A novel strategy for the quality control of carbonized Typhae pollen using colorimeter, liquid chromatography-mass spectrometry, and efficacy evaluation coupled with multivariate statistical analysis.

In this study, a novel quality control strategy was proposed, aiming to establish a multivariate specification for the processing step by exploring the correlation between colors, chemical components, and hemostatic effects of the carbonized Typhae pollen (CTP) using multivariate statistical analysis. The CTP samples were stir-fried at different durations. Afterward, the colorimeter and LC-MS techniques were applied to characterize the CTP samples, followed by the determination of bleeding time and clotting time using mice to evaluate their hemostatic effect. Then, principal component analysis, hierarchical cluster analysis, and multi-block partial least squares were used for data analysis on colors, chemical components, and their correlation with the hemostatic effect. Consequently, 13 critical quality attributes (CQAs) of CTP were identified via multivariate statistical analysis-L*, a*, b*, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, quercetin-3-O-glucoside, azelaic acid, kaempferol-3-O-glucoside, quercetin, naringenin, kaempferol, and isorhamnetin. The multivariate specification method involving the 13 CQAs was developed and visualized in the latent variable space of the partial least squares model, indicating that the proposed method was successfully applied to assess the quality of CTP and the degree of carbonization. Most importantly, this study offers a novel insight into the control of processing for carbonized Chinese herbal medicines.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

System modeling on Chinese herbal medicine process based on multi-block partial least squares / 中国中药杂志

The system model of Chinese herbal medicine process is the basis for improving the precision of pharmaceutical process and ensuring the stable transmission of quality between different sections of the process. By taking the wet granulation-tableting process as the research object and using the Panax notoginsengs sapions (PNS) as a model drug, multi-block partial least squares method (MBPLS) was used in this article to build the system model of Chinese herbal medicine process, analyze the mass transmission rules in the process and improve the understanding on pharmaceutical process system of Chinese medicine. According to the process flow, the quality attributes of raw materials, granules and tablets collected in the process were divided into different data blocks, and the MBPLS method was used to establish system model. The R²Y and Q²Y of MBPLS model were 89.1% and 65.5%, respectively, indicating that the performance of the MBPLS model was good. By analyzing the parameters of MBPLS model, it was determined that the physical quality attributes of PNS raw materials and quality attributes of PNS granules were the key factors to affect the quality of PNS tablets. The particle size, bulk density and tapped density of PNS raw materials were the critical quality attributes which caused the quality variations of PNS granules and PNS tablets. MBPLS can quantify the contributions of each unit to the product quality by dividing the quality attributes into different units. It was helpful to analyze the interactions between the process units of Chinese herbal medicine and it could be applied to build system model of other Chinese herbal preparations processes.

Establishment and reliability evaluation of the design space for HPLC analysis of six alkaloids in Coptis chinensis (Huanglian) using Bayesian approach / 中国天然药物

Coptis chinensis (Huanglian) is a commonly used traditional Chinese medicine (TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance liquid chromatography (RP-HPLC) method allowing the separation of six alkaloids in Huanglian was for the first time developed under the quality by design (QbD) principles. First, five chromatographic parameters were identified to construct a Plackett-Burman experimental design. The critical resolution, analysis time, and peak width were responses modeled by multivariate linear regression. The results showed that the percentage of acetonitrile, concentration of sodium dodecyl sulfate, and concentration of potassium phosphate monobasic were statistically significant parameters (P < 0.05). Then, the Box-Behnken experimental design was applied to further evaluate the interactions between the three parameters on selected responses. Full quadratic models were built and used to establish the analytical design space. Moreover, the reliability of design space was estimated by the Bayesian posterior predictive distribution. The optimal separation was predicted at 40% acetonitrile, 1.7 g·mL(-1) of sodium dodecyl sulfate and 0.03 mol·mL(-1) of potassium phosphate monobasic. Finally, the accuracy profile methodology was used to validate the established HPLC method. The results demonstrated that the QbD concept could be efficiently used to develop a robust RP-HPLC analytical method for Huanglian.

