Mechanism of Schisandra Chinensis-mediated microglia phenotypic transformation by regulation of the TLR4 pathway based on miR-124 / 药学学报

To investigate the mechanism by which Schisandra Chinensis mediates the phenotypic transformation of microglia via microRNA-124 (miR-124)-based regulation of the Toll-like receptor 4 (TLR4) pathway, a model was established using lipopolysaccharide (LPS) stimulation of BV2 cells. Cells were treated with different doses of Schisandra Chinensis extract (SCE). MiR-124 inhibitors and negative control sequences (NC inhibitor) were transfected into LPS-induced BV2 cells and treated with SCE. The MTT assay was used for cell activity detection; an NO kit was used to measure NO release; ELISA kits were used to measure the levels of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Microglia markers, including ionized calcium binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1), and the nuclear translocation of nuclear factor-kappa B (NF-κB) were evaluated by immunofluorescent staining. NF-κB p65, IBA-1, Arg-1, TLR4, myeloid differentiation primary factor 88 (MyD88), inhibitor of nuclear factor-kappa B kinases-α (IKK-α), IL-10, TNF-α were detected by immunoblot. SCE at concentrations ranging from 31.25 to 250 μg·mL-1 had no significant effect on cell activity. SCE treatment significantly inhibited NO release induced by LPS (P < 0.001, P < 0.01), increased the level of IL-10 (P < 0.05), and decreased the level of TNF-α (P < 0.001). In addition, SCE significantly reduced the expression of TNF-α, IBA-1, TLR4, and MyD88 (P < 0.01, P < 0.001) and elevated the expression of IL-10, Arg-1, NF-κB P65 and IKK-α (P < 0.001, P < 0.01, P < 0.05). SCE treatment could also promote the expression of miR-124 (P < 0.01). However, transfection with the miR-124 inhibitor increased TNF-α (P < 0.001), decreased the level of IL-10 (P < 0.05), increased the mRNA level and the protein expression of TNF-α and IBA-1 (P < 0.05, P < 0.01, P < 0.001), and decreased the mRNA level and protein expression of IL-10 and Arg-1 (P < 0.001, P < 0.01). In addition, the inhibition of TLR4 and MyD88 was attenuated. In conclusion, SCE appears to inhibit the activation of TLR4 signaling pathway by upregulating miR-124 so as to inhibit microglia M1 polarization and promote microglia M2 polarization.

Chemical constituents of diterpenoids from Boswellia carterii / 中国中药杂志

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

Quality standard of Lobeliae Chinensis Herba / 中国中药杂志

In light of related methods in Chinese Pharmacopoeia(2020 edition), this study established the quality standard for Lobeliae Chinensis Herba. The TLC identification method was established with silica gel GF_(254) thin layer plate, diosmin standard, linarin standard, and the reference material of Lobeliae Chinensis Herba. The loss on drying, total ash, acid-insoluble ash, and ethanol-soluble extracts of 18 batches of Lobeliae Chinensis Herba samples were determined according to the general principles in Chinese Pharmacopoeia. Then, HPLC was adopted in the establishment of characteristic chromatogram and content determination. The results showed that the established method can achieve good separation for diosmin, linarin, and lobetyolin. Based on the results of detection for 18 batches of Lobeliae Chinensis Herba samples, the draft quality standard was established, which was expected to provide reference for the revision of this medicinal herb in Chinese Pharmacopoeia.

National Nutrition and Health Systematic Survey for Children 0-17 Years of Age in China / 生物医学与环境科学（英文）

The main purpose of the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC) was to collect basic data on the nutrition, development, and health status for children in different regions across China using evidence-based, reliable, and cost-effective approaches. Children and their parents or guardians from seven regions (south, southwest, north, northwest, eastern, central, and northeast China) in China were recruited. A multi-stage stratified randomized sampling method was used. Two provinces were randomly sampled from each of the seven regions, from which one urban district and one rural country were also randomly sampled, resulting in a total of 28 survey counties/districts. Dietary surveys, health examinations, laboratory testing, and questionnaires were used to collect dietary intake, nutritional status, child development, and health status information. Nutrition, health, and lifestyle assessment of children and their parents was determined using the Knowledge Attitude Practice (KAP) survey. Greater than 100,000 children (38,000 children < 6 years of age and 66,000 children 6-17 years of age) completed the survey. The survey provided comprehensive data on child nutrition and health status for future studies and will serve as the basis for an integrated nutrition and health improvement strategies proposal for children in China.

