[Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology].

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Herbal formula LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis in Zucker diabetic fatty rats.

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.

[Transcriptome analysis and validation of key genes involved in biosynthesis of iridoids in Gentiana lhassica].

As the main chemical constituents, iridoids are widely distributed within Gentiana, Gentianaceae, with promising bioactivities. Based on the previous work, the transcriptome of G. lhassica, an original plant of Tibetan herb "Jieji Nabao", was sequenced and analyzed in this study, and the transcriptome databases of roots, stems, leaves, and flowers were constructed so as to explore unigenes that may encode the key enzymes in the biosynthetic pathway of iridoids. Then, qRT-PCR was used to validate the relative expression levels of 11 genes named AACT, DXS, MCS, HDS, IDI, GPPS, GES, G10H, 7-DLNGT, 7-DLGT, and SLS in roots, stems, leaves, and flowers. Also, the total contents of gentiopicroside and loganic acid were determined by HPLC, respectively. The results are as follows:(1)a total of 76 486 unigenes with an average length of 852 bp were obtained;(2)335 unigenes were involved in 19 stan-dard secondary metabolism pathways in KEGG database, with phenylpropanoid biosynthesis having the maximum number(75 unigenes), and no isoflavone biosynthetic pathway was annotated;(3)171 unigenes participatedin 27 key enzymes encoding in the biosynthetic pathway of iridoids, and 1-deoxy-D-xylulose-5-phosphate reductoisomerase(DXR) gene was highly expressed;(4)qRT-PCR results were approximately consistent with RNA-Seq data and the relative expression levels of the 11 genes were higher in the aboveground parts(stem, leaf, and flower) than in the underground part(root);(5)the total contents of gentiopicroside and loganic acid were higher in the aboveground parts(stem, leaf, and flower) than in the underground part(root), and the difference was significant. This study provides basic scientific data for accurate species identification, evaluation of germplasm resources, research on secondary pro-duct accumulation of medicinal plants within Gentianaceae, and protection of endangered alpine species.

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common, and the incidence increases with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular (IM) vitamin B12. Doctors may not be prescribing oral vitamin B12 formulations because they may be unaware of this option or have concerns regarding its effectiveness. OBJECTIVES: To assess the effects of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov. The latest search date was 17 July 2017. We applied no language restrictions. We also contacted authors of relevant trials to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of oral versus IM vitamin B12 for vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were serum vitamin B12 levels, clinical signs and symptoms of vitamin B12 deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, haemoglobin and mean corpuscular volume, total homocysteine and serum methylmalonic acid levels, and socioeconomic effects. We used GRADE to assess the quality of the evidence for important outcomes. We did not perform meta-analyses due to the small number of included trials and substantial clinical heterogeneity. MAIN RESULTS: Three RCTs met our inclusion criteria. The trials randomised 153 participants (74 participants to oral vitamin B12 and 79 participants to IM vitamin B12). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B12 in the oral and IM groups varied among trials. Only one trial had low or unclear risk of bias across all domains and outcome measures. Two trials reported data for serum vitamin B12 levels. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 µg/day oral vitamin B12, there was no clinically relevant difference in vitamin B12 levels when compared with IM vitamin B12. One trial used 2000 µg/day vitamin B12 and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B12. Two trials reported data on adverse events (very low-quality evidence due to risk of performance bias, detection bias, and serious imprecision). One trial stated that no treatment-related adverse events were seen in both the oral and IM vitamin B12 groups. One trial reported that 2 of 30 participants (6.7%) in the oral vitamin B12 group left the trial early due to adverse events. Orally taken vitamin B12 showed lower treatment-associated costs than IM vitamin B12 in one trial (low-quality evidence due to serious imprecision). No trial reported on clinical signs and symptoms of vitamin B12 deficiency, health-related quality of life, or acceptability of the treatment scheme. AUTHORS' CONCLUSIONS: Low quality evidence shows oral and IM vitamin B12 having similar effects in terms of normalising serum vitamin B12 levels, but oral treatment costs less. We found very low-quality evidence that oral vitamin B12 appears as safe as IM vitamin B12. Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B12 deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting.

Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy.

BACKGROUND: Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). METHODS: DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. RESULTS: The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. CONCLUSION: The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.

Studies on chemical constituents of Ophiopogon japonicus.

Two new and six known steroidal glucosides were isolated from the tuber of Ophiopogon japonicus. The new steroidal glucosides were established as (20R,25R)-26-O-ß-d-glucopyranosyl-3ß,26-dihydroxycholest-5-en-16,22-dioxo-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (1) and 26-O-ß-d-glucopyranosyl-(25R)-furost-5-en-3ß,14α,17α,22α,26-pentaol-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (3) on the basis of spectroscopic data as well as chemical evidence.

