Gualou xiebai decoction ameliorates cardiorenal syndrome type II by regulation of PI3K/AKT/NF-κB signalling pathway.

BACKGROUND: Cardiorenal syndromes type II (CRS2) is a multi-organ ailment that manifests as a combination of cardiac and renal dysfunction, resulting in chronic kidney disease due to chronic cardiac insufficiency. It affects at least 26 million people worldwide, and its prevalence is increasing. Gualou Xiebai Decoction (GXD), a traditional Chinese medicine (TCM) with a rich history of application in the management of coronary artery disease, has been explored for its potential therapeutic benefits in CRS2. Nevertheless, the mechanism by which GXD alleviates CRS2 remains obscure, necessitating further investigation. PURPOSE: The aim of this study was to assess the effects of the ethanolic extract of GXD on CRS2 and to elucidate the underlying mechanism in a rat model of myocardial infarction, offering a potential target for clinical treatment for CRS2. STUDY DESIGN AND METHODS: A rat model of CRS2 was induced by surgical myocardial infarction and treated with GXD for 10 weeks. Cardiac function was assessed using echocardiography, while serum and urine biochemistry were analyzed to evaluate potential cardiac and renal damage. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active compounds, potential therapeutic targets, and interventional pathways through which GXD could potentially exert its effects on CRS2. Subsequently, these predictions were confirmed in vivo and vitro through various analyses. RESULTS: The current investigation employed echocardiography to exhibit the apparent cardiac remodeling following the induction of myocardial infarction. Damage to the heart and kidneys of CRS2 rats was effectively ameliorated by administration of GXD. The outcomes derived from the analyses of HE and Masson staining indicated that the pathological damage to the heart and kidney tissues of rats in the GXD groups was considerably alleviated. Using network pharmacology analysis, AKT1, IL-6, and TNF-α were identified as plausible therapeutic targets for the treatment of CRS with GXD. Subsequent functional and pathway enrichment analysis of the underlying targets disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the mechanism of GXD in the treatment of CRS2. Immunohistochemical, western blot, RT-PCR and immunofluorescence staining were employed to demonstrate that GXD can regulate the PI3K/AKT/NF-κB signaling pathway in the CRS2 rat model. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the effect of diosmetin, which was one of the potential active components of GXD analysed by compound-target-disease network, on p-PI3K and p-AKT in vitro. CONCLUSIONS: The findings of this study suggest that GXD improves cardiac and renal function in CRS2 rats and that the underlying mechanism involves inhibition of the PI3K/AKT/NF-κB pathway.

Levetiracetam attenuates diabetes-associated cognitive impairment and microglia polarization by suppressing neuroinflammation.

Introduction: Cognitive impairment is a common complication and comorbidity of diabetes. However, the underlying mechanisms of diabetes-associated cognitive dysfunction are currently unclear. M1 microglia secretes pro-inflammatory factors and can be marked by CD16, iNOS, Iba1 and TNF-ɑ. The decline of M2 microglia in the diabetic rats indicates that high glucose promotes the differentiation of microglia into the M1 type to trigger neuroinflammatory responses. Moreover, there is a lack of strong evidence for treatments of diabetes-associated cognitive impairment in addition to controlling blood glucose. Methods: Diabetic rats were established by intraperitoneal injection of one dose of streptozotocin (60 mg/kg). Polarization transitions of microglia were induced by high glucose treatment in BV2 cells. Levetiracetam was orally administered to rats 72 h after streptozotocin injection for 12 weeks. Results: In STZ-induced diabetic rats, the results demonstrated that levetiracetam improved rat cognitive function (Morris water maze test) and hippocampus morphology (Hematoxylin-eosin staining), and the effect was more evident in the high-dose levetiracetam group. Microglia activation in the hippocampus was inhibited by levetiracetam treatment for 12 weeks. Serum levels of TNF-α, IL-1ß, and IL-6 were reduced in the LEV-L and LEV-H groups, and IL-1ß level was obviously reduced in the LEV-H group. In vitro, we found that levetiracetam 50 µM attenuated high-glucose induced microglial polarization by increasing IL-10 level and decreasing IL-1ß and TNF-α levels. Moreover, levetiracetam 50 µM increased and decreased the proportion of CD206+/Iba1+ and iNOS+/Iba1+cells, respectively. Western blot analysis illustrated that LEV 50 µM downregulated the expression of MyD88 and TRAF6, and phosphorylation of TAK1, JNK, p38, and NF-κB p65. The effect of levetiracetam on the anti-polarization and expression of p-JNK and p-NF-κB p65 were partly reversed by anisomycin (p38 and JNK activators). Discussion: Together, our data suggest that levetiracetam attenuates streptozotocin-induced cognitive impairment by suppressing microglia activation. The in vitro findings also indicate that the levetiracetam inhibited the polarization of microglia via the JNK/MAPK/NF-κB signaling pathway.

