Liuwei Dihuangtang Alleviates Myelin Injury in vHIP and Depression-like Behavior of Diabetes Mellitus Combined with Comorbid Depression Rats via AMPK/Akt/GSK3β/Nrf2 Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang on depression-like behavior of diabetes mellitus combined with comorbid depression （DD） rats， so as to explore its action mechanism. MethodFifty male SD rats of SPF grade were fed with high fat diet and injected with low-dose streptozotocin （STZ） via tail vein for inducing diabetes. Afterwards， the diabetic rats were exposed to chronic unpredictable mild stress （CUMS） for 28 d. The successfully modeled DD rats were randomly divided into five groups： model group， fluoxetine （10 mg·kg-1·d-1） group， and low-， medium-， and high-dose （3.375， 6.75， 13.5 g·kg-1·d-1） Liuwei Dihuangtang groups， with 10 in each group. Another 10 rats were classified into the normal control group and treated with intragastric administration of normal saline for four weeks. The tail suspension test and open field test were conducted to evaluate the depressive-like phenotype of rats. The contents of malondialdehyde （MDA）， reactive oxygen species （ROS）， 8-hydroxy-2 deoxyguanosine （8-OHdG）， superoxide dismutase （SOD）， and glutathione （GSH） in ventral hippocampus （vHIP） were measured by enzyme-linked immunosorbent assay （ELISA）， and the myelin basic protein （MBP） expression in vHIP by immunofluorescence assay. The expression levels of MBP， myelin protein lipoprotein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， phosphorylated adenosine 5'-monophosphate-activated protein kinase （p-AMPK）/AMPK， phosphorylated protein kinase B （p-Akt）/Akt， phosphorylated glycogen synthase kinase 3β （p-GSK3β）/GSK3β， and nuclear factor erythroid-2 related factor 2（Nrf2） were determined by Western blotting. ResultCompared with the normal control group， the model group exhibited significantly prolonged immobility in the tail suspension test （P<0.01） and shortened residence at the central area in the open field test （P<0.01）. The immobility time in the medium- and high-dose Liuwei Dihuangtang groups declined to different degrees as compared with that of the model group （P<0.01）， while the residence time at the central area was significantly increased （P<0.05， P<0.01）. Compared with the normal control group， the model group displayed down-regulated MBP， PLP， and MOG protein expression in vHIP （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the low dose up-regulated the expression of MBP （P<0.05）， but did not obviously affect the expression of MOG and PLP. Fluoxetine and Liuwei Dihuangtang at the medium and high doses up-regulated the expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Comparison with the normal control group revealed that the MBP fluorescence intensity in vHIP of the model group was significantly weakened （P<0.01）. After the intervention， the MBP fluorescence intensities in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were enhanced in contrast to that of the model group （P<0.05， P<0.01）. SOD and GSH in the model group were lower than those in the normal control group （P<0.01）， whereas the MDA， ROS， and 8-OHdG expression levels were higher （P<0.01）. Compared with the model group， Liuwei Dihuangtang at the medium and high doses and fluoxetine all down-regulated the expression levels of MDA， ROS， and 8-OHdG （P<0.05，P<0.01）， while up-regulated SOD and GSH expression （P<0.05，P<0.01）. The expression levels of p-AMPK， p-Akt， and Nrf2 in the model group were down-regulated as compared with those in the control group， and the expression of p-GSK3β was up-regulated （P <0.01）. As demonstrated by comparison with the model group， the protein expression of p-AMPK in the low-dose Liuwei Dihuangtang group was elevated （P<0.05）， while p-Akt and Nrf2 were slightly increased， exhibiting no statistical significant difference. However， the protein expression levels of p-AMPK， p-Akt， and Nrf2 in the medium- and high-dose Liuwei Dihuangtang groups and fluoxetine group were up-regulated， while those of p-GSK3β were down-regulated （P<0.05，P<0.01）. ConclusionLiuwei Dihuangtang improves the depressive-like behavior of DD rats， which may be related to its activation of the AMPK/Akt/GSK3β/NRF2 pathway， regulation of the oxidative stress in vHIP， and enhancement of myelin repair.