Physical fingerprint for quality control of traditional Chinese medicine extract powders / 中国中药杂志

The physical properties of both raw materials and excipients are closely correlated with the quality of traditional Chinese medicine preparations in oral solid dosage forms. In this paper, based on the concept of the chemical fingerprint for quality control of traditional Chinese medicine products, the method of physical fingerprint for quality evaluation of traditional Chinese medicine extract powders was proposed. This novel physical fingerprint was built by the radar map, and consisted of five primary indexes (i.e. stackablity, homogeneity, flowability, compressibility and stability) and 12 secondary indexes (i.e. bulk density, tap density, particle size<50 μm percentage, relative homogeneity index, hausner ratio, angle of repose, powder flow time, inter-particle porosity, Carr index, cohesion index, loss on drying, hygroscopicity). Panax notoginseng saponins (PNS) extract was taken for an example. This paper introduced the application of physical fingerprint in the evaluation of source-to-source and batch-to-batch quality consistence of PNS extract powders. Moreover, the physical fingerprint of PNS was built by calculating the index of parameters, the index of parametric profile and the index of good compressibility, in order to successfully predict the compressibility of the PNS extract powder and relevant formulations containing PNS extract powder and conventional pharmaceutical excipients. The results demonstrated that the proposed method could not only provide new insights into the development and process control of traditional Chinese medicine solid dosage forms.

Study on manufacturing process performance index of Qingkailing injection / 中国中药杂志

In this paper, the process performance indexes (PPIs) P(p) and P(pk) were introduced and applied to evaluate the process capability and quality consistence of Chinese medicine products. The historical quality analysis data of Qingkailing injection were collected and taken as the research object. The confidence intervals of P(p) and P(pk) were estimated based on the Bootstrap sampling methods. Results showed that the value and width of the confidence interval P(p) of were smaller that of P(pk) suggesting that the P(pk) index was more sensitive than P(p) in process capability analysis. Within the production period concerned, the P(pk) values estimated from different quality indexes of Qingkailing injection, such as baicalin, cholic acid, geniposide and total nitrogen, were 1.122, 2.055, 1.564 and 0.891, respectively. It could be found that the cholic acid had the highest process capability, followed by the geniposide and baicalin. The total nitrogen had the lowest process capability, indicating that it is necessary to reinforce the quality management of total nitrogen related manufacturing processes. The case studies demonstrate the effectiveness and feasibility of PPIs, which are convenient to be used in production practice of Chinese medicine.

HPLC-fingerprint-based quality evaluation on a Tibetan medicine Phyllanthus emblica and its tannin parts / 中国中药杂志

This study is to establish the fingerprint for Phyllanthus emblica and their tannin parts from different habitats by HPLC for its quality control. The determination was carried out on a Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column, with methanol-0.2% glacial acetic acid as mobile phase with gradient elution at a flow rate of 1 mL x min(-1). The temperature was maintained at 30 degrees C and the detected wavelength is 260 nm, Thirteen chromatographic peaks were extracted as the common peaks of the fingerprint of P. emblica, and eleven as the common peaks of P. emblica tannin parts, and five peaks were identified by comparing with referent samples. The fingerprints of 8 samples were compared and classified by similarity evaluation, cluster analysis and principal component analysis (PCA). The similarity degrees of eight P. emblica were between 0.763 and 0.993, while tannin parts were between 0.903 and 0.991. All the samples of P. emblica and their tannin parts were classified into 3 categories. The method was so highly reproducible, simple and reliable that it could provide basis for quality control and evaluation of P. emblica from different habitats.

Effect of short-term high-dose atorvastatin on systemic inflammatory response and myocardial ischemic injury in patients with unstable angina pectoris undergoing percutaneous coronary intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Percutaneous coronary intervention (PCI) could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property. The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.</p><p><b>METHODS</b>From March 2012 to May 2014, one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital, were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes, 24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase-myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at baseline and then 24 hours following PCI.</p><p><b>RESULTS</b>Plasma CRP and IL-6 levels increased from baseline after PCI in all groups. CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group ((9.14±3.02) mg/L) than in the LD group ((11.06±3.06) mg/L) and ND group ((12.36±3.08) mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group ((16.19±5.39) ng/L and (14.26±4.12) ng/L, respectively)) than in the LD group ((19.26±6.34) ng/L and (16.03±4.08) ng/L, respectively, both P < 0.05) and ND group ((22.24±6.98) ng/L and (17.24±4.84) ng/L, respectively). IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours after the procedure in all groups, the elevated CK-MB and cTnI values were lower in the HD group ((4.71±4.34) ng/ml and (0.086±0.081) ng/ml, respectively) than in the ND group ((7.24±6.03) ng/ml and (0.138±0.103) ng/ml, respectively, both P < 0.01) and LD group ((6.80±5.53) ng/ml and (0.126±0.101) ng/ml, respectively, both P < 0.01).</p><p><b>CONCLUSION</b>Short-term high-dose atorvastatin treatment before PCI significantly reduced systemic inflammatory response and myocardial ischemic injury elicited by PCI.</p>

