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Context Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.

Background Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD at different eras in Taiwan. Materials and methods Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998 and April 2022 in these two hospitals for review. A total of 42 individuals were included. Results Compared to that reported worldwide, our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed in the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT proved to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms of GD3 patients progressed despite ERT intervention. Conclusion ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.

Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS).A randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strainsNGS data showed elevated populations ofHere, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines.ClinicalTrials.gov, identifier NCT03880760.

Background. Chronic hyperglycemia in type 1 diabetes (T1D) patients results in ocular problems over time, but only a few studies emphasized on cataracts. Aim. To evaluate the epidemiology of cataracts in the T1D population. Method. A two-part study was conducted using data from the National Health Insurance Research Database in Taiwan. Information from the Longitudinal Health Insurance Database (LHID) was served as a template of the general population. In the first part, a total of 3,622 T1D cases registered between 1998 and 2007 were enrolled and compared with a matched group from the LHID. For identifying risk factors of cataracts in the T1D population in the second part, a total of 9032 T1D cases registered between 1998 and 2013 were included. Result. Compared to the LHID, the hazard ratio (HR) of cataracts in the T1D group was 5.81 (95% CI 4.60–7.33), and the HR was higher in females (6.29, 95% CI 4.63–8.55). The peak incidence of cataracts occurred between age 20 and 29 in the T1D group, while in the LHID, it was after 60. The overall incidence of cataracts in the T1D group was 9.1%. In T1D patients with cataracts, they were found with higher rates of associated diabetic complications. Conclusion. Compared to the nondiabetic population, cataracts seemed more rampant and premature in T1D patients, especially those of female gender. Early ophthalmologic examination should be considered in T1D patients.

Background Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. Results Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn’t inhibit the psoralen-induced ER stress in SMMC7721 cells. Conclusions Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma. Electronic supplementary material The online version of this article (10.1186/s40659-019-0241-8) contains supplementary material, which is available to authorized users.

Ethnopharmacological relevance Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing mortality in China. Screening and identifying effective anticancer compounds from active traditional Chinese herbs for HCC are in demand. Akebia trifoliata (Thunb) Koidz, with pharmacological anti-HCC activities in clinical, has been shown in previous research. In the present research, we elucidated a potential anticancer effect of Akebia saponin E (ASE), which is isolated from the immature seeds of Akebia trifoliata (Thunb.) Koidz, and revealed that ASE could induce severe expanded vacuoles in HCC cells. But the potential mechanism of vacuole-formation and the anti-HCC effects by ASE remain uncover. Aim of this study To elucidate the potential mechanism of vacuole-formation and the proliferation inhibition effects by ASE in HCC cell lines. Materials and methods MTT assay, colony formation assay and flow cytometry were performed to detect cell viability. Immunofluorescence analysis was used to examine the biomarkers of endomembrane. Cells were infected with tandem mRFP-GFP-LC3 lentivirus to assess autophagy flux. RNA-seq was conducted to analyze the genome-wide transcriptional between treatment cell groups. In vitro PIKfyve kinase assay is detected by the ADP-GloTM Kinase Assay Kit. Results ASE could inhibit the proliferation of HCC with severe expanded vacuoles in vitro, and could significantly reduce the size and weight of xenograft tumor in vivo. Further, the vacuoles induced by ASE were aberrant enlarged lysosomes instead of autophagosome or autolysosomes. With cytoplasmic vacuolation, ASE induced a mTOR-independent TFEB activation for lysosomal biogenesis and a decrement of cholesterol levels in HCC cells. Furthermore, ASE could reduce the activity of PIKfyve (phosphoinositide kinase containing a FYVE-type finger), causing aberrant lysosomal biogenesis and cholesterol dyshomeostasis which triggered the expanded vacuole formation. Conclusion ASE can prospectively inhibit the kinase activity of PIKfyve to induce lysosome-associated cytoplasmic vacuolation, and may be utilized as an alternative candidate to treat human HCC.

