Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice / 中国结合医学杂志

OBJECTIVE@#To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC).@*METHODS@#A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot.@*RESULTS@#Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01).@*CONCLUSION@#ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

Effect of Tanhuo Formula on the expression of Caspase-3, GFAP, and angiogenesis in rats with cerebral ischemia / 国际中医中药杂志

Objective:To study the effect of Tanhuo Formula (THW) on the expression of Glial Fibrillary Acidic Protein (GFAP), Caspase-3 and angiogenesis.Methods:Rats were divided into sham group, model group, low-dose THW group, medium-dose THW group, high-dose THW group and Ginaton group according to random number table method. Except the sham group, rats in other groups were subjected to the middle cerebral artery occlusion via a suture method. After 2 hours,rats in the low, medium and high dose of THW groups were gavaged with 0.92, 1.84 and 3.68 g/kg of THW dry extract powder solution respectively, and the Ginaton group were gavaged with 60 mg/kg of Ginaton, once every 24 hours for 3 days. Rats in sham operation group and model group were given equal volume of normal saline by gavage. The limb symmetry score was used to evaluate limb dysfunctions. The immunofluorescence staining of GFAP and Caspase-3 were applied to assess astrocyte activation and neuronal apoptosis, respectively. The double-labeled immunofluorescence staining of platelet-endothelial cell adhesion molecule (CD31) and chondroitinsulphate peoteoglycan (NG2) were performed to detect angiogenesis.Results:Compared with the model group, rats in the high-dose of THW group showed increased limb symmetry score ( P<0.01 or P<0.05), increased number of Caspase-3 (cortex: 765.0±122.4 vs. 1 131.0±392.9; striatum: 895.9±389.8 vs. 1 401.9±453.1) ( P<0.01 or P<0.05) and CD31 +/NG2 + (cortex: 1 355.0±257.9 vs. 825.4±308.1; striatum: 1 290.9±400.9 vs. 675.2±259.7) ( P<0.01) positive cells in the periinfarct cortex and striatum, and attenuated the integrated optical density of GFAP in the perilesional cortex (4 210.00±1 226.38 vs. 7 935.78±2 001.98) ( P<0.01). Conclusions:THW could ameliorate the limb functional disorders, inhibit astroglia activation, down-regulate the expression of Caspase-3, and enhanced angiogenesis in MCAO rats.

Multi-dimensional fixation of patellar multi-fragmentary fractures with locking plates / 中华创伤骨科杂志

Objective:To report the surgical techniques and clinical outcomes of multi-dimensional fixation of patellar multi-fragmentary fractures with locking plates.Methods:A retrospective study was performed in the 26 patients with patellar multi-fragmentary fracture who had undergone open reduction and 3-D internal fixation with locking plates from November 2016 to July 2020 at Department of Orthopaedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University. There were 17 males and 9 females, with an average age of 62.6 years (from 31 to 90 years). The patellar fractures were exposed and reduced via the longitudinal anterior midline incision of the knee. After the reduction was initially maintained with a cerclage wire, a trimmed and pre-contoured 3.5 mm locking plate was applied onto the patellar surface. After-wards, locking screws were inserted from the lower pole to the upper pole of the patella, from the anterior to the posterior and from the lateral to the medial, respectively, to complete the multi-planar fixation. Follow-ups assessed the B?stman score, knee pain visual analogue scale (VAS), radiographic image and fracture healing, range of motion of the knee, and complications.Results:All the 26 patients were followed up for 12 to 56 months (average, 28 months). Crutches were used while walking until an average of 1.6 months (from 1 to 3 months) after operation in all patients. At the last follow-up, the B?stman score averaged 27.5 points (from 17 to 30 points), yielding 12 excellent, 13 good and 1 poor case with an excellent to good rate of 96.2% (25/26); the knee pain VAS averaged 1.2 points (from 0 to 5 points); the active knee flexion averaged 125° (from 100° to 150°). No breakage, loosening or displacement of the patellar plates or screws was observed during follow-up, but cerclage wire breakage occurred without any symptom in 11 cases. Four patients complained of hardware irritation, and 4 patients underwent hardware removal after fracture union.Conclusion:Multi-dimensional fixation with locking plates is a viable and safe surgical option for patellar multi-fragmentary fractures, due to its satisfactory therapeutic outcomes.

Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years / 中国中药杂志

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years / 中国中药杂志

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.

Efficacy of apatinib on multiple advanced-stage nongastric cancers

Background: Apatinib has been approved for the treatment of advanced gastric adenocarcinoma and gastric-esophageal junctional adenocarcinoma, but its efficacy is unknown for other advanced solid tumors. Aims and Objectives: We retrospectively reviewed the use of apatinib for multiple advanced-stage non-gastric cancers. Ninety-two patients from 7 hospitals who received additional treatment except apatinib more than once were enrolled. Materials and Methods: The primary end-point was the overall response rate (ORR), and the secondary end-points included progression-free survival (PFS), disease control rate (DCR), overall survival, and adverse reactions. We categorized all the patients into six groups according to their cancer type. Results: In the lung cancer group, the ORR was 9% (95% confidence interval [CI], 3%–23%), DCR was 88% (95% CI, 74%–96%), and median PFS was 3 months (95% CI, 1.9–5.4 months). In the cervical cancer group, the ORR was 25% (95% CI, 3%–65%), DCR reached 100%, and median PFS was 3.5 months (95% CI, 0.6–9.0 months). There were different ORRs between the other cancer groups. In addition, the most common adverse effect of apatinib was palmar–plantar erythrodysesthesia syndrome (37%), followed by proteinuria (14%) and hypertension (13%). Conclusion: These results suggest that apatinib might be effective for not only gastric cancer but also other carcinomas including lung cancer, colorectal cancer, cervical cancer, liver cancer, breast cancer, and nasopharyngeal cancer. Thus, apatinib is a promising targeted drug for multiple types of cancer

Expression and clinical significance of aldo-keto reductase 1-A1 in hilar cholangiocarcinoma / 第二军医大学学报

Objective: To explore the expression and clinical significance of aldo-keto reductase 1-A1 (AKR1A1) in hilar cholangiocarcinoma tissues. Methods: Immunohistochemical assay was used to detect the expression of AKR1A1 in 49 hilar cholangiocarcinoma and adjacent normal tissues (at least 2 cm from the edge of the tumor). The correlation between the AKR1A1 expression and clinical variables of hilar cholangiocarcinoma patients was analyzed by χ2 test. Results: The high-expression rate of AKR1A1 in cancer tissues was 59.2% (29/49), which was significantly higher than that in matched adjacent normal tissues (25.0% [3/12], P<0.05). We also noticed that the high-expression of AKR1A1 in hilar cholangiocarcinoma patients tissues was associated with tumor size (P=0.028) and lymph node metastasis (P=0.001). Survival analysis showed that the overall survival (median 15 months vs 39 months, P=0.012) and progression free survival (median 15 months vs 32 months, P = 0.022) of AKR1A1-high-expression patients were significantly shorter compared with the low-expression patients. Multivariate analysis showed that the depth of invasion was associated with overall survival (odds ratio [OR] 0.174, 95% confidence interval [CI] 0.041-0.741, P=0.018) and progression free survival (OR 0.083, 95% CI 0.011-0.618, P=0.015). Conclusion: AKR1A1 is involved in the progression and metastasis of hilar cholangiocarcinoma, suggesting that it might be a potential biomarker for predicting tumor recurrence and prognosis of patients with hilar cholangiocarcinoma.

Buyang-Huanwu decoction combined with enriched environment on the abnormal activation of astrocytes and the expression of angiogenic factors in rats with cerebral ischemia / 国际中医中药杂志