[Clinicopathologic characteristics of primary thyroid-like follicular carcinoma in kidney].

OBJECTIVE: To explore the clinicopathological characteristics of primary thyroid-like follicular carcinoma of the kidney. METHODS: A case of primary thyroid-like follicular carcinoma of the kidney was studied with histology and immunohistochemical staining, and its clinical and pathological findings were further analyzed with review of the literature. RESULTS: The patient was a 26-year-old asymptomatic woman who had a kidney mass during her annual physical examination. The tumor was well-circumscribed. Pathologically, the tumor showed follicular structures with colloid-like material in the lumina. Immunohistochemically, the tumor cells showed intense staining for CK7 and vimentin and negative for thyoid transcripation factor-1, thyroglobulin, thyoid peroxidase and RCC. CONCLUSIONS: The diagnosis of primary thyroid-like follicular carcinoma of the kidney is based on the characteristic follicular architecture with colloid-like material, and the metastasis from a thyroid follicular carcinoma must be excluded clinically and pathologically before making the final diagnosis.

[Assessment of the results of syndrome in clinical trials of dementia treated by Chinese herbal medicine].

Chinese medical syndrome efficacy, as a second efficacy indicator, has been widely used in clinical trials of treating dementia by Chinese herbal medicine. The syndrome assessment tool is a key point in assessing the efficacy of Chinese medical syndrome. The syndrome assessment tool for dementia used nowadays needs to be optimized in content, reliability, and validity. In this paper, the authors reviewed some problems correlated with the design of Chinese medical assessment questionnaire on the basis of Chinese medical theories by combining the common requirements for questionnaire development.

A new triterpenoid saponin from Gymnema sylvestre.

Besides four known compounds, a new triterpenoid saponin was isolated from the stems of Gymnema sylvestre. The structure of the new triterpenoid saponin was established as 3ß,16ß,22α-trihydroxy-olean-12-ene 3-O-ß-D-xylopyranosyl-(1 → 6)-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranoside (1) on the basis of 1D and 2D NMR techniques, including COSY, HMBC, HMQC, and NOESY correlations. Four known compounds 2, 3, 4, and 5 were identified on the basis of spectroscopic data.

[Comparative study between primary mediastinal B-cell lymphoma and non-mediastinal diffuse large B-cell lymphoma by immunoglobulin gene rearrangement and Epstein-Barr virus infection detection].

OBJECTIVE: To investigate the differences between primary mediastinal B-cell lymphoma (PMBCL) and non-mediastinal conventional diffuse large B-cell common lymphoma (DLBCL) in immunoglobulin gene rearrangement and EB virus infections. METHODS: Twenty cases of PMBCL and 30 cases of non-mediastinal DLBCL were collected from September, 2000 to May, 2011. Pathological data were retrospectively analysed. Immunoglobulin heavy chain and light chain gene rearrangements and EBER in-situ hybridization were performed. RESULTS: Six of 20 cases of PMBCL showed monoclonal gene rearrangement, all of which were weakly detected. Twenty-seven of 30 cases of ordinary diffuse large B-cell lymphoma showed monoclonal gene rearrangement, which were strongly detected (90.0%). Only 1 of 20 cases PMBCL and 2 of 30 cases of DLBCL were positive for EBER in-situ hybridization. CONCLUSIONS: The detection rate of immunoglobulin gene rearrangement is significantly lower in PMBCL than that of non-mediastinal DLBCL. However, EB virus infection rates are very low in both types of lymphomas.

[Tubulolobular carcinoma of breast: a clinicopathologic study of 8 cases].

OBJECTIVE: To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC). METHODS: Eight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34ßE12 and CK8. RESULTS: Among the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34ßE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now. CONCLUSIONS: TLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34ßE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.

[The clinicopathological analysis of 4 cases of IgG4-related nonspecific interstitial pneumonia].

