Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay / 药物分析学报

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management / 药物分析学报

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

Analysis of lactate dehydrogenase gene polymorphisms and prediction of B cell epitopes in four human Plasmodium species / 中国血吸虫病防治杂志

Objective To analyze the polymorphism of Plasmodium lactate dehydrogenase (pLDH) gene and predict B-cell epitopes in pLDH peptides in four species of human malaria parasites. Methods The blood samples and epidemiological characteristics were collected from malaria cases in Yunnan Province registered in the National Notifiable Disease Report System. The pLDH genes of four human Plasmodium species were amplified using nested PCR assay and sequenced. The polymorphisms of pLDH genes was analyzed using the software MEGA version 7.0.26 and DnaSP version 5.10, and the B-cell epitopes were predicted in pLDH peptides using the Immune Epitope Database (IEDB). Results The sequences of P. vivax LDH (PvLDH), P. falciparum LDH (PfLDH), P. ovale LDH (PoLDH) and P. malariae LDH (PmLDH) genes were obtained from 153, 29, 17 and 11 blood samples from patients with P. vivax, P. falciparum, P. ovale and P. malariae malaria, respectively, which included 15, 2, 4 and 2 haplotypes and had a nucleotide diversity (π) of 0.104. A high level of intra-species differentiation was seen in the PoLDH gene (π = 0.012), and the π values were all < 0.001 for PvLDH, PfLDH and PmLDH genes. Active regions of B-cell antigen were predicted in the pLDH peptide chain of four human malaria parasites, of 4 to 5 in each chain, and the activity score was approximately 0.430. Among these peptide chains, the “86-PGKSDKEWNRD-96” short-peptide was a B-cell epitope shared by all four species of human malaria parasites, and the “266-GQYGHS (T)-271” short-peptide was present in PvLDH and PoLDH peptide chains, while “212-EEVEGIFDR-220” was only found in the PvLDH peptide chain, and “208-LISDAE-213” was only seen in the PfLDH peptide chain. Conclusions The PoLDH gene polymorphism may be derived from the weak negative purification selection, while PvLDH, PfLDH and PmLDH genes may maintain a relatively conservative state. There may be two B-cell epitopes “212-EEVEGIFDR-220” and “208-LISDAE-213” in the proximal region of the C terminal in the pLDH peptide chain, which is feasible to differentiate between P. vivax and P. falciparum infections.

Establishment of multiple evidence-integrated evaluation and prediction method for "toxic" Chinese medicines / 中国中药杂志

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.

Advances in Evaluation Methods and Models on Angiogenesis / 中国药学杂志

Angiogenesis, the process of shaping new vessels from existing or posteriorvessels. It occurs mainly after birth and is the basis for the formation of many vascular structures and participates ina variety of physiological and pathological processes.Due to the particularity of the research objects and the diversity of the species, the experimental results obtained from one model may not be confirmed on the other model. At present,the comprehensive evaluation of angiogenesis requires mutual verification of different model results. Herein, this review mainly summarizes the literatures on the evaluation of angiogenesis activity within recent ten years. From three parallel dimensions of cell, tissue, and animal,the up-to-date evaluation methods and angiogenesis models with wide recognitions are reviewed, in order to provide the reference for related drug research and development.

Inflammatory myofibroblastic tumor of the prostate after transurethral resection of the prostate with negative expression of anaplastic lymphoma kinase: a case report

ABSTRACT CONTEXT: Inflammatory myofibroblastic tumors are a rare type of soft-tissue tumor. Inflammatory myofibroblastic tumors are characterized by rearrangements involving the anaplastic lymphoma kinase gene locus on 2p23. Case Report: We report the case of a 67-year-old Chinese male who presented with dysuria and fever. Magnetic resonance imaging showed an irregular prostatic mass with an isointense signal and obscure boundary. Histopathological evaluation showed that the mass consisted mainly of spindle-shaped cells. Immunohistochemical evaluation showed that the tumor cells were negative for anaplastic lymphoma kinase. CONCLUSIONS: Inflammatory myofibroblastic prostate tumors are rare lesions with unclear etiology. The pathological diagnosis is very important.