Objective To observe the effects of Buyang-Huanwu decoction (BYHWD) combined with enriched environment (EE) on the abnormal activation of astrocytes and expression of angiogenic factors in rats with cerebral ischemia. Methods The rat model of permanent middle cerebral artery occlusion (pMCAO) was established by using suture method. Male SD rats were randomly divided into sham, model, EE, BYHWD and BYHWD+EE group. Rats in the BYHWD and BYHWD+EE groups were intragastrically adminstratered with BYHWD (16.1g/kg) 24h after MCAO and once daily for consecutive 15 days. Accordingly, rats in the sham, model, and EE groups were adminstratered with the sam volume normal saline. Rats treated with EE and BYHWD+EE were housed in the enriched environment 12 h every day. The EE, BYHWD and BYHWD+EE group rats were given relative treatment continuously for 15 days. Beam walking test was performed to examine the motor function of rats. Next, the HE staining was conducted to detect the pathological alterations of the brain. Immunohistochemical staining with DARPP-32 and GFAP were applied to respectively observe the changes of multiple spinous neurons and activation of astrocytes in the striatum. Subsequently, the mRNA expressions of angiogenic factors including VEGF/VEGFR2 and Ang1/Ang2 were detected by RT-PCR. Results The rats treated with BYHWD+EE revealed markedly elevated beam walking scores on the 7th and 15th day after MCAO compared with model group (P<0.01). Compared with the model, BYHWD+EE treatment significantly increased the number of neurons (31.08 ± 8.06 vs. 19.00 ± 9.12, P<0.01), elevated the number of DARPP-32-positive cells (975.3 ± 589.68 vs. 271.25 ± 164.98) and integral optical density (18621.87 ± 6996.64 vs. 4071.60 ± 2477.27) of DARPP-32 (P<0.01), suppressed the expression of GFAP (6094.07 ± 3211.74 vs. 10002.91 ± 8430.34, P<0.01) and up-regulated the mRNA levels of VEGF (1.59 ± 0.80 vs. 0.77 ± 0.33), VEGFR2 (1.58 ± 0.88 vs. 0.70 ± 0.37), Ang1 (1.58 ± 0.52 vs. 0.84 ± 0.13), and Ang2 (1.25 ± 0.25 vs. 0.90 ± 0.22) in the striatum (P<0.05 or P<0.01). Conclusions The Buyang-Huanwu decoction combined with enriched environment exerted synergistic effect on ischemic rats and promoted motor function by inhibiting the excessive activation of astrocytes and improving the expression of angiogenic factors.

Berberine enhances mitomycin C-induced cell cycle arrest and apoptosis of T24 bladder cancer cells / 中国病理生理杂志

AIM:To observe the effects of the combination of berberin (Ber) and mitomycin C (MMC) on the cell cycle arrest and apoptosis of T24 bladder cancer cells and the underlying mechanisms. METHODS:The T24 cells were exposed to MMC in the presence or absence of difference concentrations of Ber. The viability of the T24 cells was de-termined by CCK-8 assay. The cell cycle distribution was detected by flow cytometry. The apoptosis was analyzed by flow cytometry with Annexin V-FITC/PI staining, and the protein expression levels of cyclin D1, survivin, CDK2, CDK4, p21 and p27 were determined by Western blot. RESULTS:CCK-8 experiments showed that Ber enhanced the inhibitory effect of MMC on the viability of T24 cells. The results of flow cytometry showed that Ber also enhanced the blockade effect of MMC on T24 cells in G0/G1 phase (P<0.05). Compared with the MMC group, Ber increased the expression of p21 and p27 up-regulated by MMC, and decreased the expression of cynlin D1, CDK2 and CDK4 (P<0. 05). Meanwhile, Ber promoted MMC to inhibit the expression of survivin (P<0. 05). Ber increased the apoptosis of T24 cells induced by MMC (P<0. 05). CONCLUSION:Ber significantly enhances the inhibitory effect of MMC on the viability of T24 cells. The mechanism may be related to up-regulation of p21 and p27, thereby inhibiting the expression of cyclin D1, CDK-2 and CDK-4. At the same time, Ber inhibits the protein expression of survivin, which eventually leads to cell arrest in G0/G1 phase and promotes apoptosis.

