Highly water-resistant paper via infiltration with polymeric microspheres from nanocellulose-stabilized plant oil-derived monomer.

Sustainable strategies to improve the water resistance of cellulose paper are actively sought. In this work, polymeric microspheres (PMs), prepared through emulsion polymerization of cellulose nanofibers stabilized rubber seed oil-derived monomer, were investigated as coatings on corrugated medium paper (CMP). After infiltrating porous paper with PMs, the water-resistant corrugated papers (WRCPn) with enhanced mechanical properties were obtained. When 30 wt% PMs were introduced, WRCP30 turned out to be highly compacted with an increased water contact angle of 106.3° and a low water vapor transmission rate of 81 g/(m2 d) at 23 °C. Meanwhile, the tensile strength of WRCP30 increased to 22.2 MPa, a 4-fold increase from CMP. When tested in a well-hydrated state, 71% of its mechanical strength in the dry state was maintained. Even with a low content of 10 wt% PMs, WRCP10 also exhibited stable tensile strength and water wettability during the cyclic soaking-drying process. Thus, the plant oil based sustainable emulsion polymers provide a convenient route for enhancing the overall performance of cellulose paper.

Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC/Nrf2 axis.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. PURPOSE: This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. METHODS: Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. RESULTS: Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tert­butylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. CONCLUSIONS: Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.

Effect of Xiaoyaosan on JNK Pathway in LPS-induced Depressive-like Behavior in Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Xiaoyaosan in alleviating lipopolysaccharide （LPS）-induced depressive-like behavior in mice based on the c-Jun N-terminal kinase （JNK） pathway. MethodAfter adaptive feeding， C57BL/6J mice were randomly divided into normal group， model group， minocycline group （intrabitoneal injection， 50 mg·kg-1）， fluoxetine group （intragastric administration， 2.6 mg·kg-1）， and low-， medium-， and high-dose Xiaoyaosan groups （intragastric administration，6.012 5， 12.025， and 24.050 g·kg-1）. After 14 days of administration， the model group and each administration group were intraperitoneally injected with 2 mg·kg-1 LPS， and the normal group was intraperitoneally injected with equal volume of normal saline. Depressive-like behavior in mice was assessed using the open field test and the elevated zero maze test. High-performance liquid chromatography （HPLC） was used to measure the levels of norepinephrine （NE） and epinephrine （E） in the mouse hippocampus. Enzyme-linked immunosorbent assay （ELISA） was performed to determine serum interleukin-1β （IL-1β） levels. Immunohistochemistry was used to measure the protein expression levels of ionized calcium-binding adapter molecule-1 （Iba-1）， c-Fos， and c-Jun. Real-time polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of IL-1β， c-Jun， c-Fos， and JNK3 in the mouse hippocampus. Protein expression levels of JNK and phosphorylated （p）-JNK in the mouse hippocampus were measured using capillary protein automated protein expression analysis system （Western）. ResultCompared with the normal group， the model group exhibited significantly reduced central area residence time， crossing times， and travel distance in the open field （P<0.01）， significantly increased serum IL-1β levels （P<0.01）， significantly decreased NE and E levels （P<0.05）， upregulated mRNA expression of IL-1β， JNK3， and c-Fos， and increased protein expression of Iba-1， c-Fos， and c-Jun （P<0.05， P<0.01）. Compared with the model group， the Xiaoyaosan groups showed increased central area residence time and open arm residence time （P<0.05）， increased NE and E levels （P<0.01）， decreased mRNA expression of IL-1β， JNK3， c-Jun， and c-Fos， and decreased protein expression of Iba-1， c-Fos， JNK， and p-JNK （P<0.05， P<0.01）. The minocycline group and the fluoxetine group showed decreased mRNA expression of JNK3， c-Jun， and c-Fos （P<0.05， P<0.01）. The minocycline group showed decreased serum IL-1β and p-JNK protein expression （P<0.01）. The fluoxetine group exhibited increased NE and E levels and decreased c-Fos protein expression （P<0.01）. ConclusionXiaoyaosan can improve depressive-like behavior induced by LPS in mice， and its mechanism may be related to the inhibition of neuroinflammatory responses and the JNK pathway.

