[Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats].

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

[Study on acute kidney injury model induced by renal ischemia-reperfusion in rats].

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 µmol·L-1 to more than 430 µmol·L-1. Among them,5 rats showed less than 100 µmol·L-1 serum Crea,20 rats with 100-200 µmol·L-1 serum Crea and 12 rats with more than 430 µmol·L-1. Rats with serum Crea between 300-430 µmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 µmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 µmol·L-1 and the group of Crea 300-370 µmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 µmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution.

Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg-1·3d-1) or PTX (7.5 mg·kg-1·3d-1) with or without SMI (0.01 mL·g-1·d-1) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 µL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.

Experiences and insomnia-associated factors in Chinese breast cancer survivors: a qualitative study.

AIMS AND OBJECTIVES: This study aimed to explore the experiences and factors associated with insomnia in Chinese breast cancer survivors. BACKGROUND: Insomnia is a common and significant symptom in breast cancer survivors. Quantitative studies are unable to describe the experience of insomnia and the sleep-associated factors from a personal point of view. A profound understanding of the experience of insomnia in breast cancer survivors can provide information for health workers and caregivers to allow them to provide more effective support. DESIGN: A descriptive qualitative research was adopted. METHODS: In-depth interviews were conducted with 22 insomniac breast cancer survivors. A qualitative content analysis was used to analyse the data. RESULTS: Three themes emerged concerning the experiences of insomnia, including sleep neglect, insomnia perception and insomnia anxiety. Participants reported their own opinions on three insomnia-associated factors, including factors associated with hospitalisation, factors associated with breast cancer and the therapies and too much attention placed on sleep. CONCLUSIONS: Survivors would neglect their sleep problems in the early stage after diagnosis. When they became aware of their sleep problems, they were inclined to worry too much and sought help from traditional Chinese medicine. Anticipatory sleep anxiety, excessive negative cognitive activities and insomnia became a vicious circle for insomniac breast cancer survivors. RELEVANCE TO CLINICAL PRACTICE: The findings provide detailed information to help nurses understand the experiences of breast cancer survivors with insomnia. Nurses could provide proper care to help prevent insomnia or improve sleep.

Optimization of Maximum Light Use Efficiency in Inner Mongolian Steppe.

For the case that the value of the maximum light use efficiency (MLUE) is not optimized for different steppes, we simulated the MLUE for meadow steppe, typical steppe and desert steppe in Inner Mongolia based on the field observed NPP and CASA ecosystem model, and analyzed the spatial and temporal pattern of the LUE and net primary productivity (NPP) in Inner Mongolia. The result indicate that the MLUE is optimized to be 0.654，0.553 and 0.511 gC·MJ-1 for meadow steppe, typical steppe and desert steppe in Inner Mongolia, respectively, with an average of 0.573 gC·MJ-1. Compared to the result that used same value of 0.541 gC·MJ-1 for MLUE, the correlation coefficient and relative mean square error was improved 0.024 and 2.62 gC·(m2·month-1)-1, respectively after optimization. Affected by the hydrothermal condition and distribution of grassland types, the LUE and NPP in Inner Mongolia decreased from northeast to southwest, and showed one crest shape. However, the maximum value of LUE and NPP was appeared in August and July. This difference could be attributed to the difference in the maximum value between absorbed photosynthetically active radiation and LUE. The LUE and NPP decreased by meadow steppe, typical steppe and desert steppe.

Posttraumatic growth and psychological distress in Chinese early-stage breast cancer survivors: a longitudinal study.

OBJECTIVE: To describe the dynamic changes in posttraumatic growth (PTG) and psychological distress in hospitalized early-stage breast cancer (BC) survivors over a 6-month period. METHODS: A longitudinal study design was adopted. The PTG inventory (PTGI) and distress management screening measure were used 3 months after diagnosis, then again at 6 and 9 months after diagnosis. For baseline data, 155 BC patients who were receiving chemotherapy were selected from four first-class tertiary hospitals in Beijing from April 2010 to March 2011 using a purposive sampling method. Of these, 120 BC patients completed the follow-up investigation. A repeated measures analysis of variance, followed by least significant difference post-hoc analysis, was used to compare PTG and psychological distress. RESULTS: The total score of the PTGI was 62.72 ± 14.66 in BC survivors at 3 months after diagnosis.There was a weak negative relationship between PTG and psychological distress (r = ­0.282, p<0.001).PTG increased and psychological distress decreased from 3 to 9 months after diagnosis. The PTGI scores were 63.24 ± 14.21, 68.26 ± 15.29, and 70.29 ± 16.07 at 3, 6, and 9 months after diagnosis, respectively, with distress thermometer scores of 3.62 ± 1.98, 2.59 ± 2.00, and 2.51 ± 1.00, respectively. CONCLUSIONS: At 3 months after diagnosis, BC survivors develop PTG at a low level while they are receiving chemotherapy. PTG showed a weak negative association with psychological distress. The level of PTG shows an increasing tendency, whereas the degree of psychological distress exhibits a downward trend in the 9 months after diagnosis.