Drug Resistance of Pathogenic Bacteria from Blood Culture and the Distribution in Clinical Departments from 2012 to 2014 / 华中科技大学学报(医学版)

Objective To analyze drug resistance of pathogenic bacteria from the blood culture and distribution in clinical departments,and to guide the rational clinical drug use.Methods We retrospectively analyzed 11 275 samples of blood cultures in The Central Hospital of Wuhan from 2012 to 2014.The blood specimens were cultured by VersaTREK(USA).The pathogenic bacteria were identified and their drug resistance was analyzed by BD-PHOENIX 100 automicrobiological identification systems(USA).Results Among the 11 275 blood cultures,636 bacterial strains were detected.The top four bacterial strains were Escherichia coli,Staphylococcus aureus,Klebsiella pneumonia and Enterococcus f aecium.A vancomycin-resistant Enterococcus faecium strain and a pandrug-resistant Klebsiella pneumoniae strain were detected.The top three clinical departments with distribution of pathogens were Gastroenterology Department,Nephrology Department and Intensive Care Unit (ICU).Pathogens isolated from ICU were evenly distributed.Conclusion Distributions of pathogenic bacteria in the blood culture are different in clinical departments.Identification of pathogenic bacteria and result of drug susceptibility can reduce use of broadspectrum antimicrobials and enhance antimicrobial de-escalation.

Research progress of pharmacokinetics and pharmacodynamics of total glucosides of peony in hepatoprotective effects / 中国中药杂志

Total glucosides of peony (TGP), containing the effective components of paeoniflorin (Pae), albiflorin (Alb) and so on, are effective parts of Radix Paeoniae Alba. And it possesses extensive pharmacological actions, one of which is hepatoprotective effect. In recent years, abundant of pharmacokinetics and pharmacodynamics research of TGP in hepatoprotective effects have been performed. However, the relative medicine of TGP in hepatoprotective effect has not been developed for clinical application. In order to provide reference for the development and rational clinical application of TGP, the research progresses of pharmacokinetics and pharmacodynamics of TGP in hepatoprotective effect were summarized in this paper. Pharmacokinetics research has clarified the process of absorption, distribution, metabolism and excretion of TGP in vivo, and liver injury disease can significantly influence its metabolic processes. Pharmacodynamics studies suggested that TGP can protect against acute liver injury, non-alcoholic fatty liver diseases (NAFLD), chronic liver fibrosis and liver cancer. However, the action mechanism and in vivo process about hepatoprotective effects of TGP have not been clearly revealed. How liver injury influences the metabolism of TGP and its integrated regulation through multiple targets need to be further studied. The combined pharmacokinetics and pharmacodynamics studies should be performed in favour of medicine development and clinical application of TGP in hepatoprotective effects.

Application progress of proteomic in pharmacological study of Chinese medicinal formulae / 中国中药杂志

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae.

Effect of rotary cell culture system-simulated microgravity environment on the expression of lncRNA in mouse fibroblasts / 解放军医学杂志

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of long non-coding RNA (lncRNA) in mouse fibroblasts L929 cell line.Methods L929 cells were cultured in vitro and randomly divided into simulated microgravity (SMG) group and normal gravity (NG) group.Each group had three samples,the rotator axis of SMG group was paralleled to the ground rotation,while the rotator axis of NG group was vertical to the ground rotation,and the speed of rotation was consistent for the two groups.The samples of two groups were collected on 7th day of culture and the total RNAs were extracted,labeled and hybridized in sequence.The lncRNA and mRNA were detected by Agilent Mouse lncRNA Chips respectively.Differentially expressed lncRNA were identified and then validated by RT-qPCR.GO and Pathway analysis were applied to determine the functional distribution of these target genes.The integration predictions of the lncRNA and mRNA co-expression had been proposed to refine the functional lncRNA-mRNA relationships.Results There were 238 differentially expressed lncRNAs including 134 lncRNAs up-regulated and 104 lncRNAs down-regulated,and 237 differentially expressed mRNAs including 53 mRNAs up-regulated and 184 mRNAs down-regulated significantly in mouse fibroblasts L929 cell line under simulated microgravity by RCCS.The RT-qPCR showed a high concordance with chip microarray results in 4 differentially expressed lncRNA.GO analysis showed that the differentially expressed lncRNAs were related to the biological processes such as negative regulation of megakaryocyte differentiation and negative regulation of wound healing.Pathway analysis showed that these target genes were related to the signal pathways of systemic lupus erythematosus and TGF-β.The lncRNA-mRNA co-expression networks were also established.Conclusion The simulated microgravity by RCCS could significantly affect the expression profiles of lncRNA and mRNA in mouse fibroblasts L929.The lncRNA target genes prediction and functional enrichment analysis based on gene chip technology may provide the theoretical basis for illustrating the mechanism and management of weightlessness stress injury.