Analysis of chemical constituents in ethyl acetate extract of Taxilli Herba by UPLC-Q-Exactive-MS and screening of potential xanthine oxidase inhibitors / 中国中药杂志

The present study analyzed and identified the chemical constituents from ethyl acetate(EA) extract of Taxilli Herba with UPLC-Q-Exactive-MS and screened active xanthine oxidase(XO) inhibitors with HPLC. The analysis was performed on an Hypersil GOLD C_(18) reversed-phase column(2.1 mm×50 mm, 1.9 μm), with the mobile phase of water containing 1% formic acid(A) and methanol(B) under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 5 μL. ESI source was used for MS and the compounds were collected in positive and negative ion modes. Xcalibur 4.1 was used to analyze the retention time, accurate relative molecular weight, and fragmentation of the compounds. The inhibitory activity of some known compounds on XO was screened by HPLC. Thirty chemical constituents were identified, including phenolic acids and flavonoids by experimental data combined with information of standards, data reported previously, and databases, such as MzCloud and ChemSpider. The activities of 10 chemical components were screened. Gallic acid and naringenin chalcone had strong inhibitory activities on XO with IC_(50) of 57 μg·mL~(-1) and 108 μg·mL~(-1). UPLC-Q-Exactive-MS allows the accurate, rapid, and comprehensive identification of main chemical constituents from Taxilli Herba. Gallic acid and naringenin chalcone may be the active components of XO inhibitors.

Clinical Study of Chaihu Shugansan Combined with Abdominal Acupuncture on Depression Caused by Chronic Pain / 中国实验方剂学杂志

Objective:To investigate the clinical effect of Chaihu Shugansan combined with abdominal acupuncture on depression caused by chronic pain，and to explore its mechanism. Method:A total of 97 patients with depression caused by chronic pain were randomly divided into control group （49 cases） and observation group （48 cases）. Patients in both groups received routine western medicine treatment，including necessary psychological intervention and taking paroxetine. Control groupobservation groupcontrol group Patients in control group were treated with Xiaoyaowan，and patients in observation group were treated with Chaihu Shugansan combined with abdominal acupuncture. Both groups were treated for 6 weeks. The levels of serum neurotransmitters，cytokines and Hamilton depression rating scale（HAMD） before and after treatment were compared between two groups<bold>.</bold> Result:There was no significant difference in HAMD scores of the two groups before treatment and the HAMD scores of two groups after treatment were significantly lower than those before treatment （<italic>P</italic><0.05），and the HAMD scores in observation group were significantly lower than those in the control group （<italic>P</italic><0.05）. There was no significant difference in the levels of serum 5-hydroxytryptamine （5-HT），norepinephrine （NE），and brain-derived neurotrophic factor （BDNF） between two groups before treatment. After treatment，the levels of serum 5-HT，NE，and BDNF in two groups were significantly higher than those before treatment （<italic>P</italic><0.05），and the levels in observation group were significantly higher than those in control group （<italic>P</italic><0.05）. There was no significant difference in the levels of serum interleukin-6 （IL-6），interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） before treatment. After treatment，the levels of serum IL-6，IL-1<italic>β</italic> and TNF-<italic>α</italic> were significantly lower than those before treatment （<italic>P</italic><0.05），and the levels in observation group were significantly lower than those in control group （<italic>P</italic><0.05）. Conclusion:On the basis of psychological intervention and paroxetine administration，the combination of Chaihu Shugansan and abdominal acupuncture exerts their respective advantages. It treats both symptoms and root causes of depression，relieves the degree of depression，reduces the classification of depression，and regulates the levels of neurotransmitter and cellular inflammatory factors，and inhibits inflammatory response. The clinical effect is significant.