Scutebarbatine A induces ROS-mediated DNA damage and apoptosis in breast cancer cells by modulating MAPK and EGFR/Akt signaling pathway.

Scutebarbatine A (SBT-A), a diterpenoid alkaloid, has exerted cytotoxicity on hepatocellular carcinoma cells in our previous works. Here, the antitumor activity of SBT-A in breast cancer cells and the underlying mechanism were explored. The anti-proliferative effect of SBT-A was measured by trypan blue staining, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assay. DNA double-strand breaks (DSBs) were evaluated by observing the nuclear focus formation of γ-H2AX. Cell cycle distribution was assessed by flow cytometry. Apoptosis was determined by a TUNEL assay. Intracellular reactive oxygen species (ROS) generation and superoxide production were measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE) staining, respectively. The results indicated that SBT-A showed a dose-dependent cytotoxic effect against breast cancer cells while revealing less toxicity toward MCF-10A breast epithelial cells. Moreover, SBT-A remarkably induced DNA damage, cell cycle arrest and apoptosis in both MDA-MB-231 and MCF-7 cells. SBT-A treatment increased the levels of ROS and cytosolic superoxide production. Pretreatment with N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to block viability reduction, DNA damage, apoptosis and endoplasmic reticulum (ER) stress caused by SBT-A. By exposure to SBT-A, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) was upregulated, while the phosphorylation of extracellular signal-regulated kinase (ERK) was downregulated. In addition, SBT-A inhibited the EGFR signaling pathway by decreasing EGFR expression and phosphorylation of Akt and p70S6K. As mentioned above, SBT-A has a potent inhibitory effect on breast cancer cells through induction of DNA damage, apoptosis and ER stress via ROS generation and modulation of MAPK and EGFR/Akt signaling pathway.

Assessing early changes in plasma HER2 levels is useful for predicting therapeutic response in advanced breast cancer: A multicenter, prospective, noninterventional clinical study.

BACKGROUND: Early prediction of treatment response is crucial for the optimal treatment of advanced breast cancer. We aimed to explore whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels using digital PCR (dPCR) could predict the treatment response in advanced breast cancer. METHODS: This was a multicenter, prospective, noninterventional clinical study of patients with advanced breast cancer. All enrolled patients underwent blood testing to measure the HER2 levels by digital PCR before treatment initiation and once every 3 weeks during the study. The primary endpoints werea the diagnostic value of dPCR for detecting HER2 status in the blood andb the relevance of potential changes in the plasma HER2 level at 3 weeks from baseline for predicting treatment response. RESULTS: Overall, 85 patients were enrolled between October 9, 2018, and January 23, 2020. dPCR had a specificity of 91.67% (95% CI: 80.61% to 97.43%) for detecting HER2 amplification, and the area under the receiver operating characteristic (ROC) curve was 0.84 (p < 0.01). A clinically relevant specificity threshold of approximately 90%, which was equivalent to a ≥15% decrease in the plasma HER2 ratio at 3 weeks from baseline, showed a positive predictive value of 97.37% (95% CI: 77.11% to 98.65%) in terms of predicting clinical benefit. Patients whose plasma HER2 ratio was reduced by ≥15% had a longer median progression-free survival (PFS) than those whose ratio was reduced by <15% (9.20 months vs. 4.50 months, p < 0.01). CONCLUSIONS: Early changes in the plasma HER2 ratio may predict the treatment response in patients with advanced breast cancer and could facilitate optimal treatment selection.