Clinicopathological characteristics and risk factors of lymph node metastasis in isthmus papillary thyroid microcarcinoma / 中华内分泌外科杂志

Objective:To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma in the isthmus (PTMCI) and the independent risk factors of central lymph node metastasis.Methods:58 consecutive patients with PTMCI admitted from Jan. 2016 to Dec. 2018 (isthmus group) were retrospectively analyzed, including 15 males and 43 females,age (42.93±12.69) years old; According to the specific location of papillary thyroid microcarcinoma (PTMC) in isthmus, PTMCI were subdivided into the right PTMCI and the left PT-MCI 67 patients with a single PTMC located in the unilateral lobe were randomly selected as a control (lobe group) , including 13 cases of male and 54 cases of female, age (47.18±11.34) years old. Index included the patient’s age, gender, tumor diameter, TPOAb, aspect ratio, microcalcification, capsular invasion, lymph node metastasis, surgical methods, operation method, and scope of lymph node dissection. SPSS 21.0 software was used for statistical analysis. The quantitative data of normal distribution was expressed as ± s,and the difference between the two groups was compared by chi-square test.The risk factors of CLNM of the isthmus group were analyzed with univariate chi-square test and multivariate Logistic regression analysis.The difference was statistically significant if P<0.05. Results:Compared with PTMC, PTMCI showed a higher rate of capsule invasion ( P=0.003) ,lymph node metastasis ( P=0.049) ,lymph node metastasis in central region ( P=0.033) ,and surgical methods between the two groups were statistically significant ( P<0.05) ;But PTMCI was significantly lower than PTMC in aspect ratio>1 ( P<0.05) . Univariate analysis showed that capsule invasion ( P=0.001) and microcalcification ( P=0.012) were risk factors for PTMCI lymph node metastasis. Multivariate Logistic regression analysis showed that capsule invasion ( P=0.016) and microcalcification ( P=0.046) were independent risk factors for central lymph node metastasis in PTMCI. Conclusions:Compared with PTMC,PTMCI indicates a higher rate of capsular invasion,lymph node metastasis in prelaryngeal and central lymph node;Compared with PTMC, PTMCI indicates a lower rate of aspect ratio>1; Capsule invasion and microcalcification are independent risk factors for central lymph node metastasis in PTMCI. For patients with the right PTMCI or the left PTMCI and also without capsular invasion and calcification,ipsilateral central lymph node dissection should be considered.

Analysis of related risk factors for the refracture of adjacent vertebral body after percutaneous kyphoplasty / 中国骨伤

OBJECTIVE@#To investigate the risk factors of vertebral refracture after percutaneous kyphoplasty (PKP) for osteoprotic vertebral compression fractures (OVCFs), and to provide reference for clinical prevention.@*METHODS@#A retrospective analysis of 228 OVCFs patients who met the inclusion criteria admitted from November 6, 2013 to December 14, 2018. There were 35 males and 193 females, with a male-to-female ratio of 3∶20, and aged 58 to 91 years with an average of (69.70±7.03) years. All patients were treated with PKP and had complete clinical data. According to whether refracture occurred after operation, they were divided into refracture group (24 cases) and non refracture group (204 cases). Factors that may be related to refracture (including gender, age, surgical segment, number of vertebral bodies in the surgical segment, whether combined with degenerative scoliosis, whether anti-osteoporosis treatment) were included in the univariate analyses, and the single factor analysis of statistically significant risk factors was carried out with multiple Logistic regression analysis to further clarify the independent risk factors for vertebral body refracture after PKP. Survival analysis was performed using the time of vertebral refracture after PKP as the end time of follow up, the occurrence of refracture after PKP as the endpoint event, and the presence or absence of degenerative lateral curvature as a variable factor.@*RESULTS@#All 228 patients were followed up for 1.8 to 63.6 months with an average of (28.8±15.6) months, and the refracture rate was 10.5%(24/228). There were statistically significant differences between two groups in age, number of operative vertebral bodies, whether combinedwith degenerative scoliosis and whether anti osteoporosis treatment (@*CONCLUSION@#Combined scoliosis is an independent risk factor for refracture after OVCFs vertebroplasty, and it is also a possible high-risk factor for refracture after surgery.

Condensed tannins from roots of Indigofera stachyodes / 中国中药杂志

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2β→O→7,4β→8)-epiafzelechin-(4β→8)-catechin(2), cinnamtannin D1(3), cinnamtannin B1(4), epicatechin-(2β→O→7,4β→8)-epiafzelechin-(4α→8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.