Ethnopharmacological relevance Osthole is an O-methylated coumadin, which was isolated and purified from the seeds of Cnidium monnieri (L.) Cusson. Osthole is a commonly used traditional Chinese medicine to treat patients with Kidney-Yang deficiency patients, who exhibit clinical signs similar to those of glucocorticoid withdrawal. However, the mechanism of action of osthole is not fully understood. Objective This study was designed to reveal the effects of osthole on corticosterone production in mouse Y1 cell. Materials and methods Mouse Y1 adrenocortical cells were used to evaluate corticosterone production, which was quantified by enzyme-linked immunosorbent assay (ELISA) kits. Cell viability was tested using the MTT assay, and the mRNA and protein expression of genes encoding steroidogenic enzymes and transcription factors was monitored by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Results Osthole stimulated corticosterone secretion from mouse Y1 cells in a dose- and time-dependent manner, and osthole enhanced the effect of dibutyryl-cAMP (Bu2cAMP) on corticosterone production. Further, osthole also increased StAR and CYP11B1 mRNA expression in a dose-dependent manner and enhanced the expression of transcription factors such as HSD3B1, FDX1, POR and RXRα as well as immediate early genes such as NR4A1. Moreover, osthole significantly increased SCARB1(SRB1) mRNA and StAR protein expression in the presence or absence of Bu2cAMP; these proteins are an important for the transport of the corticosteroid precursor cholesterol transport into mitochondria. Conclusions Our results show that the promotion of corticosterone biosynthesis and secretion is a novel effect of osthole, suggesting that this agent can be utilized for the prevention and treatment of Kidney-Yang deficiency syndrome.

Ethnopharmacological relevance The high recurrence rate postoperative and extensive metastases have become the obstacle of Hepatocellular Carcinoma (HCC) efficacy improvements, which contribute to most of the patient mortality. Akebia trifoliata (Thunb.) Koidz has been shown pharmacological activities in clinical and anti-HCC biological activity in previous research, but its potential function of anti-metastasis remains unknown. Aim of this study To make sure whether ATKSE inhibits migration and invasion in HCC cell lines in vitro and the potential mechanism. Materials and methods A UHPLC-HRMS analysis was adopted to identify and control the quality of the ethanol extract of Akebia trifoliata (Thunb.) Koidz Seed (abbreviated ATKSE). Cell viability of three kinds of HCC cell lines (HEPG2, HUH7, and SMMC7721) was detected using MTT assay and Flow cytometry. Adhesion capacity was measured by cell-matrigel adhesion assay. Wounded healing and Matrigel-transwell invasion assays were performed to assess cell migration and invasion, respectively. Western blot assay was used to detect several metastasis-related protein molecules, including FAK adhesion signaling, cadherin molecules, and MMPs. ELISA assay was used to evaluate the secreted MMP9 level. Results ATKSE significantly suppressed HCC cells viability and proliferation (from 0.9 up to 3.0 mg/ml); then under sub-lethal concentration (from 0.25 up to 1.0 mg/ml), ATKSE inhibited cell adhesion, migration, and invasion in a way of dose-dependent. Several metastatic-related molecules or pathway, including FAK adhesion signaling, cadherin molecules, and MMPs, took part in this process. There are both differences and commonalities in various cell lines: typically such as p-FAK was down-regulated by ATKSE in both HEPG2 and SMMC7721, while was raised in HUH7; Further attempts on the combination of ATKSE and FAK inhibitors, provide us with the enhanced inhibitory effects of invasion and migration in HEPG2 and HUH7 cells, as well as antagonistic effects in SMMC7721. As a target or potential mechanism, it may be more valuable to concern FAK inhibition by ATKSE in HEPG2 cells than in the other two cells. Conclusions These results suggest that ATKSE has anti-metastasis potency in HCC cells.

