Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology / 中国中药杂志

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.

Effect of Gegen Qinliantang on TLR4/IKKβ/NF-κB Pathway in KKAy Mice with Diabetes / 中国实验方剂学杂志

ObjectiveTo observe the effect of classical prescription Gegen Qinliantang（GGQLT） on inflammatory factors and key targets in the inflammatory pathways mediated by lipopolysaccharide in KKAy mice and explore its mechanism in improving spontaneous type 2 diabetes mellitus （T2DM）. MethodSixty-five SPF KKAy mice with spontaneous T2DM and 13 C57BL/6J mice （control） were selected in the barrier system and fed on a high-fat diet. The model was properly induced in 44 mice in the context of random blood glucose exceeding or equal to 13.9 mmol·L-1. Then the mice were assigned into a normal group （20 mL∙kg-1 normal saline）， a model group （20 mL∙kg-1 normal saline）， an acarbose group （3.9 mg∙kg-1）， and high- and low-dose GGQLT groups （1.82 and 0.45 g∙kg-1）， with 11 mice in each group. The mice in each group were treated correspondingly by gavage for eight weeks， once per day. Blood glucose and body weight were systematically evaluated. Twelve hours after the last administration， blood samples were collected from the eyes， and the serum and muscle and liver tissues were extracted. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and glucose transporter type 4 （GluT4） were detected by semi-quantitative enzyme-linked immunosorbent assay （ELISA）. The protein expression of IκB kinase β （IKKβ） and nuclear factor-κB （NF-κB） in muscle tissues and Toll-like receptor 4 （TLR4） in liver tissues was detected by Western blot. ResultCompared with the normal group， the model group showed increased body weight and blood glucose （P<0.01）. Compared with the model group， the acarbose group and the GGQLT groups showed reduced body weight and blood glucose （P<0.05， P<0.01）. As revealed by ELISA results， compared with the normal group， the model group showed increased levels of TNF-α and IL-6 （P<0.01） and deceased GluT4 level （P<0.05）. Compared with the model group， the groups with drug treatment showed reduced levels of TNF-α and IL-6 （P<0.05， P<0.01）， and the acarbose group and the high-dose GGQLT group showed increased GluT4 level （P<0.05， P<0.01）. As displayed by Western blot results， compared with the normal group， the model group showed increased protein expression of IKKβ， NF-κB， and TLR4 （P<0.01）. Compared with the model group， the acarbose group and the GGQLT groups showed reduced protein expression of IKKβ， NF-κB， and TLR4 （P<0.05， P<0.01）. ConclusionGGQLT can inhibit the inflammatory cascade effect and improve T2DM by down-regulating the levels of key inflammatory factors in the TLR4 pathway， inhibiting their activation， and increasing the translocation and activity of GluT4 on the basis of the regulation of intestinal flora.

Progress on Hypoglycemic Effect and Mechanism of Momordica charantia / 中国实验方剂学杂志

Momordica charantia has been a traditional Chinese medicine （TCM） and food since ancient times. The discussions on its nature， taste and efficacy in ancient books of TCM are almost the same. With a high nutritional value， M. charantia is rich in a variety of vitamins and minerals， and has been widely used in the production of a wide range of dietary supplements and functional foods. At the same time， M. charantia is one of the most deeply studied natural medicines in traditional alternative medicine， with a wide range of pharmacological effects， especially in the treatment of metabolic diseases. Clinical trials have confirmed that M. charantia has a hypoglycemic effect， and could reduce blood lipids and weight loss， so as to improve metabolism in a comprehensive manner. According to the study on the mechanism of M. charantia in the treatment of diabetes， M. charantia could reduce blood sugar by improving islet β-cell function， improving insulin resistance， inhibiting intestinal glucose absorption and resisting inflammation and oxidative stress. However， at present， there is a lack of unified standards for the hypoglycemic effects and various mechanisms of action of M. charantia， and the safety has not been fully confirmed. Further studies shall be conducted to investigate the hypoglycemic effect and mechanisms of M. charantia， explore active components of M. charantia， define the pharmacodynamics material basis， extract monomer compounds with a clear structure and confirm its effectiveness and safety， which is helpful to develop and utilize the homologous value of medicine and food of M. charantia and further apply it in clinic. The application of the hypoglycemic effect of M. charantia in clinic has important economic benefits and a social significance.

Transcriptome analysis and validation of key genes involved in biosynthesis of iridoids in Gentiana lhassica / 中国中药杂志

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.

