Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network / 中国药房

OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction， liquid-to-material ratio， and extraction time as investigation factors. The parameters used were the contents of hesperidin， nobiletin， tangeretin， gallic acid， chebulagic acid， chebulinic acid， liquiritin， glycyrrhizin， eugenol， and the paste-forming rate. The analytic hierarchy process （AHP） was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm （GA）-back propagation neural network （BP neural network）. RESULTS The optimal ethanol extraction process parameters， as optimized by orthogonal experiment， were as follows: ethanol volume fraction of 60%， liquid-solid ratio of 14∶1 （mL/g)， extraction time of 90 min， and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile， the optimal ethanol extraction process parameters， optimized by GA-BP neural network， were ethanol volume fraction of 65%， liquid-solid ratio of 14∶1 （mL/g )， extraction time of 60 min， and extraction for 2 times. The comprehensive score obtained by verification was 85.30， higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.

Optimization of processing methods for Terminalia chebula based on fingerprint，antioxidant spectrum-effect correlation and multi-component contents / 中国药房

OBJECTIVE To compare the similarities and differences between raw and different preparations of Terminalia chebula based on fingerprint， antioxidant spectrum-effect correlation and multi-component contents， and to provide a reference for searching for modern processing methods of T. chebula that are similar to classical ancient methods. METHODS Ten batches of raw and different preparations of T. chebula （single stir-fried products， bran-roasted products， sand-scorched products， ash-roasted products， stir-fried charcoal products， and wine-steamed products） were used as test samples. The high-performance liquid chromatography （HPLC） fingerprints of different samples were established by using the Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition）， the chromatographic peaks were identified， and chemometrics analysis was carried out. At the same time， HPLC method was used to determine the contents of 8 identified components. The antioxidant capacity of raw and different preparations of T. chebula was determined by DPPH free radical scavenging method， and the spectrum- effect relationship was analyzed. RESULTS A total of 20 common peaks were identified in the fingerprints of the raw and different preparations of T. chebula， and the similarity of each sample was ＞0.9. Nine common peaks were identified from the raw and different preparations of T. chebula， including chromatographic peak 2 （chebulic acid）， 3 （gallic acid）， 6 （punicalagin A）， 8 （punicalagin B）， 12 （corilagin）， 15 （chebulagic acid）， 18 （ellagic acid）， 19 （1，2，3，4，6-O-pentagalloyl glucose）， 20 （chebulinic acid）， etc. Compared with crude drug， the contents of the above 8 components （punicalagin A and B are recorded as punicalagin） in different preparations of T. chebula were changed， and the changes of the contents of the stir-fried charcoal and wine-steamed products were more obvious than those of other processed products. Chemometric analysis showed that the fingerprints of stir-fried charcoal and wine-steamed products of T. chebula were obviously distinguished from other processed products， and the fingerprint information of raw products and other processed products of T. chebula was partially overlapped. Four main differential components （chebulinic acid， chebulagic acid， gallic acid， ellagic acid） were obtained between raw and processed products of T. chebula； and four main effective components （chebulinic acid， chebulagic acid， gallic acid， corilagin） were obtained by analyzing the spectrum-effect relationship of antioxidant activity. The single stir-fried product of T. chebula showed the strongest antioxidant activity. CONCLUSIONS The single stir-frying method is a modern processing method of T. chebula which is similar to the classical ancient method and is more excellent.

Content changes of chemical constituents and comparison of the anti-ulcerative colitis effect of processed products of Terminalia chebula at different temperatures / 中国药房

