determined by immunohistochem-istry (IHC) staining. Results The serum level of TNF-a in mice increased after intraperitoneal injection of MDP (P < 0.05), and increased significantly after L18-MDP injection (P < 0.01). Meanwhile, the levels of IL-6 and IL-8 were also markedly induced by L18-MDP (P < 0. 01, P < 0. 01). ETN treatment evidently inhibited the increased levels of these above cytokines induced by L18-MDP (P < 0. 05, P < 0. 01). After the intravitreous injection of MDP in SD rats, there were numerous inflammatory cells infiltrated in retina and vitreous, and the retina was seriously damaged. The staining levels of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in eyeball tissues were significantly enhanced. Conclusions The systemic animal model of BS can be successfully established by intraperitoneal injection of L18-MDP in C57BL/6J mice, and the good BS-relat-ed uveitis can be induced by intravitreous injection of MDP in SD rats, which provides the simple, convenient, repeatable and i-deal animal models for exploring the pathogenesis of BS and e-valuating the efficacy of drugs.

Research progress of NOD2-mediated signaling pathways and relationship with autoinflammatory diseases and its inhibitors / 药学学报

Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is a member of intracellular pattern recognition receptor. After being activated, it will induce the release of inflammatory factors through a series of signal cascade transduction, thus playing an important role in the innate immune response. The abnormal NOD2 signaling pathway is involved in the occurrence and development of many diseases, especially the single nucleotide polymorphisms (SNPs) of the NOD2 gene have been identified to be closely associated with autoinflammatory diseases (AIDs). Therefore, inhibitors targeting NOD2 pathway have great potential in the treatment of inflammatory immune diseases. This review presents the recent progress of NOD2 receptor-mediated signal transduction pathways and its regulation mechanisms, the relationship between NOD2 and AIDs, and the inhibitors of NOD2 pathway.

Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology / 中国中药杂志

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Current research status on pelvic autonomic nerve monitoring in rectal cancer surgery / 中华胃肠外科杂志

Rectal cancer is a common malignant tumor of the digestive tract, and surgery is the main treatment strategy. Disorders of bowel, anorectal and urogenital function remain common problems after total mesorectal resection (TME), which seriously decreases the quality of life of patients. Surgical nerve damage is one of the main causes of the complications, while TME with pelvic autonomic nerve preservation is an effective way to reduce the occurrence of adverse outcomes. Intraoperative nerve monitoring (IONM) is a promising method to assist the surgeon to identify and protect the pelvic autonomic nerves. Nevertheless, the monitoring methods and technical standards vary, and the clinical use of IONM is still limited. This review aims to summarize the researches on IONM in rectal and pelvic surgery. The electrical nerve stimulation technique and different methods of IONM in rectal cancer surgery are introduced. Also, the authors discuss the limitations of current researches, including methodological disunity and lack of equipment, then prospect the future direction in this field.

Outcomes in randomized controlled trials of acupuncture for vascular cognitive impairment during recent five years / 中国针灸

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.

Overview of systematic reviews of acupuncture for vascular cognitive impairment / 中国针灸

OBJECTIVE@#To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ).@*METHODS@#The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system.@*RESULTS@#A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy.@*CONCLUSION@#Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.

Effect of single hyperbaric oxygen treatment on attention networks in young migrants in Tibet / 生理学报

Many studies have shown that high-altitude exposure could significantly influence human cognition, and the approaches which could enhance the human cognition in high-altitude hypoxia environment attract great attention. In the present study, we recruited a total of 60 subjects who had been migrated to Tibet University as adults for more than one year. These participants were randomly divided into the experimental group and the control group. The participants in the experimental group were instructed to complete a hyperbaric oxygen treatment, and those in the control group just completed a wait condition. By using the attention network test (ANT), the changes of the attention function before and after a single session of hyperbaric oxygen treatment were explored. The results showed that single hyperbaric oxygen treatment significantly improved the orienting function of attention, with an obvious post-intervention effect, but not the alerting and conflict function of attention. We also found a strong association between alerting function and conflict function after the end of intervention, suggesting the change of the overall performance of attention function. The present findings might suggest that the improvement of attention function by a single session of hyperbaric oxygen intervention is derived from the increase of general cognitive resources, rather than the transfer of cognitive resources within the attention system.