Correlation study of multimodal ultrasound characteristics with HCK and MRPL13 expression in breast cancer / 中华内分泌外科杂志

Objective:To investigate the correlation between hematopoietic cell kinase (HCK) and the expression level of the mitochondrial ribosomal protein L13 (MRPL13) and hematopoietic multimode ultrasound.Methods:204 female breast cancer patients treated by surgery in Quzhou people’s Hospital from Jan. 2017 to Sep. 2020 were selected as study subjects. Breast cancer tissues and adjacent normal tissues were extracted intraoperatively. Preoperative conventional ultrasound, shear wave elastography (SWE) and contrast-enhanced Ultrasonography (CEUS) were used to detect HCK and MRPL13 expression levels. Univariate analysis and binary Logistic regression were used to analyze the correlation between multi-mode ultrasonic features and HCK and MRPL13.Results:The positive expression ratios of HCK and MRPL 13 in breast cancer tissues were significantly higher than those in adjacent tissues ( χ2 was 5.625, 7.197; P was 0.018, 0.007) . In conventional ultrasound features, the proportions of HCK-positive breast cancer patients with irregular mass edges, microcalcifications, and grade II to III blood flow classification were significantly higher than those of HCK-negative patients ( χ2 was 7.437, 16.684, 23.262; P was 0.006, <0.001, <0.001) ; The proportion of MRPL13-positive breast cancer patients with a maximum diameter of ≥2 cm, irregular edges of the tumor, and grade II-III blood flow classification was significantly higher than that of MRPL13-negative patients ( χ2 was 4.676, 11.118, 8.389; P was 0.031, 0.001, 0.004) . For SWE signs, the proportion of HCK positive breast cancer patients with hard ring sign was significantly higher than that of HCK negative patients ( χ2=11.220, P=0.001) ; the proportion of MRPL13 positive breast cancer patients with hard ring sign and black hole sign was significantly higher than that of MRPL13. Those who were negative ( χ2 was 4.482, 8.775; P was 0.034, 0.003) . Among CEUS characteristics, the proportion of HCK-positive patients with high enhancement was significantly higher than that of HCK-negative patients ( χ2=7.356, P=0.007) ; the proportion of MRPL13-positive patients with high enhancement and late regression was significantly higher than that of MRPL13-negative patients ( χ2 was 9.165, 7.631; P was 0.002, 0.006) . The results of binary logistic analysis showed that there was microcalcification ( OR=4.619, 95% CI=2.657-8.119, P=0.009) , blood flow classification II to III ( OR=4.150, 95% CI=2.547-7.954, P=0.015) and high enhancement of CEUS ( OR=4.150, 95% CI=2.547-7.954, P=0.015) are independent risk factors for positive expression of HCK; blood flow grade II to grade III ( OR=4.213, 95% CI=3.145-8.557, P=0.012) , appearance of black hole sign ( OR=5.246, 95% CI=2.864-10.378, P<0.001) and high enhancement of CEUS ( OR=3.872, 95% CI=1.887~6.438, P=0.026) were the independent risk factors for the positive expression of MRPL13. Conclusion:The multimodal ultrasonographic features of breast cancer are helpful to predict the expression levels of HCK and MRPL13, so as to provide new imaging ideas for early diagnosis of breast cancer, the designation of treatment options and the preoperative non-invasive assessment of breast cancer prognosis.

Jiaotai Pill () Alleviates Insomnia through Regulating Monoamine and Organic Cation Transporters in Rats / 中国结合医学杂志

OBJECTIVE@#To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats.@*METHODS@#The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs.@*RESULTS@#Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05).@*CONCLUSION@#JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.

One new cembranoid diterpene from gum resin of Boswellia carterii / 中国中药杂志

This study aims to study the chemical components from the gum resin of Boswellia carterii. Five cembranoid diterpenes were isolated from the gum resin of B. carterii by various of column chromatographies including silica gel, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, mass spectrometry(MS), nuclear magnetic resonance(NMR), Ultraviolet(UV) and infrared(IR) spectroscopic data. These compounds were identified as(1S,2E,4R,5S,7E,11E)-4-methoxy-5-hydroxycembrane(1),(1R~*,4R~*,5E,8E,12E,15E)-4-hydroxycembra-5,8,12,15-tetraene(2), cembrene A(3),(3S,4S,7R)-4-hydroxycembrane(4), and pavidolide D(5). Compound 1 was a new compound. Compounds 2, 4, and 5 were obtained from the gum resin of B. carterii for the first time. Compound 2 showed weak inhibition on the human liver cancer cell line HepG2.

Regulatory effect of Jiaotai Pills on central and peripheral neurotransmitters in rats with heart-kidney imbalance insomnia / 中国中药杂志

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.