To explore the relationship between occupational stressors and the incidence of type 2 diabetes mellitus among police officers. Baseline data were collected from policemen who completed the Occupational Stress Inventory-Revised (OSI-R) questionnaire, a self-designed questionnaire, and underwent free clinical measurements at the Medical Center of Police Hospital in Tianjin, China, in April 2007. A total of 5811 policemen participated in follow-up with the dynamic observation of new-onset diabetes (NOD) events occurring annually between 2008 and 2011. Occupational stress was measured by the OSI-R questionnaire, which contains 14 different scales. Cox proportional hazards regression was used to calculate the hazard ratios (HR) of the incidence of type 2 diabetes mellitus (T2DM) by occupational stressors. A total of 3.1 % of the participants (n = 179) developed NOD in the follow-up period from 2008 to 2011, and the incidence rates of NOD were 0.58 % in 2008, 0.98 % in 2009, 0.52 % in 2010, and 1.01 % in 2011. Role overload (RO), role boundary (RB), physical environment (PE), interpersonal strain (IS), and physical strain (PHS) were associated with the incidence of T2DM (RO: HR = 1.574, 95 % CI = 1.071–2.372; RB: HR = 1.645, 95 % CI = 1.144–2.365; PE: HR = 2.292, 95 % CI = 1.545–3.400; IS: HR = 1.537, 95 % CI = 1.079–2.191; and PHS: HR = 1.680, 95 % CI = 1.167–2.006) after adjustment for confounding factors. A subgroup Cox regression analysis among traffic control police officers showed the specific work stressors remained robust except RO. Several aspects of stressors were independent predictors of T2DM in a prospective cohort study in Tianjin, China. This practical information can be applied to the development of psychological interventions against T2DM.

Objectives: This meta-analysis aimed to evaluate the risk of clonal evolution of granulocyte colony-stimulating factor (G-CSF) in acquired aplastic anemia (AA), and whether the use of G-CSF increases the occurrence of secondary malignant neoplasms, mainly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) or paroxysmal nocturnal hemoglobinuria (PNH). Methods: Data were gathered from randomized controlled trials (RCTs) to evaluate the effect of G-CSF versus no G-CSF at the risk of developing the clonal complications of acquired AA. Electronic searches in PubMed, Embase, and the Cochrane Library were performed to identify studies up to 1 January 2017. Only RCTs performed on patients who were randomly assigned to receive G-CSF or not to receive G-CSF were included. Results: Four relevant trials that met the inclusion criteria were identified. In a pooled analysis, the G-CSF groups of AA patients were not associated with a statistically significant higher occurrence of secondary malignant neoplasm, mainly MDS and AML (relative risk [RR] 0.86; 95% confidence interval [CI] 0.34–2.19; 4 trials). No significant heterogeneity was found (p = 0.67, I2 = 0%). There was no statistically significant higher occurrence of PNH in the G-CSF groups with AA (RR 1.17; 95% CI 0.51–2.71; 4 trials) and no significant heterogeneity was found (p = 0.42, I2 = 0%). Conclusions: G-CSF for patients with AA is not associated with a higher occurrence of secondary malignant neoplasm, mainly MDS/AML, or PNH.

Recently, the entrapment of hydrophobic drugs in the form of water-soluble drug-cyclodextrin (CD) complex in liposomes has been investigated as a new strategy to combine the relative advantages of CDs and liposomes into one system, namely drug-in-CD-in-liposome (DCL) systems.For DCLs preparation, an overall understanding of the interaction between CDs and lipid components of liposomes is necessary and valuable. The present article reviews the preparation, characterization and application of DCLs, especially as antitumor or transdermal carriers. Double-loading technique, an interesting strategy to control release and increase drug-loading capacity, is also discussed.DCL approach can be useful in increasing drug solubility and vesicles stability, in controlling the in vivo fate of hydrophobic drugs and in avoiding burst release of drug from the vesicles. To obtain stable DCL, the CDs should have a higher affinity to drug molecules compared with liposomal membrane lipids. DCLs prepared by double-loading technique seem to be a suitable targeted drug delivery system because they have a fast onset action with prolonged drug release process and the significantly enhanced drug-loading capacity. In particular, DCLs are suitable for the delivery of hydrophobic drugs which also possess volatility.

