Mechanism of Wumeiwan in Treatment of Emotional Disorders Based on Secrets for Auxiliary Cultivation Life / 中国实验方剂学杂志

Wumeiwan are recorded in the Jueyin chapter of Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）， and many doctors in the past dynasties believed that they had the effects of calming intestinal ascarid by warming Zang organs. The clinical application was limited. Since KE Qin， a doctor in the Qing dynasty， proposed that Wumeiwan were the primary prescription against Jueyin diseases， Wumeiwan have been valued by doctors， and their clinical application has also been expanded. The syndrome indicated for Wumeiwan is attributed， not only to the ascarid internal harassment， but to the abnormal Qi movement of wind and wood in Jueyin and the dysfunction of Yin and Yang. According to the functions of six meridians based on the theory of "open-close axis" in Huangdi's Internal Classic （《黄帝内经》） and the original texts of Treatise on Cold Damage and Miscellaneous Diseases， Yinshu refers to Jueyin. Wumeiwan， the primary prescription against Jueyin diseases， have the function of connecting Yin and Yang， and they can treat diseases caused by Qi disturbance of Jueyin and cold and heat in complexity. Sharing the same resource， the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） and Treatise on Cold Damage and Miscellaneous Diseases both consult Models of the Classic of Decoction （《汤液经方》）. The formulation rules of tonic/purgative and collapse-saving prescriptions in Secrets for Auxiliary Cultivation Life follow the recorded "Tang Ye Jing Fa Tu" （an image revealing the compatibility principles of Chinese herbal drugs） and are closely related to the five elements theory. By exploring the formulation rules in "Tang Ye Jing Fa Tu" and the five elements of drugs， this study analyzed Wumeiwan and proved that Wumeiwan mainly acted on the liver， spleen， and heart. According to the Five Zang-organs Storing Spirit theory from Huangdi's Internal Classic， the above three organs are closely related to emotional adjustment. Therefore， the treatment of emotional disorders caused by qi disturbance of Jueyin and cold and heat in complexity with Wumeiwan is supported by evidence. At the end of this article， the reports on the treatment of emotional disorders with Wumeiwan in recent years were listed and reviewed. This article provides new ideas for the clinical application of Wumeiwan in the treatment of emotional disorders and expands the application range.

Activation of lung endothelial cells by extracellular histone in mice with acute respiratory distress syndrome / 中华劳动卫生职业病杂志

Objective@#To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) .@*Methods@#The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model.@*Results@#The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells.@*Conclusion@#Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.

The comparison of heparan sulfate and its fragments on the protection against extracellular histones during the pathogenesis of acute respiratory distress syndrome / 中华劳动卫生职业病杂志

Objective@#In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared.@*Methods@#Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured.@*Results@#After CTH injection, the ratio of wet/dry lung weight (5.7±0.95) was much higher than the saline control group (3.1±0.15). The protein content (0.47±0.086mg/ml) , total leukocyte[ (97.4±15.6l) ×104/ml] and neutrophil (18±3.4/LPF) in BALF were obviously increased compared with the saline control group. The intervention of HS evidently decreased ratio of wet/dry lung weight (4.2±0.41) , protein content[ (0.26±0.019) mg/ml], leukocyte[ (61.3±5.74) ×104/ml] and neutrophil (12±1.8/LPF) in BALF. HS fragments also decreased ratio of wet/dry lung weight, protein content, leukocyte and neutrophil count in BALF though the strength was much less than HS.@*Conclusion@#HS and its fragments could provide protection against extracellular histones during the pathogenesis of ARDS. For the protective effect full length HS was much better than HS fragments.