Research progress on chemical constituents, pharmacological activities and clinical application of Bolbostemma paniculatum / 中国中药杂志

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.

Combining humic acid with phosphate fertilizer affects humic acid structure and its stimulating efficacy on the growth and nutrient uptake of maize seedlings.

This paper analyzed the compositional and structural changes of humic acid (HA) after combined with phosphate fertilizer (PHA), and investigated its effects on the growth of maize seedlings with four humic acid concentrations. The results showed that the atomic ratios of O/C and (O + N)/N of PHA were significantly lower than those of HA, which indicated that PHA had poor hydrophilicity compared with HA. The spectra of FTIR and NMR results suggested that the relative content of carboxyl group in PHA was higher than that in HA. X-ray photoelectron spectroscopy technology showed that the relative amount of C-C in PHA was lower than that in HA, while C-H was the opposite. The above changes were attributed to the crack of HA structure during the preparation of humic acid enhanced phosphate fertilizer, which was verified by the results from the determination of gel permeation chromatography that there were more low molecular weight components in PHA than that in HA. However, compared with HA, PHA showed a worse effect in promoting growth and the uptake of nitrogen, phosphorus and potassium by maize seedlings. This worse effect might be attributed to the poor hydrophilicity and unsuitable addition amount of PHA.

Panax ginseng C.A. Meyer (Rg3) Ameliorates Gastric Precancerous Lesions in Atp4a-/- Mice via Inhibition of Glycolysis through PI3K/AKT/miRNA-21 Pathway.

Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3-treated GPL in Atp4a-/- mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB-PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF-1α, LDHA, and HK-II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA-21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl-2 and caspase-3 were attenuated in Rg3-treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF-1α, LDHA, HK-II, and miRNA-21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells.

Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice.

Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.

Weipiling ameliorates gastric precancerous lesions in Atp4a-/- mice.

BACKGROUND: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4-17, 2014; Kim and Bae, Curr Opin Hematol 25:52-59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. METHODS: Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a-/- mouse model (Spicer etal., J Biol Chem 275:21555-21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a-/-mice. RESULTS: In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a-/- mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). CONCLUSIONS: Conclusively, WPL could ameliorate GPLs in Atp4a-/- mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

An assessment of the Chinese medicinal Dendrobium industry: Supply, demand and sustainability.

ETHNOPHARMACOLOGICAL RELEVANCE: A high proportion of species native to China from the genus Dendrobium (Orchidaceae) have been used as folk medicine for more than 2300 years. The fresh or dried stem of many Dendrobium species are regarded as "superior grade" tonic in Traditional Chinese Medicine (TCM), for their traditional properties of nourishing the kidney, moisturizing the lung, benefiting the stomach, promoting the production of body fluids and clearing heat. AIM OF THE STUDY: This review aims to provide comprehensive and updated information on the diversity of Dendrobium species used in TCM and the development of the Dendrobium industry. The supply and demand of the Chinese medicinal Dendrobium are investigated. Moreover, we discuss the problems the industry faces and the relationship between the cultivation and species conservation. MATERIALS AND METHODS: The available information on many Dendrobium species (especially D. officinale) was collected from the electronic databases (using Pubmed, CNKI, Baidu scholar, Google scholar and Web of Science). We also obtained information from communication with specialists with profound knowledge in related research field and industry practitioners. Information was also obtained from website of the Forestry Bureau or relevant government departments, online databases, books, Ph.D. dissertations and M.Sc. theses. RESULTS: Approximately 41 species in genus Dendrobium have been recorded in TCM. The development of the Dendrobium industry could be divided into three phases: (a) the wild-collection phase, (b) the massive commercial artificial-sheltered cultivation phase and (c) the diversified ecologically-friendly cultivation phase. The development of seedlings production technology, the improvement of substrates and the integration of cultivation technology support the rapid increase of Dendrobium herbs in the Chinese TCM market. Doubts around the quality and efficacy of product in artificial-sheltered cultivation, the lack of product standards and the low level of product development have limited the utilization for TCM and hampered the development of the Dendrobium industry. Both the artificial-sheltered cultivation and ecologically-friendly cultivation contribute to the conservation of Dendrobium species, through the use seedlings derived from seeds of sexual reproduction rather than meristematic-based clonal propagation. CONCLUSIONS: This review summarizes the species and cultivation history of medicinal herbs in the Dendrobium. The review can help inform future scientific research towards the TCM in Dendrobium, including mycorrhizal technology and microorganism fertilizer, pharmacological studies, the directed cultivation of varieties and diversified product. It is suggested that Dendrobium cultivation has a great potential to link the commercial TCM industry together with initiatives of biodiversity conservation.