With the growth with the citys population of elderly people, the symptoms of aging are becoming more and more significant. Older people are faced with complex circumstances when they are outdoors, a correct and efficient system of road signs should help them reach their destinations safely. Therefore, a well designed system for the elderly is vital. The following research is concentrated on the design of the road sign system focusing upon the aspects of placement positions, height of the text and symbols, and the amount of information included on the sign. This will assist in the design of the most useful and efficient sign board system for the elderly. This will be determined through the experimental method.

To study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells.Y1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM-F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR).Y1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P0.05). Star gene expression was further enhanced after 48-h intervention (P0.05). However, Ost showed no effect on Cyp11a1 (P0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions.Ost could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes.

This paper compares legislative difference of EPR on WEEE in eight developed countries and districts. We study the ways of implementing EPR on WEEE through analyzing compliance mechanisms and returned logistics network. Combing with their results and taking national actual conditions into account, certain recommendations for implementing EPR in China are given, from the perspective of local authorities and producers.

Objective To study the gene expression characteristics of steroid- and catecholamine-synthesizing enzymes in adrenal gland of spontaneously hypertensive rats (SHRs), Goto-Kakizaki (GK) rats and normal Wistar rats with the same traditional Chinese medicine syndromes. Methods Sixteen-week-old Wistar rats, SHRs and GK rats were used. By the quantitative four diagnosis and syndrome differentiation methods and GeneChip Mouse Exon 1.0 ST Array, we observed adrenal gland gene expressions in normal Wistar rats, qi deficiency Wistar rats, SHRs with qi deficiency and qi excess, GK rats with qi deficiency and qi excess. Differentially expressed genes of steroid- and catecholamine-synthesizing enzymes and their regulatory factors were analyzed. Results Thirty-one genes were differentially expressed among all syndromes. Hsd3b6 was down-regulated significantly 6.0-fold in GK rats with qi deficiency syndrome and qi excess syndrome, and Cyp11b2 was up-regulated 1.5 times in GK rats with qi deficiency syndrome. Por, Hsd11b2, and Nr2f6 were up-regulated in all syndromes, and Cyp2c23, Cyp4a3, Cyp4a8 and Cyp2e1 were down-regulated. However, Srd5a1 and Nr4a1 were up-regulated only in GK rats, and Lss was down-regulated only in SHRs. Th was up-regulated 1.5 times in SHRs with qi deficiency syndrome, GK rats with qi deficiency syndrome and GK rats with qi excess syndrome. Ddc was up-regulated 1.5 times in GK rats with qi excess syndrome. Dbh was up-regulated 3.0 times in GK rats with qi deficiency syndrome and qi excess syndrome. However, Comt was down-regulated 1.5 times in GK rats with qi deficiency syndrome and qi excess syndrome, and Mao was up-regulated 1.5 times in SHRs with qi deficiency syndrome and qi excess syndrome. Conclusion Some genes associated with steroid- and catecholamine-synthesizing pathways were differentially expressed in SHRs and GK rats, and the differentially expressed genes may be related to the development of traditional Chinese medicine syndromes.