Liuwei Dihuangtang Alleviates Myelin Injury in Anterior Cingulate Cortex and Depression-like Behaviors of Rats with Diabetes Mellitus and Depression via Promoting Autophagy and Regulating Microglial Phenotype / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang （LWDHT） on depression-like behaviors of rats with diabetes mellitus and depression （DD） and explore its mechanism. MethodThe diabetes mellitus （DM） model was induced by the high-fat diet and tail vein injection of low-dose streptozotocin （STZ） in 50 male Sprague-Dawley rats of SPF grade. Then the DD model was induced by chronic unpredictable mild stress （CUMS） for 28 days in DM rats. Fifty DD rats were randomly divided into model group， fluoxetine group （10 mg·kg-1·d-1）， and low-， medium-， and high-dose LWDHT groups （3.375， 6.75， 13.5 g·kg-1·d-1）， with 10 rats in each group. Another 10 healthy rats were assigned into a control group and received normal saline by gavage. After four weeks of drug intervention， the forced swimming assay was carried out to assess the depression-like behaviors of rats. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in the anterior cingulate cortex （ACC） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to detect the expression of myelin basic protein （MBP） in ACC and the co-localization of ionized calcium-binding adapter molecule 1 （Iba1） with intracellular microtubule-associated protein 1 light chain 3 （LC3）. The protein expression levels of MBP， myelin proteolipid protein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， Beclin-1， LC3， p62， and microglia （MG） phenotypic protein-related inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg1） were detected by Western blot. ResultCompared with the control group， the model group showed shortened swimming time and prolonged immobility time （P<0.01）. Compared with the model group， the medium- and high-dose LWDHT groups showed reduced immobility time （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased protein expression of MBP， PLP， and MOG in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated protein expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased MBP fluorescence intensity in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased MBP fluorescence intensity in the ACC region （P<0.05， P<0.01）. Compared with the control group， the model group showed increased expression of iNOS （P<0.01） and slightly increased Arg1 protein expression. Compared with the model group， the medium- and high-dose LWDHT groups and the fluoxetine group showed down-regulated iNOS expression and up-regulated Arg1 protein expression （P<0.05， P<0.01）， but there was no significant difference between the fluoxetine group and the medium-，high-dose LWDHT groups. Compared with the control group， the model group showed increased expression levels of proinflammatory factors IL-1β and TNF-α in the ACC region （P<0.01） and slightly increased expression levels of anti-inflammatory factors IL-4 and IL-10. Compared with the model group， the fluoxetine group， and the medium- and high-dose LWDHT groups showed down-regulated expression of IL-1β and TNF-α （P<0.05， P<0.01） and up-regulated expression of IL-4 and IL-10 （P<0.05， P<0.01）. Compared with the control group， the model group showed reduced expression levels of Beclin-1 and LC3Ⅱ （P<0.01） and increased expression level of p62 （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated Beclin-1 and LC3Ⅱ expression （P<0.01） and down-regulated p62 expression （P<0.01）. Compared with the control group， the model group showed decreased LC3+Iba1+ cells in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased LC3+Iba1+ cells （P<0.05， P<0.01）. ConclusionLWDHT can alleviate the depression-like behaviors in DD rats presumedly by promoting MG autophagy， regulating MG phenotypic changes， and increasing MG clearance of myelin sheath fragments. Meanwhile， MG phenotypic transformation also inhibits ACC inflammation in DD rats， improves the local microenvironment of oligodendrocyte proliferation and differentiation， and ultimately promotes the repair and remyelination of damaged myelin sheath.

Natural ingredients from Chinese materia medica for pulmonary hypertension / 中国天然药物

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis / 华西口腔医学杂志

OBJECTIVES@#To identify the differentially expressed genes (DEGs) during the pathogenesis of periodontitis by bioinformatics analysis.@*METHODS@#GEO2R was used to screen DEGs in GSE10334 and GSE16134. Then, the overlapped DEGs were used for further analysis. g:Profiler was used to perform Gene Ontology analysis and pathway analysis for upregulated and downregulated DEGs. The STRING database was used to construct the protein-protein interaction (PPI) network, which was further visua-lized and analyzed by Cytoscape software. Hub genes and key modules were identified by cytoHubba and MCODE plug-ins, respectively. Finally, transcription factors were predicted via iRegulon plug-in.@*RESULTS@#A total of 196 DEGs were identified, including 139 upregulated and 57 downregulated DEGs. Functional enrichment analysis showed that the upregulated DEGs were mainly enriched in immune-related pathways including immune system, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and chemokine receptors bind chemokines. On the contrary, the downregulated DEGs were mainly related to the formation of the cornified envelope and keratinization. The identified hub genes in the PPI network were CXCL8, CXCL1, CXCR4, SEL, CD19, and IKZF1. The top three modules were involved in chemokine response, B cell receptor signaling pathway, and interleukin response, respectively. iRegulon analysis revealed that IRF4 scored the highest.@*CONCLUSIONS@#The pathogenesis of periodontitis was closely associated with the expression levels of the identified hub genes including CXCL8, CXCL1, CXCR4, SELL, CD19, and IKZF1. IRF4, the predicted transcription factor, might serve as a dominant upstream regulator.