OBJECTIVE To study the content changes of ch emical constituents of processed products of Terminalia chebula at different temperatures ，and to compare its anti-ulcerative colitis effect. METHODS Processed products of T. chebula at different temperatures（160，180，200，220，240，260，280，300 ℃）were prepared by sand scalding technology. HPLC method was adopted to determine the contents of gallic acid ，chebulagic acid ，chebulinic acid and ellagic acid in crude drug and processed products of T. chebula at different temperatures. The mice were divided into blank group ，model group ，Mesalazin enteric-coated tablets group （positive control ，0.4 g/kg），crude drug and processed products groups of T. chebula at different temperatures （1.3 g/kg），with 10 mice in each group. Except for blank group ，other groups were given 6％ acetic acid 0.1 mL via anus to induce ulcerative colitis model. After modeling ，blank group and model group were given water intragastrically ，and other groups were given relevant drug intragastrically ，20 mL/kg，once a day ，for consecutive 7 days. The general physical signs of mice in each group were observed and the body weight was recorded. The colorectal length and index ，serum levels of related inflammation indexes [superoxide dismutase （SOD），malondialdehyde （MDA），interleukin-10 （IL-10），IL-1 β ，tumor necrosis factor α （TNF-α）] were detected. The pathomorphological changes of colon and rectum were observed ，and the comprehensive score of pharmacodynamics was performed. RESULTS With the increase of processing temperature ，the contents of chebulagic acid and chebulinic acid decreased gradually ，the content of gallic acid increased first and then decreased ，and the content of ellagic acid increased. Compared with model group ，the general physical signs ，body weight ，colorectal length ，colorectal index and related inflammation indexes were all improved significantly in crude drug and processed products groups of T. chebula at different temperatures（P＜0.05 or P＜0.01）. The glandular recess structure of colorectal tissue was repaired ，the infiltration of inflammatory cells was reduced ，and the comprehensive score of efficacy of processed products prepared at 260 ℃ was the highest. CONCLUSIONS The contents of chemical components in T. chebula processed at different temperatures change significantly and their anti-ulcerative colitis effects are different. The processed products of T. chebula prepared at 260 ℃ show the best anti-ulcerative colitis effect.

Establishment and validation of a nomogram prediction model for early preoperative diagnosis of hepatocellular carcinoma with microvascular invasion / 中华肝胆外科杂志

Objective:To establish a convenient preoperative nomogram prediction model for early diagnosis of hepatocellular carcinoma (HCC)with microvascular invasion (MVI), and to evaluate the model through internal and external validations for use informulating reasonable and individualized treatment strategies for patients with early-staged HCC.Methods:The clinical data of 294 patients who underwent hepatectomy at the General Hospital of Ningxia Medical University from January 2017 to December 2020 were retrospectively collected and analyzed. Based on the different admission times, they were divided into the training group ( n=231) and the validation group ( n=63). Based on the results from previous published literatures and our relevant clinical experience, risk factors including γ-glutamyltranspeptidase (GGT), platelet-lymphocyte ratio (PLR), fibrinogen albumin ratio (FAR), lymphocyte monocyte count ratio (LMR) and ALT-platelet ratio (APRI) were subjected to multi-factor logistic regression analysis to determine independent risk factors of HCC with MVI, and a nomogram prediction model was then constructed. The validation group was applied to the model for validation. Results:Of 294 patients who were enrolled in this study, there were 231 patients in the training cohort, with an average age of (55.1±10.9) years. In the training group, 95 patients were MVI positive and 136 patients were MVI negative. In the validation group, 38 patients were MVI positive and 25 patients were MVI negative. Logistic regression analysis showed that FAR>0.06, GGT>50 U/L, APRI>0.16, tumor diameter>5 cm, LMR>3.57 and PLR>98.75 were independent risk factors ( P<0.05), and a nomogram prediction model was established. The correction curve of the nomogram showed that the actual prediction result was close to the ideal result of the prediction model. The internal validated results showed the C-indexes to be between 0.71 and 0.90, and the prediction model had good discrimination. DCA curve was used to evaluate the clinical net benefit of the predictive model. When the net benefit rate was above zero, the threshold of the prediction model was 4%-77%, indicating that the prediction model had good clinical practicability. Conclusion:The established nomogram prediction model based on preoperative clinical indexes of GGT, APRI, LMR, PLR, FAR and diameter of tumor could be used to predict early diagnosis of HCC with MVI. The nomogram has good clinical application values.

Inokosterone Is A Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Patients: Analysis from Active Ingredient of Cyathula Officinalis / 中国结合医学杂志

OBJECTIVE@#To elucidate the active compounds and the molecular mechanism of Cyathula Officinalis as a drug treatment for rheumatoid arthritis (RA).@*METHODS@#The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine. The protein-protein interaction between the target genes were analyzed using STRING and Genemania. The transcriptome of RA patients compared to healthy people (GSE121894) were analyzed using R program package Limma. The relative expression of the target genes was obtained from the RNA-seq datasets. The molecular docking analyses were processed based on the molecular model of estrogen receptor 1 (ESR1) binding with estradiol (PDB ID:1A52). The binding details were analyzed by SYBYL.@*RESULTS@#Inokosterone, ecdysterone, and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes. Of all the significantly changed genes from RA patients, ESR1, ADORA1, and ANXA1 were significantly increased in mRNA samples of RA patients.@*CONCLUSION@#ESR1, the transcription factor that binds inokosterone in the molecular binding analysis, is the target protein of Cyathula Officinalis.