Systematic evaluation and meta-analysis of Chinese medicine in the treatment of centrally mediated abdominal pain syndrome.

BACKGROUND: This study aimed to evaluate the clinical efficacy of Chinese medicine for the treatment of centrally mediated abdominal pain syndrome (CAPS) using a meta-analysis system. METHODS: Six databases, including China National Knowledge Infrastructure, Vendor Information Pages, Chinese Biomedical Database, Wanfang, PubMed, and Embase were searched for randomized controlled trials related to the treatment of CAPS with traditional Chinese medicine. The bias risk assessment tool and RevMan5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) were used to conduct quality assessment and meta-analysis, and the GRADE grading system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fifteen articles were included in this study. Meta-analysis results showed that the treatment group was more effective in terms of the total effective rate (relative risk = 1.27; 95% confidence interval [CI], 1.19-1.34; P < .00001), Behavioral Rating Scale-6 pain score (mean difference [MD] = -0.79; 95% CI, -0.99 to -0.59; P < .00001), and traditional Chinese medicine (TCM) symptom score (MD = -1.74; 95% CI, -2.23 to -1.26; P < .00001) than the control group (P < .05). However, in terms of numerical rating scale pain score (MD = 0.79; 95% CI, -1.70 to 0.12; P = .09), the efficacy was comparable between the 2 groups, and the difference was not statistically significant (P > .05). In terms of verbal rating scale pain, depression, and anxiety scores, the data could not be combined due to inconsistent scoring criteria, and only descriptive analysis was performed. The results showed that the treatment group was slightly better than the control group in terms of relieving verbal rating scale pain and improving anxiety and depression (P < .05). CONCLUSION: Chinese medicine can effectively improve the pain and TCM clinical symptoms of patients with CAPS and relieve patients' anxiety and depression with fewer adverse effects, which has certain therapeutic advantages. However, because of the low methodological quality assessment of the included literature, the quality of GRADE evidence for outcome indicators is of mostly low and very low quality, the strength of recommendation is weak, and the credibility of the conclusion is average. More rigorous, larger sample, and higher-quality clinical trials are required to provide a higher level of evidence-based medicine for the development of TCM treatment standards for CAPS.

Network Pharmacology-Based Approach Uncovers the Mechanism of GuanXinNing Tablet for Treating Thrombus by MAPKs Signal Pathway.

BACKGROUND: GuanXinNing tablet (GXNT), a traditional Chinese patent medicine, has been found to have remarkable antithrombotic effects and can effectively inhibit pro-thrombotic factors in previous studies. However, the mechanism of its antithrombotic effects remains little known. METHODS: In this study, we first determined and identified the sources of each main compound in GXNT using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the action targets of the active components, mapped the target genes related to thrombus, and obtained potential antithrombotic targets for active ingredients. We then performed gene ontology (GO) enrichment analyses and KEGG signaling pathway analyses for the action targets, and constructed networks of active component-target and active component-target-pathway for GXNT. Additionally, we evaluated the pharmacodynamic effects of GXNT on thrombus using the rat thrombus model induced by FeCl3, observed the effects of antiplatelet aggregation via platelet assay, and further verified the results predicted by network pharmacology via Western blot. RESULTS: In total, 14 active ingredients were identified in GXNT, and 83 action targets were predicted, 17 of which are antithrombotic targets that potentially participate in processes including response to oxidative stress and positive regulation of blood vessel endothelial cell migration. KEGG pathway analyses revealed that the predicted action targets were involved in multiple signal pathways, such as MAPK, IL-17, and platelet activation. Pharmacodynamics study found that GXNT could significantly reduce the thrombus length and weight, lower platelet aggregation function, and decrease the levels of Fbg and PAI-1. In addition, GXNT could significantly increase 6-keto-PGF1α content and regulate the ratio of TXB2/6-keto-PGF1α, while not having dramatic effects on TXB2. GXNT was also observed to visibly inhibit maximum platelet aggregation. Herein, we further studied the thrombus-related MAPKs signaling pathway and found that GXNT could significantly reduce the phosphorylation levels of p38MAPK, ERK, and JNK proteins in platelet. CONCLUSIONS: This study revealed the pharmacodynamic material basis of GXNT and its potential multicomponent-multitarget-multipath pharmacological effects, confirmed the antithrombotic effects of GXNT, and showed that its mechanism may be related to inhibiting phosphorylation of p38, ERK, and JNK proteins in MAPKs signaling pathway, partially verifying the results from network pharmacology. The results from this study could provide a theoretical basis for the development and clinical application of GXNT.