Xiaoyaosan Promotes Myelin Regeneration and Alleviates Depressive Symptoms in Vascular Dementia Mice with Depression via Promoting Microglia Polarization / 中国实验方剂学杂志

Objective:To investigate the effect of Xiaoyaosan on depressive behavioral phenotype in mice with vascular dementia （VaD） mice and its possible mechanism. Method:Sixty three-month-old male C57/BL6 mice were divided into the normal control group， model group， positive control group， as well as low-， medium-， and high-dose Xiaoyaosan groups. Mice in all groups except for the normal control group underwent bilateral carotid artery stenosis. Two weeks later， they were subjected to chronic restraint stress， 6 h per day， for inducing VaD complicated with depression. Mice in the low-， medium-， and high-dose Xiaoyaosan groups were treatment with intragastric administration of Xiaoyaosan decoction （5， 10， 20 g·kg^-1）， the ones in the positive control group with fluoxetine （10 mg·kg^-1）， and those in the normal control group and model group with an equal volume of normal saline for four weeks， during which the restraint stress was maintained. The depressive behavioral phenotype of mice was observed in sugar water preference test and tail suspension test. The fluorescence expression of myelin basic protein （MBP） in ventral hippocampus （vHIP） was detected by fluorescence immunoassay. The ultrastructure of myelin sheath in vHIP was observed by transmission electron microscopy. The protein expression levels of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， triggering receptor expressed on myeloid cells-2 （TREM2）， inducible nitric oxide synthase （iNOS）， arginase 1 （Arg1）， interleukin-I<italic>β</italic> （IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） were assayed by Western blot. Result:As revealed by behavioral test， compared with the normal control group， the model group exhibited prolonged immobility time and decreased percentage of sugar water preference （<italic>P</italic><0.01）. Compared with the model group， Xiaoyaosan significantly shortened the immobility time of mice （<italic>P</italic><0.05） and increased the percentage of sugar water preference （<italic>P</italic><0.01）. Western blot results showed that the protein expression levels of MBP， MOG， and MAG in vHIP of the model group were remarkably decreased as compared with those of the normal control group （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， and MAG in vHIP of the low-dose Xiaoyaosan group were increased in contrast to those in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the protein expression of iNOS was decreased （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， MAG， TREM2， Arg1， IL-4， and IL-10 in the medium- and high-dose Xiaoyaosan groups were up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas those of iNOS， IL-1<italic>β</italic>， and TNF-<italic>α</italic> were down-regulated （<italic>P</italic><0.01）. The immunofluorescence findings demonstrated that the mean fluorescence intensity of MBP in the model group declined in comparison with that in the normal control group （<italic>P</italic><0.01）， while the mean fluorescence intensities of MBP in the low-， medium-， and high-dose Xiaoyaosan groups were enhanced to different degrees （<italic>P</italic><0.01）. It was observed under the transmission electron microscope that the myelin structure of the model group was loosened and the dense layer was separated and irregularly arranged. Xiaoyaosan improved the structural integrity of myelin sheath and the looseness of lamellar structure. Conclusion:Xiaoyaosan ameliorates the depressive behavioral phenotype of VaD mice， which may be related to the up-regulation of TREM2， the induction of M2 polarization of microglia cells， the enhancement of their anti-inflammatory and phagocytic abilities， and the promotion of damaged myelin sheath regeneration.

ADAMTS4 is upregulated in colorectal cancer and could be a useful prognostic indicator of colorectal cancer

SUMMARY OBJECTIVE ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. Methods The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. Results The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. Conclusion The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.

