Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Research progress in global digital mental health services for adolescents / 中国学校卫生

Abstract@#The increasing fragile and vulnerable adolescents mental health determines the increasing demand for psychological health services among teenagers, which indicates the inadequacy of traditional mental health service models. This article summarizes the necessity of digital mental health services for adolescents, and then lists the application examples of digital mental health services across the world, aiming to provide reference for digital mental health services among Chinese adolescents.

Comparison of Cyclosporine A and Cyclosporine A Combined with Corticosteroid in the Treatment of Acquired Pure Red Cell Aplasia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA).@*METHODS@#The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms.@*RESULTS@#96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05).@*CONCLUSION@#CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy / 中国天然药物

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

The effect of radiotherapy on survival in newly-diagnosed metastatic head and neck squamous cell carcinoma(HNSCC) / 中华放射肿瘤学杂志

Objective:To evaluate the survival outcomes of radiotherapy in patients with newly-diagnosed metastatic head and neck squamous cell carcinoma (HNSCC) based on data from the Surveillance, Epidemiology and End Results (SEER) database.Methods:A total of 1226 patients newly-diagnosed with metastatic HNSCC between 2010 and 2015 were selected from the SEER database. There were 762 patients (62.1%) in the radiotherapy group and 464 patients (37.9%) in the non-radiotherapy group. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS) and overall survival (OS). The effect of radiotherapy on survival was assessed by Cox multivariate regression and Propensity score-matched analyses (PSM). According to the results of multivariate analysis, the patients were further divided into low-, intermediate- and high-risk groups, and the effect of radiotherapy on survival was analyzed in different risk groups.Results:The median CSS and OS time of the whole group was 11.0 months and 10.0 months, respectively. For patients in the radiotherapy group and non-radiotherapy group, the median CSS time was 13.0 months and 6.0 months, and the median OS time was 12.0 months and 6.0 months, respectively. Multivariate analysis showed that age (CSS, P=0.045;OS, P=0.002), primary tumor site (CSS, P=0.021;OS, P<0.001), T stage (CSS, P=0.001;OS, P=0.002), N stage (CSS, P=0.002;OS, P<0.001), number of metastatic organs (CSS, P<0.001;OS, P<0.001), surgery (CSS, P<0.001;OS, P<0.001), radiotherapy (CSS, P<0.001;OS, P<0.001), and chemotherapy (CSS, P<0.001;OS, P<0.001)were the independent prognostic factors. After PSM, patients with and without radiotherapy in the low-,intermediate-,and high-risk groups, the 3-year CSS rates were 62.5% vs 23.5%( P=0.008), 22.4% vs 15.7%( P=0.001)and 10.5% vs 9.6%( P=0.203), respectively; the 3-year OS were 58.0% vs 20.8%( P=0.002), 19.8% vs 12.7%( P=0.001)and 7.0% vs 6.1%( P=0.166), respectively. Conclusion:Radiotherapy significantly improves CSS and OS in the low- and intermediate-risk groups, but patients in the high-risk group do not benefit from radiotherapy.

Cross-sectional study of association between dietary pattern and cognitive performance in people aged 50 and above years in Shanghai / 中华流行病学杂志

Objective: To investigate the association between dietary pattern and cognitive performance in local residents aged ≥50 years in Shanghai. Methods: Data were obtained from the second round of Study of Global Ageing and Adult Health (SAGE) survey in Shanghai. Dietary patterns were surveyed by factor analysis. Cognitive tests were conducted to assess subjects' cognitive performance, including verbal recall, verbal fluency and digit test. Multiple linear regression analysis was used to evaluate the relationship between dietary patterns and cognition performance. Results: A total of 4 132 subjects with complete dietary and cognitive performance test data were included. Factor analysis was used to obtain three dietary patterns: including plant-based pattern, high animal-food pattern, high salt-oil pattern. After controlling for gender, age, education level and other factors, it was found that plant-based pattern (β=0.26,95%CI: 0.17-0.36) and high animal-food pattern (β=0.18, 95%CI:0.06-0.29) were positively associated with total cognitive test score while high salt-oil pattern (β=-0.28, 95%CI:-0.85--0.07) was negatively associated with verbal fluency test score. Conclusion: A dietary pattern with high intake of plant food and appropriate intake of animal food might be associated with better cognitive function of residents aged ≥50 years.