Two new phenylpropanoid amide glycosides from whole plants of Corydalis racemosa / 中国中药杂志

Two new phenylpropanoid amide glycosides and ten analogues were isolated from the CH_2Cl_2 layer of 95% ethanol extract of the whole plants of Corydalis racemosa by using various chromatographic techniques, including silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data as N-cis-sinapoyltyramine-4'-O-β-glucoside(1), N-cis-sinapoyl-3-methoxytyramine-4'-O-β-glucoside(2), N-cis-sinapoyltyramine(3), N-cis-feruloyltyramine(4), N-trans-cinnamoyltyramine(5), N-trans-feruloylphenethylamine(6), N-trans-p-methoxycinnamoyl-3-hydoxyoctopamine(7), N-cis-feruloyl-3-methoxytyramine(8), N-trans-feruloyltyramine(9), N-trans-feruloyl-3-methoxytyramine(10), N-trans-sinapoyltyramine(11), and N-trans-p-coumaroyltyramine(12). Compounds 1 and 2 are new compounds. Compounds 3-7 are obtained from the plants of Papaveraceae for the first time, and compounds 8-12 are firstly isolated from C. racemosa.

Analysis of in Vivo and in Vitro Metabolites of Coptisine in Rats by HPLC-MS/MS / 中国实验方剂学杂志

Objective::To investigate in vivo and in vitro metabolites of coptisine and their metabolic pathways. Method::SD rats were given coptisine by single gavage (dose of 25 mg·kg-1). Urine and feces from 0 h to 48 h, bile from 0 h to 24 h, and plasma and brain tissue samples at 0.25, 1, 2 h after administration were collected.In vitro metabolism was incubated with rat liver microsomes and intestinal flora.The metabolites were analyzed and identified by the high-resolution HPLC-MS/MS technique.The liquid chromatography separation was carried out on ZORBAX SB-C18 column (4.6 mm×150 mm, 5 μm) with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution, the flow rate was 1.0 mL·min-1, and column temperature was 25 ℃.The mass spectra were obtained in positive and negative ion mode with electrospray ionization (ESI), the scanning range was m/z 50-1 200.The relative molecular weight was determined according to the quasi-molecular ion peaks.The structures of metabolites were elucidated by comparing the data with literature data, including main ion peaks, UV spectrum and HPLC retention time information. Result::A total of 17 metabolites were identified in each sample, including 11 phase Ⅰ metabolites and 6 phase Ⅱ metabolites.The pathways to these metabolites were hydroxylation, demethylation, dehydrogenation, sulfation and glucuronide conjugation. Conclusion::Coptisine can produce metabolic reaction of phase Ⅰ and phase Ⅱ in rat, and metabolites are predominantly present in urine, and the main metabolic site is liver.Coptisine is poorly absorbed and rarely metabolized in gastrointestinal tract, so it is mostly excreted through feces by prototype.This experiment can provide material basis for the pharmacodynamics and pharmacology of coptisine.

Effect of Warming and Heat-clearing Method on Expressions of FoxP3 and ROR-γt in Colon Tissue of Rats with Intestinal Endotoxemia Caused by Acute-on-chronic Liver Failure / 中国实验方剂学杂志

Objective::To study the effect of warming and heat-clearing method (Wenyang Jiedu Huayu decoction) on the expressions of Forkhead box P3 (FoxP3), Retinoic acid-related orphan receptor gamma t (ROR-γt) in colon tissue of mice with acute-on-chronic liver failure (ACLF), in order to explore the possible regulatory mechanism on intestinal endotoxemia (IETM) in liver failure mice. Method::The 130 SD rats were randomly divided into normal group (10 rats) and model group (120 rats). The ACLF mice model was established through the subcutaneous injection with bovine serum albumin and the intraperitoneal injection with D-galactosamine(D-Gal) and lipopolysaccharide (LPS). The model mice were randomly divided into model group, heat-clearing group (Yinchenhao decoction, 6.68 g·kg-1), warming group (Yinchen Zhufu decoction, 7.09 g·kg-1) and warming and heat-clearing group (Wenyang Jiedu Huayu decoction, 19.53 g·kg-1). The normal group and the model group were given distilled water by gastric lavage, while the other groups were given equal volume of corresponding Chinese herbal medicines for a week. The value of each index at 1, 12 and 24 h was measured. The ratio of Treg/Th17 cell in peripheral blood were detected and calculated by flow cytometry. Real-time fluorescence quantitative PCR (Real-time PCR) was used to detect the expressions of FoxP3 and ROR-γt in colon tissues of mice at different time points. In situ hybridization and immunohistochemistry were used to observe the expressions of FoxP3 and ROR-γt genes and proteins. Result::Compared with normal group, the ratio of Treg/Th17 in the model group decreased significantly at each time point (P<0.01). Compared with the model group, the Treg/Th17 ratio increased only in the warming and heat-clearing method group (P<0.05). Compared with normal group, the expression of ROR-γt in the model group was significantly higher (P<0.01), and the expression of ROR-γt in the model group was higher than FoxP3.Compared with the model group, the expressions of FoxP3 and ROR-γt mRNA in the heat-clearing group and the warming group decreased at each time point (P<0.05), and the expressions of FoxP3 and ROR-γt in the warming and heat-clearing method group decreased significantly (P<0.01). The expressions of FoxP3 and ROR-γt mRNA in warming and heat-clearing group decreased compared with those in the warming group and heat-clearing group (P<0.05). Conclusion::The mechanism of the warming and heat-clearing method on IETM in liver failure may be related to the regulation of FoxP3 and ROR-γt expressions.

