Critical quality attribute assessment of big brand traditional Chinese medicine: visualization of blending process for rare medicines in Tongren Niuhuang Qingxin Pills based on spatial distribution uniformity / 中国中药杂志

The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control of Tongren Niuhuang Qingxin Pills in texture and sensory attributes / 中国中药杂志

Texture sensory attributes are the key items in quality control of Chinese medicinal honeyed pills. The purpose of this study is to develop a quality control method for assessing the texture sensory attributes of Chinese medicinal honeyed pills based on real-world Tongren Niuhuang Qingxin pilular masses and finished products. First, parameters of texture profile analysis(TPA) were optimized through single factor and central composite design(CCD) experiments to establish a detection method for texture sensory attri-butes of Tongren Niuhuang Qingxin Pills. The results showed that the established detection method was stable and reliable, with the optimal parameters set up as follows: deformation percentage of 70%, detection speed at 30 mm·min~(-1), and interval time of 15 s. Furthermore, 540 data points yielded form six texture sensory attributes of pills from 30 batches were subjected to multivariate statistical process control(MSPC) with Hotelling T~2 and squared prediction error(SPE) control charts to establish the quality control method of Tongren Niuhuang Qingxin Pills. This study is expected to provide a reference for improving the quality control system of Chinese medicinal honeyed pills.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control method of ginkgo leaves extract material based on powder physical properties / 中国中药杂志

The physical properties of ginkgo leaves extract(GLE) are the critical quality attributes for the control of the manufacturing process of ginkgo leaves preparations. In this study, 53 batches of GLE with different sources from the real world were used as the objects to carry out the research from 3 levels. First, based on micromeritics evaluation method, a total of 29 physical attribute quality parameters in five dimensions were comprehensively characterized, with a total of 1 537 data points. Further, with use of physical fingerprinting technology combined with similarity evaluation, the powder physical properties of 53 batches of GLE showed obvious differences from an overall perspective, and the similarity of the physical fingerprints was 0.876 to 1.000. Secondly, hierarchical clustering analysis(HCA) and principal component analysis(PCA) models were constructed to realize the reliable identification and differentiation of real-world materials produced by GLE from different sources. Multivariate statistical process control(MSPC) model was used to create GLE material Hotelling T~2 and squared prediction error(SPE) control charts. It was found that the SPE score of B_(21) powder exceeded the 99% confidence control limit by 22.495 9, and the SPE scores of A_1 and C_(10) powder exceeded the 95% confidence control limit by 16.099 2, realizing the determination of abnormal samples in the materials of GLE from the production in real world. Finally, the physical quality control method of GLE in the production process of ginkgo leaves preparations was established in this study, providing a reference for the quality control methods of ginkgo leaves preparations in their manufacturing process.

Critical quality attribute assessment of big brand traditional Chinese medicine: process quality control method of Suhuang Zhike Capsules intermediate based on physical properties of powder and granules / 中国中药杂志

The physical properties of powder and granules are the critical quality attributes for the process control of Suhuang Zhike Capsules, a big brand traditional Chinese medicine. This paper took the production of 25 batches of real-world Suhuang Zhike Capsules dry extract powder and granules intermediates as the research object. Firstly, a method for testing the physical properties of Suhuang Zhike Capsules powder and granules with 19 physical indicators was established. The results showed that the granules of dry extract powder after granulation had a smaller particle size, wider particle size distribution range and poor fluidity, which easily caused the problem of over-limit capsule loading. Secondly, correlation analysis, principal component analysis and cluster analysis were used for mathematical statistics. The correlation analysis showed that the density of dry extract powder could affect the chroma and fluidity. At the same time, the particle size in the granules had a stronger effect on the chroma and fluidity than the density. The study also found that the particle size and hygroscopicity of dry extract powder were potentially key physical properties that affected the physical properties of granules. Furthermore, the results of principal component analysis and cluster analysis showed that the consistency of the physical properties between the dry extract powder and intermediate granules was relatively poor. To this end, similarity analysis was carried out, and the quality control method of powder and granules based on physical fingerprint was established. The results showed that the physical fingerprint similarity of 25 batches of dry extract powder was 0.639-0.976, and the physical fingerprint similarity of the gra-nules was 0.716-0.983. With the similarity of 0.85 as the threshold, the batches with abnormal physical properties could be identified. In this study, the process quality control method of Suhuang Zhike Capsules based on the physical properties of powder and granules was established finally, which realized the identification of abnormal batches, and provided a reference for the process quality control of Suhuang Zhike Capsules.