The clinical study on the correlation of lysophosphatidic acid and vascular endotheli growth factor and endothelin in serum of pneumoconiosis / 中华劳动卫生职业病杂志

Objective@#To explore the role of lysophosphatidic acid, vascular endothelial growth facor and endothelin in the pathogenesis of pulmonary fibrosis in coal workers’pneumoconiosis patients, the relationship of lysophosphatidic acid, VEGF and ET in serum was studied.@*Methods@#Sixty two pneumoconiosis patients were selected as cases group, which included 23 cases of stage Ⅰ, 25 cases of stageⅡand 14 cases of stageⅢ. Twenty workers were selected as dust exposure group who exposed to coal dust for more than 2 years and had not been diagnosed as pneumoconiosis. Ten healthy people who had no occupational dust exposure were simultaneously selected as the control group. The serum levels of LPA, VEGF and ET were measured by ELISA.@*Results@#The serum levels of VEGF and ET in coal dust exposed group and pneumoconiosis group were much higher than in the control group. The differences were statistically significant among the three groups (P<0.01) . The serum levels of LPA increased in the dust exposed group, stage Ⅰand stage Ⅱgroup. The serum levels of LPA correlated positively with the levels of VEGF and ET (P<0.05) .@*Conclusions@#The serum levels of LPA, VEGF and ET had evident correlation with the pulmonary fibrosis caused by coal dust, which indicate that LPA, VEGF and ET may play a pivotal role in the process of pulmonary fibrosis. The study will throw light on both pathogenesis and early intervention for pneumoconiosis.

The study on the change of extracellular histones in human plasma during the pathogenesis of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the plasma level of extracellular histones in patients with silicosis, and to explore the role of extracellular histones in the pathogenesis of pulmonary fibrosis in silicosis.</p><p><b>METHODS</b>Sixty-two patients with silicosis were enrolled as the silicosis group, consisting of 23 patients with stage I silicosis, 25 with stage II silicosis, and 14 with stage III silicosis; sixty workers who had a history of occupational exposure to silica dust for more than 2 years and had not been diagnosed with silicosis were enrolled as the silica dust exposure group; sixty-five healthy workers without a history of occupational exposure to dust were enrolled as healthy controls. Enzyme-linked immunosorbent assay was applied to measure the plasma levels of plasma extracellular histone (H4) and transforming growth factor-β(TGF-β).</p><p><b>RESULTS</b>Compared with healthy controls [(0.82±0.67) μg/ml], the silica dust exposure group[(4.14±2.85) μg/ml] and silicosis group[(9.50±5.04) μg/ml] had significant increases in plasma level of H4 (P<0.01). The plasma level of H4 was significantly correlated with the stage of silicosis(r=0.8955, P=0.0388). The silicosis group had a significantly higher plasma level of TGF-β than the silica dust exposure group and healthy controls(P <0.05). In the patients with silicosis, the plasma level of H4 was significantly correlated with that of TGF-β(r=0.5375, P<0.01).</p><p><b>CONCLUSION</b>The plasma level of extracellular histones increases significantly in the pathogenesis of silicosis, and extracellular histones may play an important role in the progression of fibrosis in silicosis.</p>

Advances in oncolytic adenovirus-loaded mesenchymal stem cells for treating tumors / 中国肿瘤临床

Oncolytic adenoviruses have been used in cancer gene therapy because of their ability to selectively transfect and repli-cate in tumor cells. However, systemically administering oncolytic adenoviruses is often inefficient because the host's immunity also at-tacks the viruses. Delivering oncolytic adenoviruses by loading them into mesenchymal stem cells effectively solves this problem. Mes-enchymal stem cells have been described to possess a tumor-homing ability, as well as the capacity to deliver oncolytic adenoviruses. This review discusses the current challenges faced by oncolytic adenovirus delivery via mesenchymal stem cells.

Observation of Tianwang Buxin Decoction in the Treatment of Heart Yin Deficiency Type of Generalized Anxiety Disorder / 浙江中医药大学学报

Objective] To observe the clinical effects of Tianwang Buxin decoction in the treatment of heart Yin deficiency type of Generalized Anxiety Disorder. [Methods] 63 patients with Generalized Anxiety Disorder(heart Yin deficiency type) were randomly divided into three groups: Tianwang Buxin decoction group, paroxetine group, Tianwang Buxin decoction combined paroxetine group, course of treatment for 8weeks.Contrast the scores of three groups by HAMA before and after treatment. [Results] The clinical efficacy was almost the same among the three groups without significant difference, but the decrease of HAMA scores of Tianwang Buxin decoction combined paroxetine group was obviously lower than Tianwang Buxin decoction group and paroxetine group(P<0.05), among which, TCM group and combination group of TCM and WM had less side effect than WM group. [Conclusion]The clinical efficacy of Tianwang Buxin decoction group is almost the same with the paroxetine group without significant difference. The clinical efficacy of Tianwang Buxin decoction combined paroxetine group is more significant.