12ß-Acetyloxyperforatin, a New Limonoid from Harrisonia Perforata.

A new A, D-seco limonoid, named 12-acetyloxyperforatin (1), along with three known ones, were isolated from the leaves of Harrisonia perforata. Their structures were elucidated on the basis of spectroscopic analysis, including extensive NMR techniques and computational modelling. These compounds showed no inhibitory activity against the 11ß-HSD1 enzyme.

Study on Improvement Effects of Liqi Sanjie Granule on Liver-qi Stagnation Model Rats / 中国药房

OBJECTIVE： To investigate the improvement effects of Liqi sanjie granule on liver-qi stagnation model rats. METHODS： According to the weight， totally 80 rats were randomly divided into blank control group （normal saline）， model control group （normal saline）， Xiaoyao pill control group （positive control a， 750 mg/kg ，calculated by crude drug）， Xiaojin pill control group （positive control b， 200 mg/kg， calculated by pill weight）， Liqi sanjie pill control group （prototype control， 1 957 mg， calculated by crude drug） and Liqi sanjie granule low-dose， medium-dose and high-dose groups （978.5， 1 957， 3 914 mg/kg， calculated by crude drug）， with 10 rats in each group. Each group was given medicine 20 mL/kg intragastrically once a day， for consecutive 21 d. 1 h after per medication， liver-qi stagnation model was established in those groups by binding method except for blank control group. The syrup preference of rats was determined by designing syrup preference test. Rattail suspension test was adopted to determine the hanging immobility time and struggling times of mice. Open-field behavior test was used to determine total behavior score so as to judge the extent of liver-qi stagnation and effect of the drug in rats. RESULTS： Compared with blank control group， hanging immobility time of model control group was significantly prolonged， the syrup preference and the total behavior score of open field test were decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Compared with model control group， the struggling times of rats were increased significantly in Xiaojin pill control group， Liqi sanjie pill control group and Liqi sanjie granule medium-dose group （P＜0.05 or P＜0.01）； the hanging immobility time of Xiaoyao pill control group， Xiaojin pill control group， Liqi sanjie pill control group， Liqi sanjie granule low-dose and medium-dose groups were shortened significantly； syrup preference and total behavior score of open-field behavior test were increased significantly （P＜0.05 or P＜0.01）. Compared with Liqi sanjie pill control group， the struggling times of rats were decreased significantly and hanging immobility time were prolonged significantly only in Liqi sanjie granule high-dose group （P＜0.05 or P＜0.01）； there was no statistical significance in above indexes of rats in Liqi sanjie granule low-dose and medium-dose groups （P＞0.05）. CONCLUSIONS： Liqi sanjie granule can significantly improve liver-qi stagnation caused by binding method， and the effects of low-dose and medium-dose Liqi sanjie granule are similar to those of Liqi sanjie pill.