Critical quality attribute assessment of big brand traditional Chinese medicine: online NIR quality control research on boiling time during extraction process / 中国中药杂志

Assessment of the status property(boiling time) is a challenge for the quality control of extraction process in pharmaceutical enterprises. In this study, the pilot extraction process of Phellodendron chinense was used as the research carrier to develop an online near-infrared(NIR) quality control method based on the status property(boiling time). First, the NIR spectra of P. chinense were collected during the two pilot-scale extraction processes, and the status property(boiling time) was assessed by observing the state of bubbles in the extraction tank using a transparent window during the extraction process, which was then used as a reference standard. Based on the moving block standard deviation(MBSD) algorithm, the assessment model using online NIR spectra for boiling time during extraction process was established. In addition, the model was optimized as follows: standard normal variable(SNV) for spectral pretreatment, modeling band of 800-2 200 nm, and window size of 4. The results showed that, with 0.002 0 as the MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process. Furthermore, the principal component analysis-moving block standard deviation(PCA-MBSD) model was developed by our group to reduce the influence of online NIR spectral noise and background signal on the model, and the number of principal components was optimized into 2 in the PCA-MBSD model. The results showed that, with 0.000 075 as the PCA-MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process, with improved reliability. This study can provide a assessment method for boiling time during extraction process using online NIR spectra, which can replace the empirical judgment in manual observation, and realize the digitalization of the extraction process for big brand traditional Chinese medicine.

Corrigendum to “Effects and mechanism of total phenols of Magnolia officinalis combined with Maijunan Tablets on blood pressure of spontaneous hypertensive rats” Chinese Herbal Medicines 11 (2019) 177–184 (Chinese Herbal Medicines (2019) 11(2) (177–184), (S1674638419300231), (10.1016/j.chmed.2018.12.004)) / 中草药·英文版

When this paper was first published the following ethical statement was omitted in error: The animal experiment was approved by the Ethics Committee of Hubei University, and complied with the guide for the care and use of laboratory animals. The authors would like to apologise for any inconvenience caused. DOI of originalarticle: https://doi.org/10.1016/j.chmed.2018.12.004

Effects and mechanism of total phenols of Magnolia officinalis combined with Maijunan Tablets on blood pressure of spontaneous hypertensive rats / 中草药·英文版

Objective: Maijunan (MJA) Tablets is a protected variety of traditional Chinese medicine (TCM) consisted of Pueraria lobata, hydrochlorothiazide (HTCZ), Uncaria rhynchophylla (366:1:980) and excipient. In the present work, MJA was consisted of the total flavones of P. lobata, HCTZ and total alkaloids of U. rhynchophylla (40:11:75). The combination of MJA and the total phenols of Magnolia officinalis (M-MJA) was consisted of the total flavones of P. lobata, the total phenols of M. officinalis, HCTZ and the total alkaloids of U. rhynchophylla (40:40:11:75). The aim of this work was to examine the effect and mechanism of M-MJA on the blood pressure of spontaneous hypertensive rats (SHRs). Methods: Adult male SHRs were randomly divided into control group, MJA group (180 mg/kg·d), and the M-MJA group (218 mg/kg·d) (n = 5). SHRs were orally administered with M-MJA and MJA respectively once a day for 8 weeks, the blood pressure of SHRs was measured every two weeks, and the biochemical indicators related to blood pressures were detected at the last dosing. Results: After oral administration of M-MJA to SHRs once a day for 8 weeks, the systolic and diastolic blood pressures of SHRs were deceased significantly. M-MJA affected renin-angiotensin-aldosterone system by decreasing the levels of Ren, Ang II and ALD, affected the endothelial function by decreasing the levels of ET-1 and 20-HETE, and increasing the level of eNOS, affected the oxidative stress by increasing the protein expression of Nrf2 and the activities of HO-1 and GSH-Px, and decreasing the protein expression of CYP2E1 and CYP4A, as well as the content of MDA. Conclusion: These results indicated that M-MJA could regulate the renin-angiotensin-aldosterone system, improve endothelial function, and inhibit CYP4A activity to reduce the production of 20-HETE, alleviate the oxidative stress disorder of the visceral organs, and eventually exert antihypertensive effect. Additionally, the anti-oxidant ability, regulating the renin-angiotensin-aldosterone system and improving endothelial function of M-MJA are more powerful than that of MJA, suggesting that M-MJA may have a better anti-hypertensive effect than MJA.