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis. Traditional Chinese herbal medicines have been used to treat patients with cancer for many years in China. This study investigated the effects of licochalcone B (LCB), a flavonoid compound isolated from the root of Glycyrrhiza uralensis Fisch., on cell proliferation, DNA damage and TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HCC cells. Our results showed that LCB inhibited cell proliferation and induced DNA damage, cell cycle arrest and apoptosis. Treatment with LCB significantly inhibited the Akt/mTOR pathway and activated endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, combined treatment with LCB and TRAIL yielded evident enhancements in the viability reduction and apoptosis. LCB upregulated death receptor 4 (DR4) and death receptor 5 (DR5) protein in a concentration- and time-dependent manner. The knockdown of DR5 significantly suppressed TRAIL-induced cleavage of PARP, which was enhanced by LCB. Treatment with an extracellular-regulated kinase (ERK) inhibitor (PD98059) or c-Jun N-terminal kinase (JNK) inhibitor (SP600125) markedly reduced the LCB-induced upregulation of DR5 expression and attenuated LCB-mediated TRAIL sensitization. In summary, LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

5-min mindfulness audio induction alleviates psychological distress and sleep disorders in patients with COVID-19.

BACKGROUND: Mindfulness meditation is beneficial to mitigate the negative effects of the coronavirus disease 2019 (COVID-19) pandemic in the general population, but no study examined such meditation in the COVID-19 patients themselves. AIM: To explore the short-term efficacy of mindfulness meditation in alleviating psychological distress and sleep disorders in patients with COVID-19. METHODS: This prospective study enrolled patients with mild COVID-19 treated at Wuhan Fangcang Hospital in February 2020. The patients were voluntarily divided into either a mindfulness or a conventional intervention group. The patients were evaluated before/after the intervention using the Short Inventory of Mindfulness Capability (SMI-C), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Seventy-five participants were enrolled in this study, with 43 and 32 in the mindfulness and conventional groups, respectively. Before the intervention, there were no differences in SMI-C, HADS, or PSQI scores between the two groups. After the 2-wk intervention, the mindfulness level (from 30.16 ± 5.58 to 35.23 ± 5.95, P < 0.001) and sleep quality (from 12.85 ± 3.06 to 9.44 ± 3.86, P < 0.001) were significantly increased in the mindfulness group. There were no differences in the conventional group. After the intervention, the mindfulness level (35.23 ± 5.95 vs 31.17 ± 6.50, P = 0.006) and sleep quality (9.44 ± 3.86 vs 11.87 ± 4.06, P = 0.011) were significantly higher in the mindfulness group than in the conventional group. Depression decreased in the mindfulness group (from 14.15 ± 3.21 to 12.50 ± 4.01, P = 0.038), but there was no difference between the two groups. CONCLUSION: Short-term mindfulness meditation can increase the mindfulness level, improve the sleep quality, and decrease the depression of patients with COVID-19.

Functional Disability After Ischemic Stroke: A Community-Based Cross-Sectional Study in Shanghai, China.

Objective: This study aimed to understand the demographics, functional disabilities, cognitive impairment, and depressive mood among stroke patients and to explore the correlation between functional disability and the other health conditions so as to provide some data for community rehabilitation among stroke patients. Methods: A cross-sectional study was conducted to investigate the functional status of ischemic stroke patients with stroke history between 1 month and 2 years by applying the modified Rankin Scale (mRS). Data were collected during October 2016 and January 2017 from 11 communities in two districts of Shanghai, China. We used face-to-face questionnaire interviews to collect information on sociodemographics, vascular risks associated with stroke, cognitive function [Mini-Mental State Examination (MMSE)], and depression [Patient Health Questionnaire-9 (PHQ-9)]; and we applied SPSS 24.0 for data analysis. Results: In this study, 305 patients with ischemic stroke were finally recruited, including 189 (61.97%) men, with an average age of 67 years. According to the mRS score, ischemic stroke patients were divided into patients without symptoms (controls, mRS = 0), patients without obvious disability (mRS = 1), and patients with mild to severe disability (mRS = 2-5). Ischemic stroke patients with different mRS levels demonstrated significant differences in age, tobacco smoke exposure, previous stroke history, cognitive function, and depression status. Compared with patients without symptoms (mRS = 0), patients with mRS = 1 had a lower MMSE score [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26-0.90]; and patients with mRS = 2-5 had a lower MMSE score [OR = 0.16, 95% CI: 0.08-0.33], had a higher PHQ-9 score [OR = 5.36, 95% CI: 2.19-13.11], and were more likely to have previous stroke history [OR = 2.18, 95% CI: 1.01-4.79]. Conclusion: Lower degrees of functional independence are related to cognitive impairment, as well as the previous stroke history and depression status.

Pulmonary arterial hypertension in critically ill elderly patients.