OBJECTIVES: To observe the immunohistochemical staining of IgG4 in nonspecific interstitial pneumonia (NSIP) and to study the clinicopathological features of IgG4-related NSIP. METHODS: Retrospective analysis was carried out for 32 patients with NSIP who had been admitted into Peking Union Medical College Hospital from November 2002 to October 2010. The diagnosis of NSIP was established by surgical lung biopsy and all specimens were fixed in neutral formalin and embedded in paraffin. Sections were cut for HE and immunohistochemical stain. According to the diagnostic criteria for IgG4-related disease, 4 cases were confirmed to be IgG4-related NSIP. The clinicopathological features including clinical history, laboratory examination, and pathologic evaluation were studied. RESULTS: The 4 patients with IgG4-related NSIP included 1 man and 3 women, with a median age of 48 years (range, 44 - 56 years). The presenting symptoms were dry cough or shortness of breath. One patient (1/4, 25.0%) was found to have a positive autoantibody but no cases showed positive RF in serum. The histological finding of the 4 cases was characterized by inflammatory cell infiltration in interstitium with fibrosis, and 1 case showed obliterative arteritis. The numbers of IgG4-positive plasma cells in the 4 cases were 42/hpf, 22/hpf, 11/hpf, and 33/hpf respectively, while the percentages of IgG4-positive to IgG-positive plasma cells were 70%, 71%, 57%, 43% respectively. CONCLUSIONS: IgG4-related interstitial pulmonary disease can be characterized as the NSIP pattern. The pathological features of IgG4-related NSIP include infiltration of lympho-plasmacytes and eosinophils in interstitium with fibrosis, and lymphoid follicles are frequently identified in the area of lymphocyte aggregation, but obliterative arteritis is infrequently identified in the lesion. Immunohistochemical staining of IgG and IgG4 is very helpful for a definite diagnosis of IgG4-related disease.

Meta-analysis Flavonoids from traditional Chinese herbs for diabetes in rats: a network Meta-analysi.

OBJECTIVE: In this Meta-analysis, we evaluated the hypoglycemic effect of 5 flavonoids found in traditional Chinese herbs (naringenin, kaempferol, puerarin, baicalein, and luteolin) on diabetic rats. METHODS: Four databases including PubMed, Web of Science, Embase, and Cochrane Library, were searched from inception to May 2020. Only studies using diabetes model rats were included in the analysis. Blood glucose data from the last measurement were collected and analyzed. Pair-wise Meta-analyses were conducted using STATA v14.0 software and a Meta-analysis was conducted using STATA v14.0, ADDIS v1.16.6, and R v3.6.1. The quality of included studies was assessed with the SYRCLE risk of bias tool for animal studies, and publication bias was evaluated with a comparisonadjusted funnel plot. RESULTS: A total of 33 studies were included in the analysis, in which all 5 flavonoids showed a beneficial effect on blood glucose level of diabetic rats were included in the final analysis. The standardized mean differences (95% confidence intervals) were -4.92 (-6.67, -3.17) fornaringenin, -12 (-18.74, -5.27) for kaempferol, -2.52 (-3.77, -1.26) for puerarin, -3.04 (-5.75, -0.34) for baicalein, and -1.94 (-2.95, -0.92) for luteolin. The network Meta-analysis showed no statistically significant differences between the effect sizes of the flavonoids. CONCLUSION: The results of the Meta-analysis showed that naringenin, kaempferol, puerarin, baicalein, and luteolin all have clear hypoglycemic effects in rat diabetes models, highlighting their therapeutic potential for preventing and treating diabetes mellitus in clinical practice.

[Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study].

OBJECTIVE: To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. METHODS: Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. RESULTS: The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected. CONCLUSIONS: Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.

Efficacy of Shouzhangshen (Rhizoma Gymnadeniae Crassinervidis) extract against acute high altitude hypoxia-induced brain injury in mice.

OBJECTIVE: To evaluate the protective effect of Shouzhangshen (Rhizoma Gymnadeniae Crassinervidis) extract against acute high altitude hypoxia-induced brain injury in mice. METHODS: Sixty C57BL/6J mice were selected and assigned to six groups (n = 10): normal control group, low-pressure hypoxia group, positive control group (dexamethasone 500 mg/kg), and three groups treated with Shouzhangshen extract (250, 500, and 750 mg/kg, respectively). The Morris water maze test was performed to evaluate alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuron damage. Hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) expression in brain tissue and serum, as well as superoxide dismutase (SOD) and glutathione (GSH) activity in brain tissues were measured by enzyme-linked immunosorbent assays, quantitative real-time-polymerase chain reaction and western blots. RESULTS: The Morris water maze test results showed that Shouzhangshen extract can significantly reduce the latency and swimming distance to escape onto a visible platform, increase neuron density and hierarchy and the number of pyramidal neurons, and decrease the expression of HIF-1α, IL-1ß, TNF-α, and VEGF mRNAs and proteins in both brain tissue and serum (P < 0.05). Furthermore, significantly lower MDA expression and higher GSH activity were detected in the three groups treated with Shouzhangshen compared with the low-pressure hypoxia group (P < 0.05). However, no significant alteration was observed for SOD activity (P > 0.05). CONCLUSION: Our findings suggest that Shouzhangshen extract may have a significant effect on acute high altitude hypoxia-induced brain injury in mice.

Mechanisms for Improving Hepatic Glucolipid Metabolism by Cinnamic Acid and Cinnamic Aldehyde: An Insight Provided by Multi-Omics.