RESUMO OBJETIVO ADAMTS4 é um membro da família ADAMTS4, que secreta proteinases. O mecanismo da metástase do tumor pode ser correlacionado a sua promoção da angiogênese. Determinou-se se ADAMTS4 participa na progressão do câncer colorretal. Métodos A expressão em amostras clínicas e linhas de células CRC foi investigada. Usando a imuno-histoquímica (IHC), a hibridação fluorescente in situ (HFIS) e o RT-PCR, a expressão de ADAMTS4 foi determinada em tumores colorretais de diferentes estágios do câncer e locais anatômicos, e em três linhas de células de níveis de agressividade distintos. Resultados A superexpressão de ADAMTS4 foi observada em amostras de tecido por IHC, e esta foi localizada principalmente no citoplasma, como detectado pelo HFIS. O qRT-PCR e a análise de wester blot corroboraram os resultados clínicos da amostra. Conclusão Os dados atuais corroboram a noção de que a superexpressão de ADAMTS4 no CRC pode ser útil como um biomarcador não invasivo para a detecção de CRC em pacientes.

Rapid Immunoassay of Aflatoxin B1 and Its Application in Traditional Chinese Medicine / 中国实验方剂学杂志

Aflatoxin B1 (AFB1) is a toxic secondary metabolite produced by toxigenic Aspergillus spp. (such as A. flavus and A. parasiticus) with carcinogenic,teratogenic and mutagenic effects. Studies have shown that AFB1 is widely found in crops,food,feed and traditional Chinese medicine,which poses a serious safety hazards to humans healthy. The establishment of a rapid detection technique that is suitable for AFB1 in different matrices has a great significance in preventing contamination,controlling food and medicines safety and ensuring human health. With the continuous improvement of small-molecule immune technology,various rapid immunoassays of AFB1 have been developed and utilized in recent years. This review systematically summarized current relevant standards for the detection of AFB1 in China and the maximum recommended levels for the application of aflatoxins in Chinese herbal medicines in some regions and countries. These standards are mainly applicable for aflatoxins in food,feed and some easily contaminated samples of Chinese herbal medicines. Some studies have shown that except the Chinese herbal medicines specified with the maximum recommended levels,some medicinal herbs and their products were also contaminated by aflatoxins. In addition,this paper reviewed the preparation technology of antigen and antibody for AFB1,and the rapid detection methods based on the specific recognition ability between antigen and antibody, including enzyme-linked immunosorbent assay,immunochromatographic assay,fluorescence immunoassay,chemiluminescence immunoassay,and novel immunosensor method, were also summarized and compared. This review aims to provide the reference for rapid,accurate,and sensitive technical standards for the detection of AFB1 in traditional Chinese medicine during the agricultural planting,distribution, trade and quality supervision and for the market, pharmacies and hospitals,so as to ensure the quality and safety of the traditional Chinese medicines.

Safety of radiofrequency ablation for fetal reduction in monochorionic twin pregnancies over 26 weeks of gestation / 中华围产医学杂志

Objective@#To investigate the efficacy and safety of radiofrequency ablation for fetal reduction in monochorionic twin pregnancies at gestational age over 26 weeks.@*Methods@#A retrospective study was performed based on the clinical data of 51 patients who underwent fetal reduction by radiofrequency ablation in the First Affiliated Hospital of Chongqing Medical University from May 2013 to July 2018. Clinical data including basic information, surgical data (such as ablation duration, power and the number of cycles), perinatal complications and pregnancy outcomes were collected. Differences in pregnancy outcomes were compared between the group with gestational age >26 weeks (n=17, group A) and that ≤26 weeks (n=34, group B) using t-test, rank-sum test and Chi-square test or Fisher's exact test.@*Results@#(1) The indications of fetal reduction were malformation in one of the twins, twin-to-twin transfusion syndrome, twin reversed arterial perfusion sequence and selective intrauterine growth restriction [45.1% (23/51), 15.7% (8/51), 19.6% (10/51) and 19.6% (10/51)]. The differences in the proportion of different indications between group A and B were statistically significant [12/17, 1/17, 0/17, 4/17 vs 32.4% (11/34), 20.6% (7/34), 29.4% (10/34), 17.7% (6/34), P=0.009]. Those in the group A required longer operation duration than the group B [M(min-max), 20(7-40) vs 15(3-29) min, Z=2.550, P=0.011]. (2) The gestational age of the 51 patients was (23.7±4.7) weeks (15+1-32+6 weeks), the overall survival rate of the remaining fetuses was 86.3% (44/51) and the preterm birth rate was 50.0% (22/44). The gestational age at operation was (28.9±2.5) weeks (26+1-32+6 week) in group A and (21.1±3.1) weeks (15+1-25+2 weeks) in group B. The survival rate of the remaining fetuses and the preterm birth rate in group A were significantly higher than those in group B [17/17 vs 79.4% (27/34), P=0.046; 12/17 vs 37.0% (10/27), χ2=4.697, P=0.030].@*Conclusions@#Fetal reduction at gestational age >26 weeks, of which the main surgical indication is malformation in one of the twins, may increase the risk of preterm birth, but can improve the overall survival rate of the remaining fetuses without increasing the maternal and infant morbidity. Therefore, radiofrequency ablation is a safe and effective procedure for twin pregnancies >26 weeks of gestation.