Objective To reveal the characteristics of gene expression in adrenal gland of H22 tumor mice with typical syndromes and in different liver cancer stages. Methods By the quantitative four diagnosis and syndrome differentiation methods and GeneChip Mouse Exon 1.0 ST Array, we observed adrenal gland gene expression in H22 tumor mice with pathogenic factor-toxin predominance syndrome and qi deficiency syndrome in the earlier stage, yang-qi deficiency syndrome in the intermediate stage, and qi-yin-yang deficiency syndrome in the advanced stage. Genes highly expressed and remarkably different were analyzed in this study. Results A total of seventy-three up-regulated coincident genes and twenty-six down-regulated coincident genes in different stages were investigated in the study. Up-regulated coincident genes included Hp, C3, Anxa1, Procr, C2, Il4ra, Cd14, Ptprc, Cd52, C4b, Eno3, Xdh, Gpx3, and so on. Down-regulated coincident genes included nervous system function-related genes such as Plp1, Mbp, Aldh1a1, Cck, Atn1, genes associated with electrolyte metabolism such as Aldh1a1 and Slc22a17, genes related to signal transduction such as Cxcr4, Spag5 and Stmn3, etc, and genes related to transcriptional control and protein biosynthesis such as Hspa1a, Dnajb1, Thra, Hhex and so on. Conclusion With the development of the tumorigenesis, the symptoms and signs and differentially expressed genes in adrenal gland of H22 tumor mice can be measured. Up-regulated and down-regulated coincident genes may be the features of H22 tumor mice different from those of normal mice.

Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China, while the molecular mechanism remains obscure. Our recent work found thatAkebia trifoliate (Thunb.) Koidzseed extract (ATSE) suppressed proliferation and induced endoplasmic reticulum (ER) stress in SMMC-7721. The present study aimed to throw more light on the mechanism. ER stress occurred after ATSE treatment in HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was the most sensitive kind in terms of morphology. Cell viability assay showed that ATSE significantly inhibited cells proliferation. Flow cytometry analysis indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the chosen ER stress-related proteins after different treatments but nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7. Affymetrix array indicated that lots of ER stress-related genes’ expressions were significantly altered, and downward is the main trend. These results suggest that ATSE have anticancer potency in HCC cells via partly inducing ER stress.

With the incorporation of edge activators into the lipid bilayer structure, elasticity properties are given to liposomes. Regardless of the debate over the precise permeation mechanism of elastic liposomes, these vesicles have been proven to enhance drug permeation into or through skin in most cases.This article provides an overview of the formulation ingredients of elastic liposomes and their relationship with skin permeation behavior. The ingredients are divided into two categories of basic and optional ingredients. The effect of stability on permeation behavior of the vesicles is highlighted.More attention should be paid to the stability of elastic liposomes. The different stability properties of the elastic liposomes following administration can induce different skin permeation behaviors of the vesicles. It is necessary to select the optimum composition of the elastic liposomes in order to control the stability and permeation behavior of the vesicles into or through the skin. Moreover, for the development of elastic liposomes, particular attention should also be paid to the drug leakage from the vesicles during long-term storage. The application of optional ingredients to improve the stability and/or elasticity of the elastic liposomes is becoming a new trend.

To study the dynamic changes of blood hormone levels in H22 liver cancer mice of poisonous pathogenic factors syndromes (PPFS) to different degrees.Two hundred and twenty mice were injected with H22 tumor cells from their armpits. On the ninth day after inoculation the mice of severe poisonous pathogenic factors syndrome (SPPFS) and of mild poisonous pathogenic factors syndrome (MPPFS) were screened. Besides, another normal control group consisting of 30 mice was set up. The mice were killed on the tenth and eleventh day after inoculation (as the 1st and 2nd time window). The weight of the tumor, the wet weight of the thymus and the spleen were weighed. The plasma adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, thyroid hormone T3 and T4, testosterone, TNF-alpha, and IFN-gamma were detected by ELISA. All the aforesaid laboratory parameters were analyzed.The tumor weight was obviously larger in mice of the SPPFS group than in those of the MPPFS group at the same time window (Por = 0.05). Compared with the normal control group, the thymus was obviously atrophied (Por = 0.05), the spleen was significantly enlarged (Por = 0.05), the plasma ACTH significantly increased (Por = 0.05) in the SPPFS group at the two time windows. But the increment of ACTH was less in the MPPFS group. The plasma corticosterone showed similar tendency as that of ACTH. At the 1st time window the plasma testosterone significantly increased in the two groups (Por = 0.05). The plasma testosterone and T4 showed a decreasing tendency in the SPPFS group. The plasma TNF-alpha and IFN-gamma levels showed an increasing trend in the two groups. Correlation study showed that the degree of PPFS was negatively correlated with qi deficiency (r = -0.766, Por = 0.05) and T4 (r = -0.738, Por = 0.05). The degrees of PPFS was positively correlated with the plasma ACTH level (r = 0.635, Por = 0.05). The degree of qi deficiency was positively correlated with yang heat syndrome (r = 0.632, Por = 0.05). The plasma ACTH was negatively correlated with T4 (r = -0.504, Por = 0.05). The plasma testosterone was positively correlated with TNF-alpha (r = 0.619, Por = 0.05).PPFS occurs naturally and shows difference to different degrees in the development of H22 liver cancer. The disorders of neuroendocrine hormones and the suppression of the immune function show dynamic changing trends.