Risk assessment of acute kidney injury after intracoronary stent implantation / 中国综合临床

Objective To investigate the risk factors of acute kidney injury(AKI) after intracoronary stent implantation in order to provide the basis for clinical prophylaxis and treatment.Methods Retrospectively analyzed 626 consecutive patients who underwent isolated intracoronary stent implantation in our institution from January 2007 to July 2011.Multivariate logistic regression model was constructed to identify the risk factors for the development of AKI defined as a serum creatinine (SCr) 130 to 199 μ mol/L or estimated creatinine clearance(Ccr) 30 to 60 ml/min per 1.73 m2.Results Ninety-three patients of 626 (14.9％) underwent isolated intracoronary stent implantation developed AKI.The results of the multivariate forward stepwise logistic regression analysis found that risk factors for the development of AKI following isolated intra-coronary stent implantation was associated with age (OR =1.570,95％ CI 1.308-1.885),ejection fraction (EF) ≤ 30％(OR =11.526,95％ CI 2.452-54.177),hypotension during perioperative and postoperation (OR =11.074,95％ CI 2.439-50.282),operation duration(OR =1.032,95％ CI 1.012-1.051),sex (OR =0.010,95％ CI 0.001-0.086),NYHA class Ⅲ & Ⅳ (OR =0.209,95％ CI 0.059-0.737),peripheral vascular disease (OR =0.528,95％ CI 0.286-0.973),chronic obstructive pulmonary diseases (OR =0.546,95％ CI 0.304-0.982),preoperation Cr (OR=1.418,95％CI 1.216-1.654) (and all P＜0.05).Conclusion AKI is the common complications after intracoronary stent implantation,especially age,EF ≤ 30％,hypotension during perioperative and postoperation,operation duration are independent risk factors.

Celecoxib combined with tamoxifen prevents methylnitrosourea-in-duced breast tumor in rats / 中国肿瘤临床

Objective:The present study aims to evaluate the chemopreventive effect of celecoxib combined with tamoxifen on breast tumor induced by methylnitrosourea (MNU) in rats. Methods:A total of 140 SD female rats were injected with MNU to estab-lish breast tumor models. The rats were divided subsequently into control, celecoxib, tamoxifen, and combination groups. The occur-rence rates, volumes of breast tumor, and expression levels of cyclooxygenase 2 (COX-2) and c-erbB-2 were observed. Results:The tu-mor occurrence rates were lower in the celecoxib and tamoxifen groups than in the control group. The combination group exhibited the lowest tumor-occurrence rate. The tumor volumes of the celecoxib and tamoxifen groups were lower than that of the control group. The combination group had the least tumor volume. The positive rates of COX-2 and c-erbB-2 in the celecoxib and combination groups were lower than those in the control and tamoxifen groups (P<0.05). Conclusion:The combination of celecoxib and tamoxifen can sig-nificantly suppress MNU-induced breast tumor in female rats.

The protective effect of chlorophyllin against oxidative damage and its mechanism / 中华内科杂志

Objective To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism.Methods The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry.The level of free radicals was detected directly by electron spin resonance spectra.The induced expression of HO-1 was shown by RT-PCR,Western blot,immunofluorescence confocal laser microscopy and enzymatic activity test.Whether the activation of PI3K/Akt pathway was involved was detected by Western blot.Results Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals.Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner.The activation of PI3K/Akt pathway was required in the induction of HO-1.LY294002,the specific inhibitor of PI3K,could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner.Conclusions Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals.Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin,while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.

