Safety Study of Raltitrexed Perfusion in Elderly Patients with Colorectal Cancer and Effect on CEA mRNA in Peritoneal Lavage Fluid.

Background: Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical surgery for elderly patients with colorectal cancer are still unclear. Methods: In accordance with computer-generated random allocation sequences, 116 elderly patients with colorectal cancer who received radical surgery were randomly grouped into the raltitrexed intraperitoneal perfusion group or the saline intraperitoneal perfusion group from January 2020 to December 2021 in the First Affiliated Hospital of Bengbu Medical University. t tests and χ2 tests were used to analyze the difference between the two groups of the clinical characteristics, pathological features, perioperative parameters, and carcinoembryonic antigen mRNA in the peritoneal lavage fluid. Results: No statistically significant differences in postoperative complications after radical surgery were observed between the two groups. No statistically significant differences in peripheral blood indexes were observed between the two groups before surgery or on the first and third days after surgery. One day after radical surgery, the alanine transaminase (54.33 ± 4.93 vs 51.01 ± 5.56) and aspartate transaminase (49.28 ± 4.30 vs 50.99 ± 3.88) in the peripheral blood were higher in the raltitrexed intraperitoneal perfusion group than in the saline intraperitoneal perfusion group. At the same time, no significant difference was found on the third day after surgery. No significant differences in side effects of chemotherapy were observed between the two groups. The positive rate of carcinoembryonic antigen mRNA in the raltitrexed intraperitoneal perfusion group (8.47%) was significantly lower than that in the saline intraperitoneal perfusion group (22.81%) after surgery. Conclusion: Raltitrexed perfusion during radical surgery is safe and feasible for elderly patients with CRC and can reduce the positive rate of carcinoembryonic antigen mRNA in peritoneal lavage fluid, so it can be explored as a treatment option.

[Heixiaoyao Powder interferes with microglia polarization in AD model mice by regulating NOX2/ROS/NF-κB signaling pathway].

The effect and mechanism of Heixiaoyao Powder on the polarization of microglia(MG) in APP/PS1 double transgenic mice were explored based on NADPH oxidase 2(NOX2)/reactive oxygen species(ROS)/nuclear factor kappaB(NF-κB) signaling pathway. Fifty 4-month-old male APP/PS1 mice were randomly divided into a model group, an MCC950 group(10 mg·kg~(-1)), and low-, medium-, and high-dose Heixiaoyao Powder groups(6.45, 12.89, and 25.78 g·kg~(-1)). Thirty male C57BL/6J mice of the same age and strain were randomly divided into a blank group, a blank + intragastric intervention group, and a blank + intraperitoneal injection group. Drug intervention lasted 90 days. Morris water maze test was used to detect learning and cognitive ability. Nissl staining and transmission electron microscopy were used to observe the pathological morphology and ultrastructure of hippocampal neurons. Immunofluorescence was used to detect the positive expression of M1-type marker CD16/32~+/Iba-1~+, M2-type marker CD206~+/Iba-1~+ of MG and the expression of hippocampal ROS. The colorimetric method was used to detect the content of malondialdehyde(MDA) and superoxide dismutase(SOD) in the hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, including interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α), in the hippocampus. Western blot was used to detect the protein expression of ß-amyloid protein(Aß), Iba-1, CD16/32, CD206, NOX2, NF-κB, p-NF-κB, NF-κB inhibitor alpha(IκBα), and p-IKBα in the hippocampus. The results showed that as compared with the blank group, the model group showed prolonged target quadrant movement distance and escape latency(P<0.01), shortened target quadrant retention time and percentage(P<0.01), disorganized neuronal cells with swelling, nuclear disappearance or bias, reduced number of cells, dissolved or absent Nissl bodies, and a clear area in the cytoplasm, damaged and shrunk cell membrane with abnormal cell morphology, few organelles in the cytoplasm, reduced and swollen mitochondria, increased MG M1-type marker CD16/32~+/Iba-1~+(P<0.01), decreased M2-type marker CD206~+/Iba-1~+(P<0.01), increased ROS activity and MDA content(P<0.01), decreased SOD level(P<0.01), elevated inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), up-regulated protein expression and phosphorylation of Aß, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and down-regulated CD206(P<0.01). There was no statistically significant difference between the blank group, the blank + intragastric intervention group, and the blank + intraperitoneal injection group. After the intervention of Heixiaoyao Powder, the Heixiaoyao Powder groups showed shortened target quadrant movement distance and escape latency(P<0.01), prolonged target quadrant retention time and percentage(P<0.01), increased and neatly arranged cells with relieved swelling, increased Nissl bodies, regular cell morphology, and intact cell membrane, relieved swelling of mitochondria, slightly expanded endoplasmic reticulum, decreased CD16/32~+/Iba-1~+(P<0.05 or P<0.01), increased CD206~+/Iba-1~+(P<0.01), decreased ROS activity and MDA content(P<0.01), increased SOD level(P<0.01), decreased content of inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), down-regulated protein expression and phosphorylation of Aß, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and up-regulated CD206(P<0.01). In conclusion, Heixiaoyao Powder can alleviate neuronal damage and improve the learning and memory abilities of APP/PS1 mice. The mechanism of action may be related to the inhibition of NOX2/ROS/NF-κB signaling pathway, regulating the polarization of MG, increasing the expression of M2 type, inhibiting the expression of M1 type, and reducing the release of inflammatory factor.