Leucine-rich repeat kinase 2 inhibitor as Parkinson’s disease novel therapeutics: Research advances / 国际药学研究杂志

Parkinson’s disease PD is a common disease caused by multiple factors and characterized by pathological degeneration in the dopaminergic neural system. Based on its pathogenic factors, PD can be divided into several subtypes, so it is essential to develop therapeutic agents based on the main pathogenic factor of each subtype of PD. Recently it is confirmed that the mutation of leucine- rich repeat kinase 2 LRRK2 gene leads to increased activity of the LRRK2 notably, and then causes neurodegeneration. Thus developing LRRK2 inhibitors to modulate the kinase activity will be a novel therapy for the PD subtype which is caused by LRRK2 gene mutation. LRRK2, either a kinase or a GTPase, has two drug binding sites. Therefore, two types of LRRK2 inhibitors are being studied, one is the kinase inhibitor and the other is GTPase inhibitor. This paper summarizes the recent progress in the discovery and development of LRRK2 inhibitors.

Rapid determination of 15 chemical drugs illegally added into slimming Chinese patent medicines and health foods by UPLC-MS/MS / 中草药

Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.

Correlation between cerebral microbleeds and cognitive impairment in patients with lacunar infarction and/or leukoaraiosis: a retrospective case series study / 国际脑血管病杂志

Objective To detect the distribution of cerebral microbleeds (CMBs) in patients with lacunar infarction (LI) and/or leukoaraiosis (LA) and to analyze the correlation between the CMB related risk factors and cognitive impairment.Methods Thirty-eight patients with LI and/or LA were divided into either a CMB group or a non-CMB group according to the findings of susceptibility weighted imaging.The number of CMB lesions was recorded.Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to conduct cognitive function tests,and the patients were also divided into a cognitive impairment group and a non-cognitive impairment group according to the MoCA scores.The demographic and clinical data in each group were compared.The independent risk factors for CMBs and cognitive impairment were identified.Results Thirteen patients had 58 CMBs in the CMB group.Their distributions were as follows:36 CMBs in basal ganglia and thalamus,14 in cortical and subcortical regions,3 in brain stem,and 5 in cerebellum.There were 25 patients in the non-CBM group,26 in the cognitive impairment group,and 12 in the non-cognitive impairment group.There were significant differences in age and the proportions of hypertension,taking antithrombotic drugs and the patients with LA between the CMB group and the non-CMB group (all P ＜ 0.05).Multivariable logistic regression analysis showed that only age was an independent risk factor for CMBs (odds ratio 1.103,95％ confidence interval 1.034-1.454; P =0.045).MMSE (26.92±2.87vs.29.00± 1.44; t=2.452,P=0.027) and MoCA (21.62±3.36vs.25.04 ± 2.59; t =-3.493,P =0.001) scores in the CMB group were significantly lower than those in the non-CMB group.There was only significant difference in the number of CMBs between the cognitive impairment group and the non-cognitive impairment group (2.08-± 3.64 vs.0.33 ±0.78; t =-1.629,P =0.010).Multivariate logistic regression analysis showed that only the number of CMBs was an independent risk factor for cognitive impairment (odds ratio,1.534,95％ confidence interval 1.100-2.576; P=0.046).Spearman rank correlation analysis showed that the number of CMBs was significantly negatively correlated with the MoCA language (r =-0.229,P=0.003) and the delayed recall (r =-0.332,P=0.042) scores.Conclusions In patients with LI and/or LA,CMBs were correlated with age.Their existence and number were associated with cognitive impairment.