Transcriptome analysis and exploration of genes involved in the biosynthesis of iridoids in Gentiana crassicaulis (Gentianaceae) / 药学学报

italic>Gentiana crassicaulis Duthie ex Burk. in Gentiana (Sect. Cruciata), Gentianaceae, is one of the original plants of both Gentianae Macrophyllae Radix and Tibetan herb Jie-Ji Na-Bao, which contain such bioactive iridoids as gentiopicroside, loganic acid and others. In this study, based on previous work, the transcriptome of G. crassicaulis was sequenced and analyzed to construct transcriptome databases of roots, stems, leaves and flowers. qRT-PCR verification was conducted for parts of unigenes that may be key enzymes in the pathway of iridoid biosynthesis. The results are as follows: ① a total of 159 534 unigenes were obtained, with an average length of 679 bp. According to the functional classification of GO, unigenes can be divided into 3 categories with 67 branches. The unigenes were aligned in the KOG database and were classified into 25 categories according to function. ② In the KEGG database, 215 unigenes were implicated in 20 standard secondary metabolism pathways. The analysis shows that 305 unigenes encoded 28 key enzymes in the pathway of iridoid biosynthesis, and their expression in different organs is different; and ③ qRT-PCR was approximately consistent with RNA-Seq results. The 7 annotated unigenes identified in this study, HMGS, DXS, MCS, GPPS, G10H, 7-DLNGT and STR, all had higher relative expression levels in the above-ground parts (stem, leaf and flower) than in the underground part (root). Iridoids are common active and index components of such traditional Chinese medicines as Qinjiao, Longdan, Dangyao, and Qingyedan, among others. Therefore, this work provides basic scientific data for further development including obtaining active components or intermediates through biotechnology, exploring the accumulation of effective components, evaluating the quality of different ecotype varieties, and identifying authentic biosynthesis pathways of medicinal materials.

Molecular markers based upon whole chloroplast genomes and identifying alpine Gentiana waltonii and G. lhassica (Gentianaceae) / 药学学报

As two original plants of Tibetan herb Jieji, Gentiana waltonii Burk. and Gentiana lhassica Burk. belong to Section Cruciata of Gentiana, Gentianaceae. Here, we report on whole chloroplast genome sequences in the alpine species, respectively, and the features of plastomes were investigated. The plastome of G. waltonii is 148 705 bp long (148 652 bp in G. lhassica) and encodes 112 genes, including 78 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. Two pseudogenes, namely ψrps16 and ψinfA, were found in plastomes. In addition, two novel loci were detected, and a species-specific polymerase chain reaction assay was developed for differentiating G. waltonii and G. lhassica from 10 alpine species in Section Cruciata. Gentiana. Our study provides basic data for identifying Tibetan herbs, alpine species conservation and molecular phylogenetic studies of Gentiana and Gentianaceae.

Effect of Zishenwan on Pyroptosis and Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells in Diabetic Nephropathy Mice / 中国实验方剂学杂志

Objective:To study the efficacy and mechanism of Zishenwan （ZSW） against pyroptosis and epithelial-mesenchymal transition （EMT） of renal tubular epithelial cells in diabetic nephropathy （DN） mice， so as to provide evidence for the treatment of DN with ZSW. Method:The <italic>db/db</italic> mice with spontaneous diabetes were randomly divided into the model group， dapagliflozin （1.0 mg·kg^-1） group， and high-， medium-， and low-dose （6.0， 3.0， 1.5 g·kg^-1） ZSW groups. The non-diabetic <italic>db/m</italic> mice were classified into the normal group. The ones in the model and normal groups were given an equal volume of deionized water by gavage， while those in the other groups were intervened with the corresponding drugs for 12 weeks. The fasting blood glucose （FBG） level was tested at tail vein once every two weeks. The levels of urine albumin-creatinine ratio （ACR）， <italic>β</italic>-N-acetyl-D-glucosaminidase （NAG）， and cystatin C （CysC） were detected once every four weeks. After 12 weeks of administration， the blood sampled from eyeballs was used for measuring the blood urea nitrogen （BUN） and serum creatinine （SCr）. The pathological changes in renal tissues were observed by light microscopy and transmission electron microscopy. The expression of EMT markers in the renal tubular epithelium was analyzed by immunohistochemistry （IHC）. The in situ terminal end-labeling （TUNEL） staining was conducted to analyze the nuclear damage of renal tubular epithelial cells. The protein and mRNA expression levels of EMT markers， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasome and pyroptosis-related inflammatory cytokines in renal tissues were separately assayed by Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Result:Compared with the normal group， the model group displayed significantly increased FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， impaired renal tissues， altered EMT marker expression intensities and levels （<italic>P</italic><0.01）， and elevated TUNEL-positive rate and protein and mRNA expression levels of pyroptosis-related inflammatory cytokines and NLRP3 inflammasome （<italic>P</italic><0.01）. Compared with the model group， ZSW and dapagliflozin significantly decreased the levels of FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， relieved the pathological injuries in renal tissues， changed the EMT marker expression intensities （<italic>P</italic><0.01） and protein and mRNA expression levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， and down-regulated the TUNEL-positive rate （<italic>P</italic><0.01） of renal tubular epithelial cells as well as the protein and mRNA expression levels of pyroptosis-related inflammatory cytokines （<italic>P</italic><0.01） and NLRP3 inflammasome （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:ZSW alleviates DN possibly by inhibiting pyroptosis and EMT in renal tubular epithelial cells.