To study the cytokines expressions in the adrenal gland and its correlation with serum adrenal corticosteroids in mice of different syndromes.Using the quantitative four diagnosis and syndrome differentiation methods, 60 normal mice and 190 H22 liver cancer bearing mice were syndrome typed. Serum corticosterone and aldosterone were tested by ELISA, and mRNA expressions of cytokines in the adrenal gland were detected using Real-time PCR.Mice of different syndromes were obtained, such as normal mice of no syndrome, normal mice of vigorous qi syndrome, normal mice of qi deficiency syndrome, liver cancer bearing mice of excessive evil toxic syndrome, liver cancer bearing mice of evil lying in the middle syndrome, liver cancer bearing mice of weak evil toxic syndrome, and liver cancer bearing mice of poisonous pathogenic factors and qi deficiency syndrome. The serum corticosteroids were significantly higher in the liver cancer bearing mice than in the normal mice (P0.05). The cortex hormones increased most significantly in the liver cancer bearing mice of excessive evil toxic syndrome (P0.05). Compared with the normal mice, IL-1beta, IL-2, IL-6, IL-10, IL-12alpha, IL-12beta, and TNF-alpha gene expressions increased in the liver cancer bearing mice, while only expressions of IL-1alpha and IL-5 decreased. But the expressions of IL-13 and transforming growth factor beta1 (TGF-beta1) showed no regularity. The expressions of IL-4 and INF-alpha were not detected in all mice. It is notable that the more severe degree of poisonous pathogenic factors, the higher the expressions of serum corticosterone and aldosterone levels as well as IL-6, the lower expressions of IL-1beta, IL-2, IL-5, IL-12alpha, IL-12beta, and TNF-alpha.The increased serum corticosteroid level in liver cancer bearing mice could possibly be induced by chronic tumor stress, partial cytokines were involved in the synthesis and secretion of the adrenal hormone. Of them, IL-6 might positively regulate the secretion of corticosteroids, while IL-1beta, IL-2, IL-5, IL-12alpha, IL-12beta, and TNF-alpha might negatively regulate their secretions.

To study the characteristics of gene expression of adrenal cortical steroid synthetase and its regulatory factor in mice with H22 liver cancer of different patterns.Syndromes revealed in mice with H22 tumor were differentiated by quantified four diagnostic methods and syndrome differentiation, and mice with commonly encountered patterns (A: evil-toxin accumulation pattern, B: qi-deficiency pattern, C: yang-qi deficiency pattern and D: qi-yin-yang deficiency pattern) were screened out for subjecting to the study. Two batches of GeneChip Mouse Exon 1.0 ST Array detection were performed in the selected mice for detecting the gene expressions of adrenal cortical steroid synthetase and its regulatory factor, with the analysis performed put stress on the differential expressions in mice of various syndrome patterns.Data obtained from the two batches detection showed well repeatability, in which similar genes of high or low expression emerged. The adrenal cortical steroid synthetase genes, such as Cyp11a1, Star, Cyp11b2, Cyp21a1, Hsd3b and Hsd17b were highly expressed, with few difference among the four patterns. However, Cyp11a1 was down-regulated and Cyp1b2 up-regulated in all patterns; Hsd3b1 and Cyp21a1 down-regulated in pattern A and B, but up-regulated in pattern C and D. As for the expressions of the relative regulatory factors, Cyb5b and Wnt4 were down-regulated but Fdx1, Fdxr, Hsd11b1, Por, Agt and Nr 0b1 were up-regulated in all patterns; Nr5al down-regulated in pattern A but up-regulated in other three patterns; Nr4al and Nr4a2 up-regulated in pattern A and down-regulated in the others.The adrenal cortical steroid synthetase genes are rather conservative and stable in mice bearing H22 liver cancer, part of the expression might be correlated to the condition of disease and essence of syndromes, embodying the differences among different patterns in the same disease.