Study on Long-term Toxicity of Liqi Sanjie Extractum in Rats with Intragastric Administration / 中国药房

OBJECTIVE： To study the long-term toxicity of Liqi sanjie extractum in rats after intragastric administration， and to provide reference for safety evaluation before clinical practice. METHODS： A total of 160 rats were randomly divided into control group （normal saline） and Liqi sanjie extractum low-dose， medium-dose and high-dose groups （7.828 0， 15.656 0， 31.312 0 g/kg， calculated by crude drug）， with 40 rats in each group. They were given relevant medicine intragastrically once a day from Monday to Saturday. The experimental period was 120 days， and the recovery period was 30 days after the end of the experiment. General information of rats was observed， and body weight and feed consumption of rats were measured once a week. At the 61st day of administration， the end of administration and the end of recovery period， 10， 20 and 10 rats were collected from each group to observe their hematology， blood biochemistry， organ coefficient and histopathology changes. RESULTS： From 61st day to 120th day of administration， the rats of Liqi sanjie extractum high-dose group had hair loss and erection， and recovered after withdrawal of medicine. During medication， the body weight of mice in Liqi sanjie extractum low-dose and medium-dose groups increased faster than control group， while the body weight of rats in Liqi sanjie extractum high-dose group increased slower than control group. Compared with control group， the feed consumption of Liqi sanjie extractum low-dose group increased， while those of Liqi sanjie extractum medium-dose and high-dose groups decreased； the rats were recovered after drug withdrawal. On the 61st day of administration and after the end of administration， some hematological indexes， blood biochemical indexes and organ coefficients of rats in administration group were significantly different from those of control group （P＜0.05 or P＜0.01）. The hematology， blood biochemistry and organ coefficients of rats were basically recovered after the end of the recovery period. The number of erythrocyte， hematocrit， standard deviation of erythrocyte width， albumin， globulin ratio and potassium K+ levels in Liqi sanjie extractum low-dose group were significantly lower than those in control group （P＜0.05 or P＜0.01）. The absolute value of intermediate cells in blood of rats in Liqi sanjie extractum medium-dose group was significantly higher than that of control group （P＜0.05）， and the mean hemoglobin concentration， K+ and uterine coefficient in blood were significantly lower than those of control group （P＜0.05）. The number of white blood cells， absolute value of lymphocyte， absolute value of intermediate cells， the percentage of intermediate cells， prothrombin time and spleen coefficient in Liqi sanjie extractum high-dose group were significantly higher than those in the control group （P＜0.05 or P＜0.01）. Mean hemoglobin concentration， granulocyte percentage， albumin， alkaline phosphatase and K+ were significantly lower than those in the control group （P＜0.05 or P＜0.01）. No abnormalities in systemic autopsy and histopathology were noticed in rats. CONCLUSIONS： Long-term intragastric administration of Liqi sanjie extractum can cause certain toxic reactions in rats， and low dose of Liqi sanjie extractum causes less and lighter toxic reactions which can be automatically recovered after drug withdrawal. It can provide reference for the determination of clinical safe dose.

Study on the Dose-time-effect Relationship of Tibetan Medicine Rannasangpei in Cerebral Ischemia-reperfusion Injury Model Rats with Intragastric Administration / 中国药房