Treatment of non-motor symptoms of Parkinson's disease patients of Gan-Shen deficiency syndrome by guling pa'an granule: a multi-center double-blinded randomized controlled trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of guiling pa'an granule (GPG) in treating non-motor symptoms of Parkinson's disease (PD) patients of Gan-Shen deficiency syndrome (GSDS).</p><p><b>METHODS</b>A multi-center,third party-central online, network randomized, double-blinded, double-dummy, and placebo controlled clinical trial was conducted. Totally 121 patients with confirmed diagnosis of PD by Western medicine and of GSDS by syndrome typing were assigned to the control group and the treatment group. Under the premise of the same treatment baseline, the placebo and GPG at the same dose was respectively administered to patients in the control group and the treatment group. The therapeutic course was 6 months for all. The changes of 8 non-motor symptoms (including witless expression, seborrhea, sialorrhea, cognitive impairment, constipation, hyperhidrosis, insomnia and dreaminess, and psychosis) were observed in the two groups, when compared with the baseline.</p><p><b>RESULTS</b>Satisfactory effectiveness in the 8 non-motor symptoms of PD patients were obtained in the treatment group (P<0.01). Besides, less adverse reactions occurred.</p><p><b>CONCLUSION</b>GPG could improve the non-motor symptoms of PD patients.</p>

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Mφ) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Mφ in hematopoietic cell injury.</p><p><b>METHODS</b>ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-γ levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Mφ in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Mφ membrane FcγIIreceptor (FcγIIR), mannitose receptor (MR), IFN-γ, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Mφ bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented.</p><p><b>RESULTS</b>In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-γ were increased. After treatment, the cytokine levels gradually became normal. The activated Mφ in the marrow highly expressed NSE and POX, and Mφ swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Mφ expressed HLA-DR, MR, ICAM-1, IFN-γ, and IL-12. For patients with humoral immunity activation and bacterial infection, Mφ weakly expressed IL-17A but highly expressed FcγIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Mφ weakly expressed FcγIIR, secretory highly expressed IL-17A, and the phenomena that Mφ adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Mφ occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve.</p><p><b>CONCLUSIONS</b>Mφ is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Mφ, upregulate the impression of immune molecule and receptors, form ADCC HI, aggravate hematopoietic injury, and accelerate the destruction on hematopoietic cell.</p>

Application of Aidi injection (艾迪注射液) in the bronchial artery infused neo-adjuvant chemotherapy for stage III A non-small cell lung cancer before surgical operation / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of Aidi Injection (艾迪注射液,ADI) applied in the bronchial artery, applied in the bronchial artery infused (BAI) neo-adjuvant chemotherapy for stage III A non-small cell lung cancer (NSCLC) before surgical operation.</p><p><b>METHODS</b>The 60 patients with NSCLC stage III A underwent two courses BAI chemotherapy before tumor incision were assigned to two groups, the treatment and the control groups, using a random number table, 30 in each group. ADI (100 mL) was given to the patients in the treatment group by adding into 500 mL of 5% glucose injection for intravenous dripping once daily, starting from 3 days before each course of chemotherapy, and it lasted for 14 successive days, so a total of 28 days of administration was completed. The therapeutic effectiveness and the adverse reaction that occurred were observed, and the levels of T-lymphocyte subsets, natural killer cell activity, and interleukin-2 in peripheral blood were measured before and after the treatment.</p><p><b>RESULTS</b>The effective rate in the treatment group was higher than that in the control group (70.0% vs. 56.7%, P<0.05). Moreover, as compared with the control group, the adverse reaction that occurred in the treatment group was less and mild, especially in terms of bone marrow suppression and liver function damage (P<0.05). Cellular immune function was suppressed in NSCLC patients, but after treatment, it ameliorated significantly in the treatment group, showing significant difference as compared with that in the control group (P<0.05).</p><p><b>CONCLUSION</b>ADI was an ideal auxiliary drug for the patients in stage III A NSCLC received BAI neo-chemotherapy before surgical operation; it could enhance the effectiveness of chemotherapy, ameliorate the adverse reaction and elevate patients' cellular immune function; therefore, it is worthy for spreading in clinical practice.</p>

