Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Effect of Guilu Erxiangao on Alzheimer's Disease and Its Mechanism Based on Kidney-brain Correlation / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Guilu Erxiangao on Alzheimer's disease （AD） model rats induced by hydrocortisone and amyloid β-protein（Aβ） based on the theory of kidney-brain correlation. MethodIntraperitoneal injection of hydrocortisone and intracerebroventricular injection of Aβ were performed to induce AD in rats， and different concentrations of Guilu Erxiangao were used for intervention. The indexes of hippocampus， kidney and adrenal gland were measured， and the spatial learning and memory ability of AD rats was observed by Morris water maze experiment. The levels of testosterone （T） and corticosterone （CORT） in serum samples were determined by enzyme-linked immunosorbent assay （ELISA）. Liquid chromatography-mass spectrometry （LC-MS） was used to collect and analyze the serum metabolic data of model rats. The active components and corresponding targets of Guilu Erxiangao were collected using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Traditional Chinese Medicine Integrated Database（TCMID）. GeneCards and Online Mendelian Inheritance in Man （OMIM） were retrieved to obtain AD-related targets， and protein-protein interaction （PPI） network was constructed to perform gene ontology （GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The expression level of interleukin-6 （IL-6） in the hippocampus of rats was detected by Western blot. ResultCompared with the model group， the low-， medium- and high-dose groups of Guilu Erxiangao exhibited significantly increased hippocampus index， kidney index and adrenal gland index， reduced CORT levels in serum and down-regulated IL-6 levels in hippocampal tissues. According to the results of water maze experiment， as compared with the model group， the platform crossing times of rats was significantly increased in the low- and high-dose groups of Guilu Erxiangao， with evidently prolonged distance traveled in quadrant Ⅲ （%） and time in quadrant Ⅲ （%）. A total of 24 serum differential metabolites associated with AD were identified by LC-MS， and 50 high-frequency common compounds and 187 high-frequency common targets for AD treatment were screened by network pharmacology method. Results demonstrated phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway plays an important role in the complex AD pathological mechanism. ConclusionGuilu Erxiangao can significantly improve the cognitive dysfunction of AD model rats induced by hydrocortisone and Aβ， reduce serum CORT levels and IL-6 levels in hippocampal tissues， and regulate the metabolic level， which provides a reference for its clinical application.

Rehmanniae Radix and Rehmanniae Radix Praeparata improve diabetes induced by high-fat diet coupled with streptozotocin in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway / 中国中药杂志

This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.

cDNA cloning of a novel lectin that induce cell apoptosis from Artocarpus hypargyreus / 中国天然药物

We isolated a novel lectin (AHL) from Artocarpus hypargyreusHance and showed its immunomodulatory activities. In this study, the amino acid sequence of AHL was determined by cDNA sequencing. AHL cDNA (875bp) contains a 456-bp open reading frame (ORF), which encodes a protein with 151 amino acids. AHL is a new member of jacalin-related lectin family (JRLs), which share high sequence similarities to KM+ and Morniga M, and contain the conserved carbohydrate binding domains. The antitumor activity of AHL was also explored using Jurkat T cell lines. AHL exhibits a strong binding affinity to cell membrane, which can be effectively inhibited by methyl-α-D-galactose. AHL inhibits cell proliferation in a time- and dose-dependent manner through apoptosis, evidenced by morphological changes, phosphatidylserine externalization, poly ADP-ribose polymerase (PARP) cleavage, Bad and Bax up-regulation, and caspase-3 activation. We further showed that the activation of ERK and p38 signaling pathways is involved for the pro-apoptotic effect of AHL.

Population pharmacokinetics of tacrolimus in idiopathic membranous nephropathy patients / 药学学报

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

Progress in Development and Application of Decision-making Systems for Individualized Dosing / 中国药学杂志

With the progress of dose individualization theory and research, decision-making systems have increasingly emerged in recent years. In this paper, common individualized dosing computer program, web platform and application on mobile devices are identified and summarized by searching literatures and internet, and compared with each other in terms of general characteristics and professional characteristics. Twenty-five systems are included in total. These systems, which estimate parameters mostly by Bayesian algorithm, cover anti-bacterial drugs and antiviral drugs, immunosuppressants, anti-tumor drugs, nervous system drugs, cardiovascular system drugs, respiratory system drugs and so on. MwPharm++, a commercial computer program, has the best comprehensive performance among all these. Besides, highlighted advantages are showed in commercial computer program Precise PK, APK, free computer program JPKD, BestDose and web platform SmartDose. Along with the development of internet and the high performance computing tools, mobile apps are booming. It is expected that the decision-making systems to be developed and promoted continuously in the future and could provide more options and references for clinical individualized dosing.

Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region, China, 2018 / 生物医学与环境科学（英文）

Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends (+2.63% per year; P < 0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.

Cancer Incidence and Mortality Survey in Wuwei, Gansu Province, Northwestern China from 2003 to 2012: A Retrospective Population-based Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Population-based cancer registry collects the data on cancer incidence and mortality deaths from covered population to describe and survey the epidemics in certain areas. The aim of this study was to estimate the cancer incidence and mortality in Wuwei, Gansu province, Northwestern China from 2003 to 2012. The goal is to better understand cancer distribution and long-term development of cancer prevention and treatment in Wuwei.</p><p><b>METHODS</b>Data were collected from the Wuwei Cancer Registry between 2003 and 2012. In this registry, data from 46 cancer report centers were included in this analysis. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, and cumulative incidence/mortality rates were calculated. Totally, 9,836,740 person-years (5,110,342 for males and 4,726,398 for females) had been monitored over this time period. The gender ratio of male/female was 1.08:1. The number of new cancer cases and related deaths was 24,705 and 17,287 from 2003 to 2012, respectively.</p><p><b>RESULTS</b>The proportion of morphological verification was 74.43%. The incidence of cases identified through death certification only was 1.21%, and the mortality to incidence ratio was 0.70. The average crude incidence was 251.15/100,000 persons (310.61 and 186.87 for males and females per 100,000 persons, respectively). The age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 207.76 and 245.42 per 100,000 persons, respectively. The crude cancer mortality was 175.74/100,000 persons (228.34 and 118.86 for males and females per 100,000 persons). ASR for China and the world was 149.57 and 175.13/100,000 persons, respectively. The most common cancers and leading causes of cancer-related deaths in Wuwei were as follows: cancers of stomach, esophagus, liver, lung, colorectum, breast, cervix, lymphoma, blood (leukemia), brain, and central nervous system. In Wuwei, during 2003 and 2012, cancer incidence and mortality rates increased by 1.32% and 1.31%/year, respectively. During this time, colorectum cancer incidence and mortality rates increased by 2.69% and 7.54%/year, respectively, in Wuwei. The incidence and mortality of other gastric, esophageal, liver, and lung cancers also all increased.</p><p><b>CONCLUSIONS</b>The results of this study report a more accurate cancer burden among the population of Wuwei, China. Active research of cancers etiology and effective prevention should be established to reduce the incidence and mortality associated with cancers.</p>

Characteristics and distribution of ERP by different field stimulation / 法医学杂志

OBJECTIVE@#To study the variation of latency and amplitude of the event related potential (ERP) and its distribution in human scalp when the normal subjects were stimulated with different visual fields.@*METHODS@#The ERP recorded in scalp with the stimulation of 10 degrees visual field and 60 degrees visual field respectively in 20 healthy volunteers with normal visual function.@*RESULTS@#Two different visual field stimulation may evoke the different exogenous components P1 (70-125 ms), N1 (90-170 ms), P2 (140-220 ms) and endogenous components N2 (190-280 ms) and P3 (290-430 ms). The latencies of all the components evoked by 10 degrees visual field were shorter than that of the 60 degrees visual field while the amplitudes of N1 and N2 were lower and appeared over the extensive encephalic region; and the amplitudes of the P1, P2 and P3 were higher and appeared in occipitotemporal, prefrontal and occipital region, respectively.@*CONCLUSION@#Two different visual field stimulation may evoke all the ERP components with significant differences in the latency, amplitude and distribution. The differences may reflect the different visual information integration and processing in human brain during the different visual field stimulation.