OBJECTIVE： To study the dose-time-effect relationship of Tibetan medicine Rannasangpei in cerebral ischemic- reperfusion injury model rats with intragastric administration. METHODS： The rats were randomly divided into sham operation group （normal saline， 10 mL/kg）， model control group （normal saline， 10 mL/kg）， positive control group （nimodipine， 30      mg/kg）， Rannasangpei different dose groups （0.52， 1.04， 2.08， 4.17， 8.33， 16.67， 33.34， 66.68， 133.36， 266.72 and 533.44    mg/kg）， with 18 rats in each group. Each group was given relevant medicine intragastrically once； 25 min after intragastric administration， cerebral ischemic-reperfusion injury model was established with suture-occluded method in those groups except for sham operation group. 24， 48， 72 h after cerebral ischemia， neuroethology of rats were graded in each group. The rate of cerebral infraction was detected to evaluate the optimal effective time， the optimal dose （Dmax） and maximal effect （the rate of minimum cerebral infraction， Emax） of Ratnasampil at different periods of cerebral ischemia. Dose-time-effect relationship of Rannasangpei dose with the rate of cerebral infraction was fitted with Thermo Kinetica 5.1 software. The area under curve （AUClast） and retention dose （MRTlast） of dose-effect curve were calculated， and detect the levels of SOD and MDA. RESULTS： Compared with sham operation group， the neurobehavior of model group was significantly abnormal （P＜0.05 or P＜0.01）， and the rate of cerebral infarction was significantly increased （P＜0.01）； the level of SOD was decreased significantly （P＜0.01， 48 h）， and the level MDA was increased significantly （P＜0.05， 48 h）. Compared with model control group， there was no significant change in neurobehavioral abnormalities in the nimodipine group （P＞0.05）， and the rate of cerebral infraction was decreased significantly （P＜0.01， 24， 48 h）. The level of SOD in rats were increased significantly （P＜0.01， 48 h）， while the level MDA decreased significantly （P＜0.05， 48 h）. Rannasangpei 2.08-33.34 mg/kg could significantly improved neurobehavioral abnormalities （P＜0.05， 24 h）； 24 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 4.17-133.36 mg/kg group （the lowest is 33.34 mg/kg group， P＜0.05 or P＜0.01）. The level of SOD in rats were increased significantly in 33.34-533.44 mg/kg groups （P＜0.05）. the level MDA was decreased significantly in 0.52-2.08， 8.33， 33.34， 266.72 and 533.44 mg/kg groups （P＜0.05）. Dmax was 33.34 mg/kg， Emax was 3.02％， AUClast was 5 141.76 mg/kg and MRTlast was 329.161 mg/kg. 48 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 2.08-133.36 mg/kg groups （the lowest is 66.68 mg/kg group， P＜0.05 or P＜0.01）， while the level of SOD was increased significantly in 1.04-533.44（except for 4.17）mg/kg groups （P＜0.05）. The level of MDA was decreased significantly in 16.67-66.68， 533.44 mg/kg groups （P＜0.05）， Dmax was 66.68 mg/kg， Emax was 2.13％， AUClast was    5 219.36 mg/kg and MRTlast was 340.521 mg/kg. 72 h after cerebral ischemia， the rate of cerebral infraction and the level of MDA had no significant decreased in Rannasangpei groups （P＞0.05）， and the levels of SOD had no significant increase （except for 0.52 mg/kg group， P＞0.05）. CONCLUSIONS： The optimal effective time of Rannasangpei for the treatment of cerebral ischemia-reperfusion injury in rats is 48 h， and the Dmax is 66.68 mg/kg. The improvement mechanism may be related to increase the level of SOD and decrease the level of MDA.

Tanshinone IIA sulfonate protects against cigarette smoke-induced COPD and down-regulation of CFTR in mice.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline. The anti-inflammatory actions of tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied. However, it remains unknown whether sodium tanshinone IIA sulfonate (STS) protects against the development of COPD. Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10 µg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations. Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS.

A historical evaluation of Chinese tongue diagnosis in the treatment of septicemic plague in the pre-antibiotic era, and as a new direction for revolutionary clinical research applications / 中西医结合学报

Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities, may have discouraged doctors to come in direct contact with their patients and take the pulse. However, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world's earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research.

Research on sinusoidal alternating magnetic field therapy system based on inverter technology / 医疗卫生装备

Objective To develop a sinusoidal alternating magnetic field therapy system in order to overcome the disadvantages of the single output frequency and the low effective value of the output magnetic field strength of the alternating magnetic field therapy system in the market,of which the frequency and magnetic density both were continuously adjustable. Methods Multi winding Helmholtz coil was used as the magnetic field generator.On the basis of inverter technology,bipolar equivalent area method considering dead zone and variable speed integral incremental PID control algorithm were used to achieve the accuracy control of magnetic frequency and density in the coil.The accuracy of the resulting waveform and the accuracy of the magnetic field strength was verified by simulation calculation and system current and magnetic field strength test.Results The magnetic field treatment system gained high performance,total harmonic distortion (THD)of sine wave met the requirements of international standards.The obtained magnetic density was as expected of the simulation and calculation. Conclusion The device provides continuously adjustable magnetic field,which has a positive effect on the research for the medical staff, and technical references are provided to the research of magnetic field therapy system.