Diagnosis and treatment strategy for advanced severe lung cancer / 中国实用内科杂志

Advanced severe lung cancer means the stage IIIB, IIIC, and IV lung cancer patients with a PS score of 2 to 4 points due to various related causes of lung cancer itself or the complication of anti-tumor drugs, with a high probability of benefiting from the existing systemic anti-tumor treatments. The diagnosis and treatment strategies emphasize the implementation of minimally invasive dynamic monitoring mutation targets and curative effects. Every drug that is useful to the patient should be used as possible, and making the best use of every drug as possible with the help of respiratory support therapy. Specific treatment concepts include combination therapy,alternating medication, paying equal attention to systemic therapy and local therapy, PS score assessment, upgrading and downgrading of drug use, and simultaneous treatment of cancer and lung itself.

Safety of radiofrequency ablation for fetal reduction in monochorionic twin pregnancies over 26 weeks of gestation / 中华围产医学杂志

Objective To investigate the efficacy and safety of radiofrequency ablation for fetal reduction in monochorionic twin pregnancies at gestational age over 26 weeks. Methods A retrospective study was performed based on the clinical data of 51 patients who underwent fetal reduction by radiofrequency ablation in the First Affiliated Hospital of Chongqing Medical University from May 2013 to July 2018. Clinical data including basic information, surgical data (such as ablation duration, power and the number of cycles), perinatal complications and pregnancy outcomes were collected. Differences in pregnancy outcomes were compared between the group with gestational age >26 weeks (n=17, group A) and that ≤26 weeks (n=34, group B) using t-test, rank-sum test and Chi-square test or Fisher's exact test. Results (1) The indications of fetal reduction were malformation in one of the twins, twin-to-twin transfusion syndrome, twin reversed arterial perfusion sequence and selective intrauterine growth restriction [45.1% (23/51), 15.7% (8/51), 19.6% (10/51) and 19.6% (10/51)]. The differences in the proportion of different indications between group A and B were statistically significant [12/17, 1/17, 0/17, 4/17 vs 32.4% (11/34), 20.6% (7/34), 29.4% (10/34), 17.7% (6/34), P=0.009]. Those in the group A required longer operation duration than the group B [M(min-max), 20(7-40) vs 15(3-29) min, Z=2.550, P=0.011]. (2) The gestational age of the 51 patients was (23.7±4.7) weeks (15+1-32+6 weeks), the overall survival rate of the remaining fetuses was 86.3% (44/51) and the preterm birth rate was 50.0% (22/44). The gestational age at operation was (28.9±2.5) weeks (26+1-32+6 week) in group A and (21.1±3.1) weeks (15+1-25+2 weeks) in group B. The survival rate of the remaining fetuses and the preterm birth rate in group A were significantly higher than those in group B [17/17 vs 79.4% (27/34), P=0.046; 12/17 vs 37.0% (10/27), χ2=4.697, P=0.030]. Conclusions Fetal reduction at gestational age>26 weeks, of which the main surgical indication is malformation in one of the twins, may increase the risk of preterm birth, but can improve the overall survival rate of the remaining fetuses without increasing the maternal and infant morbidity. Therefore, radiofrequency ablation is a safe and effective procedure for twin pregnancies >26 weeks of gestation.