Strategies and ideas of comprehensive development and utilization of medicine and food homologous variety Phyllanthus emblica / 中国中药杂志

Phyllanthus emblica is a kind of traditional medicine and medicinal and edible plant, with rich variety resources and high development value. It is a key poverty alleviation variety in China at present. As P. emblica processing industry is rising gradually in recent years, in order to fully develop and utilize its industrial resources, this paper systematically introduces current comprehensive development and utilization of P. emblica, discusses the problems in P. emblica processing industry, and puts forward comprehensive development and utilization strategies and industrial models in terms of cultivation, breeding, grading, quality evaluation and waste recycling, so as to provide a certain reference for promoting the high-quality development of P. emblica industry in China.

Changes in forms of Indigo Naturalis slices in ancient and modern times: a systematic study on quality of purified Indigo Naturalis and crude Indigo Naturalis / 中国中药杂志

Indigo Naturalis has a long history of medicinal use with particularity and complexity in its processing. Before the Ming dynasty,Indigo Naturalis was extracted from the top layer of zymotic fluid,called " purified Indigo Naturalis". In modern processing,the precipitate " crude Indigo Naturalis" is dried to produce Indigo Naturalis after impurity removal. The form of Indigo Naturalis slices has undergone significant changes in ancient and modern times. In view of this,the quality comparison between crude Indigo Naturalis and purified Indigo Naturalis was conducted in this study with modern analytical techniques. Firstly,chemical composition was analyzed with UPLC-Q-TOF-MS,and the chemical composition of scent with HS-SPME/GC-MS/MS. The content of indigo,indirubin,total ash,and water-soluble extract was determined as well as the inorganic composition in crude Indigo Naturalis and purified Indigo Naturalis. Then,their microscopic morphology was observed and the surface element composition was investigated. Finally,the antipyretic activities of crude Indigo Naturalis and purified Indigo Naturalis were compared in the fever rat model induced by lipopolysaccharide and 2,4-dinitrophenol. The results demonstrated that the purified Indigo Naturalis had a faster and more lasting antipyretic effect,while the crude Indigo Naturalis had almost no antipyretic effect. This study is of great significance to the research on processing technology of Indigo Naturalis and provides reference for the formulation of its quality standards,production specifications and calibration procedures.

Effect of Removing Core on Quality of Phyllanthi Fructus / 中国实验方剂学杂志

Objective:The differences of chemical compositions and pharmacological activities between the core and pulp of Phyllanthi Fructus were investigated by chemical analysis and <italic>in vitro</italic> test to explore the effect of the core on the quality of this medicinal material. Method:Literature， medicinal material standards and market research on the appearance of Phyllanthi Fructus were conducted based on existing databases. Ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to identify the constituents of the core and pulp. The analysis was performed on Thermo Scientific Accucore C₁₈ column （2.1 mm×100 mm， 2.6 μm） with the mobile phase of 0.1% formic acid aqueous solution （A）-methanol （B） for gradient elution （0-25 min， 5%B； 25-30 min， 5%-95%B； 30-35 min， 95%-5%B）， the flow rate was 0.2 mL·min^-1， heating electrospray ionization （HESI） was adopted with positive and negative ion modes， and the scanning range was <italic>m</italic>/<italic>z</italic> 100-1 500. High performance liquid chromatography （HPLC） was used to determine the contents of gallic acid， corilagin， chebulagic acid and ellagic acid in the core and pulp of Phyllanthi Fructus. Analysis was performed on Welchrom C₁₈ column （4.6 mm×250 mm， 5 μm） with mobile phase of methanol （A）-0.05% phosphoric acid aqueous solution （B） for gradient elution （0-6 min， 5%A； 6-15 min， 5%-7%A； 15-20 min， 7%-15%A； 20-25 min， 15%-21%A； 25-31 min， 21%-22%A； 31-41 min， 22%A； 41-47 min， 22%-28%A； 47-51 min， 28%-32%A； 51-57 min， 32%-38%A； 57-70 min， 38%-45%A； 70-80 min， 45%-65%A； 80-85 min， 65%-5%A）， the detection wavelength was set at 270 nm. The antibacterial effects of the core and pulp of Phyllanthi Fructus on <italic>Escherichia coli</italic> and <italic>Staphylococcus aureus</italic> were investigated by filter paper method， and their antioxidant activities were compared by 1，1-diphenyl-2-picrylhydrazyl （DPPH） free radical scavenging assay. Result:A total of 47 compounds were identified in the core and pulp of Phyllanthi Fructus， mainly including tannins， flavonoids， phenolic acids， fatty acids， amino acids， organic acids， saccharides and glycosides， most of which were concentrated in the pulp， and the fatty acids in the core accounted for a higher proportion. The contents of gallic acid， corilagin， chebulagic acid， ellagic acid and other phenolic compounds in the pulp of 20 batches of Phyllanthi Fructus were much higher than those in the core. The results of antibacterial test showed that the core of Phyllanthi Fructus with different concentrations had no antimicrobial effect. The DPPH radical scavenging test showed that the antioxidant activity of the core ［half-inhibitory concentration （IC₅₀）=199.632 mg·L^-1］ was much less than that of the pulp （IC₅₀=12.688 mg·L^-1）. Conclusion:From the perspectives of polyphenol content， antibacterial and antioxidant activities， it is scientific to use Phyllanthi Fructus pulp in ancient and modern times， which may be to remove the secondary parts of Phyllanthi Fructus， so as to enhance the actual utilization rate and therapeutic effect of medicinal materials. In view of the large proportion of the core of Phyllanthi Fructus and its high content of fatty acids and other components， whether or not to use it remains to be further studied in clinical application.