Cinnamic acid (AC) and cinnamic aldehyde (AL) are two chemicals enriched in cinnamon and have been previously proved to improve glucolipid metabolism, thus ameliorating metabolic disorders. In this study, we employed transcriptomes and proteomes on AC and AL treated db/db mice in order to explore the underlying mechanisms for their effects. Db/db mice were divided into three groups: the control group, AC group and AL group. Gender- and age-matched wt/wt mice were used as a normal group. After 4 weeks of treatments, mice were sacrificed, and liver tissues were used for further analyses. Functional enrichment of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. DEPs were further verified by parallel reaction monitoring (PRM). The results suggested that AC and AL share similar mechanisms, and they may improve glucolipid metabolism by improving mitochondrial functions, decreasing serotonin contents and upregulating autophagy mediated lipid clearance. This study provides an insight into the molecular mechanisms of AC and AL on hepatic transcriptomes and proteomes in disrupted metabolic situations and lays a foundation for future experiments.

Two new furostanol saponins from Tribulus terrestris.

Two new furostanol saponins were isolated from the fruits of Tribulus terrestris L. Their structures were established as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furost-20(22)-en-3beta,26-diol-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 4)]-beta-D-galactopyranoside (1) and 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furost-20(22)-en-12-one-3beta,26-diol-3-O-beta-D-galactopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside (2) on the basis of spectroscopic data as well as chemical evidence.

Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism.

OBJECTIVE: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. METHODS: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test. RESULTS: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects. CONCLUSION: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.

[Morphological diagnosis of endometrial intraepithelial neoplasia and expression of PTEN].

OBJECTIVE: To investigate the diagnostic applications of endometrial intraepithelial neoplasia (EIN), and the expression of PTEN in endometrial lesions. METHODS: Fifty-one cases of endometrial lesions were enrolled in this study. Using diagnostic criteria of EIN, the diagnosis were made and compared with the original results. Immunohistochemistry for PTEN was performed in all cases. RESULTS: Two cases of simple hyperplasia originally diagnosed were reclassified as EIN. Three cases with atypia originally diagnosed showed no EIN pattern. PTEN deletion rates were 50.0%, 50.0%, 66.7% and 81.8% in proliferative endometrium, benign hyperplasia, EIN and endometrial carcinoma, respectively. CONCLUSIONS: Diagnosis of EIN is applicable and its morphology and diagnostic criteria are different from the classical one (WHO94) for endometrial hyperplasia. Detection of PTEN deletion by immunohistochemistry is useful in identifying EIN, but cannot be used as an ultimate confirming factor.

[Pulmonary adenocarcinoma with micropapillary pattern: a clinicopathologic and immunohistochemical study].

OBJECTIVE: To study the clinicopathologic characteristics and immunohistochemical profile of lung adenocarcinomas with a micropapillary pattern (MPP). METHODS: Among 135 cases of lung adenocarcinomas, the clinical, histological and immunohistochemical features of 48 cases of lung adenocarcinomas with a micropapillary components (the micropapillary components > or = 10%) were studied. The literature was reviewed. RESULTS: All the 135 cases were resected pulmonary adenocarcinomas. Among 48 cases of lung adenocarcinomas with a micropapillary components, the age of patients ranged from 43 to 85 years (mean = 60.7 years). The male-to-female ratio was 9:7. Histologically, 36 cases of lung adenocarcinomas with the MPP were characterized by small papillary tufts lacking a central fibrovascular core lying freely within alveolar spaces (IA type) or in the clefts of fibrous tissue just like those in MPP breast cancers (IB type). Another type of the micropapillary pattern consisted of 12 cases, the micropapillary tufts floating within cystic spaces lined by tumor cells (II type). In micropapillary pattern-positive cases, lymphatic invasion and lymph node metastasis were identified significantly more frequently than in micropapillary pattern-negative cases (P < 0.01). The percentages of cases positive for various markers were 97.9% (47/48) for E-cadherin, 89.5% (43/48) for beta-catenin, 91.7% (44/48) for Muc-1, 70.8% (34/48) for epidermal growth factor receptor, 35.4% (17/48) for p53, 93.8% (45/48) for Ki-67. The percentages of cases with high expression (including 3+ or 4+) for these markers were 72.3% (34/47) for E-cadherin, 90.7% (39/43) for beta-catenin, 88.6% (39/44) for Muc-1, 52.8% (19/36) for epidermal growth factor receptor, 58.8% (10/17) for p53, 46.7% (16/36) for Ki-67. Adequate clinical follow-up information was available for 36 patients. The mean follow-up time was 21.1 months. Among these, 16 of 36 patients (44.4%) were alive with no evidence of tumor, 12(33.3%) were died, and 8 (22.2%) were alive with tumor. CONCLUSION: Lung adenocarcinomas with the MPP correlates positively with lymphatic invasion and lymph node metastasis, and are likely to have a potential for high malignancy, suggesting a poor prognosis.