Research progress of proto-oncogene c-myb in megakaryocyte-erythroid hematopoiesis / 中国实验血液学杂志

The nuclear proto-oncogene c-myb is an essential regulator of hematopoiesis, it involves in the growth, survival, proliferation and differentiation of hematopoietic cells. More recently, different cell lines and transgenic mouse studies have suggested that c-myb plays a pivotal role in the megakaryocyte-erythroid progenitor cell lineage commitment. The deletion of the proto-oncogene c-myb would lead to profoundly impaired definitive erythropoiesis, but little influence in definitive megakaryopoiesis. Moreover, transient transfection and immunoprecipitation studies have demonstrated that c-myb exerts its physiological function in normal hematopoiesis by influencing a network of regulator molecules. Now therefore, insight into the structure, function and related molecular regulation mechanism of c-myb gene can help to further clarify its function in megakaryocyte-erythroid hematopoiesis and can provide new ideas for molecular target therapy of the platelet diseases and red blood cell diseases. In this article, c-myb structure, function and related effects involved in megakaryocyte-erythroid hematopoiesis as well as related molecular mechanisms are reviewed.

Orphanin FQ combined with adriamycin reverses multi-drug resistance of K562/ADM and its molecular mechanism / 中国实验血液学杂志

Our study have confirmed that orphanin FQ (OFQ) alone can reverse the multi-drug resistance of K562/ADM at the cellular level. Thus, this study was purposed to investigate the molecular mechanism of OFQ combined with ADM that reverses multi-drug resistance of K562/ADM, as well as its correlation with the expression of MDR1 mRNA and P-glycoprotein (P-gp). MTT method was used to detect the proliferation ability of K562/ADM treated with OFQ and ADM alone and their combination; flow cytometry was performed to measure the cell apoptosis rate; real time-PCR was applied to detect the MDR1 mRAN expression; Western blot was used to determine the P-gp expression. The results showed that OFQ (0.1 µmol/L) combined with ADM (15 mg/L) significantly inhibited the cell proliferation of K562/ADM, compared with ADM group; the date gained at 48 h was statistically significant (P < 0.05), and cell apoptosis rate was significantly raised (P < 0.01); MDR1 mRNA and P-gp expression levels of OFR combined with ADM were significantly lower than that of ADM alone, and were time-dependent within 48 h. It is concluded that OFQ combined with ADM can reverse the multi-drug resistance of K562/ADM in time-dependent manner, and the 48 h after treatment with these 2 drugs is the best reverse time, which may be related with down regulating the expression of MDR1 mRNA and P-gp.

Research progress on necroptosis regulation mechanism and its clinical relevance / 中国实验血液学杂志

Necroptosis is a caspase-independent programmed cell death, its regulation, induction and blocking mechanism are a complex process involving in a series of molecular expression and regulation. The studies found that the necroptosis is not only involved in the physiological regulation mechanism, but also directly correlated to the occurrence, development and final outcome of some necrotic diseases, such as neurodegenerative diseases, ischemic disease, inflammation and viral infection. Moreover, the studies on multidrug-resistant tumor cell line demonstrated that necroptotic induction agents possess excellent "broad-spectrum" to escape the multidrug resistance. Therefore, exploration of the signaling pathways, physical characteristics, clinical relevance of necroptosis may provide new prospects for molecular target therapy and drug discovery of tumours. This review summarizes the research progress on possible regulation mechanism of necroptosis, physiologic characteristics and relation of necroptosis with clinical diseases and multi-drug resistance.

Correlation of pattern reversal visual evoked potentials P100 with visual acuity / 法医学杂志

OBJECTIVE@#To explore pattern reversal visual evoked potential (PRVEP) P100 components in the patients with different visual acuity and the correlation of P100 components with visual acuity using different visual simulation angles.@*METHODS@#PRVEPs were recorded at Oz point in the patients (100 eyes) with different visual acuity including 0.2, 0.4, 0.6, 0.8 and 1.0 and induced by pattern reversal visual simulation with the different spatial frequencies(check sizes: 8 degrees-7.5'). The latency and amplitude of components P100 were analyzed and statistical analysis was performed using SPSS 13.0 software.@*RESULTS@#The latency and amplitude of P100 wave showed a curvilinear relationship with check sizes. With check size 10 simulation in 0.2 visual acuity group, the P100 latency reached to the minimum and the P100 amplitude showed peak value. Other groups displayed the best value with check size 30'. The P100 latency and amplitude showed a linear correlation with visual acuity. With the increase of visual acuity, the P100 wave latency decreased and the amplitude increased gradually. Regression models between visual acuity and the Pic wave latency and amplitude were also established.@*CONCLUSION@#The regression functions can be an objective and accurate method to evaluate the visual acuity based on the better simulation angles using PRVEP examination.