Effect and Safety of Guanxinning Tablet () for Stable Angina Pectoris Patients with Xin (Heart)-Blood Stagnation Syndrome: A Randomized, Multicenter, Placebo-Controlled Trial.

OBJECTIVE: To investigate the effect and safety of Guanxinning Tablet (, GXN) for the treatment of stable angina pectoris patients with Xin (Heart)-blood stagnation syndrome (XBSS). METHODS: One hundred and sixty stable angina pectoris patients with XBSS were randomly assigned to receive GXN (80 cases) or placebo (80 cases, Guanxinning simulation tablets, mainly composed of lactose), 4 tablets (0.38 g/tablet), thrice daily for 12 weeks. After treatment, an exercise stress test (treadmill protocol), Chinese medicine (CM) syndrome score, electrocardiogram (ECG), and nitroglycerin withdrawal rate were evaluated and compared in the patients between the two groups. Meanwhile, adverse events (AEs) were evaluated during the whole clinical trial. RESULTS: Compared with the control group, the time extension of exercise duration in the GXN group increased 29.28 ±17.67 s after treatment (P>0.05); moreover, the change of exercise duration in the GXN group increased 63.10 ±96.96 s in subgroup analysis (P<0.05). The effective rates of angina pectoris, CM syndrome and ECG as well as nitroglycerin withdrawal rate were 81.33%, 90.67%, 45.76%, and 70.73%, respectively in the GXN group, which were all significantly higher than those in the control group (40.58%, 75.36%, 26.92%, 28.21%, respectively, P<0.05). CONCLUSION: GXN was a safe and effective treatment for stable angina pectoris patients with XBSS at a dose of 4 tablets, thrice daily.

Anemoside B4 Protects Rat Kidney from Adenine-Induced Injury by Attenuating Inflammation and Fibrosis and Enhancing Podocin and Nephrin Expression.

Anemoside B4 (B4) isolated from Radix Pulsatilla has anti-inflammatory activities in the colon and antitumor effects. However, its role in the prevention and treatment of kidney injury has not been reported. Here, we reported the effects of B4 on chronic kidney injury (CKI) and studied its related mechanism based on an adenine-induced kidney injury model in rats. The results showed that serum BUN (blood urea nitrogen), Crea (creatinine), and urinary proteins increased significantly after oral administration of adenine. Meanwhile, the adenine contents in both renal tissue and urine increased markedly compared with those of normal rats. Moreover, IL-1ß, IL-6, TNFα, and NFκB expression was upregulated in the kidney. Simultaneously, the expression of NLRP3 (the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3) in the inflammasome, which consists of Caspase 1, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and IL-18, was significantly upregulated. B4 could significantly decrease BUN and Crea; reduce urinary proteins in rats; suppress the expression of IL-6, IL-1ß, NFκB, NLRP3, Caspase 1, ASC, and IL-18; and increase urinary adenine contents and promote its excretion. In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation.

Chronic corticosterone (CORT) stress is an anxiety and depression inducing factor that involves the dysfunction of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and neuronal plasticity. However, the regulation of proteomic profiles in neurons suffering CORT stress is remaining elusive. Thus, the proteomic profiles of mouse neuronal C17.2 stem cells were comprehensively investigated by TMT (tandem mass tag)-labeling quantitative proteomics. The quantitative proteomics conjugated gene ontology analysis revealed the inhibitory effect of CORT on the expression of mitochondrial oxidative phosphorylation-related proteins, which can be antagonized by berberine (BBR) treatment. In addition, animal studies showed that changes in mitochondria by CORT can affect neuropsychiatric activities and disturb the physiological functions of neurons via disordering mitochondrial oxidative phosphorylation. Thus, the mitochondrial energy metabolism can be considered as one of the major mechanism underlying CORT-mediated depression. Since CORT is important for depression after traumatic stress disorder, our study will shed light on the prevention and treatment of depression as well as posttraumatic stress disorder (PTSD).

[Effects of Manganese on the Growth and Fluorescence Induction Kinetics of Conticribra weissflogii].