Enhanced Biocompatibility and Osseointegration of Calcium Titanate Coating on Titanium Screws in Rabbit Femur / 华中科技大学学报（医学）（英德文版）

This study aimed to examine the biocompatibility of calcium titanate (CaTiO3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO3 coating as an alternative to current implant coating materials.CaTiO3-coated titanium screws were implanted with hydroxyapatite (HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits.Imaging,histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation.Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO3 were fully regenerated and they were also.well integrated with the screws.An interfacial fibrous membrane layer,which was found in the HA coating group,was not noticeable between the bone tissues and CaTiO3-coated screws.X-ray imaging analysis showed in the CaTiO3 coating group,there was a dense and tight binding between implants and the bone tissues;no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture.In contrast,uncoated screws exhibited a fibrous membrane layer,as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues.Additionally,biomechanical testing revealed that the binding strength of CaTiO3 coating with bone tissues was significantly higher than that of uncoated titanium screws,and was comparable to that of HA coating.The study demonstrated that CaTiO3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.

nhibitory effect and mechanism of deoxyschizandrin on NLRP3 inflammasome / 药学学报

This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome. Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8. The expression of IL-1β, caspase-1 in the supernatant and the expression of pro-caspase-1, pro-IL-1 β, ASC, NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 μmol·L-1) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25-400 μmol·L-1. Deoxyschizandrin (25, 50, 100, and 200 μmol·L-1) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1 β, which was associated with inhibiting the cleavage of pro-caspase-1. The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3, ASC, pro-caspase-1 and pro-IL-1 β mediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25-200 μmol·L-1 to reduce the inflammation response.

The three dimensional organoids-based high content imaging model for hepatotoxicity assessment / 药学学报

The drug hepatotoxicity assessment method in vitro was established by 3D organoid model of HepaRG cell line in combination with high content imaging analysis. HepaRG cells were differentiated into hepatocyte-like morphology and bile canaliculus-like structures by treatment with hydrocortisone and dimethyl sulfoxide(DMSO), inducing the expressions of drug-metabolizing enzymes, transporters, nuclear receptors and hepatocyte-specific protein albumin(ALB)genes, finally forming the stable organoids with closely resembling liver function in vitro. Through the high content imaging analysis and the specific, multi-targets fluorescent dye, the number of live/dead cells, mitochondrial membrane potential(MMP), intracellular reactive oxygen species(ROS)were analyzed for the drug hepatotoxicity evaluation. The results showed that the organoids evaluation model of HepaRG cells in vitro could be used to assess accurately the difference between hepatotoxicity positive control drugs of amiodarone(AMD), cyclosporin(CSP)and the negative control drug of aspirin(ASP): AMD and CSP concentration-dependently decreased the number of total and live organoid cells. The number of dead organoid cells was increased sharply when the concentration of AMD was more than 50 μmol·L-1, while no significant changes was observed for ASP. AMD and CSP concentration-dependently caused the MMP declined and the ROS increased, with AMD showing a greater degree than CSP and ASP presenting no markedly effect. In conclusion, the organoid evaluation method of HepaRG cells in combination with high content imaging analysis can be used for the drug hepatotoxicity assessment in vitro. It displays the advantages of multi-target, high throughput, intuitive results as well as quantitatively.

Study on the mechanism of PPAR-γ dependent immunological idiosyncrasy liver injury induced by Polygonum multiflorum / 药学学报

To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.

Protective effects of oxymatrine against H2O2-induced damage in L02 cells / 中国中药杂志

To investigate the protective effects of oxymatrine (OMT) against H2O2-induced damage in L02 cells and research the mechanism,L02 cells were used as the research object. The oxidative stress model of L02 was established by hydrogen peroxide (H2O2). CCK-8 was used to detect the cell activation of L02 cells treated by different OMT. FCM (flow cytometry) assay was used to evaluate the cell proliferation of L02 cells treated by OMT. The apoptosis of L02 cells was detected using Annexin-V/7-AAD apoptosis detection kit. The level of ROS was detected by DCFH-DA fluorescence probe. The GSH-PX and SOD were detected by micro plate and colorimetric method. Results showed that when the concentration of OMT is between 6.25 and 100 mg•L⁻¹, it could promote the production of NADPH and strengthen the activity of GSH-PX and SOD to get rid of the ROS to protect the L02 cell from the apoptosis of L02 cell induced by H2O2.