A practical multi-electrode extracellular recording system based on virtual testing / 生理学报

Extracellular recording is a key technology to study many types of brain functions. However the amplitudes of extracellular spikes are typically about 100 muV and should be picked up and amplified specially, then recorded and analyzed online. Most of the equipment for extracellular recording are either very expensive, or too large for recording in the brains of freely moving small animals. In this paper we developed a practical multi-electrode recording system based on virtual testing technology. The system includes microelectrode amplifier, analog input device NI4472 with 24-bit resolution, and data processing software SPKrec. The features of the hardware are low noise, high input impedance, a total gain of 2 000, and large dynamic range. The software developed in LabVIEW is capable of online analysis, data recording, spike detection, fire rate histograms, etc. The system functions have been verified in extracellular recording in the olfactory bulb of Gekko gecko. The result indicates that the system with performance comparable to that of commercial products meets the requirements of recording experiments.

Study on the effect of a community-based early education and service program regarding intelligence development of infants / 中华流行病学杂志

<p><b>UNLABELLED</b>Study on the effect of a community-based early education and service program regarding intelligence</p><p><b>OBJECTIVE</b>To assess the effect on a community-based early education and service programs regarding the development of infants' intelligence.</p><p><b>METHODS</b>A community-based intervention study was carried out among 359 infants and their families. Base-line survey were carried out when infants reached their one month, where after infants and their families in the intervention group received instructions and services focused on baby fostering and intelligence development. When the infants reached their six-months and twelve-months of age, their families were informed to complete the follow-up surveys, using both questionnaire investigation and testing the infants' intelligence quotients. The infants' intelligence quotients were measured by Development Screening Test for children under six. By comparing intelligence quotients of infants in two study groups in the follow-up surveys, this paper evaluated the impacts of community intervention on the infants' intelligence development.</p><p><b>RESULTS</b>During two follow-ups, no statistical difference had been detected between the two groups of infants in term of gender or delivery process. Baseline data showed that infants' mental index (MI) scored 98.26 in the intervention group and 101.79 in the control one, and development quotient (DQ) scored 94.50 and 99.36 in respective groups. Infants' MI score increased 6.07 and 8.86 at the six-month and twelve-month follow-up periods respectively in the intervention group compared during the baseline, higher than the MI increments of the control group at the two follow-up periods (-2.46 and 1.05 respectively). DQ score of infants in the intervention group increased 12.94 and 11.24 respectively in the two follow-up surveys, which were also higher than increments in the control group (-0.18 and 0.34). The group x time effect(interaction effect) of MI and DQ in six-month and twelve-month follow-ups were both significantly higher than that of the baseline level.</p><p><b>CONCLUSION</b>The community-based early education and service programs could effectively improve the infants' intelligence.</p>

Behavior,attitude and influencing factors of smoking among residents aged 15 to 69 years in Hongkou District of Shanghai / 上海第二医科大学学报

Objective To investigate the prevalence and attitude of smoking and its influencing factors among residents in Hongkou District of Shanghai,so as to provide evidence for tobacco control. Methods Nine hundred and sixty residents in Hongkou District of Shanghai aged 15 to 69 years were selected by multi-level random sampling,among whom 958 completed the investigations on smoking status. Results The smoking rate and standardized smoking rate were 20.04% and 18.73%,respectively.The smoking rate and standardized smoking rate of males were 41.05% and 30.07%,and those of females were 0.80% and 1.70%,respectively.The smoking rate of males was higher than that of females(RR=0.02,95%CI: 0.01-0.03).The smoking rates of age groups of 25 years old and over were higher than those of 15 to 24 years old,and the smoking rate of subjects with or above junior college education was lower than that of subjects with or below middle school education(RR=0.45,95%CI: 0.25-0.79).Subjects who drank alcohol smoked more than those did not(RR=2.68,95%CI: 1.76-4.09).Lower annual per capita income and higher knowledge on smoking hazard led to more tendance to object to smoking and agree with anti-smoking. Conclusion The prevalence of smoking of residents aged 15 to 69 years in Hongkou District of Shanghai was relatively lower.Age,gender,education status and alcohol drinking were influencing factors of smoking.Education on tobacco control among subjects aged more than 35 years should be strengthened,and more attention should be paid to those with lower education.Besides,education on alcohol control should be managed together with tobacco control.