The manganese (Mn4) cluster, as a part of the oxygen-evolving complex (OEC) in the photosystemⅡ (PS Ⅱ) of microalgae and plants, assists in the electrolysis of water to oxygen, protons, and electrons. To examine the relationships among manganese (Mn) concentrations in the culture medium, algae growth, and chlorophyll fluorescence characteristics, we exposed the diatom Conticribra weissflogii to a broad range of Mn concentrations from 0 to 9000 nmol·L-1. Chlorophyll fluorescence induction dynamics analysis, an effective way to investigate photosynthetic characteristics, can be used as indicator of the photosynthetic apparatus of photosynthesizers under different stressors. Here, we studied the effects of Mn exposure on C. weissflogii using this fluorescence analysis method. The results show that the growth of C. weissflogii is independent of the Mn exposure at concentrations below 9000 nmol·L-1. Moreover, chlorophyll fluorescence parameters of C. weissflogii respond to exposed Mn concentrations, whereby the strongest induction occurred at 90 nmol·L-1 Mn and the responses are enhanced over time. Although Mn in culture media may not be a major limiting factor of the growth of C. weissflogii, it significantly enhances the photosynthesis of C. weissflogii via two ways. First, Mn improves the integrity of the OEC structure and electron transfer from OEC to Tyr on the donor side of PS Ⅱ; second, Mn also enhances the energy transfer and electron transport after reaching the primary quinone acceptor (QA) on the acceptor side of PS Ⅱ. Energy transfer-related fluorescence parameters are positively correlated with the level of ROS in C. weissflogii, indicating that Mn plays an important role in both photosynthesis processes and reactive oxygen species(ROS)production.

Psychometric evaluation of the Simplified Chinese Version of the Posttraumatic Growth Inventory for assessing breast cancer survivors.

PURPOSE: Due to the rapid increase in the number of breast cancer survivors in China, it is important to have a valid instrument to assess their posttraumatic growth. We carried out a study to validate the psychometric testing of the Simplified Chinese Version of the Posttraumatic Growth Inventory (PTGI-SC) in breast cancer survivors. METHODS AND SAMPLE: A convenience sampling method was used to collect data from 1227 breast cancer survivors at eight tertiary hospitals and some anticancer groups in Beijing between April 2010 and April 2012. We tested the item discrimination, content validity, construct validity, and internal consistency of the PTGI-SC. KEY RESULTS: The difficulties of the items ranged from 0.432 to 0.737, and their discrimination correlation coefficients ranged from 0.324 to 0.721. The content validity index of the inventory was 0.98. Five factors were extracted using exploratory factor analysis, and their cumulative contribution was determined to be 68.3%. The results of the confirmatory factor analysis include χ(2)/df=3.912, SRMR = 0.046, RMSEA = 0.055, IFI = 0.932, CFI = 0.932, and Cronbach's α = 0.90. CONCLUSION: The validity and reliability of the PTGI-SC support its use for evaluating Chinese breast cancer survivors. This reliable and valid inventory can be used in practice to measure PTG in breast cancer survivors and provide information about their psychological adjustment. It can also facilitate further psychological research among Chinese breast cancer survivors.

Posttraumatic growth and associated socio-demographic and clinical factors in Chinese breast cancer survivors.

PURPOSE: The factors that affect posttraumatic growth (PTG) in breast cancer survivors have been discussed for many years, but it remains unclear which are most influential. The purpose of this study was to determine the level of PTG and identify associated socio-demographic and clinical factors in Chinese breast cancer survivors. METHODS AND SAMPLE: A descriptive research design with a convenience sampling method was employed to collect data using the simplified Chinese version of the Posttraumatic Growth Inventory (PTGI-SC). This questionnaire was administered to 1227 participants recruited from eight tertiary hospitals and cancer survivor groups in Beijing between April 2010 and April 2012. KEY RESULTS: PTG is present in Chinese breast cancer survivors, with an average PTGI-SC score of 70.18 ± 15.85. There were five variables in the regression model: exercise, other chronic disease, income, education level, and work status. Exercise showed the strongest positive association with PTG after breast cancer. Household income and educational level also positively influenced PTG. Survivors with other accompanying chronic diseases had lower PTG. Retired survivors had the highest PTG, those working had moderate PTG, and those on sick leave had the lowest PTG. CONCLUSIONS: PTG is common among Chinese breast cancer survivors. It is positively associated with exercise, income, education, and retirement, and negatively associated with the presence of other chronic diseases and working. The results may provide information on how to promote the development of PTG while nursing breast cancer survivors.