Emerging Landscape of Preclinical Models for Studying COVID-19 Neurologic Diseases.

COVID-19 (Coronavirus Disease 2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and has globally infected 768 million people and caused over 6 million deaths. COVID-19 primarily affects the respiratory system but increasing reports of neurologic symptoms associated with COVID-19 have been reported in the literature. The exact mechanism behind COVID-19 neurologic pathophysiology remains poorly understood due to difficulty quantifying clinical neurologic symptoms in humans and correlating them to findings in human post-mortem samples and animal models. Thus, robust preclinical experimental models for COVID-19 neurologic manifestations are urgently needed. Here, we review recent advances in in vitro, in vivo, and other models and technologies for studying COVID-19 including primary cell cultures, pluripotent stem cell-derived neurons and organoids, rodents, nonhuman primates, 3D bioprinting, artificial intelligence, and multiomics. We specifically focus our discussion on the contribution, recent advancements, and limitations these preclinical models have on furthering our understanding of COVID-19's neuropathic physiology. We also discuss these models' roles in the screening and development of therapeutics, vaccines, antiviral drugs, and herbal medicine, and on future opportunities for COVID-19 neurologic research and clinical management.

Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study.

BACKGROUND: Coffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents. METHODS: Based on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs). RESULTS: In epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (ß = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (ß = 0.0019, P = 0.7552), and total spine BMD (ß = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (ß = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (ß = 0.0202, P = 0.7828). CONCLUSIONS: Our study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

The top 100 most cited articles on COVID-19 vaccine: a bibliometric analysis.

This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.

Establishment and Optimization of Soil Cd Risk Threshold in Typical Karst Area with Potato Production, China.

The threshold is key to risk assessment of soil cadmium (Cd) pollution. However, there is limited research on the soil Cd risk threshold of potatoes. Soil and potato samples (n = 256) were used to establish and optimize the Cd risk threshold by using relative cumulative frequency, bioconcentration factor, and regression model. The results showed that suggested risk screening values (SRSVs) for soil Cd were divided into 2.465 (pH ≤ 5.5), 2.564 (5.5 < pH ≤ 6.5), 2.778 (6.5 < pH ≤ 7.5), and 4.348 mg kg-1 (pH > 7.5). SRSVs were applied to classify soil Cd risk assessment by collecting soil samples (n = 100). Low-risk areas only comprised 0.98% of the total area using risk screening values (RSVs) (GB15618-2018), and risk areas comprised as much as 99.02%. Low-risk area and risk area comprised 97.75% and 2.25% of the total area based on SRSVs. SRSVs are appropriate for potato production in typical karst areas.

Calcareous Materials Effectively Reduce the Accumulation of Cd in Potatoes in Acidic Cadmium-Contaminated Farmland Soils in Mining Areas.