Polycyclic polyprenylated acylphloroglucinols from Hypericum species and their biological activities / 中国中药杂志

Hypericum species are distributed widely in China, especially in the southwest. This genus is rich in species types in China, including 55 species and 8 subspecies. The main chemical constituents of Hypericum species are flavonoids, xanthones and polycyclic polyprenylated acylphloroglucinols(PPAPs). PPAPs are characterized by polycyclic and branched-chain substitutions in their structures, which make their structure types diverse. Moreover, they have been found to have antitumor, antiviral, antibacterial, anti-inflammatory and other biological activities. This research classified and summarized 344 polycyclic polyprenylated acylphloroglucinols from Hypericum plants in order to provide a scientific basis for further development and utilization of PPAPs from the genus.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study / 中华医学杂志(英文版)

Background@#Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF).@*Methods@#In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.@*Results@#Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648–0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622–0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685–0.795, P < 0.001).@*Conclusions@#GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.@*Clinical trial registration@#ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Apprenticeship system of American NCCAOM Certification of acupuncture and oriental medicine / 中国针灸

The National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) is the only national institution for the accreditation of clinical practice of acupuncture and Oriental (Chinese) Medicine in the United States. Its qualification certificate or examination certificate is a mandatory document for 47 states and Washington, D.C. to issue the practice license. According to the latest information of the NCCAOM official website, this paper introduced the preceptor qualifications of the apprenticeship, studying hours, quality control, and the evaluation at the end of apprenticeship. The paper also discussed the enlightening and referential effects of the American system to apprenticeship policy in China.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF).@*METHODS@#In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.@*RESULTS@#Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648-0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622-0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685-0.795, P < 0.001).@*CONCLUSIONS@#GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.@*CLINICAL TRIAL REGISTRATION@#ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Protective effect of Salvia chinensis Benth. polysaccharides on lipopolysaccharide and D-galactosamine induced acute liver failure in mice / 中国药理学与毒理学杂志

OBJECTIVE To explore the protective effect of polysaccharides from Salvia Chinensis Benth. (PSSC) on lipopolysaccharide (LPS) and D- galactosamine (GalN)- provoked mouse acute liver failure (ALF) and the possible molecular mechanism. METHODS Kunming mice were randomly divided into four groups: normal control, model, model+PSSC 30 and 100 mg·kg- 1 groups. PSCC was given once a day and for a week. To establish an ALF model, mice of model and PSSC groups were ip injected with LPS 10 μg·kg-1 and GalN 700 mg·kg-1 at the end of PSSC treatment. The microscopic structure of the liver was detected by HE staining. Serum and hepatic biochemical parameters of glutamic-oxalacetic transaminase (GOT), glutamic- pyruvic transaminase (GPT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and glutathione (GSH) were detected by colorimetric methods. The relative content of hepatic reactive oxygen species (ROS) was measured by DCFH-DA fluorescent probes. Levels of cytokines tumor necrosis factor-α (TNF-α), interleukin 1β(IL-1β) and IL- 6 in the serum and liver were detected by ELISA. Activity of caspase 3 in liver homogenates was detected by aspase 3 activity assay kit. RESULTS Compared with normal control group, in the liver of model group, hepatocytes were arrayed in disorder, cytoplasm of hepatocytes shrank, and boundaries between cells were fuzzy, the infiltration of a large number of inflammatory cells and tissue hemorrhage could be detected, pathological scores were elevated significantly (P<0.01), levels of MDA and ROS in the liver of ALF model mice were elevated to 2.2 and 4.3 times that of the normal control, respectively (P<0.01), the level of GSH decreased to 51% (P<0.01), and the activities of SOD, CAT and GSH- Px declined to 74%, 36% and 42%, respectively (P<0.01). Levels of TNF- α, IL- 1β and IL- 6 in the serum and liver of model group were increased (P<0.01), and caspase 3 activity was increased to 5.3 times that of the normal control (P<0.01). Compared with the model group, the number of surviving mice in PSSC groups increased, liver pathological scores declined (P<0.01), levels of MDA and ROS increased (P<0.01), levels of GSH, TNF-α, IL-1β and IL-6 in the liver and serum declined (P<0.01), and caspase 3 activity decreased (P<0.01). CONCLUSION PSSC is able to alleviate LPS and GalN-induced ALF in mice. Inhibition of hepatic oxidative stress, inflammatory response, and cell apoptosis is possibly implicated in the protective effect of PSSC.