A label-free and real-time method for evaluating cytotoxicity of CD19 CAR-T cells / 医学研究生学报

ObjectiveUsing Chromium-51 release assay, lactate dehydrogenase release assayand other methods to detect the cytotoxicity of CD19 CAR-T cells is cumbersome, with low repeatability and poor stability. This study aims to establish a label-free and real-time method for detectingspecific cytotoxicity of CD19 CAR-T cells.MethodsIn order to establish target cell models for cytotoxic assay of CD19 CAR-T cells by using Real Time Cellular Analysis (RTCA) system,the adherent human breast cancer cells were infected with lentiviral vectors encoding CD19. CD19 expression on the transduced cells was detected by flow cytometry. The cellsexpressing CD19 stably werethen sorted by fluorescence activated cell sorting (FACS).With such cells as target cells, CD19 CAR-T cells and BCMA CAR-T cells as effector cells, RTCAsystem was used to evaluate the cytotoxicity of CAR-T cells against target cells.ResultsMDA-MB-231 and SKBR3cells with stable expression CD19were obtained in this study.The results of flow cytometry showed that positive expression rate of CD19 in MDA-MB-231/CD19 cells and SKBR3/CD19 monoclonal cells were 99.03% and 98.91%,respectively.RTCA results showed that with MDA-MB-231 and MDA-MB-231/CD19 cells as target cells,CD19 CAR-T cells showed significant cytotoxicity to MDA-MB-231/CD19 cellsat the effector-target ratio of 5∶1, 1∶1 and 1∶5,but not to MDA-MB-231 cells. With SKBR3 and SKBR3/CD19 cells as target cells, CD19 CAR-T cells showed significant cytotoxicity to SKBR3/CD19 cellsat the effector-target ratio of 5∶1and 1∶1. When the effector-target ratio was 1∶5, there was no obvious cytotoxicity.The data of MDA-MB-231/CD19 or SKBR3/CD19 as target cells and CD19 CAR-T as effector cells were analyzed separately, showing that when the number of target cells was the same, the cytotoxicity detected by RTCA increased as the number of CD19 CAR-T cells increased.The cytotoxic assays of CD19 CAR-T cells showed specificity and dose-response relationship of CD19 CAR-T cytotoxicity against the target cells.ConclusionThis study established a method for evaluating cytotoxicity of CD19 CAR-T cells that is real-time, label-free, simple and convenient.

Effect of dexmedetomidine on stress response and immune balance in mechanical ventilation patients with acute respiratory distress syndrome / 中国基层医药

Objective@#To investigate the effect of dexmedetomidine on stress response and immune balance in patients with acute respiratory distress syndrome(ARDS) undergoing mechanical ventilation.@*Methods@#From March 2016 to September 2018, 90 ARDS patients with mechanical ventilation in Chongqing Three Gorges Center Hospital were randomly divided into dexmedetomidine group(D group, 30 cases), propofol group(P group, 30 cases), midazolam group(M group, 30 cases) by random number table method.Another 30 healthy workers in our hospital were selected as normal control group(C group). In M, P and D groups, the sedative drugs were infused by micro-pump on the basis of analgesic treatment(fentanyl citrate). The heart rate(HR), mean arterial pressure(MAP), Murray score, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, plasma norepinephrine(NS), plasma cortisol(Cor), and blood T lymphocyte subsets(CD4+, CD8+, CD4+/CD8+) were observed in all patients at T0(the beginning of sedation), T1 (6h after sedation), T2 (24h after sedation), T3(48h after sedation). The levels of NS and Cor in plasma and blood T lymphocyte subsets(CD4+, CD8+, CD4+/CD8+) in C group were measured at 8∶00 a. m.the next day.@*Results@#The plasma NS and Cor at T0 in M, P and D group were higher than those in C group (all P<0.05), while the levels of CD4+ were lower than those in C group(all P<0.05). Compared with T0, the plasma NS and Cor decreased at T3 in M, P and D group (all P<0.05). The plasma Cor at T3 in P group was lower than that in M group[(475.77±49.69)μg/L vs.(502.33±60.92)μg/L](t=-26.57, P<0.05). The plasma NS and Cor at T3 in D group were lower than those in M group[(20.64±4.70)ng/L vs.(25.29±4.03)ng/L, (442.83±66.59)μg/L vs.(502.33±60.92)μg/L](t=-4.51, -59.50, all P<0.05), and were lower than those of P group[(20.64±4.70)ng/L vs.(23.60±4.49)ng/L, (442.83±66.59)μg/L vs.(475.77±49.69)μg/L](t=-2.96, -32.93, all P<0.05). Compared with T0, the level of CD4+ decreased at T1, T2 and T3(except T3 in D group) in M, P and D group (all P<0.05), and the level of CD8+ decreased at T1, T2 and T3 in M and P group (all P<0.05), but those in D group at T1, T2 and T3 were not significantly decreased(all P>0.05). The levels of CD8+ at T2 and T3 in P and D groups were higher than that of M group (all P<0.05). The level of CD4+/CD8+ at T3 in D group were higher than that in M and P group[(1.46±0.30) vs.(1.26±0.33), (1.46±0.30) vs.(1.32±0.34)](t=0.21, 0.15, all P<0.05).@*Conclusion@#Sedation with dexmedetomidine or propofol can alleviate stress response and improve immune function in ARDS patients undergoing mechanical ventilation, and dexmedetomidine is better than propofol.