Investigation of potential toxic factors for fleece-flower root： from perspective of processing methods evolution / 中国中药杂志

In recent years, the rapid growth of reports on fleece-flower root-caused liver damages has drawn wide attention of both at home and abroad, however, there were rare literature on toxicology of fleece-flower root in ancient Chinese medicine. But why there are so many reports on toxicology of fleece-flower root now compared with the ancient literature? As a typical tonic medicine, the clinical utility of fleece-flower root was largely limited by its standardization and reliability of processing methods in ancient Chinese medicine. The ancient processing methods of fleece-flower root emphasized nine times of steaming and nine times of drying, while the modern processes have been simplified into one time of steaming. Whether the differences between ancient and modern processing methods are the potential cause of the increased events of fleece-flower root-caused liver damages. We will make deep analysis and provide new clues and perspectives for the research on its toxicity. This article, therefore, would discuss the affecting factors and key problems in toxicity attenuation of fleece-flower root on the basis of sorting out the processing methods of fleece-flower root in ancient medical books and modern standards, in order to provide the reference for establishing specification for toxicity attenuation of fleece-flower root.

Protective effects of Liuwei Wuling tablet on acute alcoholic-induced liver injury in mice / 中国中药杂志

The protective action and the relevant mechanism of Liuwei Wuling tablet on acute alcoholic hepatic injury in mice were investigated. All the C57BL/6 mice were divided randomly into 7 groups including blank, model, bifendate (150 mg•kg⁻¹, positive control) and experimental groups consisted of extremely low dose (0.1 g•kg⁻¹), low (0.5 g•kg⁻¹), upper (4 g•kg⁻¹) and high dose (8 g•kg⁻¹) of Liuwei Wuling tablet groups. The acute liver injury model was induced by modified method that the model, positive control and experimental groups were orally administrated 56% alcohol (6 g•kg⁻¹) twice at 12 hour intervals on the fifth day after drugs administration. After 12 hours, the mice were sacrificed to contribute blood and liver for biochemical and histological examinations. Compared with the model, the activities of ALT and AST in serum decreased significantly in different Liuwei Wuling tablet groups. Meanwhile, in liver tissue, the levels of TG, MDA, TNF-α and IL-1β reduced obviously while the GSH and SOD activities showed markedly increase with a dose-dependent manner. Correspondingly, the microscopically pathological differences of the liver tissue observed by HE and oil red O staining indicated that the liver cell swelling, hydropic degeneration and lipid droplets formation induced by alcohol were significantly improved, which suggested the Liuwei Wuling tablet can reduce the liver injure. In conclusion, the Liuwei Wuling tablet had the protective effect on acute alcoholic hepatic injury which maybe depended on the mechanism of relieving lipid peroxidation, elevating antioxidant enzymes activity, inhibiting oxidative stress and reducing inflammation factors expression.

Simultaneous Determination of Eight Active Components in Liuwei Wuling Tablet Using HPLC / 中草药·英文版

Objective To develop an effective method for simultaneous determination of eight major components in Liuwei Wuling Tablet (LWT). Methods Reversed phase HPLC method was used with variously improved conditions. Results Salidroside, forsythoside A, specnuezhenide, phillyrin, schisandrol A, schizandrol A, schizandrin A, and schizandrin B in LWT were successfully separated on a Kromasil 100-5-C18 reverse phase column (250 mm × 4.6 mm, 5 μm) using acetonitrile-0.1% phosphoric acid (gradient elution) as mobile phase. The detection wavelength was 275 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 35 oC. The recovery rate of the method was within the range of 95.13%–104.56% and the precision (RSD) was less than 3% for all eight analytes. All the compounds showed good linearities (r2 > 0.9980) in a relatively wide concentration range. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation of LWT.