Preliminary Study on Commodity Grade Classification of Phyllanthi Fructus Based on Color Component Correlation / 中国实验方剂学杂志

Objective:To provide a scientific basis for the classification of Phyllanthi Fructus product grades. Method:A total of 30 batches of Phyllanthi Fructus currently available in the market were collected for quantification based on such appearance indexes as diameter， thickness， grain weight， and crust colour （<italic>L</italic>^*， <italic>a</italic>^*， and <italic>b</italic>^* values）. The contents of gallic acid， corilagin， chebulagic acid， and ellagic acid were measured by high performance liquid chromatography （HPLC）， followed by descriptive statistical analysis （DSA）， analysis of variance （ANOVA）， and principal component analysis （PCA） to determine the importance of each main index and explore the correlations between the appearance indexes and internal components. The classification standard of Phyllanthi Fructus product grades was formulated， and its scientificity was verified in hepatocelular carcinoma HepG2 cells. Result:The correlation analysis revealed that the crust colour <italic>L</italic>^*， <italic>a</italic>^*， and <italic>b</italic>^* values were significantly negatively correlated with corilagin， chebulagic acid， and ellagic acid （<italic>|r|</italic>>0.5， <italic>P</italic><0.01）， but irrelevant to gallic acid （<italic>|r|</italic><0.1）. Considering the variable coefficient of each index， PCA results， and the requirement of gallic acid as quality indicator for Phyllanthi Fructus in <italic>Chinese Pharmacopoeia</italic>， the crust colour <italic>L</italic>^*， <italic>a</italic>^*， and <italic>b</italic>^* values and gallic acid content were determined to be the classification indexes. The K-means cluster analysis confirmed that products with crust colour <italic>L</italic>^*<44， <italic>a</italic>^*<7， and <italic>b</italic>^*<10 and gallic acid content >1.6% could be classified into the first class， and those failing to meet the above requirements into the second class. The cell experiment demonstrated that the half-maximal inhibitory concentration （IC₅₀） of the first-class product against hepatocelular carcinoma HepG2 cells was lower than that of the second-class product. A colourimetric card was developed based on crust colour <italic>L</italic>^*， <italic>a</italic>^*， and <italic>b</italic>^* values to provide a visual tool for on-site evaluation of Phyllanthi Fructus products. Conclusion:This study has initially established the classification standard of Phyllanthi Fructus product grades， which contributes to guiding price negotiation of Phyllanthi Fructus products based on quality grade and thus ensuring high quality and high price.