Recent advances in analysis of endogenous toxic components in traditional Chinese medicines / 中国中药杂志

Endogenous toxic components have become an important topic in the field of traditional Chinese medicines (TCMs). Since the endogenous toxic components in TCMs are often used as clinical effective components, the safety and effectiveness of endogenous toxic substances has become an important part of the research of TCMs. In this paper, the classification and evaluation criteria of toxic Chinese medicinal materials are described, and the analytical methods of endogenous components in TCMs are summarized and expounded base on with the techniques of chromatography, spectroscopy, immunoassay, and so on. On this basis, the problems in terms of endogenous toxic components are analyzed and discussed. This paper could provide ideas and methods for the evaluation of the validity and safety of TCMs containing endogenous toxic components.

Indoor Allergen Levels and Household Distributions in Nine Cities Across China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households.</p><p><b>METHODS</b>Dust samples were collected from nine cities. Major allergens Der p 1 and Der f 1 from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.</p><p><b>RESULTS</b>HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from <0.006 to 9.2 µg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.</p><p><b>CONCLUSION</b>HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.</p>

Association between awareness of smoking-related evidence and smoking cessation treatments provided by hospital chest physicians in Guangzhou, China: a multi-institutional cross-sectional survey / 中华流行病学杂志

<p><b>OBJECTIVE</b>Factors associated with smoking cessation interventions initiated by hospital chest physicians in China had not been studied. We examined if the physicians' awareness of emerging evidence regarding negative effects of smoking was associated with the initiation of smoking cessation.</p><p><b>METHODS</b>A cluster randomized cross-sectional survey was conducted from July 2011 to August 2011 in hospital-based chest physicians (n = 354) in Guangzhou, China.</p><p><b>RESULTS</b>Of those who responded (n = 354, 92.2%), 63.8% were aware of emerging evidence regarding negative effects of smoking and 64.5% initiated smoking cessation programs with their patients who smoked. Regarding the related awareness on smoking differed across physicians depending on their affiliation to evidence hospitals(χ(2) = 54.7, P > 0.001), i.e., primary (44.9%), secondary (55.1%)and tertiary hospitals (87.0%)was further supported by the related odds ratio (OR = 1.732, 95%CI:1.072-2.797, P < 0.05). Smoking status of physicians was related to their practice on smoking cessation, supported by the odds ratio (OR = 4.251, 95% CI:1.460-12.380, P = 0.008). Smoking cessation practice by physicians also depended on their affiliated hospitals. Physicians working at primary and secondary hospitals were less aware of the fact that smoking could reduce patients' responsiveness to inhaled corticosteroids than those working at the tertiary hospitals(χ(2) = 37.9, P > 0.001). Furthermore, these physicians would less frequently prescribed medication related to smoking cessation(χ(2) = 137.71, P < 0.001).</p><p><b>CONCLUSION</b>Physicians who were better aware of the health hazards of smoking might more actively provide smoking cessation advice in their clinics. The awareness might correlate with the hospital levels they worked and the smoking status while the the advice they provided might correlate with their educational background, job title, department affiliation and smoking status, but not with the level of hospitals.</p>

Evaluation of the efficacy and safety of tiotropium bromide (5 µg) inhaled via Respimat in Chinese patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A pharmacokinetic study in an Asian population showed that tiotropium 5 µg via Respimat leads to the same plasma levels compared to 18 µg via HandiHaler. The objective of the trial was to compare the efficacy and safety of longterm treatment (1 year) with tiotropium bromide (5 µg) via Respimat® with placebo in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>A total of 3991 patients were randomized in this double-blind, placebo controlled, parallel group study, while in China 338 patients (309 males, 29 females) received either tiotropium bromide (n = 167) or placebo (n = 171). Tiotropium bromide solution or matching placebo was delivered via Respimat® at a dosage of 5 µg (2×2.5 µg/puff) once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.</p><p><b>RESULTS</b>Statistically significant improvements in trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group. A statistically significant difference (P = 0.0027) in favour of tiotropium was also observed for the time to first exacerbation. The total numbers of exacerbations during treatment were 90 and 128 in the tiotropium and placebo groups, respectively, with a rate ratio of 0.69 (P = 0.0164). The difference between the treatment groups in the adjusted mean changes from baseline of St. George Respiratory Questionnaire (SGRQ) total score was -3.9 (95% CI: -7.5, -0.2) and was of statistical significance (P = 0.0367). The incidences of serious adverse events (SAEs) in the tiotropium and placebo groups were 16.2% and 17.0%, respectively. Seven deaths occurred whilst patients were on treatment, four in the tiotropium group and three in the placebo group, all of which were assessed as non-related study drugs by the investigators.</p><p><b>CONCLUSIONS</b>Tiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbations. Overall, tiotropium was well tolerated.</p>

Visualization of Peripheral Pulmonary Artery Red Thrombi Utilizing Optical Coherence Tomography

Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.