OBJECTIVE: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. METHODS: We selected 122 cases admitted to the ICU, ages 60-93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient's pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. RESULTS: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. CONCLUSIONS: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis.

Risk factors and clinical features in ischemic stroke patients with different tongue conditions.

OBJECTIVE: To investigate the risk factors and clinical features in ischemic stroke patients with different tongue conditions. METHODS: A total of 168 successive acute ischemic stroke inpatients (within 7 days of stroke onset) were recruited. Patients were assigned to groups according to tongue color (pink, pale, red, purple), tongue coating (no coating, thin coating, thick coating) and sublingual vessel (normal, abnormal). Risk factors and clinical features including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI), clinical classification, laboratory data and pulmonary infection complications were compared. RESULTS: There were no significant differences in risk factors and clinical features among groups with different tongue colors. The incidence of smoking (4.5%) was lower in the no coating group compared with the thin (30.0%) and thick (39.3%) coating groups (P<0.017). NIHSS (19.05±10.68) in the no coating group was higher than the thin (6.40±6.18) and thick (7.41±7.05) coating groups (P<0.017), BI (20.91±29.99) was lower than the thin (67.61±28.78) and thick (63.02±33.54) coating groups (P<0.017), and the percentage of mRS >3 (90.9%) was higher than the thin (42.2%) and thick (42.9%) coating groups (P<0.017). The percentage of partial anterior circulation infarction patients in the no coating group was higher than the thin coating group (77.3% vs. 42.2%), and the percentage of lacunar infarction patients was lower than the thin coating group (4.5% vs. 37.8%, P<0.017). NIHSS in the abnormal sublingual vessel group was lower than the normal group (5.28±4.38 vs. 10.57±9.58, P=0.000), and BI was higher than the normal group (67.61±29.29 vs. 54.64±36.23, P=0.015). CONCLUSION: Tongue conditions of acute stroke patients were relevant to clinical features.

[Some Discussions on the Combination of Disease Identification and Syndrome Typing].

The combination of disease identification and syndrome typing is a conceptual combi- nation of modern medicine and Chinese medicine. Authors reviewed related domestic literatures in recent 10 years, and preliminarily explored combination of disease identification and syndrome typing from its formation and its application in diagnosis, treatment, therapeutic efficacy evaluation. Authors also looked into its future.

Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson's disease: a meta-analysis.

To assess the long-term use of L-dopa alone vs L-dopa-sparing therapy, as initial treatment, provides the most efficient long-term control of symptoms and best quality of life for people with early Parkinson's disease (PD). PubMed; Google scholar; Cochrane Central Register of Controlled Trials and the Web of Science were searched for randomised, placebo-controlled trials (RCTs) on L-dopa alone and L-dopa sparing as initial treatment in early PD patients. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. Eleven RCTs were included. The results showed that L-dopa alone could evidently improve the UPDRS part I (p = 0.005), part II (p < 0.0001), part III (p < 0.0001) and UPDRS total score (p = 0.004) compared with L-dopa-sparing therapy in PD patients. Meanwhile, a reduced risk of dyskinesia (p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off phenomenon (p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated initially with L-dopa-sparing therapy compared to L-dopa has been consistently reported. What is more, we found more patients on aL-dopa-sparing therapy were more than triple as likely to discontinue treatment prematurely due to adverse events than L-dopa treatment patients (43.7 vs 15.8 %). L-Dopa alone is the most effective medication available for treating the motor symptoms of PD patients, despite the greater incidence of involuntary movements. Meanwhile, more patients on dopamine agonists or MAOBI were more likely to discontinue treatment prematurely than L-dopa alone treatment patients within the long follow-up period.

Silencing of RegIV by shRNA causes the loss of stemness properties of cancer stem cells in MKN45 gastric cancer cells.