Effect of dexmedetomidine on stress response and immune balance in mechanical ventilation patients with acute respiratory distress syndrome / 中国基层医药

To investigate the effect of dexmedetomidine on stress response and immune balance in patients with acute respiratory distress syndrome ( ARDS) undergoing mechanical ventilation.Methods From March 2016 to September 2018,90 ARDS patients with mechanical ventilation in Chongqing Three Gorges Center Hospital were randomly divided into dexmedetomidine group (D group,30 cases),propofol group(P group,30 cases), midazolam group(M group,30 cases) by random number table method.Another 30 healthy workers in our hospital were selected as normal control group (C group).In M,P and D groups,the sedative drugs were infused by micro -pump on the basis of analgesic treatment ( fentanyl citrate ).The heart rate ( HR),mean arterial pressure ( MAP), Murray score,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score,plasma norepinephrine ( NS), plasma cortisol(Cor),and blood T lymphocyte subsets (CD+4 ,CD+8 ,CD+4 ／CD+8 ) were observed in all patients at T0 (the beginning of sedation),T1 (6h after sedation),T2 (24h after sedation),T3(48h after sedation).The levels of NS and Cor in plasma and blood T lymphocyte subsets (CD+4 ,CD+8 ,CD+4 ／CD+8 ) in C group were measured at 8:00 a.m.the next day.Results The plasma NS and Cor at T0 in M,P and D group were higher than those in C group (all P＜0.05),while the levels of CD +4 were lower than those in C group ( all P＜0.05).Compared with T0,the plasma NS and Cor decreased at T3 in M,P and D group (all P＜0.05).The plasma Cor at T3 in P group was lower than that in M group[(475.77 ±49.69)μg／L vs.(502.33 ±60.92) μg／L] (t＝-26.57,P＜0.05).The plasma NS and Cor at T3 in D group were lower than those in M group [(20.64 ±4.70) ng／L vs.(25.29 ±4.03) ng／L, (442.83 ±66.59) μg／L vs.(502.33 ±60.92) μg／L] ( t＝-4.51,-59.50,all P＜0.05),and were lower than those of P group [( 20.64 ±4.70) ng／L vs.( 23.60 ±4.49) ng／L, (442.83 ±66.59) μg／L vs.( 475.77 ± 49.69)μg／L](t＝-2.96,-32.93,all P＜0.05).Compared with T0,the level of CD +4 decreased at T1,T2 and T3 (except T3 in D group) in M,P and D group (all P＜0.05),and the level of CD +8 decreased at T1,T2 and T3 in M and P group (all P＜0.05),but those in D group at T1,T2 and T3 were not significantly decreased (all P＞0.05). The levels of CD +8 at T2 and T3 in P and D groups were higher than that of M group ( all P＜0.05).The level of CD+4 ／CD+8 at T3 in D group were higher than that in M and P group [(1.46 ±0.30) vs.(1.26 ±0.33),(1.46 ± 0.30) vs.(1.32 ±0.34)]( t＝0.21,0.15,all P＜0.05).Conclusion Sedation with dexmedetomidine or propofol can alleviate stress response and improve immune function in ARDS patients undergoing mechanical ventilation ,and dexmedetomidine is better than propofol.