The in situ chemical immobilization method reduces the activity of heavy metals in soil by adding chemical amendments. It is widely used in farmland soil with moderate and mild heavy metal pollution due to its high efficiency and economy. However, the effects of different materials depend heavily on environmental factors such as soil texture, properties, and pollution levels. Under the influence of lead-zinc ore smelting and soil acidification, Cd is enriched and highly activated in the soils of northwestern Guizhou, China. Potato is an important economic crop in this region, and its absorption of Cd depends on the availability of Cd in the soil and the distribution of Cd within the plant. In this study, pot experiments were used to compare the effects of lime (LM), apatite (AP), calcite (CA), sepiolite (SP), bentonite (BN), and biochar (BC) on Cd accumulation in potatoes. The results showed that the application of LM (0.4%), AP (1.4%), and CA (0.4%) had a positive effect on soil pH and cations, and that they effectively reduced the availability of Cd in the soil. In contrast, the application of SP, BN, and BC had no significant effect on the soil properties and Cd availability. LM, AP, and CA treatment strongly reduced Cd accumulation in the potato tubers by controlling the total 'flux' of Cd into the potato plants. In contrast, the application of SP and BN promoted the migration of Cd from the root to the shoot, while the effect of BC varied by potato genotype. Overall, calcareous materials (LM, CA, and AP) were more applicable in the remediation of Cd-contaminated soils in the study area.

Potential of Black Phosphorus in Immune-Based Therapeutic Strategies.

Black phosphorus (BP) consists of phosphorus atoms, an essential element of bone and nucleic acid, which covalently bonds to three adjacent phosphorus atoms to form a puckered bilayer structure. With its anisotropy, band gap, biodegradability, and biocompatibility properties, BP is considered promising for cancer therapy. For example, BP under irradiation can convert near-infrared (NIR) light into heat and reactive oxygen species (ROS) to damage cancer cells, called photothermal therapy (PTT) and photodynamic therapy (PDT). Compared with PTT and PDT, the novel techniques of sonodynamic therapy (SDT) and photoacoustic therapy (PAT) exhibit amplified ROS generation and precise photoacoustic-shockwaves to enhance anticancer effect when BP receives ultrasound or NIR irradiation. Based on the prospective phototherapy, BP with irradiation can cause a "double-kill" to tumor cells, involving tumor-structure damage induced by heat, ROS, and shockwaves and a subsequent anticancer immune response induced by in situ vaccines construction in tumor site, which is referred to as photoimmunotherapy (PIT). In conclusion, BP shows promise in natural antitumor biological activity, biological imaging, drug delivery, PTT/PDT/SDT/PAT/PIT, nanovaccines, nanoadjuvants, and combination immunotherapy regimens.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in ß-amyloid Protein-induced Alzheimer's Disease Rat Model.

OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

The Discovery of Potential MDM2 Inhibitors: A Combination of Pharmacophore Modeling, Virtual Screening, Molecular Docking Studies, and in†vitro/in†vivo Biological Evaluation.

Small-molecule inhibitors of MDM2 that block the MDM2-p53 protein-protein interaction have been considered as potential therapeutic agents for the treatment of cancer. Here, we identify five highly potent inhibitors of MDM2 (termed as WY 1-5) that display significant inhibitory effects on MDM2-p53 interaction by using a combined strategy of pharmacophore modeling, virtual screening, and molecular docking studies. Among them, WY-5 is the most active MDM2 inhibitor with an IC50 value of 14.1±2.8 nM. Moreover, WY-5 significantly up-regulate the protein level of p53 in SK-Hep-1 cells harboring wild-type p53. In vitro anticancer study reveals that WY-5 markedly inhibits the survival of SK-Hep-1 cells. In vivo anticancer study suggests that WY-5 significantly inhibits the growth of SK-Hep-1 cells-derived xenograft in nude mice, with no observable toxicity. Our results demonstrate that WY-5 may be a promising candidate for the treatment of cancer harboring wild-type p53.

[Systematic evaluation on efficacy and safety of Gingko Ketone Ester Dropping Pills in treatment of angina pectoris and coronary heart disease].

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.

Study on Potential of Meridian Acupoints of Traditional Chinese Medicine.

In recent years, Traditional Chinese Medicine (TCM) has attracted more and more attention due to its good therapeutic effect, low cost, and convenience. This research is also a part of the goal of the modernization of TCM. Based on the meridian electric potential acquisition system independently developed by our project team, in this paper, we designed the human body's meridian electric potential acquisition scheme. We use principal component analysis (PCA) to prove that the meridional potential signal is derived from the ECG signal. Then, Inception ResNet V2 was used to classify acupoints and nonacupoints. Finally, the classification accuracy rate reached 86.59045265, and the F1 score = 0.72161642. This shows that acupoints and nonacupoints can be distinguished by their surface potential.