Regenerating islet-derived family member 4 (RegIV) is overexpressed in several types of tumours, including pancreatic and gastric cancer (GC). However, the role it plays in gastric cancer stem cells (GCSCs) remains unknown. The present study tested the hypothesis that the silencing of RegIV by shRNA in GC cells may cause the loss of their stemness properties, indicating the inhibition of growth, proliferation and increased sensitivity to chemoradiation-induced cell death. MKN45 poorly differentiated human GC cells were propagated as mammospheres in stem cell culture conditions. Mammospheres were identified as CSCs using generally acknowledged CSC markers such as CD44. A panel of 21-nucleotide shRNAs were designed to target RegIV gene expression. Several shRNA constructs were identified that led to significant reduction in RegIV mRNA expression. Furthermore, the stemness properties of control mammospheres and RegIV knockdown mammospheres were compared by tumourigenicity assay in vivo and plate colony formation assay in vitro. Finally, we evaluated the treatment response in both mammospheres which underwent chemoradiation. The knockdown expression of RegIV by shRNA deprived CSCs of their stemness properties and increased the effectiveness of cell killing following chemoradiation. Inhibition of endogenous RegIV expression may be a new therapeutic strategy for human GC.

CD44+ gastric cancer cells with stemness properties are chemoradioresistant and highly invasive.

CD44 has been confirmed as a cancer stem cell marker in a variety of human cancer cell lines and primary tumours, but whether this marker is applicable to gastric cancer (GC) remains unknown. The responses of CD44+ GC stem-like cells to chemoradiation and the roles they play in cancer invasion are not well understood. In the present study, cell sorting was applied to the poorly differentiated human GC cells to isolate a pure concentration of the CD44+ cell populations (<1% CD44- cells). The stemness properties of the CD44+ cell population were confirmed by two 'gold standard' methods; an in vivo tumourigenicity assay and an in vitro spheroid colony formation assay. In addition, the treatment response was evaluated in CD44+ and CD44- cell fractions that underwent chemoradiation. In general, CD44+ stem-like cells tended to respond more poorly to chemoradiation than their non-stem-like counterparts. Further experimentation revealed that the CD44+ stem-like cells that recorded positive scores in the migration and invasion assay in vitro formed invasive tumours in vivo. Therefore, we hypothesized that CD44+ stem-like cells may significantly express invasion-associated genes. Consistent with this prediction, increased expression of the cancer invasion-related genes matrix metalloproteinase (MMP)-1, MMP-2, epidermal growth factor receptor (EGFR) and cyclooxygenase 2 (COX-2) were detected in the CD44+ stem-like cells. To the best of our knowledge, this is the first study that reveals the correlation between CD44+ GC cells and cancer invasion. By selectively eliminating CD44+ stem-like cells, it may be possible to treat patients with aggressive, non-resectable GCs, as well as preventing the tumours from metastasizing.

Activation of the phosphorylation of ATM contributes to radioresistance of glioma stem cells.

Ionizing radiation (IR) is currently the most efficient therapy available for malignant glioma. Unfortunately, this strategy is palliative due to the characteristics of radioresistance of malignant glioma. The aim of our study was to compare glioma stem cells (GSCs) with glioma cells (GCs) to determine whether GSCs are responsible for the radioresistance phenotype and to elucidate whether cell cycle checkpoint proteins are responsible for the radioresistance of GSCs. In this study, CD133 (a marker of brain cancer stem cells) and nestin were co-expressed in GSCs isolated from GCs. The percent of CD133+ cells in GSCs and GCs were >80 and <2%, respectively. Significantly more GSCs survived following 2, 4, 6 and 8 Gy IR than GCs. IR kills cancer cells primarily through DNA double-strand breaks (DSBs). The neutral comet assay is often used to intuitively show the level of DSBs. Significantly fewer GSCs showed DNA damage than GCs following 2 Gy IR. This demonstrated that GSCs are more resistant to in vitro radiation than GCs. Furthermore, activated ataxia telangiectasia mutated (ATM) is essential for the activation of downstream effector kinases, such as checkpoint kinase 2 (Chk2) and p53 which mainly contribute to the proper regulation of IR-induced arrest in the G1 phase. DNA damage induced by IR potently initiated activation of phosphorylation of the ATM, p53 and Chk2 checkpoint proteins. Activation of the phosphorylation of these checkpoint proteins was significantly higher in the GSCs compared to GCs. We found that inhibition of ATM activation induced cell cycle checkpoint defects and increased the rate of apoptosis of GSCs following IR. Our results suggest that GSCs were more resistant to radiation compared to GCs due to high expression of phosphorylated cell cycle checkpoint proteins, and inhibition of ATM could significantly reduce the radioresistance of GSCs and GCs. ATM may represent a source of radioresistance in GSCs and a target of improved radiosensitivity of GSCs.

[Influence of continuous cropping years on yield and active compounds in Salvia miltiorrhiza f. alba].