Treatment of malignant gliomas with stem cells mediated oncolytic adenovirus / 国际肿瘤学杂志

Oncolytic adenoviruses are genetically altered to replicate within tumor cella while exhibiting a high degree of infectivity,good safety and specificity.The use of oncolytic adenoviruses to treat malignant brain tumors has been proved to be a promising mode of cancer therapy.Local injection of adenoviral vectors fails to reach scattered infiltrative tumor cells within the brain parenchyma and the therapeutic effect of intracereberal injections of oncolytic adenoviruses is only seen in the vicinity of the injection site.To remedy this and prevent possible tumor recurrence,stem cells have been explored as vehicles for gene therapy in brain tumors given that they possess an intrinsic tropism for brain glioma.

Cell-based delivery of oncolytic viruses / 国际肿瘤学杂志

Oncolytic viruses,a novel class of virus vectors,which selectively replicate only in tumor cells,have excellent tumor targeting and good tansfection efficiency.Many oncolytic viruses have apparent curative effect when administered intratumorally.However,the host immune system remains a critical obstacle to systemic administration of virotherapeutics.It appears that cell-based delivery of oncolytic viruses could offer one solution to this critical problem,which provides a new platform to the biological therapy of cancer.

Oncolytic adenoviruses harboring IL-24 gene induce the apoptosis of melanoma cells / 中华皮肤科杂志

Objective To study the effects of oncolytic adenoviruses ZD55 harboring IL-24 gene (ZD55-IL-24) on the apoptosis of human melanoma cell line A375. Methods The oncolytie adenoviruses ZD55-IL-24 were verified by PCR. Then, the viruses were propagated, purified, and titrated by HEK293 cell plaque assay. A375 cells were cultured, divided into three groups transfected with ZD55-1L-24, ZD55 fused with enhanced green fluorescent protein (ZD55-EGFP), and replication-deficient adenovirus ZD55 carrying IL-24 gene (AD-IL-24), respectively. The multiplicity of infection was 0.1, 1, 10 and 100, respectively.Subsequently, the eytotoxity of these viruses and proliferation of A375 cells were determined by crystal violet staining and methyl thiazolyl tetrazolium (MTT) assay, respectively. The expressions of EIA and IL-24 protein were detected by Western blot in A375 cells. Results PCR verified that the adenoviruses ZD55-IL-24 contained IL-24 gene without wild adenovirns contamination. Crystal violet staining revealed that ZD55-IL-24 had an obvious eytotoxic effect on A375 cells, and MTT assay indicated that ZD55-IL-24 inhibited the proliferation of A375 cells in a time-and concentration-dependent manner. As shown by Western blot analysis, ZD55-1L-24 expressed IL-24 and E1A protein in A375 cells with a high efficiency. Conclusions The oncolytic adenoviruses ZD55-IL-24 can efficiently express IL-24 gene, inhibit the proliferation of, and induce the apoptosis in A375 cells.

Advancement of Reovirus-based therapy for cancer / 国际肿瘤学杂志

Reovirus,a kind of oncolytic viruses, is seldom pathogenic, but is selectively able to replicate in cancer cells through activation of Ras signaling. Pre-clinical studies have demonstrated that treatment with reovirus is associated with significant anticancer activity across a range of tumor types. Further clinical evaluation of reovirus therapy has shown that it is well tolerated when administered locally or systemically. Encouraging anticancer efficacy has been observed with single-agent treatment and in combination with chemotherapy and radiotherapy. High safety and promising efficacy of reovirus has raised hopes that it will become a new anticancqt agent.

Research progress in conditionally replicative adenoviruses targeting cancer stem cells / 国际肿瘤学杂志

Cancer stem cells (CSC) are capable of self-renewal and differentiation, properties that are critical to tumor growth, metastasis, and radioresistance. Eradication of CSC is the key to the success of cancer therapy. Conditionally replicative adenoviruses(CRAd) are a novel class of viral agents which selectively replicate in tumor cells but not in normal cells. CRAd can specifically target and eradicate CSC ,representing a promising cure for cancer.