Efficacy of auxiliary therapy with Danggui Buxue Decoction No.1 in treating patients of non-small cell lung cancer at peri-operational stage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of Danggui Buxue Decoction No.1 in treating patients of non-small cell lung cancer (NSCLC) at the peri-operational stage and its impact on the patients' immune function.</p><p><b>METHODS</b>Eighty-two NSCLC patients were randomly assigned to two groups equally, the control group and the test group, they were given conventional treatment, while to the test group, DB1 were given additionally. The observation was conducted by testing the changes of T-lymphocyte subsets, natural killer (NK) cell activity, serum levels of immunoglobulin (IgA, IgM, IgG), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha), cytokeratin fragment 19 (CYFRA21-1) and carcinoembryonic antigen (CEA) in NSCLC patients before and after administration of DB1, and analyzing the patients' general condition.</p><p><b>RESULTS</b>The level of CD3(+), CD4(+), the ratio of CD4 and CD8(+), IgA, IgM, IgG and IL-2 decreased in patients with NSCLC on day 1 after operation, and the level of CD8 and TNF-alpha increased compared to pre-operation. While the levels of CD3(+), CD4(+), CD4 /CD8(+), NK cell activity, serum IgA, IgM, IgG, IL-2 began to elevate, CD8 and TNF-alpha levels began to decline in patients administered with DB1 on day 3 after the operation, earlier than patients who did not use the decoction. The level of CYFRA21-1 and CEA, was immediately decreased after operation in both groups.</p><p><b>CONCLUSIONS</b>Applying DB1 to NSCLC patients at an early post-operational stage could alleviate the impairment and accelerate the recovery of immune function of patients to enhance their immunity. DB1 also shows an anti-tumor action to a certain degree.</p>

Investigation on the changes of dependent signal on the amplitude of low frequency fluctuations at blood oxygen level in brain after acupuncture Neiguan (PC 6) / 中国针灸

<p><b>OBJECTIVE</b>To investigate the relationship of the acupoint and its functional location in the brain.</p><p><b>METHODS</b>Ten healthy participants were examined with the resting state functional magnetic resonance imaging (fM-RI). The scanning includes the resting state 1 (R 1), acupuncture stimulating (AP) Neiguan (PC 6) and the resting state 2 (R 2). All data were analyzed with the amplitude of low frequency fluctuations (ALFF).</p><p><b>RESULTS</b>1) During the R1, the regions with active signal on the ALFF contained bilateral superior frontal gyrus, medial frontal gyrus and some part of cerebellum (including right declive, culme, tonsil and left uvula), as well as left precuneus, right superiour temporal gyrus. 2) As for AP, the active regions with higher ALFF were bilateral superior frontal gyrus and right cuneus, as well as left middle frontal gyrus, declivis and right semi-lunar lobule. 3) The main difference on ALFF between R1 and AP appeared within bilateral cingulated gyrus and declivis, left lingualgurus, and cuneus, as well as right precuneus, fusiform gyrus, superior frontal gyrus, medial frontal gyrus and superior temporal gyrus, etc.</p><p><b>CONCLUSION</b>After acupuncture stimulating the left Neiguan (PC 6), the active regions on ALFF are detected on bilateral cingulated gyrus, right superior frontal gyrus and medial frontal gyrus, as well as bilateral declivis and left lingual gurus, etc. These regions have the close relationship with the mental disorder and nervous diseases, which might be the possible neural mechanism of acupuncture stimulating Neiguan (PC 6) for treating some of related mental disorder and nervous diseases.</p>

Clinical observation on acupoint sticking therapy for treatment of chronic pain of cervical intervertebral disc / 中国针灸

<p><b>OBJECTIVE</b>To probe into an effective therapy for chronic pain of cervical intervertebral disc.</p><p><b>METHODS</b>Sixty-six cases of chronic pain of cervical intervertebral disc were randomly divided into an acupoint sticking group and an acu puncture group, 33 cases in each group. The acupoint sticking group was treated with acupoint sticking therapy, and the acupuncture group with acupuncture. Tianding (LI 17), Futu (LI 18), Dazhui (GV 14), Tianzong (S 11), etc. were selected in the two groups. After treatment for 3 therapeutic courses, their therapeutic effects were observed.</p><p><b>RESULTS</b>The effective rate was 93.5% in the acupoint sticking group and 72.4% in the acupuncture group, the former being better than the latter (P<0.05); in a 3-month following-up survey, the effective rate was 90.3% in the acupoint sticking group and 65.5% in the acupuncture group, the former being better than the latter (P<0.05).</p><p><b>CONCLUSION</b>The acupoint sticking therapy has an satisfactory therapeutic effect on chronic pain of cervical intervertebral disc.</p>