Precision medicine-oriented safety assessment strategy for traditional Chinese medicines:disease-syndrome-based toxicology / 药学学报

Drug toxicity is commonly divided into intrinsic and idiosyncratic types. The former can be generally uncovered in the preclinical safety evaluation stage by conventional toxicological experiments, while the latter is usually found only in the clinical evaluation stage, which is the main cause of severe adverse reactions and withdrawal of post-marketing drugs. Assessment and prediction of idiosyncratic toxicity is a challenging problem worldwide, and is an essential in the development of translational toxicology and precision medicine. Since traditional Chinese medicines (TCMs) have been applied for thousands of years with long experience in clinical efficacy and safety, idiosyncratic toxicity is regarded as an important factor for traditional "non-toxic" medicines and is associated with multiple individual states including different diseases, syndromes, habitus, etc. However, these individual conditions related to disease are often difficult to be resolved in conventional toxicological experiments, leading to insufficient translation of the experimental results into clinical application. We took an approach of systematic analysis of the differences and similarities in toxic property, medication rule and evaluating requirement between TCMs and chemical synthetic medicines. We present a novel and clinic-associated safety assessment strategy, namely as "disease-syndrome-based toxicology", for TCMs. The strategy is able to access the relativity, susceptibility and controllability of the toxicity of TCMs. The new strategy provides a theoretical and methodological guidance to practice and development of the TCM in favor of precision medicine.

The Efficacy and Safety of Fusidic Acid Cream Combined with Halometasone Cream in the Treatment of Psoriasis Vulgaris / 昆明医科大学学报

Objective To observe the efficacy and safety of fusidic acid cream and halometasone cream in the treatment of psoriasis vulgaris.Methods Fifty-four patients with psoriasis vulgaris were enrolled in this study and were divided into observation group and control group.26 patients in observation group were treated with halometasone cream,28 patients in control group were treated with fusidic acid cream combined with halometasone cream.The psoriasis area and severity index (PASI) and abverse events of treatment were recorded.At the same time,34 normal people taking physical examination were selected as health group,the infections of pathogenic microorganism were compared between psoriasis vulgaris patients and normal people.Results The pathogenic infection rate of patients with psoriasis vulgaris was 72.22％,the infection rate was 75.00％ in observation group and 69.23％ in control group.The infection rate in health group was 38.24％,the difference in the pathogenic infection rate was statistically significant between paitents with psoriasis vulgaris and normal people (P ＜0.05).After treatment,the rate of negative infections was 95.24％ in observation group and 72.22％ in control group,there was significant difference between two groups (P＜0.05).The PASI scores and VAS scores of observation group were significantly lower than those of control group (P＜0.05).The total effective rate of treatment was 71.43％ in observation group and 34.62％ in control group,the difference was statistically significant (P＜0.05).There was no significant difference in rate of adverse events between observation group and control group (P ＞0.05)Conclusion The pathogenic infection is closely correlated with psoriasis vulgaris,fusidic acid cream combined with halometasone cream has good efficacy and safety in treatment of psoriasis vulgaris and worth of popularization and application.

The idiosyncratic hepatotoxicity of Polygonum multiflorum based on endotoxin model / 药学学报

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.

Anatomy study on the fixation technique of buttress plate in the posterior column of the acetabulum / 中国骨伤