Indoor mite allergen levels, specific IgE prevalence and IgE cross-inhibition pattern among asthmatic children in Haikou, southern China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Haikou locates in tropical island with unique mite propagation. The aim of this stuy is to determine mite allergens levels in Haikou, and to investigate the prevalence of mite specific IgE-sensitization and IgE cross-reactivity between house dust mites.</p><p><b>METHODS</b>Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay (ELISA). Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur(®).</p><p><b>RESULTS</b>Allergen or antigen Dermatophagoides pteronyssinus (Der p 1), Blomia tropicalis (Blo t) and Tyrophagus putrescentia (Tyr p) were detected in dust samples. Dermatophagoides farinae (Der f 1), Lepidoglyphus destructor (Lep d 2), and Acarus siro (Aca s) were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and Blo t. Storage mites, Blo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit Blo t from 40% to 80%. Blo t was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p.</p><p><b>CONCLUSIONS</b>Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. Blo t represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and Blo t. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and Blo t.</p>

Using optical coherence tomography to detect peripheral pulmonary thrombi / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images of small vessels and has been widely used in interventional cardiology. However, application of OCT in peripheral pulmonary arteries in patients has been seldom documented.</p><p><b>METHODS</b>Three patients who were highly suspected peripheral pulmonary arteries thrombi and had undergone CT pulmonary angiography but tested negative for thrombi in peripheral pulmonary arteries were enrolled. Subsequently, OCT imaging was performed in peripheral pulmonary arteries. The patients received more than three-month anticoagulative treatment if thrombi were detected by OCT. Thereafter, OCT re-evaluation of the thrombolized blood vessels detected earlier was performed. The changes of thrombi before and after anticoagulative treatment were compared.</p><p><b>RESULTS</b>Three patients underwent OCT imaging of peripheral pulmonary arteries. Thrombi were found in most of imaged vessels in these patients. Red and white thrombi can be differentiated, according to features of the thrombus on OCT images. After anticoagulation treatment, these patients' symptoms and hypoxemia improved. Repeated OCT imaging showed that most thrombi disappeared or became smaller.</p><p><b>CONCLUSION</b>OCT may be used as a potential tool for detecting peripheral pulmonary artery thrombi and differentiating red thrombi from white ones.</p>

Preliminary establishment of cytological examination and the normal reference values for hypertonic saline solution-induced sputum of healthy children in Guangzhou / 中华儿科杂志

<p><b>OBJECTIVE</b>To establish the method of cytological examination and the normal reference values for hypertonic saline solution-induced sputum of healthy children (age range from 5 to 15 years) with physical examination in Guangzhou.</p><p><b>METHOD</b>A total of 352 children, 5 to 15 years old, were enrolled from primary school and middle school in Guangzhou from January to December, 2010. All subjects completed a standardized questionnaire on the presence of respiratory, allergic symptoms and family history, the medical history and the physical examination was performed by doctors, lung function (forced expiratory volume at 1 s in predicted normal, FEV(1)%) was determined. There were 266 healthy children (137 males, 129 females) who were selected and undergone hypertonic saline solution induction of sputum, and cytological examination was performed. Hypertonic saline (5%) was nebulized and inhaled for 15 - 30 min. No expectoration within 30 min was defined as failure, and the procedure was terminated. The part of opaque and higher density sputum samples was detected by cytology. The proportion of neutrophils, lymphocytes, eosinophils, macrophages and monocytes was calculated. This study was approved by the institutional Ethics Review Committee of First Affiliated Hospital of Guangzhou Medical College. Informed consent was obtained from the legal guardians of all participants following a detailed description of the purpose and potential benefits of the study.</p><p><b>RESULT</b>There were 175 subjects' induced sputum specimens (175/266, 65.8%), non-qualified sputum samples were obtained from 16 of the subjects. The proportions of median (IQR) of lymphocytes were 0.012 (0.020), 95%CI were ranged from 0.015 to 0.022; neutrophils 0.207 (0.330), 95%CI 0.266 - 0.356 macrophages 0.761 (0.327), 95%CI 0.607 - 0.699; eosinophils 0.004 (0.019), 95%CI 0.013 - 0.022. There were no significant differences in proportions of cytological findings of female or male, different age groups and second-hand smoking or not (all P > 0.05). The incidence of adverse event was 4.40% (7/159).</p><p><b>CONCLUSION</b>The method and the preliminary data may be used for research, diagnosis and treatment of patients with chronic cough and airway inflammation.</p>