Effect of Partial Body Weight Support Treadmill Training Combined with Brain Function Therapy on Walking Ability of Stroke Patients / 中国康复理论与实践

@#Objective To explore the effects of partial body weight support treadmill training (PBWSTT) combined with brain function therapy on walking ability of stroke patients. Methods 112 stroke patients with hemiplegia were randomly allocated into treatment group (n=57) and control group (n=55). The control group received routine rehabilitation training, while the treatment group received PBWSTT combined with brain function therapy in addition. They were assessed with lower limb's movement and balance function assessment of the Fugl-Meyer Assessment (FMA), Functional Ambulation Category (FAC), and Modified Barthel Index (MBI) before and after the treatment. Results The scores of FMA, FAC, and MBI improved more in treatment group than in control group after treatment (P<0.05). Conclusion Based on the conventional rehabilitation, PBWSTT combined with brain function therapy may improve the motor function of lower limb, balance function，walking ability, and ADL more significantly in stroke patients with hemiplegia.

Antitumor effects of oncolytic adenovirus expressing human IL-18 gene on malignant melanoma implanted in nude mice / 中华皮肤科杂志

Objective To evaluate the antitumor effect of oncolytic adenovirus expressing human IL-18 gene on malignant melanoma implanted in nude mice.Methods BALB/c nude mice were subcutaneously inoculated with A375 cells to establish a model of malignant melanoma.When the volume of implanted tumor reached 100-150 mm3,murine models were randomly divided into three groups to receive a 3-day intratumoral injection of IL-18 gene-expressing human oncolytic adenovirus named ZD55-IL-18,IL-18 gene-expressing adenovirus named Ad-IL-18,phosphate buffer saline(PBS),respectively.The tumor size was measured at an interval of 4 days for 9 weeks.Hematoxylin and eosin (HE)staining was performed to observe the morphological changes of tumor cells.The protein expression of IL-18 and E1A.microvessel density in tumor tissue,and apoptosis of tumor xenografts were detected by immuno fluorescence assay,immunohistochemistry and in situ end labeling technique (TUNEL).respectively.Results The treatment with ZD55-IL-18 significantly inhibited the growth of tumor.Forty-four days after the treatment,the mean tumor volume was 1039.378±29.67 mm3 in ZD55-IL-18-treated mice.significantly smaller than that in Ad-IL-18 treated mice(2900.46±62.65 mm3)and PBS-treated mice(3980.24±63.78 mm3).HE staining showed that the nuclei of tumor cells were heavily stained with few nucleoli in ZD55-IL-18-treated mice.Increased positivity rate of IL-18 was noticed in ZD55-IL-18-treated mice vs.AD55-IL-18-treated mice(83.4%±3.2%vs 24.4%±2.1%.P＜0.01).Moreover,immunofluorescence assay revealed the presence of E1A protein in tumor tissue.A decrease was found in the microvessel density in ZD55-IL-18-treated mice compared with the PBS-treated mice(P＜0.01).The apoptosis rate in tumor cells from high to low was 86.28%±3.25%in ZD55-IL-18-treated mice,43.67%±3.46%in Ad-IL-18-treated mice,and 10.73%±2.48%in PBS-treated mice;there was a significant difference between the three groups(all P＜0.05).Conclusion The oncolytic adenovirus expressing human IL-18 gene,ZD55-IL-18,has a significant inhibitory effect on the growth and metastasis of malignant melanoma implanted in nude mice.

Effect of Zhenganxifeng Decoction and Buyanghuanwu Decoction on Early Rehabilitation of Stroke / 中国康复理论与实践

@#Objective To observe the effect of Zhenganxifeng decoction and Buyanghuanwu decoction on the early rehabilitation of the stroke.Methods 101 cases with acute stroke were randomly divided into the treatment group(n=51) and control group(n=50).All patients were treated with routine medical therapy,physiotherapy and electric stimulation for a month.The treatment group was treated with Zhenganxifeng decoction while the control group with Buyanghuanwu decoction in addition.Results The motor function and Activities of Daily Living(ADL) in both groups were improved after treatment,but were better in treatment group than in control group(P<0.01).Conclusion It is better to use Zhenganxifeng decoction in the early rehabilitation of the stroke than Buyanghuanwu decoction.