Application progresses of CT texture analysis in digestive malignant neoplasms / 中国医学影像技术

The early diagnosis, efficacy and prognosis evaluation of digestive malignant neoplasms are still difficult problems in the medical field. CT texture analysis (CTTA) is a new imaging post-processing technique, also an emerging area of radiomics. In recent years, CTTA has been widely used in digestive system neoplasms' classification, treatment efficacy evaluation, survival assessment and so on, having more advantages than conventional morphological evaluation. The application progresses of CTTA in diagnosis of digestive malignant neoplasms were reviewed in this article.

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry / 中华医学杂志(英文版)

<p><b>Background</b>Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS.</p><p><b>Methods</b>This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups.</p><p><b>Results</b>In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers.</p><p><b>Conclusions</b>This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.</p>

Enteral nutrition treatment on nutritional status of patients with esophageal cancer during radiotherapy in Chinese population: a meta-analysis / 预防医学

Objective To evaluate enteral nutrition treatment on nutritional status of patients with esophageal cancer during radiotherapy in Chinese population. Methods We searched domestic and foreign relevant databases (PubMed, Medline, Cochrane Library, Wanfang Data, Chinese Journal Database, VMIS) by key words (esophageal cancer, chemoradiotherapy, enteral nutrition) , meeting the conditions of the clinical randomized controlled trials, and evaluated the quality of each document. We used meta-analysis method to analysis the published literatures about clinical randomized controlled trials, which were enteral nutrition treatment on nutritional status of patients with esophageal cancer during radiotherapy in Chinese population.RevMan5.1 statistical analysis software were used. Results Seven separate clinical randomized controlled trials including 503 cases were included into the meta-analysis. The following five indexes of nutritional status in enteral nutrition treatment (ENT) group were superior to routine treatment (RT) group (P<0.05): body weight, Body Mass Index (BMI), hemoglobin, serum albumin, serum prealbumin. The MD Values and 95％CI (confidence interval) were 5.54 (3.61-7.46), 2.20 (2.02-2.39), 12.46 (5.86-19.05), 4.04 (2.48-5.61), 49.53 (20.93-78.13) .The funnel plot showed no significant publication bias in each indexes. Conclusion Enteral nutrition treatment can improve the nutritional status of patients with esophageal cancer during radiotherapy compare only with routine treatment.

Meta-analysis of serum copper and heart failure / 中国药理学与毒理学杂志

OBJECTIVE The purpose of this study is to clarify the association between Cu levels and heart failure(HF)using a meta- analysis approach. METHODS We searched articles in the PubMed, EMbase, CNKI, Wanfang ,VIP and CBM Database published as of August 2016. The case control study on the relationship between serum copper levels and HF were collected and read and extracted by two independent researchers. A Meta analysis was conducted using Stata 12.0 software. RESULTS A total of twenty- one eligible articles, including 893 HF and 654 control subjects, were enrolled. The Meta analysis showed that serum copper levels in HF were higher than control group〔SMD=0.881, 95%CI: (0.487 ,1.264), Z=4.5, P<0.001〕. The sensitivity analysis indicated that the results were reliable. Begg's tests did not find the existence of publication bias. CONCLUSION This meta-analysis indicates that there is a significant association between high Cu serum level and HF.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion.</p><p><b>METHODS</b>Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation.</p><p><b>RESULTS</b>Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05).</p><p><b>CONCLUSIONS</b>Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.</p>

Research progress on anti-cancer mechanisms of arsenic trioxide and artemisinin / 药学学报