Biological characteristic of Salvia miltiorrhiza f. alba in field was studied. HPLC method was used to determine the lipophilic constituents (dihydrotanshinone, cryptotanshinone, tanshinone, tanshinone II (A) and miltione) and hydrophilic constituents (salvianolic acid, rosemarinic acid). The results showed that the fresh weight of S. miltiorrhiza f. alba which cropped for 2 years was decreased by 80.47%, while dry weight decreased by 79.42%. The normal diameter of the root was 0.3-0.5 cm, however, the diameter was 0.2-0.4 cm after 2 years, it was said that the decrease of the root diameter was the main reason for the decrease of the yield. The average contents of dihydrotanshinone, cryptotanshinone, tanshinone, tanshinone II (A), miltione, salvianolic acid and rosemarinic acid were decreased by 35.26%, 32.26%, 19.35%, 3.39%, 64.40%, 66.93% in plant which continuously cropped for 2 years, respectively. The yield and active constituents were mostly effected in the plant of S. miltiorrhiza f. alba, which continuously cropped for 2 years.

TGFbeta1 T29C polymorphism and cancer risk: a meta-analysis based on 40 case-control studies.

Transforming growth factor-beta1 (TGFbeta1) plays a significant role in regulating cellular proliferation and apoptosis. The TGFbeta1 T29C polymorphism reportedly affects cancer risk, but pertinent studies offer conflicting results. We therefore performed a meta-analysis based on 40 studies from 32 publications, assessing the strength of the association using odds ratios with 95% confidence intervals. Overall, no evidence has indicated that individuals carrying CC or CT genotypes had significantly increased cancer risks, compared with TT genotype carriers [CC vs. TT: odds ratio (OR)=1.10, 95% confidence interval (95% CI)=1.00-1.21, P=0.06; CT vs. TT: OR=1.07, 95% CI=0.99-1.16, P=0.09). However, stratified analysis by cancer type and ethnicity indicated a significantly increased risk of prostate cancer (CT vs. TT: OR=1.28, 95% CI=1.01-1.61, P=0.04) and cancer in those of Asian descent (CC vs. TT: OR=1.26, 95% CI=1.03-1.53, P=0.02; CT vs. TT: OR=1.20, 95% CI=1.01-1.43, P=0.04). This association was also observed in the dominant model for prostate cancer. Although not all bias could be eliminated, this meta-analysis suggested that TGFbeta1 29C was a low-penetrant risk factor for prostate cancer and cancer in Asians. A larger single study is still required to evaluate any association with other types of cancer or in other populations.

Risk factor, pattern, etiology and outcome in ischemic stroke patients with cancer: a nested case-control study.

BACKGROUND: Coagulation disorders are seen in cancer patients, but it is not clear whether cancer predisposes stroke patients to unique characteristics. The aim of the study was to investigate risk factors, pattern,etiology and outcome in stroke patients with cancer. METHODS: A retrospective review of all ischemic stroke (IS) patients with cancer (n = 56) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted and comparison made to age- and gender-matched noncancer IS patients admitted to the same hospital during the same period. RESULTS: Vascular risk factors and stroke pattern were comparable in cancer and noncancer groups. Post-stroke thrombotic episodes (myocardial infarction, deep vein thrombosis or pulmonary emboli) were more common in the cancer group than in the noncancer group (11 vs. 0%, p = 0.031). Depression was also more common in the cancer group than in the noncancer group (14 vs. 2%, p = 0.039). There was a tendency for more patients in the cancer group to die in hospital (30 vs. 14%, p = 0.078). CONCLUSIONS: Coagulation disorders were more likely to be seen in stroke cancer patients, and patients with cancer tended to have a higher in-hospital post-stroke mortality. Larger sample size studies may identify further differences in the characteristics of stroke patients with cancer.

Delirium within three days of stroke in a cohort of elderly patients.