Clinical characteristics of bronchiolitis obliterans in pediatric patients / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, image findings, laboratory examination, the therapeutic methods and clinical outcomes of bronchiolitis obliterans (BO) in pediatric patients.</p><p><b>METHOD</b>Twenty-six pediatric patients with BO were reported. All data were collected from cases who were hospitalized in the Department of Pediatrics, First Affiliated Hospital of Guangzhou Medical College from June 1(st), 2009 to the April 30(th), 2011, and infectious agents, clinical manifestations, risk factors, changes in imageology, laboratory examination, therapeutic methods and treatment responses were analyzed.</p><p><b>RESULT</b>The ranges of age at onset was 4.5 months-8 years in 26 cases (18 boys and 8 girls). The course of disease was (6.2 ± 3.5) months. The period of followed-up ranged from 2 to 24 months. The common clinical characteristics were persistent wheezing of different severity (26 cases, 100%), cough (24 cases, 92%), intolerance to exercise (22 cases, 85%), short of breath (21 cases, 81%), retraction (20 cases, 77%), wheezy phlegm (16 cases, 62%), keeping with crackles (10 cases, 38%), cyanosis around the mouth (3 cases, 12%) and no clubbed fingers (toes). In 18 cases the etiology was detected, mycoplasma (11 cases, 42%), respiratory syncytial virus (4 cases, 15%), parainfluenza virus (2 cases, 8%), influenza virus A (2 cases, 8%) and influenza virus B (2 cases, 8%), human bocavirus (HBoV) (1 case, 4%). There were 8 cases (31%) with combined infection. Chest X-ray in 10 cases indicated changes suggestive of bronchopneumonia (38%), in only 1 case there was an image of interstitial pneumonia disease (4%). All the patients were diagnosed by high-resolution computerized tomography (HRCT). All cases were demonstrated to have air retention, poor blood perfusion in lung, just like "Westemark sign" with HRCT. In 19 cases antineutrophil cytoplasmic antibody (ANCA) was determined and 10 patients (53%) were positive for P-ANCA, and 8 cases (42%) were positive for C-ANCA. All patients received oral corticosteroid and low doses azithromycin. In 13 cases (50%) the treatment effectively reduced the severity of disease and the frequency of cough and wheezing. The average number of days for symptom improvement was (7.1 ± 4.8) days.</p><p><b>CONCLUSION</b>Respiratory infection plays an important role in BO in children. The chronic and persistent wheezing, cough, intolerance to exercises, short breath, retraction were the main clinical manifestations. But these symptoms are non-specific. Chest X-ray can not provide enough information for diagnosis. Classical "Westemark sign" with HRCT is an important sign. ANCA with a high positive rate (approximately 50%) suppose immuno-lesion in BO. Oral corticosteroid and methotrexate may relieve clinical symptoms.</p>

The effects of a hot water soluble extract (S-03) isolated from Isatis indigotica root on influenza A and B viruses in vitro / 病毒学报

This study was to investigate the antiviral effects of a hot water soluble extract S-03 isolated from Isatis indigotica root on different subtypes of influenza A and B viruses in MDCK cell cultures, using plaque reduction, immunofluorescence and hemo-agglutination inhibition (HAD) assays. Chemical analysis of the extract S-03 showed that it contained high proportion of polysaccharides. The antiviral effects in vitro showed that the S-03 had no effect on different influenza viruses if the drug was used before virus adsorption, but S-03 showed obvious activities against influenza viruses if treatment after virus adsorption or direct reaction of drug and virus before virus adsorption. Hemagglutination inhibition assay showed that S-03 inhibited HA activities of different human influenza viruses (inhibition concentration ranged from 3.12 to 25 mg/mL), avain influenza viruses (inhibition concentration ranged from 25 to 50 mg/mL). The antiviral effects of S-03 on different influenza A and B viruses in vitro might be through the inhibition of the HA to prevent infection.