The formation and metastasis of tumor cells are closely related to the gene regulation. It is critical to elucidate the molecular mechanism of a compound using in cancer therapy. In this article, we reviewed the anti-cancer molecular mechanism of arsenic trioxide and artemisinin. Its anti-cancer function mainly includes:regulation of ① cell cycle regulatory proteins to inhibit tumor cell proliferation, ② cell apoptosis signal transduction pathway to promote apoptosis in tumor cells, ③ immortalization associated genes to reduce the life of tumor cells, ④ angiogenesis/invasion/metastasis gene to block the spread of tumor cells, ⑤ promoter methylation and protein ubiquitination gene to enhance anti-oncogene expression and ubiquitin-mediated protein degradation, ⑥ microRNA to inhibit proliferation or induce apoptosis in tumor cells, ⑦ DNA synthesis and repair of DNA damage and repair gene to decrease the DNA synthesis of tumor cells, ⑧ signal transduction pathways of cell proliferation/apoptosis and invasion/metastasis etc., ⑨ the expression of hor-mone receptors and so on. We indicated the problems existing in current studies and also prospected the future of using the compound to fight cancer.

Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells / 中国天然药物

Gambogic acid (GA) is an anticancer agent in phase ‖b clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay. Possible target-related proteins of GA at early (3 h) and late stage (24 h) of treatment were searched using a proteomic technology, two-dimensional electrophoresis (2-DE). The possible network of GA was established using bioinformatic analysis. The intracellular expression levels of vimentin, keratin 18, and calumenin were determined using Western blotting. GA inhibited cell proliferation and induced cell cycle arrest at G2/M phase and apoptosis in MDA-MB-231 cells. Additionally, GA exhibited anti-migration effects at non-toxic doses. In 2-DE analysis, totally 23 possible GA targeted proteins were found, including those with functions in cytoskeleton and transport, regulation of redox state, metabolism, ubiquitin-proteasome system, transcription and translation, protein transport and modification, and cytokine. Network analysis of these proteins suggested that cytoskeleton-related proteins might play important roles in the effects of GA. Results of Western blotting confirmed the cleavage of vimentin, increase in keratin 18, and decrease in calumenin levels in GA-treated cells. In summary, GA is a multi-target compound and its anti-cancer effects may be based on several target-related proteins such as cytoskeleton-related proteins.

Treatment regimen selection for newly diagnosed type 2 diabetes after short-term intensive insulin therapy with insulin pump * / 重庆医学

Objective To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) in newly diag-nosed type 2 diabetes mellitus(T2DM ) and to evaluate the treatment regimen conversion after CSII therapy .Methods 72 patients with newly diagnosed T2DM were treated with CSII for 2 weeks .Then they were randomly divided into two groups :the basal insu-lin group(glargine) and the oral anti-diabetic drug(OAD) group .Both groups were followed up for 2 years .Blood glucose ,insulin and HbA1c were measured before and after CSII and during the 2-year follow-up .Results CSII significantly controlled the glucose levels ,reduced the TG ,TC ,LDL levels and the homeostasis model assessment of insulin resistance ( HOMA-IR) and increased the homeostasis model assessment of insulin secretion (HOMA-IS)(all P< 0 .05) .During 1-year follow-up ,HbA1c in the glargine group and the OAD group was (6 .13 ± 0 .47)% and(6 .21 ± 0 .38)% respectively .During 2-year follow-up ,the HbA1c values in the two groups were (6 .91 ± 0 .57)% and(6 .43 ± 0 .62)% respectively .T HOMA-IR and HOAM-IS obtained the long tern improve-ment without significant body weight increase .Conclusion Short-term intensive insulin therapy can effectively control the blood glucose ,improve the sensitivity of insulin and the β-cell function ;after CSII ,adopting basic insulin and oral antidiabetic drugs can a-chieve the ideal glycemic control .

p38 mitogen-activated protein kinases and bone metabolism / 国际药学研究杂志

Mitogen-activated protein kinase (MAPK) s a serine/tyrosine kinase which s expressed widely and regulates various signal transduction pathways in mammalian cell. As one of the key branches of MAPK pathway, p38 MAPK signaling pathway plays an important role in various physiological and pathological processes, such as cell proliferation, differentiation, apoptosis and cell cycle regulation. In recent years, the research on p38MAPK signaling pathway in cell growth, metabolism and function of osteoclast, osteoblast and chondrocyte related to bone metabolism has attracted increasing attention. This article reviews the relationship beween p38MAPK and bone metabolism, in order to investigate the mechanism of action of p38MAPK in bone metabolism related diseases.