[Tongmai Yangxin Pills in treatment for angina pectoris of coronary heart disease: a systematic review of randomized clinical trails].

To systematically review the efficacy and safety of Tongmai Yangxin Pills in treatment for angina pectoris of coronary heart disease. CNKI, WanFang, VIP, SinoMed, PubMed, EMbase and the Cochrane Library databases were retrieved online to collect randomized controlled trials(RCTs) of Tongmai Yangxin Pills for angina pectoris of coronary heart disease since the establishment to November 2018. Two investigators screened out literatures independently, extracted data and assessed the risk of bias of included studies. The risk assessment of included references was made according to criteria recommended by Cochrane Handbook 5.3. Meta-analysis was then performed by RevMan 5.3 software. A total of 9 RCTs were included. The results of Meta-analysis showed that compared with the single application of chemotherapy, the combined administration with Tongmai Yangxin Pills and Western medicine could significantly improve the clinical efficacy of angina(RR=1.22, 95%CI[1.13, 1.31]), the improvement rate of electrocardiogram(RR=1.31, 95%CI[1.21, 1.42]), and the clinical efficacy of traditional Chinese medicine(TCM) syndrome(RR=1.17, 95%CI[1.02, 1.35]). Only one study reported adverse events, while 5 studies reported no adverse event. According to current evidences, in the treatment of angina pectoris of coronary heart disease, Tongmai Yangxin Pills has a better clinical efficacy in the treatment of angina pectoris of coronary heart disease in terms of the improvement rate of electrocardiogram and the clinical efficacy of TCM syndrome. Due to the limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.

[Network Meta-analysis of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris].

To assess the clinical efficacy of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris by using network Meta-analysis method. The relative randomized controlled trials( RCTs) of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris were retrieved from China National Knowledge Infrastructure( CNKI),Wan Fang,VIP and Chinese Biomedical Literature Database( CBM) in July 2018. Two researchers independently completed the literature screening,data extraction and quality evaluation according to the pre-determined inclusion and exclusion criteria,and the results were cross-checked.The data were analyzed by Win Bugs,and STATA software was used for plotting. Finally,114 RCTs were included,involving 7 Yiqi Huoxue Chinese patent medicines and 11 775 patients. Network Meta-analysis showed that the total effective rate for improvement in AP symptoms had 7 direct comparisons and 21 indirect comparisons,8 of which were statistically significant. The ECG improvement had 7 direct comparisons and 21 indirect comparisons,7 of which were statistically significant. In terms of the total effective rate of improvement in AP symptoms,the order of efficacy was as follows: Shensong Yangxin Capsules > Shexiang Baoxin Pills > Qishen Yiqi Dropping Pills > Tongxinluo Capsules > Wenxin Granules > Qishen Capsules > Naoxintong Capsules. In terms of ECG improvement,the order of efficacy was as follows: Shexiang Baoxin Pills > Tongxinluo Capsules > Naoxintong Capsules > Qishen Yiqi Dropping Pills> Wenxin Granules > Shensong Yangxin Capsules > Qishen Capsules. The results showed that Shensong Yangxin Capsules and Shexiang Baoxin Pills had certain advantages in the treatment of coronary heart disease with angina pectoris. Due to the small sample size,more studies were required to further verify the evidences.

Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats.

OBJECTIVE: To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD). METHODS: Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively. RESULTS: The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05). CONCLUSION: Puerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.

Concomitant presentation of Anderson-Tawil syndrome and myasthenia gravis in an adult patient: A case report.

Andersen-Tawil syndrome (ATS) is an autosomal dominant, multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias and distinctive dysmorphic facial or skeletal features. The disorder displays marked intrafamilial variability and incomplete penetrance. Myasthenia gravis (MG) is an autoimmune disorder that demonstrates progressive fatigability, in which the nicotinic acetylcholine receptor (AChR) at neuromuscular junctions is the primary autoantigen. The present study reports a rare case of a 31-year-old woman with a history of morbid obesity and periodic weakness, who presented with hemodynamic instability, cardiogenic shock and facial anomalies. Laboratory results revealed hypokalemia and an elevated anti-AChR antibody expression levels. Electrocardiography demonstrated prolonged QT-interval, ST-elevation, and subsequent third-degree atrioventricular block. Neurological examination revealed bilateral ptosis, horizontal diplopia, dysarthria and generalized weakness. No mutations in the potassium channel inwardly rectifying subfamily J member 2 gene were detected in the present case. The patient was treated with oral potassium supplementation and an acetylcholinesterase inhibitor (pyridostigmine), after which the symptoms were improved. To the best of our knowledge, the present case report was the first to describe concomitant presentation of both ATS and MG, which represents a diagnostic and therapeutic challenge.