OBJECTIVES: To evaluate the incidence of stroke, risk factors for stroke, and outcomes in elderly stroke patients with delirium. DESIGN: Cohort study with 12-month follow-up. SETTING: Bankstown-Lidcombe Hospital, a 450-bed teaching hospital of the University of New South Wales, Sydney, Australia. PARTICIPANTS: One hundred fifty-six stroke patients aged 65 and older recruited over 1 year. MEASUREMENTS: Incidence of delirium (defined in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria) within 3 days poststroke, length of hospital stay, discharge destination, short- and long-term mortality, Functional Independence Measure (FIM) scores, and Mini-Mental State Examination (MMSE) scores. RESULTS: Thirty-nine (25%) elderly stroke patients had delirium within 3 days after stroke. Logistic regression analysis found that older age (P=.04), hemorrhagic stroke (P=.02), metabolic disorders (P=.003), dementia prestroke (P=.02), Glasgow Coma Scale (GCS) score less than 15 on admission (P<.001), and inability to lift both arms on admission (P=.03) were independent predisposing factors for delirium. Patients who had a cardioembolic stroke (odds ratio (OR)=5.58) or total anterior circulation infarction (OR=3.42) were also more likely to develop delirium. Patients with delirium were associated with higher 6- and 12-month mortality (P<.05), lower 12-month FIM and MMSE scores, and a higher 12-month institutionalization rate. CONCLUSION: Delirium occurred frequently in acute stroke patients aged 65 and older. Factors independently associated with delirium included old age, intracerebral hemorrhage, metabolic factors, prestroke dementia, initial GCS less than 15, and inability to lift both arms on admission. Patients with delirium had higher long-term mortality and a worse functional outcome.

[Effects of pravastatin, fosinopril and their combination on myocardium TNF-alpha expression and ventricular remodeling after myocardial infarction in rats].

OBJECTIVE: To investigate the effects of pravastatin, fosinopril and their combination on ventricular remodeling, cardiac function, tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and matrix metalloproteinases (MMPs) activities after myocardial infarction (MI) in rats. METHODS: Acute myocardial infarction (AMI) was established by ligation of the anterior descending coronary artery in male Sprague-Dawly (SD) rats. Twenty-four hours after the procedure, the 48 surviving rats were grouped randomly as AMI control, fosinopril (10 mg.kg(-1).d(-1)), pravastatin (20 mg.kg(-1).d(-1)) and a combined use of the 2 drugs. Sham-operated group (n = 8) was taken randomly as non-infarction control. Six weeks after treatment with the drugs by gastric gavage, heart function and left ventricular remodeling were assessed. Left ventricular weight (LVW)/body weight (BW) ratio was determined. The relative expression of myocardium TNF-alpha mRNA was assessed by reverse transcription-polymerase chain reaction. Left ventricular myocardium MMPs activities were assessed by Zymography. RESULTS: There were no significant differences among the four AMI groups in infarction size (P > 0.05). In comparison with the AMI group, left ventricular end-diastolic pressure, left ventricular end-diastolic diameter, LVW/BW all decreased significantly (P < 0.05 - 0.01); while dp/dtmax, dp/dtmin, fractional shortening (FS) and ejection fraction (EF) increased significantly in all three drug-treated groups (P < 0.05 - 0.01); increments of FS, LVEF and dp/dtmax were more evident in the combination group than either the fosinopril or pravastatin group (P < 0.05). The levels of TNF-alpha mRNA in AMI rats treated with fosinopril, pravastatin and their combination reduced 29%, 26% and 33%, respectively (P < 0.01); MMP-2 activity reduced 25%, 30% and 35%, respectively (P < 0.01); MMP-9 activity reduced 20%, 18% and 24%, respectively (P < 0.01). There were no significant differences in other variables among the 3 treatment groups (P > 0.05). CONCLUSION: Pravastatin, fosinopril and their combination showed favorable effects on left ventricular remodeling after AMI in rats and demonstrated improved cardiac function. The combined treatment group yielded better results in the context of improving left ventricular systolic function. These effects could be relevant to the attenuation of increased MMP-2 and MMP-9 activities and left ventricular expression of TNF-alpha.

[Traditional Chinese medicine in treatment of Parkinson's disease].

Parkinson's disease is a commonly encountered central nervous retrograde affection in elder persons. According to the theories of traditional Chinese medicine, Parkinson's disease is characterized by deficiency in the Ben (root) and excess in the Biao (branch). The Ben (root) is insufficiency of liver and kidney and deficiency of qi and blood; and the Biao (branch) is wind, fire, phlegm and stasis. Good therapeutic effects have been obtained by treatment based on syndrome differentiation, treatment with specific prescriptions and acupuncture. The further study on literatures, standardized criterion of symptoms differentiation and therapeutic effect determination as well as the screening and further research on the effective prescriptions and herbs should be paid more attention, meanwhile, the integration of herbs and acupuncture will be conducive to raise the therapeutic effect.