The Role of the Pelvis in Sagittal Alignment of Lumbar Degenerative Disease Patients

STUDY DESIGN: Literature review. OBJECTIVES: To present updated information on the relationship of the pelvis and lumbar degenerative disease (LDD) patients and to emphasize the importance of the pelvis in sagittal alignment of LDD patients. SUMMARY OF LITERATURE REVIEW: Although the relationship of the pelvis and sagittal alignment of LDD patients is controversial, many authors have reported a significant impact of the pelvis on LDD sagittal alignment. MATERIALS AND METHODS: The authors identified references through a literature search on the pelvis and LDD and continuous monitoring of the literature during the past 30 years. RESULTS: The pelvis and lumbar levels were related to whole-body sagittal alignment. The pelvis is also closely related to sagittal alignment of LDD patients. Therefore, the entire area should be regarded as a lumbopelvic complex. CONCLUSIONS: We need to consider the concept of a lumbopelvic joint and lumbopelvic lordosis, not a lumbosacral joint and lumbar lordosis. We must also evaluate the lumbopelvic complex to assess whole-body sagittal alignment and dynamic balance.

Clinical Characteristics of Coronary Slow Flow in Relevant Patients / 中国循环杂志

Objective: To explore the clinical and anatomical characteristics of coronary slow lfow (CSF) in relevant patients. Methods: We summarized the patients without coronary angiography (CAG) proved coronary stenosis (stenosis 27 and Control group,n=55 patients with normal coronary lfow. The related laboratory indexes were examined and relationship between MCV and CSF was studied by multi-logistic regression analysis. Results: In CSF group, MCV 90.4 (87.48, 92.65) fL and RDW-CV 12.5 (12.30, 13.18) % were lower than those in Control group 92.3 (90.1, 94.3) fL and 13(12.7, 13.4) %,P Conclusion: Deformability of red blood cells might be involved in pathogenesis of CSF in relevant patients.

Demethylating agent decitabine induces autologous cancer testis antigen specific cytotoxic T lymphocytes in vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cancer testis antigens (CTAs) are a novel group of tumor associated antigens. Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism, thus enhance the immunogenicity of leukemia cells. However, few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes (CTLs) in vivo, and if so, whether this effect contributes to disease control. In this study, we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo.</p><p><b>METHODS</b>Several mouse CTAs were screened by RT-PCR. CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry. The activity of specific CTLs was measured by real time RT-PCR.</p><p><b>RESULTS</b>We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs. Then we measured the CTLs' activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment. Finally, we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells.</p><p><b>CONCLUSIONS</b>Our study showed the autologous immune response induced by decitabine in vivo. And more importantly, we firstly proved that this response may contribute to disease control. We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine, and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.</p>

Comparison of real-time myocardial contrast echocardiography and DISA-SPECT in dectecting hibernating myocardium / 中华超声影像学杂志

Objective To compare the accuracy of real-time myocardial contrast echocardiography (RT-MCE) with DISA-SPECT in detecting hibernating myocardium. Methods Fourteen hospitalized patients with regional wall motion abnormalities (RWMA) underwent RT-MCE, DISA-SPECT, coronary angiography and percutaneous coronary intervention(PCI). Every left ventricular myocardial segment image was acquired and evaluated according 16-segment model of American Society of Echocardiography. The Motion of every segment was observed by echocardiography after 1,3,6 months. The gold standard is that the motion of ventricular segment get better after PCI. The images of RT-MCE and DISA-SPECT were analyzed semi-quantitatively. Results The sensitivity,specificity,accuracy of RT-MCE and DISA-SPECT in detecting hibernating myocardium were 74.60%, 91.7%, 81.3% and 93.3%, 75.0%, 86.2%, respectively. RT-MCE had more value in specificity while DISA-SPECT had more value in sensitivity. The correlation between two methods was good in detecting hibernating myocardium. Conclusions RT-MCE and DISA-SPECT can be used as valuable methods to detect hibernating myocardium, the correlation between two methods is good and they have more value in specificity and sensitivity respectively.

Construction and expression of the soybean isoflavonoid biosynthetic pathway in Escherichia coli / 生物工程学报

The natural isoflavones biosynthetic pathway is only limited in legumes plant. To study the isoflavone in bacteria by metabolic engineering requires transformation of multi-gene of the whole pathway into the host strain to resembling the expression and metabolism of the genes. The multi-gene transformation and expression strategy become necessary because of this. This article talks about the multi-gene transformation strategy using one or many vectors, taking the five genes of isoflavonoid biosynthetic pathway to E. coli. The recombinant bacteria carry five genes with two vectors, the whole Isoflavonoid biosynthetic pathway was constructed into E. coli. Fermented with L-tyrosine as substrate and IPTG as an inducer, the recombinant bacteria can produce a new isoflavone related metabolite showed on HPLC analysis profile.