Study on PK-PD characteristics of ginsenoside Rg1 and Rb1, in rats with myocardial ischemia following intravenous administration of shengmai injection / 中国中药杂志

It is the objective of this paper to study pharmacokinetics-pharmacodynamics (PK-PD) characteristics of ginsenoside Rg1 and Rb1 on the effect of inducing nitric oxide (NO) release after intravenous administration of Shengmai injection to rats with myocardial ischemia. The model of myocardial ischemia rats was produced by subcutaneous injection of isoproterenol. The serum samples were collected at different time points after intravenous administration of Shengmai injection to rats with the dose of 10.8 mL x kg(-1). The concentrations of ginsenoside Rg1 and Rb1 in serum were determined, and then the concentration-time curves were drawn. Pharmacokinetic parameters of ginsenoside Rg1 and Rb1 were calculated after the construction of pharmacokinetic models. Meanwhile, NO2- and NO3-, the metabolites of NO, in serum were determined, and then the effect-time curve was drawn. The combined PK-PD model was established based on the theory of effect compartment by Sheiner et al. Then pharmacodynamic parameters were calculated. The results indicated that the pharmacokinetics of ginsenoside Rg1 and Rb1 conformed to a two-compartment model. Ginsenoside Rg1 and Rb1 exhibited quick and slow elimination in rats respectively. The effect of Shengmai injection on inducing NO release did not relate directly with and lagged behind the concentrations of ginsenoside Rg1 and Rb1 in serum. The effect exhibited good correlation with ginsenoside Rg1 and Rb1 levels in effect compartment. The relationship between effect and serum concentration fits Sigmoid-E(max) model. This study successfully established the combined PK-PD model of ginsenoside Rg1 and Rb1 after intravenous administration of Shengmai injection to rats. The model can efficiently predict the concentration and effect of Shengmai injection in vivo.

Effect of DC-CIK cells combined with oridonin on cytotoxicity against RPMI 8226 cells / 实用医学杂志

Objective To investigate the changes in cytotoxicity of DC-CIK cells to human multiple myeloma RPMI 8226 cells before and after treatment with oridonin. Methods Normal human peripheral blood mononuclear cells were isolated and induced to obtain DC-CIK cells. Cytotoxicity of DC-CIK cells against RPMI 8226 cells which were treated by oridonin was analyzed by LDH releasing assay. The variation for expression of NKG2D ligands on RPMI 8226 cells were measured by flow cytometry. Results DC-CIK cells were successfully induced from the peripheral blood mononuclear cells. At the same effector to target ratio, oridonin obviously enhanced the cytotocixity of DC-CIK cells against RPMI 8226 cells (P<0.01). Flow cytometry showed the expression of NKG2D ligands ULBP1 of RPMI8226 cells was most significantly increased as the cells were treated by oridonin [(9.19 ± 1.85) vs. (15.47 ± 0.67), P<0.01]. Correlation analysis indicated that cytotocixity was positively correlated with changes in ULBP1. Conclusions Oridonin can improve the cytotoxicity of DC-CIK cells against RPMI 8226 cells, which may be related with the increased expressions of NKG2D ligands on the tumor cell surface.

Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice / 中国实验血液学杂志

The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.

Clinical observation of bone marrow mesenchymal stem cells transplantation in treatment of 22 patients with aplastic anemia / 白血病·淋巴瘤

ObjectiveTo explore the efficacy and safety of bone marrow mesenchymal stem cells (BMSC)in treatment of aplastic anemia(AA). MethodsTwenty-two patients with aplastic anemia were enrolled with median age of 31 (12-70) years old,including 11 severe aplastic anemia (SAA),and 3 of whom were cyclosporine and anti-thymocyte globulin-resistant. BMSC were isolated from bone marrow of healthy donors and cultured.The third to fifth generation cells were administered intravenously in 1×106/kg to patients once or twice a week.After infusion,complete blood count,bone marrow aspiration,bone marrow biopsy,flow cytometry analysis of lymphocyte subsets of CD3+ CD4+ and CD3+ CD8+ and clinical symptoms were involved in outcome measurement.ResultsAll patients finished 16-time median (5-83 times) infusions of BMSC with 13-month median (2-33 months) treatment course and 23-month median (2-34 months) follow-up.The total response rate was 72.7 ％(16/22), including one patient with essential cure, 9 with remission, 3 with remarkably improvement and 3 with transfusion interval extension.Two of three front-line immunosuppressiveresistant SAA patients achieved remission. Ten of 14 patients recovered from inverted ratio of CD4+/C8+ cells after BMSC treatment. There were no treatment-related side effects observed in the course of treatment.ConclusionBMSC are effective and safe for the treatment of AA in our preliminary study and they deserve further research with larger-scale and long-term clinical trials.