<p><b>OBJECTIVE</b>To solve the problem of screw penetrating the joint surface easily by determining the angle of inclination and the mean longth screw plated on the posterior column.</p><p><b>METHODS</b>Ten specimens of adult male cadavers, aged 20 to 74 years old, averaged 54.5 years old, were collected. After removal of the bilateral femurs from the hip joints, and sawing through the sacral and pubic symphysis in the median sagittal plane, 20 semi pelvic specimens were used for this study when the osseous abnormalities were excluded. The specimens were air dried naturelly after the soft tissue attaching to the pelvis had been eliminated. The margin of superior acetabular and inferior acetabular were determined, and the serial cross-sections of the acetabular posterior column were made. The width of posterior column,the width of acetabulum,the width ratio of acetabulum to posterior column, the angle of inclination and the mean length of screw on all entry points were measured. Defined the level parallel to 1/2 section of superior acetabulum was cross-section B; 1/2 section of acetabulum was C; 1/2 section of inferior acettabulum was D. At the different levels, defined the entry point on the outer edge of posterior column of the acetabulum or the trailing edge of acetabulum was B0, C0 or D0; lateral 1/2 of posterior column of the acetabulum was B1, C1 or D1; 1/2 of posterior column of the acetabulum was B2, C2 or D2; medial 1/2 of posterior column of the acetabulum was B3, C3 or D3; the inner edge of posterior column of the acetabulum was B4,C4 or D4.</p><p><b>RESULTS</b>On cross-section B, the angle of inclination and the mean length of screw at B0 was 41 degrees and 44.0 mm; at B1 was 66 degrees and 42.2 mm; at B2 was 91 degrees and 59.5 mm; at B3 was 107 degrees and 64.0 mm; the maximum angle and the mean length at point B4 was 123 degrees and 65.5 mm; the minimum angle and the mean length at point B4 was 109 degrees and 59.0 mm. On cross-section C,the angle and the mean length at point CO was 39 degrees and 39.0 mm; at C1 was 57 degrees and 36.0 mm; at C2 was 74 degrees and 36.0 mm;at C3 was 90 degrees and 36.0 mm; at C4 was 106 degrees and 76.0 mm. On cross-section D,the angle and the mean length at DO was 42 degrees and 35.5 mm; at D1 was 61 degrees and 33.0 mm; at D2 was 81 degrees and 32.0 mm; at D3 was 100 degrees and 31.0 mm; at D4 was 120 degrees and 74.0 mm.</p><p><b>CONCLUSION</b>When using the fixation technique of acetabular posterior column plate, the angles of screw-posterior column are 40 degrees to 60 degrees, 60 degrees to 75 degrees, 75 degrees to 90 degrees and 90 degrees to the angle of parallel to the square area respectively on the region of outer 1/4,outer-middle 1/4,inner-middle 1/4 and inner 1/4 of the acetabulum region, and the screw length is 30 mm.</p>

Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by hcmv-miR-UL36.

MicroRNAs (miRNAs) are small RNAs, 19–23 nucleotides in length, which regulate a variety of cellular processes. Human cytomegalovirus (HCMV) encodes only one intronic miRNA: human cytomegalovirus microRNA UL36 (hcmv-miR-UL36). In this study, we found that over-expression of hcmv-miR-UL36 resulted in a more than threefold increase in HCMV DNA synthesis at 24 h post infection. Fifteen putative targets of hcmv-miR-UL36 were identified using hybrid PCR, one being the HCMV UL138 gene that has previously been identified as a novel latency-associated determinant of HCMV infection. Down-regulation of UL138 expression by hcmv-miR-UL36 was validated using luciferase reporter assays and Western blot analysis in HEK293 cells. In the presence of hcmv-miR-UL36, we observed a 74.6% decrease in luciferase activity and a 46.2% decrease in HCMV UL138 protein expression. Our results indicate that hcmv-miR-UL36 may be a viral miRNA contributing to HCMV replication.

Relationship between occupational stress and type 2 diabetes mellitus / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the association of occupational stress and related factors with type 2 diabetes mellitus (T2MD).</p><p><b>METHODS</b>In case-control study, a questionnaire survey was conducted in 201 T2MD patients and 201 controls, who were selected from the staff members of organizations, enterprises, and institutions in Ningxia Hui Autonomous Region, China according to inclusion and exclusion criteria, to acquire the information on general condition and occupational stress. These subjects also underwent physical examinations and blood biochemical analyses.</p><p><b>RESULTS</b>The T2MD group had significantly higher total occupational stress score, as well as the scores on such factors as workload, interpersonal relationship, and home/work balance than the control group (P < 0.01). After adjustment for age, gender, education level, smoking, and drinking, the odds ratios for T2MD were 2.538 and 3.075 in the people with moderate and severe stress, respectively, compared to those with mild stress. The risk factors for T2MD included drinking, family history of diabetes, waist circumference, triglyceride level, and total occupational stress score, while the protective factors included educational level and high-density lipoprotein level.</p><p><b>CONCLUSION</b>Occupational stress is associated with the incidence of T2MD; the higher the degree of stress, the greater the risk of T2MD. Relevant measures should be taken to reduce the occupational stress or improve the ability of workers to cope with the stress, thus decreasing the incidence of T2MD among occupational population.</p>