DNA fingerprinting and genetic diversity in a threatened alpine medicinal plant, Gentiana crassicaulis (Gentianaceae) using AFLP / 药学学报

Jieji Nabao is a common Tibetan herb. According to our ethnobotanical studies, one of its original plants is identified as Gentiana crassicaulis Duthie ex Burk. (Gentianaceae). Endemic to the Qinghai-Tibet Plateau, this medicinal alpine plant is a threatened species. In this study, 163 individuals from 20 populations of G. crassicaulis were collected throughout its geographical range and amplified fragment length polymorphism (AFLP) was used to investigate genetic variation in this species. A cluster analysis was performed on the AFLP data with Halenia elliptica and Gentiana straminea as the outgroups. From 64 pairs of AFLP primer combinations, 12 pairs were selected for amplification and a total of 315 bands were amplified, of which 254 bands were polymorphic, accounting for 80.63%. High genetic differentiation was detected between populations (87%), and low within populations (13%). The UPGMA (unweighted pair-group method with arithmetic means) tree was topologically consistent with the traditional taxonomic treatments at the species level, and the populations of G. crassicaulis were divided into two branches: one from Yunnan and Guizhou, the other from Tibet, Qinghai, Sichuan and Gansu. PCA analysis and the Mantel test showed that there was a positive correlation between genetic distance and geographical distance. In addition, combined with SSR and SNP markers within cpDNA, the genetic differentiation within the Sichuan population S1 was validated.

Research Progress on Medicinal Effect of Flower of Edgeworthia gardneri / 中国实验方剂学杂志

Tibetan medicine Edgeworthia gardneri is the flower bud of Edgeworthia gardneri, mainly distributed in the eastern Tibet as well as the northwest and west parts of Yunnan. It is called one of the " Eighteen treasures of Qinghai-Tibet" and has been used in many Tibetan secret recipes for a long time. Nowadays, the local people often drink E. gardneri Meisn tea for blood glucose regulation and health care. In this study, the related papers were searched in CNKI, Wanfang, Weipu, PubMed and other databases by using the keywords " Lv luo hua" and " flower of E. gardneri Meisn" . Then the status quo of the flower of E. gardneri was summarized from three aspects: provenance, chemical compositions and extraction method, as well as efficacy and function. It is found that E. gardneri mainly contains coumarins, flavonoids, polysaccharides and polyphenols. The extraction methods of E. gardneri include ultrasonic extraction, microwave extraction, supercritical CO2 extraction, and bio-enzyme-assisted extraction method, et al. The extraction of flavonoids and polyphenols is more common. In terms of medicinal efficacy, it has many medicinal effects such as regulating blood sugar, lowering blood fat, anti-oxidation, enhancing immunity and anti-tumor. The flower of E. gardneri has broad pharmacological effect, attracting more and more scholars to research it. However, studies on its medicinal effectiveness both at home and abroad are mainly focusing on it' s crude extractions or extracts, with no in-depth studies on action mechanism. This review aims to summarize the provenance, main chemical compositions and extraction methods, efficacy and effect of the flower of E. gardneri, especially focusing on the research on the medicinal efficacy and mechanism of the flower of E. gardneri, and provide a reference for the further research of the flower of E. gardneri.