Development of a novel and practical bioassay for the quality evaluation and control of Galli Gigerii Endothelium Corneum based on the detection of digestive enzyme activity / 药学学报

Galli Gigerii Endothelium Corneum (GGEC) represents digestion-promoting medicines with measurable effects and extensive clinical application. However, its effective components are not clear. The quality control index in the current edition of Chinese Pharmacopoeia is rather elementary and does not reflect its clinical efficacy. In this study, a bioassay method based on pepsin activity was proposed as a novel quality control method. With pepsin activity as the evaluation index, the extraction of GGEC was optimized and a method for the determination of biological potency was established by using the qualitative reaction parallel line method. The biological potency and consistency of 20 batches of GGEC were investigated. To provide scientific evidence in support of this bioassay method, two validation experiments were designed. One was to study the viscosity-reducing activity of a nutritional semi-solid paste after adding GGEC samples with differing potency. The other was to correlate the gastric residual rate in mice and pepsin activity with the alcohol soluble extract content. The results showed that the optimal preparation method was to dilute crude powder of GGEC with 50 volumes of water and subject to ultrasonic extraction at 300 W and 40 kHz for 0.5 h. The shape of the dose-response curve was similar to that of the positive control drug multienzyme tablets and the precision, intermediate precision and repeatability met the methodology requirements. The results showed that the potency of 20 batches of samples ranged from 13.49 to 34.69 U·mg-1, with an average value of 22.21 U·mg-1. The validation experiment demonstrated that the effect of reducing the viscosity of the nutrient paste became more significant as GGEC sample potency increased. The correlation coefficient R of gastric residual rate with pepsin potency and alcohol soluble extract content was 0.867 and 0.518, respectively, which indicated that the pepsin potency was highly correlated with in vivo activity. This study shows that a bioassay method based on pepsin activity is reliable and reproducible for GGEC and could provide reference method for the quality evaluation of other digestant herbs.

Efficacy and toxicities of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma / 中华放射医学与防护杂志

Objective:To assess the efficacy and toxicity of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL).Methods:Retrospective review was conducted for 174 patients with pathological proved early stage ENKTCL who were treated in the Department of Radiation Oncology, Peking University Cancer Hospital & Institute. The Kaplan-Meier survival analysis was adopted to calculate the local-regional control (LRC), overall survival (OS), and progression free survival (PFS), and the Log-rank test COX regression model were applied to univariate and multivariate analyses.Results:The patients in this study included 102 and 72 patients diagnosed with Ann Arbor stage-Ⅰ and stage-Ⅱ, respectively. Among them, two patients received radiotherapy alone and 172 patients were treated with combined chemoradiotherapy. The overall response rate of all the patients was 94.2%, with a complete response (CR) rate of 87.9% (153). Furthermore, the rates of 5-year OS, PFS, and LRC were 87.3%, 83.1%, and 91.9%, respectively. The most common toxicities during the chemotherapy and radiotherapy included myelosuppression and oral mucositis, with grade ≥ 3 myelosuppression and grade ≥ 3 oral mucositis accounting for 62.1% and 10.9% of all patients, respectively. As shown by multivariate analysis, the adverse prognostic factors for OS included age > 60, B symptoms, and stage Ⅱ, while the adverse prognostic factors for PFS included age > 60 and stage Ⅱ. Meanwhile, the PFS rate was significantly improved by increasing the radiation dose (≥ 50 Gy vs.<50 Gy), and the 5-year PFS rates of the two groups were 83.5% and 76.5%, respectively [hazard ratio ( HR) 0.374; 95% CI, 0.169-0.826; P=0.015]. Conclusions:A good therapeutic effect can be achieved for early stage NK/T-cell lymphoma and the toxicities after combined chemoradiotherapy can be tolerated.

Research progress of Phyllanthi Fructus and prediction of its Q-markers / 中国中药杂志

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.

Comparison of hidden blood loss between minimally invasive percutaneous locking plate fixation and intramedullary nail fixation in the treatment of tibial shaft fracture / 中国骨伤

OBJECTIVE@#To analyze and compare the hidden blood loss of minimally invasive percutaneous plate osteosynthesis(MIPPO) combined with locking plate fixation and intramedullary nail fixation in the treatment of tibial shaft fracture.@*METHODS@#One hundred and ninety-one cases of tibial shaft fracture treated from January 2017 to January 2019 were analyzed retrospectively. The patients were all treated with closed reduction and divided into two groups:group A (110 cases) and group B (81 cases). In group A, 78 males and 32 females were treated with MIPPO combined with locking plate. The age ranged from 19 to 74 (45.32±11.79) years old. According to AO classification, 42cases were type 42-A, 45 were type 42-B and 23 were type 42-C fractures. Group B was treated with intramedullary nail, including 65 males and 16 females, aged 19 to 84 (45.44± 14.32) years old. According to AO classification, there were 39 cases of type 42-A, 29 cases of type 42-B and 13 cases of type 42-C. The operation time, intraoperative blood loss and hidden blood loss were observed and compared between the two groups.@*RESULTS@#On the first day, the hidden blood loss was (155.27±47.89) ml in group A and (160.43±131.42) ml in group B, the difference was statistically significant (0.05).@*CONCLUSION@#In the treatment of tibial shaft fracture with intramedullary nail, there is obvious hidden blood loss, which is much higher than expected.