To investigate the epidemiological characteristics of subclinical target organ damage (TOD) among urban adult residents with hypertension in Tianjin and evaluate its relationships with circulating renin-angiotensin-aldosterone system (RAAS).An epidemiological survey was conducted on urban adult residents in Tianjin. The participants with uncomplicated hypertension were followed up to examine for target organ involvement, including left ventricular hypertrophy (LVH), carotid plaque or intima-media thickening (IMT), microalbuminuria (MAU) and estimated glomerular filtration rate (eGFR). Multivariate logistic regression was used to evaluate the relations between subclinical TOD and RAAS.A total of 1547 subjects with uncomplicated hypertension underwent further examinations for target organ involvement. The prevalence rates of LVH, carotid plaque, carotid IMT, MAU and eGFR60 ml×min(-1)×(1.73 m(2))(-1) were 37.7%, 38.2%, 35.4%, 33.7% and 4.4%, respectively. The prevalence rates were categorized according to the absence or presence of one marker, two or three markers of TOD at 20.5%, 34.7%, 33.7% and 11.1% respectively. According to the logistic regression analysis adjusting for age, gender, current smoking, current drinking, previous antihypertensive treatment, body mass index, mean systolic blood pressure, mean diastolic blood pressure, duration of hypertension and other risk factors, plasma renin activity (OR 0.870, 95%CI 0.791 - 0.958, P = 0.005) and plasma angiotensin II (OR 1.005, 95%CI 1.001 - 1.009, P = 0.021) levels were independently associated with LVH, serum aldosterone level was independently associated with carotid IMT or plaque (OR 1.025, 95%CI 1.000 - 1.050, P = 0.048) and MAU (OR 1.049, 95%CI 1.024 - 1.074, P0.001).Subclinical TOD is fairly common among urban adult residents with hypertension in Tianjin. And RAAS plays an important role in the pathogenesis of subclinical TOD.

To assess the influence of growth hormone receptor (GHR) Ex3 genotype on the short-term response to recombinant human growth hormone (rhGH) therapy in children with idiopathic short stature (ISS).Thirty prepubertal children with ISS receiving rhGH treatment [0.116±0.02 IU/(kg/d)] were randomly recruited. The GHR Ex3 locus was genotyped using a PCR multiplex assay. The growth data including growth velocity, height SDS for chronological age (HtSDSCA), height SDS for bone age (HtSDSBA) and predict final height were compared in children with different GHR genotypes 6 months after rhGH treatment.After 6 months of rhGH treatment, the children with ISS carrying d3/d3 alleles showed a significantly higher increment in growth velocity than those carrying fl/fl alleles (6.3±1.6 cm/year vs 3.4±0.5 cm/year; P0.05).The polymorphism in GHR Ex3 is associated with the responsiveness to rhGH treatment, showing that the growth velocity in ISS children with d3/d3 genotype is significantly higher than those with fl/fl genotype.