Mechanism of Salidroside in Improving Glucose and Lipid Metabolism in Liver of Diabetic Rats / 中国实验方剂学杂志

Objective: To explore the mechanism of salidroside(SAL) in improving glucose and lipid metabolism in liver of diabetic rats. Method: According to blood glucose, 24 male ZDF(fa/fa) rats of 6-7 week old were randomly divided into model group, SAL-low group (0.05 g·kg-1), SAL-high group (0.1 g·kg-1), 8 rats in each group. Another 8 ZDF (fa/+) rats were selected as normal group. All the rats were administered continuously for 6 weeks. After experiment, fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), free fatty acids(FFA), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), fasting insulin(Fins), and homeostasis model assessment insulin resistance(HOMA-IR) were measured. Western blot was used to detect phosphorylated PKR-like ER kinase(p-PERK), NF-E2-relatedfactor2(Nrf2), heme oxidase-1(HO-1) protein expression levels in liver. Result: As compared with normal group, FBG, Fins, HOMA-IR, TC, TG, FFA, and MDA were increased significantly in model group (P PPPPPPPPPPPConclusion: The Salidroside can improve metabolism of glucose and lipid, IR in diabetic rats, and the mechanism may be associated with inhabiting oxidative stress through the up-regulation of p-PERK, Nrf2, and HO-1 protein expression.

Chemical constituents from the stems of Gymnema sylvestre / 中国天然药物

AIM@#To study the chemical constituents of stems of Gymnema sylvestre (Retz.) Schult.@*METHODS@#Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis (1D and 2D NMR), as well as chemical methods.@*RESULTS@#Seven compounds were isolated and their structures were elucidated as conduritol A (1), stigmasterol (2), lupeol (3), stigmasterol-3-O-β-D-glucoside (4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-β-D-glucopyranosyl-(1→3)-β-D-glu-curono-pyranosyl-28-O-α-L-rhamnopyranoside (5), oleanolic acid-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside (7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated.@*CONCLUSION@#Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.

Assessment of the results of syndrome in clinical trials of dementia treated by Chinese herbal medicine / 中国中西医结合杂志

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.

Clinicopathologic characteristics of primary thyroid-like follicular carcinoma in kidney / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological characteristics of primary thyroid-like follicular carcinoma of the kidney.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

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 / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Tubulolobular carcinoma of breast: a clinicopathologic study of 8 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC).</p><p><b>METHODS</b>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, CK34βE12 and CK8.</p><p><b>RESULTS</b>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), CK34βE12 (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.</p><p><b>CONCLUSIONS</b>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 CK34βE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.</p>

Research progress on the mechanism of single-Chinese medicinal herbs in treating diabetes mellitus / 中国结合医学杂志

Treating diabetes mellitus (DM) with Chinese medicine (CM) has had a few thousands years of history. Past Chinese medical texts had already recorded numerous medicinal herbs as well as recipes for treating DM and accumulated much clinical experience. In the following article, the prevention of DM using CM in the past 5 years is retrospectively studied, and mainly focuses on the usage of simple Chinese herbal extracts or monomers in terms of cellular as well as molecular biology.

Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Influence of TangNaiKang on VEGF protein expression of GK rats thoracic aorta / 国际中医中药杂志

Objective To investigated the effect of TangNaiKang (TNK) on VEGF protein expression of GK rats Thoracic aorta. Methods 51 male GK rats were divided into five groups randomly: model group, pioglitazone group, and TNK treatment group (low, immediate and high dose). Another 10 male Wistar rats were served as normal control group. GK rats were fed with high-grease forage, while normal control group was fed with a standard diet. Fasting blood glucose, general HE staining and VEGF protein expression were detected by immunohistochemistry. Results The fasting glucose had a significant decline in TNK treatment groups. HE staining showing TNK can ameliorate intima thickness, reduce hyperplasia of shallow vascular smooth muscle cell, and improve wavy and plexiform arrangement of elastic lamina. Immunohistochemistry also showed that TNK decreased VEGF protein expression of great vessels. Conclusion TangNaiKang can prevent and cure diabetic vascular complication of GK rats.

Morphological diagnosis of endometrial intraepithelial neoplasia and expression of PTEN / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic applications of endometrial intraepithelial neoplasia (EIN), and the expression of PTEN in endometrial lesions.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Pulmonary adenocarcinoma with micropapillary pattern: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics and immunohistochemical profile of lung adenocarcinomas with a micropapillary pattern (MPP).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>