Application of four-dimensional flow MRI in hemodynamic study of autogenous arteriovenous fistula in renal dialysis patients / 上海交通大学学报（医学版）

Objective · To investigate the feasibility of four-dimensional flow MRI (4D flow MRI) in evaluating the hemodynamics of forearm autologous arteriovenous fistula (AVF) in renal dialysis patients. Methods · Forty-five patients from Renal Division of Renji Hospital, Shanghai Jiao Tong University School of Medicine were included. Patients with forearm AVF underwent ultrasonography and MRI. The consistency of 4D flow MRI hemodynamic parameters measured by two radiologists and hemodynamic parameters at the same plane of AVF by 4D flow MRI and ultrasonography were analyzed by paired t test. The morphological parameters of AVF were acquired from black blood sequence, and they were used for Pearson correlation analysis with the hemodynamic parameters obtained from 4D flow MRI. Results · Forty-two patients completed the forearm AVF ultrasonography and MRI successfully.Paired t test showed that the consistency of 4D flow MRI hemodynamic parameters by two radiologists was good (all P=0.000), and all hemodynamic parameters measured by 4D flow MRI and ultrasonography were in good agreement (r=0.292-0.569, all P＜0.05) except for the peak flow velocity at anastomosis (r=-0.078, P＞0.05). Pearson correlation analysis showed that the cephalic venous flow volume of AVF was correlated with the diameter ratio of the cephalic venous to radial artery and the anastomosis area (r=-0.671, r=0.482, both P＜0.05), and the wall shear stress (WSS) near the anastomosis was correlated with the anastomosis angle and wall thickness (r=0.530, r=0.462, both P＜0.05). Conclusion · 4D flow MRI can be used to evaluate the hemodynamic parameters of forearm AVF in renal dialysis patients, which can provide a reference for further study of AVF dysfunction.

Pyruvate dehydrogenase activity and pyruvate dehydrogenase kinase 4 expression in skeletal muscle of end-stage renal disease patients / 上海交通大学学报（医学版）

Objective·To explore the changes of pyruvate dehydrogenase (PDH) activity and pyruvate dehydrogenase kinase 4 (PDK4) expression in the end-stage renal disease (ESRD) patients' skeletal muscles. Methods·Skeletal muscle samples were collected from non-chronic kidney disease (non-CKD) patients and ESRD patients. PDH activity was detected by ELISA assay. Real-time qPCR was performed to examine gene transcription levels of PDK1-PDK4 and PDH subunits.Western blotting analysis was used to detect protein expression levels of PDK1 and PDK4. Results·There were no demographic differences between two groups of patients. Plasma creatinine and urea nitrogen were significantly elevated in ESRD group (both P<0.05), while estimated glomerular filtration rate, hemoglobin and plasma albumin in ESRD group were significantly lower than those in non-CKD group (all P<0.05).Skeletal muscle PDH activity in ESRD group was markedly lower than that in non-CKD group(P=0.014).There were no differences in PDK1-PDK4 and PDH subunits mRNA transcription levels between ESRD and non-CKD group.PDK4 protein expression was significantly higher than that in non-CKD group (P=0.000). Conclusion·The decreased PDH activity in ESRD patients' skeletal muscle may be related to up-regulation of PDK4.

Assessment of volume status in maintenance hemodialysis patients / 上海交通大学学报（医学版）

Objective · To assess volume status in maintenance hemodialysis (MHD) patients.Methods · Body composition analysis was performed on 128 MHD patients from Renji Hospital,Shanghai Jiao Tong University School of Medicine.The volume status was assessed based on body composition data and predialysis systolic blood pressure (preBPsys),edema grade,brain natriuretic peptide (BNP).Patients were divided into hyperhydrated group (percentage of hydration status,HS％＞ 15％) or normohydrated group (HS％ ≤ 15％).Body composition data were compared,including lean tissue index (LTI) and fat tissue index (FTI).The blood pressure,edema grade,serum calcium,serum phosphate,intact parathyroid hormone (iPTH),hemoglobin,albumin,pre-albumin,hypersensitive C-reactive protein (hs-CRP),serum sodium,and urea clearance Kt/V were compared between two groups.Results · Sixtynine patients were normohydrated and preBPsys reached target;10 patients were overhydrated with higher preBPsys;18 patients had overhydration but preBPsys was in target range.Compared to normohydraed group,patients in hyperhydmted group had more obvious edema,higher BNP level,significantly lower LTI,serum albumin and pre-albumin levels,while serum sodium was significantly higher (P＜0.05).Conclusion· Volume status of hemodialysis patients can be objectively and accurately assessed by body composition analysis using bioimpedance technique with blood pressure,edema grade and biochemical parameters.Hyperhydrated patients may have higher serum sodium level,lower serum albumin,lower hemoglobin,and less lean tissue mass concomitantly.Sodium intake control,nutrition status improvement,and anemia correction may be useful to reduce hyperhydration.