Hyperosmotic treatment synergistically boost efficiency of cell-permeable peptides.

Therapeutics delivery into cells has been hurdled due to the barrier of cytoplasmic membrane. Although cell penetrating peptide (CPP) can potentially serve as an intracellular drug delivery vehicle, the application of CPP-based delivery is limited because the unsatisfactory delivery efficiency of CPP conjugated potent cargos is challenging their applications in present. Thus, the development of strategies for enhancing the penetrating efficiency of CPP would therefore urgent need to be explored to increase the scope of potential applications. We report here the effects of glucose, sucrose and manntiol (abbreviated as GSM) combination facilitating the penetration efficiency of CPP peptide alone or CPP-GFP (green fluorescence protein) conjugation in cultured cell lines or primary cells. Moreover, osmoprotectants glycerol and glycine supplementation help cells cope with the stress from GSM combination. Thus, our present study suggests that GSM combination in the presence of osmoprotectant can work as a new strategy for CPP penetration enhancement.

Inhibitory effect of baicalin on allergic response in ovalbumin-induced allergic rhinitis guinea pigs and lipopolysaccharide-stimulated human mast cells.

OBJECTIVE: Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has generally been used for the treatment of various allergic diseases. However, there is little information about the anti-inflammatory effects of baicalin for allergic rhinitis. This study aims to investigate the anti-allergic effect of baicalin on allergic response in ovalbumin (OVA)-induced allergic rhinitis guinea pigs and lipopolysaccharide (LPS)-stimulated human mast cells. METHODS: Using in vivo models, we evaluated the effect of baicalin on allergic rhinitis symptoms via recording the number of nasal rubs and sneezes. The levels of histamine, OVA-specific immunoglobulin E(IgE), eosinophil cationic protein (ECP) and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The histological changes of nasal mucosa were observed by light microscope after HE staining. In vitro, the release of histamine and ß-hexosaminidase of compound 48/80-induced human mast cells were measured by ELISA and PNP-NAG colorimetry, respectively. The productions of inflammatory cytokines of LPS-stimulated human mast cells were determined using ELISA. Western blot was used to test the protein expression of JAK2, p-JAK2, STAT5, p-STAT5, IKKß, p-IKKß, IκBα, p-IκBα and NF-κB (p65) of LPS-stimulated human mast cells. RESULTS: The oral administration of baicalin at doses of 50 and 200 mg/kg improved allergic rhinitis symptoms and the histological changes of nasal mucosa and decreased the serum levels of histamine, ECP, interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α and OVA-specific IgE in OVA-induced allergic rhinitis guinea pigs. In vitro, baicalin suppressed the release of histamine and ß-hexosaminidase in compound 48/80-induced human mast cells. In addition, baicalin also inhibited the productions of inflammatory cytokines such as IL-1ß, IL-6, IL-8 and TNF-α and suppressed the phosphorylation of JAK2, STAT5, IKKß, IκBα and the nuclear translocation of NF-κB (p65) subunit in LPS-stimulated human mast cells. CONCLUSIONS: These results suggest that baicalin can effectively prevent allergic response in OVA-induced allergic rhinitis guinea pigs and inhibit inflammatory response via blocking JAK2-STAT5 and NF-κB signaling pathways in LPS-stimulated human mast cells. Considered together,the results show that baicalin may be a useful drug in the treatment of allergic rhinitis.

[Effect of Heixiaoyao Powder on Hippocampal Gene Expression Profile of Alzheimer's Disease Rats].