Semi-continuous production of high-activity pectinases by immobilized Rhizopus oryzae using tobacco wastewater as substrate and their utilization in the hydrolysis of pectin-containing lignocellulosic biomass at high solid content.

In this study, highly reactive endo- and exo-polygalacturonases (PGs) were produced from the tobacco industry wastewater using immobilized Rhizopus oryzae. Compared with free cells, immobilized cells increased enzyme activity 2.8-fold and reduced production time to 24h by shake-flask production. Moreover, the immobilized cells enabled the semi-continuous production of enzymes through repeated-batch mode for seven consecutive cycles in a scale-up bioreactor. During the first five cycles, the average endo-PG and exo-PG activities reached 307.5 and 242.6U/ml, respectively. The addition of crude enzyme for the hydrolysis of pectin-containing lignocellulosic biomass under high-gravity conditions increased glucose release 4.2-fold (115.4 vs. 29.0g/L), compared with hydrolysis using cellulase alone. This process achieves the efficient production of pectin-degrading enzymes, provides a cost-effective method for tobacco wastewater treatment, and offers the possibility to obtain fermentable sugars with high-titer from pectin-containing lignocellulosic biomass, which has important potential for the commercial production of bio-fuels.

Sustainable Elastomers from Renewable Biomass.

Sustainable elastomers have undergone explosive growth in recent years, partly due to the resurgence of biobased materials prepared from renewable natural resources. However, mounting challenges still prevail: How can the chemical compositions and macromolecular architectures of sustainable polymers be controlled and broadened? How can their processability and recyclability be enabled? How can they compete with petroleum-based counterparts in both cost and performance? Molecular-biomass-derived polymers, such as polymyrcene, polymenthide, and poly(ε-decalactone), have been employed for constructing thermoplastic elastomers (TPEs). Plant oils are widely used for fabricating thermoset elastomers. We use abundant biomass, such as plant oils, cellulose, rosin acids, and lignin, to develop elastomers covering a wide range of structure-property relationships in the hope of delivering better performance. In this Account, recent progress in preparing monomers and TPEs from biomass is first reviewed. ABA triblock copolymer TPEs were obtained with a soft middle block containing a soybean-oil-based monomer and hard outer blocks containing styrene. In addition, a combination of biobased monomers from rosin acids and soybean oil was formulated to prepare triblock copolymer TPEs. Together with the above-mentioned approaches based on block copolymers, multigraft copolymers with a soft backbone and rigid side chains are recognized as the first-generation and second-generation TPEs, respectively. It has been recently demonstrated that multigraft copolymers with a rigid backbone and elastic side chains can also be used as a novel architecture of TPEs. Natural polymers, such as cellulose and lignin, are utilized as a stiff, macromolecular backbone. Cellulose/lignin graft copolymers with side chains containing a copolymer of methyl methacrylate and butyl acrylate exhibited excellent elastic properties. Cellulose graft copolymers with biomass-derived polymers as side chains were further explored to enhance the overall sustainability. Isoprene polymers were grafted from a cellulosic backbone to afford Cell-g-polyisoprene copolymers. Via cross-linking of these graft copolymers, human-skin-mimic elastomers and high resilient elastomers with a well-defined network structure were achieved. The mechanical properties of these resilient elastomers could be finely controlled by tuning the cellulose content. As isoprene can be produced by engineering of microorganisms, these elastomers could be a renewable alternative to petroleum products. In summary, triblock copolymer and graft copolymer TPEs with biomass components, skin-mimic elastomers, high resilient biobased elastomers, and engineering of macromolecular architectures for elastomers are discussed. These approaches and design provide us knowledge on the potential to make sustainable elastomers for various applications to compete with petroleum-based counterparts.