Clinical study of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis of hepatitis B / 中国生化药物杂志

Objective To investigate the clinical efficacy of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis with hepatitis B virus. Methods 100 cases of decompensated cirrhosis of hepatitis B in our hospital (February 2015 to October 2016) were randomly divided into control group and experimental group, each with 50 cases. The control group was treated with adefovir dipivoxil, and the experimental group was treated with entecavir and adefovir dipivoxil. The clinical symptoms of the two groups were compared and analyzed. Results After treatment, the level of ALT in the experimental group was (46.20±3.21) U/L, and the level of AST was (52.40±3.90) U/L.The level of ALT in the control group was (70.43±10.90) U/L, and the level of AST was (70.33±9.19)U/L, and the two groups had statistical significance (P＜0.05). The negative rate of HBV-DNA in the experimental group was 76.0%, which was significantly higher than that in the control group (58.0%), and there was statistical difference (P＜0.05). The negative rate of HBeAg in the two groups was 22.0% and 24.0% respectively, and there was no significant difference. Conclusion Entecavir and adefovir dipivoxil in the treatment of hepatitis B liver cirrhosis patients clinical effect is ideal,can significantly improve the liver function, improve clinical symptoms, high safety, has clinical significance.

Clinical study of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis of hepatitis B / 中国生化药物杂志

Objective To investigate the clinical efficacy of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis with hepatitis B virus. Methods 100 cases of decompensated cirrhosis of hepatitis B in our hospital (February 2015 to October 2016) were randomly divided into control group and experimental group, each with 50 cases. The control group was treated with adefovir dipivoxil, and the experimental group was treated with entecavir and adefovir dipivoxil. The clinical symptoms of the two groups were compared and analyzed. Results After treatment, the level of ALT in the experimental group was (46.20±3.21) U/L, and the level of AST was (52.40±3.90) U/L.The level of ALT in the control group was (70.43±10.90) U/L, and the level of AST was (70.33±9.19)U/L, and the two groups had statistical significance (P＜0.05). The negative rate of HBV-DNA in the experimental group was 76.0%, which was significantly higher than that in the control group (58.0%), and there was statistical difference (P＜0.05). The negative rate of HBeAg in the two groups was 22.0% and 24.0% respectively, and there was no significant difference. Conclusion Entecavir and adefovir dipivoxil in the treatment of hepatitis B liver cirrhosis patients clinical effect is ideal,can significantly improve the liver function, improve clinical symptoms, high safety, has clinical significance.

Activation of Kupffer cell and related signal pathway proteins in the liver of high fat and high fructose diet induced NAFLD mice / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression of F4/80, NF-kappaB, p-AKT, AKT in the liver of nonalcoholic fatty liver disease (NAFLD) mice. To determine the role of Kupffer cells (KCs) in the development of NASH (non-alcoholic steatohepatitis), and understand the pathogenic mechanism of NASH.</p><p><b>METHODS</b>Five C3H/HeN mice fed with normal diet were served as controls, while fifteen fed with high fat, high fructose, high fat combined fructose diet respectively for 16 weeks were as NAFLD mice models. The liver inflammation and hepatic damage were examined, and the expression of F4/80, NF-Kb, p-AKT, AKT and the content of lipid in the liver were also detected.</p><p><b>RESULTS</b>Chronic intake of high fat and 30% fructose solution caused a significant increase in hepatic steatosis in animals in comparison to water controls. Liver F4/80 and NF-kappaB were significantly higher in high fat and high fat combined fructose diet fed mice than that in controls (P < 0.01, P < 0.01), F4/80 protein were higher in high fat diet treated mice than those in fructose and high fat combined fructose groups (P < 0.01, P < 0.01). Markers of insulin resistance (e. g, hepatic phospho-AKT, AKT) were only altered in fructose-fed or high fat combined fructose animals (P < 0.01, P < 0.01).</p><p><b>CONCLUSION</b>High fat and fructose diet may induce NAFLD in C3H/HeN mice. Kupffer cells and signal pathway proteins were activated, and they may play key roles in the initiation and progression of NASH.</p>

The effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells.</p><p><b>METHODS</b>RAW2647 mice mononuclear macrophage leukemia cells were observed. The tested group was interfered by Tlr4-mus-1567 RNA which had the best result confirmed by QPCR, cells interfered by Negative Control RNA as NC group, and normal cell as control. We perform the phagocytosis test on each group.</p><p><b>RESULTS</b>The tested group has lower phagocytes percentage than control (17.67% +/- 3.51% vs 32.00% +/- 3.00%, P < 0.01), and lower phagocytic index (46.33% +/- 7.51% vs 82.00% +/- 6.08%, P < 0.01).</p><p><b>CONCLUSIONS</b>Decreased phagocytic activity was observed on Kupffer cells by RNA interference.</p>

Development of multicolour real time PCR for detection of drug resistance mutation in hepatitis B virus / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To set up a rapid method for detection of drug resistance mutation in HBV, based on multicolour real time PCR. To detect the mutation of blood serum, which were collected from patients.</p><p><b>METHOD</b>To establish two reaction systems, each reaction system contains four resistance loci. On the new multicolor real time PCR method, the sensitivity and specificity were analysed, and detecting the drug resistant mutation of blood serum collected from 30 cases patients.</p><p><b>RESULTS</b>Construction of a multicolor fluorescence PCR for detection drug resistance in HBV was constructed, better specificity, sensitivity analysis of up to 1 x 10(3) copies/ml. Sample of 30 cases were detected, there were 2 YVDD (6.67%), 1 YIDD (3.33%), and there were 5 cases of 1896 variation, accounting for 16.67%. Other sites were not detected mutations.</p><p><b>CONCLUSION</b>The multicolor real time PCR detection system could be used for rapid and simple analysis of drug resistance for the clinical hospital. The 1986 mutation in HBV pre-C region are relatively high.</p>

Study on the changes of the T-lymphocyte subsets and their significance in influenza A (H1N1) virus patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the changes of T-Lymphocyte and activated T-Lymphocyte subsets in influenza A (H1N1) virus patients.</p><p><b>METHODS</b>The percentages of the subsets of Lymphocyte were detected by flow cytometry in influenza A (H1N1) virus patients (n = 144) and normal controls (n = 41). Furthermore, the subsets of T-Lymphocyte and activated T-lymphocyte were analyzed in 83 among those patients before and after treatment.</p><p><b>RESULTS</b>Compared with the control group, the counts of Lymphocyte in patients with influenza A (H1N1) virus was significantly discreased, the counts of Lymphocyte in patients with influenza A virus concurrent pneumonia was significantly discreased those of no concurrent pneumonia; Compared with the control group, the percentage of T-lymphocyte in patients with influenza A virus concurrent pneumonia was significantly discreased. The counts and percentage of CD3 and CD8 cells was significantly discreased in patients (n = 83) before treatment; The counts of CD4 cells was significantly discreased before treatment. The percentage of HLA-DR+ CD+, HLA-DR+ CD4+ and HLA-DR+ CD8+ cells was significantly discreased in patients (n = 83) before treatment.</p><p><b>CONCLUSIONS</b>To understand the expression of the T-Lymphocyte and activated T-Lymphocyte subsets in influenza A (H1N1) virus patients may help to evaluate the patients' cellular immune status, but also be a guideline of early diagnosis of Influenza A (H1N1) virus.</p>

The expression of CD95 and activated antigens in peripheral blood lymphocyte subsets in patients with hand foot and mouth disease (HFMD) / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression of CD95 and special marker for activation of peripheral blood lymphocytes in patients with hand foot and mouth disease (HFMD) and its significance.</p><p><b>METHODS</b>Immunofluorescent two-color flow cytometry was used to study the expression of CD95 and HLA-DR on lymphocytes in 58 patients with HFMD and 34 normal controls.</p><p><b>RESULTS</b>Expression of CD3+ T cells was significantly lower in patients (63.82 +/- 7.74)% than that in controls (P < 0.001), meanwhile the expression of CD4+ T cells was (34.29 +/- 7.33)%, significantly lower than that of the controls (P < 0.005). The percentage of lymphocytes expressing HLA-DR in patients was (23.77 +/- 5.78)%, significantly higher than that of the controls (P < 0.005). Significant difference was observed in the expression of HLA- DR on CD8+ T cells in patients (1.34 +/- 1.12)% as compared with controls (P < 0.005). No significant difference in the expression of CD95 on lymphocytes was observed between patients and the controls (P > 0.05).</p><p><b>CONCLUSION</b>The findings support that cellular immunodeficiency exists in patients and that lymphocytes were abnormally activated in the patients. The activation of peripheral blood T lymphocytes in patients mainly involves CD8 subset and it may play an important role in the immune response to antiviral infection.</p>