Objective To observe the effect of Heixiaoyao Powder (HP) on gene microarray profile of hippocampus in Aß23₋35 fragments induced Alzheimer's disease rat model. Methods Female SD rats were chosen to establish AD model by injecting Aß25₋35 amyloid into hippocampus ,and then they were divid- ed into 6 groups, i.e., the sham-operation group, the model group,the Western medicine (WM) group, high, middle, and low dose HP groups, 14 in each group. After 7 days of modeling, all rats were administered with respective solution at the daily dose of 3 mL/kg by gastrogavage for 28 successive days. Normal saline was administered to rats in the sham-operation group and the model group. Huperzine A Tablets wa- ter solution was administered to rats in the WM group at the daily dose of 0. 02 mL/kg. HP at the daily dose of 4. 25, 8. 50, 17. 00 g/kg was administered to rats in the low, middle, high HP groups. All rats were sacri- ficed after ending gastrogavage, and their hippocampal tissues were collected to extract tissue RNA. Rat gene microarray was used to screen differentially expressed genes, and then differentially expressed genes with partial dose-dependently changing obtained by microarry were verified by qRT-PCR. Results Compared with the sham-operation group, 538 genes were up-regulated, and 579 genes were down-regulated in the model group. mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 increased, while mRNA expressions of casq2 and bcl-2 decreased in the model group (P <0. 05). Compared with the model group, 276 genes were up-regulated, and 170 genes were down-regulated in the 3 HP groups. Of them, 71 up-regulated genes dose-dependently and 70 down-regulated genes dose-dependently. mRNA expressions of igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 in- creased in the WM group (P <0. 01). mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 increased in the high dose HP group (P <0. 01). mRNA expressions of crebbp, igfbp-1, znf483, zfp37, and zic4 decreased (P <0. 01, P <0. 05), while mR- NA expressions of casq2 and bcl-2 increased in the middle dose HP group (P <0. 01, P <0. 05). mRNA ex- pressions of igfbp-1 , znf483, zfp37, and zic4 decreased in the low dose HP group (P <0. 01). Compared with the middle dose HP group, mRNA expressions of crebbp, zfp37, and zic4 increased (P <0.01) , mR- NA expressions of igfbp-1 and bcl-2 decreased in the middle dose HP group (P <0. 01, P <0. 05); mRNA expressions of crebbp, znf483, and zfp37 increased (P <0. 01, P <0. 05), mRNA expressions of igfbp-1, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01). Compared with the middle HP group, mRNA expressions of casq2, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01, P <0. 05). Conclusion HP could affect the occurrence of AD by regulating mRNA expressions of zfp37, znf483, and zic4, and af- fect the metabolism of Aß and abnormal phosphorylation of Tau protein by inhibiting wnt signal pathway re- lated genes such as wisp-1 , crebbp, igfbp-1 , and casq2.

Effect of Abnormal Savda Munziq on hypertrophic scar formation in a rabbit ear model.

OBJECTIVE: To investigate whether administrating Abnormal Savda Munziq (ASMq), a traditional Uighur herbal preparation used for the prevention or treatment of diseases, affects hypertrophic scar (HTS) formation by using an established rabbit ear model. METHODS: The HTS rabbit model was created by circular fullthickness skin excisions on both ears of rabbits. Twenty rabbits were randomized into four groups, with 5 rabbits and 60 wounds in each group. Group A was the control group, treated with normal saline daily. Groups B, C, and D were the treatment groups at three different doses of ASMq (400, 800, and 1200 mg/kg body weight, respectively, daily, by gastrogavage). Twenty wounds were randomly chosen from each group on the 40th day after treatment and specimen were examined. Scar elevation index (SEI) was analyzed with histological assessment, and ultrastructure analysis was analyzed with a transmission electron microscopy. RESULTS: Groups B, C, and D demonstrated significant reductions in SEI as compared with the control group at 35.9% (P=0.0212), 48.2% (P=0.0108), and 52.7% (P=0.0103), respectively in a dose-response manner. SEI was lowered in Group D compared with Group B with a significant difference (P=0.015). However, there were no significant differences between Groups B and C, or between Groups C and D. Histological analysis showed that highdose ASMq (1200 mg/kg) could enhance the softening of HTS of rabbit ears and increase the compliance as shown in general. Ultrastructure analysis showed that with increased ASMq dose, the fibroblasts, pro-collagen, collagen, endoplasmic reticulum and ribosomes were reduced gradually. CONCLUSIONS: Orally administered ASMq significantly reduces the severity of HTS in the rabbit ear model. The findings of this study may have clinical implications on the management of human HTS.