Methodology of syndrome differentiation and syndrome-based treatment in rats and mice has professional characteristics and caters to the research and development of traditional Chinese medicine (TCM). In this paper, the authors introduced their systematic research in five aspects. 1) Rats and mice can be used to simulate TCM clinical practice. Diagnosis and syndrome differentiation can be done to the rats and mice, and information collected by the four diagnostic methods from the experimental animals meets the requirements of treatment based on syndrome differentiation. 2) Standardized and quantified four diagnostic methods and syndrome differentiation for rats and mice can be established, and are operational and applicable for general use. 3) There exists constitution and syndrome diversity in normal rats and mice. A spontaneous syndrome can develop in diseased rats and mice, and it can be accompanied by or even change to another syndrome, similar to that in human beings. 4) There is a complicated material base for syndromes inferred from the different gene expressions and splices in neuroendocrine-immune network. 5) Individualized treatment based on syndrome differentiation, as well as quantified evaluation and comparison of the treatment efficacy can be done in the rat and mouse models of syndromes. The established methodology and criteria for syndrome differentiation and syndrome-based treatment in rats and mice can be used in the following four research fields: 1) syndrome identification on rat or mouse models; 2) research on the basic theories of TCM, such as the research on the viscera manifestation theory, the material base of syndromes, function mechanisms of the treatment based on syndrome differentiation, and the diagnostics of TCM; 3) study in clinical subject of TCM, such as evaluation and comparison of the efficacy of treatment based on syndrome differentiation, protocol optimization of syndrome differentiation and treatment, and preventive treatment of diseases; 4) study in traditional Chinese drugs, such as the research on properties of Chinese herbal drugs, and pharmacological research on Chinese herbal medicines and formulas.

Summary form only given. We demonstrate an electronically tunable semiconductor laser capable of generating relatively high-power, narrow multiple wavelengths with suppression ratio. This is realized by using a folded telescopic grating-loaded external cavity with a liquid crystal pixel mirror (LCPM) at the focal plane of the folded telescope. With 50 pixels, the digital tuning range was 8.12 nm in 0.16 nm steps. We also demonstrate electronically tunable cw dual and triple wavelength operation for this laser.

A reflection-type spatial light modulator using twisted nematic (TN) liquid crystal (the liquid crystal pixel mirror or LCPM) is employed to realize a new type of digitally tunable, narrow line-width (less than 0.1 nm, instrument-limited), multi-wavelength semiconductor laser. The laser is based on a novel folded telescopic grating-loaded external cavity with LCPM at the focal plane of the folded telescope. With a 50-pixel LCPM, the single wavelength digitally tunable range of a visible laser diode was from 650.8 to 661.24 nm in 0.21 nm steps by biasing the individual pixels. Further, the wavelength can be switched and reset with a response time of 13.6 ms. By biasing two pixels at the same time, obtain dual-wavelength output with the wavelength tunable from 0.21 to 10.4 nm. Generation of tunable triple wavelengths with equal or arbitrary wavelength separation are also demonstrated. Preliminary results on such a laser operating at 1550 nm is also shown.

Objective To investigate the relevance of the pituitary to liver syndromes and cancer by studying the pituitary transcriptome profile in liver cancer mice with different syndromes. Methods The quantitative four diagnosis and syndrome differentiation methods were used to screen normal control mice without syndromes (NC), liver cancer mice with poisonous pathogenic factors syndrome (PPFS), and Qi deficiency syndrome mice (QDS). An Affymetrix GeneChip Mouse Exon 1.0 ST Array was performed to detect the gene expression of different groups. Gene clustering was applied to analyze the gene expression patterns of the PPFS and QDS groups compared with the NC group. The transcriptional networks analysis tool, FunNet, was used to enrich the biological categories of differentially expressed genes in the PPFS and QDS groups. Results Biological categories of differentially expressed genes showed that excessive metabolism and extracellular matrix interaction, insufficient communication of cells (especially nerve cells), and the bidirectional regulation of genetic information processing were enriched in both syndromes. However, the degree of excessive metabolism in the PPFS group was higher than that in the QDS group. The hyperfunction of cancer and infection, and the hypofunction of the nervous and endocrine systems were obvious in the QDS group. Conclusion The pituitary plays an important role in the development of liver cancer and syndromes. This study further studied the role of the pituitary in the combination of disease and syndromes.