Research advances in endogenous neural stem cells promoting neural repair after ischemic stroke / 生理学报

Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases. It is noteworthy that some stroke patients showed an ability to repair brain several months after the stroke happened, suggesting an existence of endogenous nerve repair in these patients. The research advances in functions of endogenous neural stem cells in neural regeneration and the related regulators after ischemic stroke are summarized in this review to provide new views of the mechanism of neural functional recovery after ischemic stroke.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Study of Xplane imaging in quantifying the maximal volume of the left and right atria and evaluating atrial function in fetuses with abnormal heart morphology / 中华超声影像学杂志

Objective@#To explore the feasibility of real-time three-dimensional ultrasound Xplane imaging in quantifying left and right atrial diastolic maximal volume (LAVmax, RAVmax) and evaluating cardiac diastolic function in fetuses with cardiac disease in second and later trimesters.@*Methods@#One hundred and forty-four fetuses with abnormal heart morphology at 16-34 weeks of gestational age were included and divided into 3 groups according to the influence of pathological changes on atrial volume: group A with symmetrical left and right atrial volume, group B with decreased left atrial volume and increased right atrial volume and group C with increased left atrial volume and decreased right atrial volume, and the fetus were also divided into 2 groups according to the law of fetal development: the middle pregnancy group (16-27+ 6 weeks) and the late pregnancy group (28-34+ 6 weeks). Using the " Xplane" mode of volume probe, the maximal atrial volume was calculated automatically by tracing method and three-path line method. The correlation between the two methods in quantitative LAVmax was validated by paired sample t test and Pearson correlation analysis. The correlation between LAVmax, RAVmax and gestational age were analyzed by curve fitting. The volumes of bilateral chambers and the average weekly growth rates of E peak, A peak and E/A value of mitral and tricuspid orifices were calculated and compared.@*Results@#There was no significant statistical difference between the maximal volume of the left atrium obtained by the tracing method and the three-diameter line method (P>0.05), and there was high correlation between the two methods in the comparison of the maximal volume of the left atrium (r=0.90, 0.88, 0.85; all P<0.01). The data of group A, B and C showed that LAVmax and RAVmax could increase with the increase of gestational weeks in a certain period of abnormal state, and had a good correlation with them(LAVmax: r=0.78, 0.74, 0.78, all P<0.005; RAVmax: r=0.79, 0.77, 0.78, all P<0.005). The average weekly growth rate of RAVmax showed an advantage in group A, B and C. Especially in group C with reduced right atrium, the growth rate of right atrium was 8.15%, which was higher than that of group B with decreased left atrium by 5.06%. The weekly growth rates of E peak and E/A in tricuspid orifice were also higher than those in mitral orifice. The E peak and E/A values of tricuspid orifice in group C were 4.05% and 0.60%, respectively, higher than those in group B, which were 2.58% and 0.02%. Peak A showed an increase in growth rate in group B and group C with decreased atria, peak A values in group B and group C increased by 4.01% and 2.19%, respectively.@*Conclusions@#The right ventricular dominance of fetal heart can still be reflected in certain stages of disease, and the atrial active systolic may play a regulatory role in the filling of cardiac blood flow. Real-time three-dimensional ultrasound Xplane imaging could be used to quantify the atrial volume of fetuses with abnormal heart morphology in second and later trimesters and to preliminary assess atrial function combined with the changes of atrioventricular valve orifice hemodynamics. Real-time three-dimensional ultrasound Xplane imaging technology has obvious advantages of simple, safe, non-invasive, simultaneous and high repeatability in measuring fetal atrial volume.