The key to fine manufacturing of liquid polyphenol preparations: the principle of multi-precipitation with steady-state reconstruction / 药学学报

Plant polyphenols have a wide range of pharmacological activities and application prospects. Liquid polyphenol preparations have special physical phases and complex chemical compositions, with problems such as poor stability and easy precipitation during production and marketing. Taking the multi-precipitation mechanism of plant polyphenol liquid preparations as an example,we discuss the chemistry and composition of the precipitation, how it forms, whether precipitationcan be controlled, and the interaction law of three precipitation approaches. An unstable mechanism model is proposed where hydrolyzed tannin hydrolysis and catechin non-enzymatic oxidative polymerization repeatedly induces associative colloid aggregation and precipitation. This study explains the complex physicochemical changes in polyphenol solutions and the microcosmic mechanism of instability in the induced system and proposes a steady state reconstruction of liquid polyphenol preparation consistent with the common law of precipitation and control. It has scientific significance for promoting the development and manufacture of high quality liquid polyphenol preparations.

Analysis of Chemical Components in Supernatant and Precipitate of Sanajon Oral Liquid Based on UPLC-Q-TOF-MSE Technology / 中国实验方剂学杂志

Objective:To analyze the main chemical components in the supernatant and precipitate of Sanajon oral liquid, so as to provide basis for establishing its quality standard and precipitation control technology. Method:UPLC-Q-TOF-MSE was used to analyze the chemical components in the supernatant and precipitate of this oral liquid. The analysis was performed on Waters ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) with the mobile phase of 0.1% formic acid solution (A) and acetonitrile (B) for gradient elution (0-1 min, 2%B; 1-2 min, 2%-5%B; 2-4 min, 5%-7%B; 4-6 min, 7%-24%B; 6-10 min, 24%-42%B; 10-12 min, 42%-54%B; 12-15 min, 54%-76%B; 15-18 min, 76%-100%B), the flow rate was set to 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 2 µL. The mass spectrographic analysis was used with electrospray ionization (ESI), sample MS data was acquired by time-dependent MSE in negative ion mode, the collection range was m/z 50-1 200 (supernatant) and m/z 50-3 000 (precipitate). Then the chemical constituents were identified by the information of retention time, accurate relative molecular mass and secondary mass spectrum fragment. Result:Totally 61 compounds were identified in the supernatant, including tannins, phenolic acids, flavonoids, amino acids, organic acids, fatty acids, etc. Totally 15 compounds were identified in the precipitate, including tannins, phenolic acids, flavonoids, fatty acids, etc. Conclusion:The hydrolyzed tannin of Sanajon oral liquid may be the potential material basis of its precipitate, and its precipitate is likely to be a complex precipitate mainly composed of ellagic acid and tanned red. The established UPLC-Q-TOF-MSE can quickly and comprehensively analyze the chemical composition of Sanajon oral liquid, which can provide a scientific basis for the researches of its material basis, precipitation mechanism and quality control.

Prescription for NAFLD Based on Relationship Between Intestinal Microecology and Spleen-stomach's Ascending and Descending Theory / 中国实验方剂学杂志

Non-alcoholic fatty liver disease (NAFLD) is a kind of metabolic stress liver injury, which has become one of most common chronic liver diseases in China and even world. Therefore, the occurrence and development of NAFLD and its prevention and treatment have been attracted more and more attention. The disturbance of intestinal microecology, especially intestinal flora, is one of important factors leading to NAFLD. The syndrome traceability, etiology and pathogenesis of nafld in traditional Chinese medicine (TCM) are related to imbalance of spleen-stomach's ascending and descending. The effect of NAFLD treatment depends on spleen-stomach's ascending and descending. The intestinal tract is main part for realizing spleen-stomach function according to principle of TCM. Intestinal flora is a regulation factor affecting host metabolism, which is consistent with biological connotation of TCM principle of spleen-stomach's ascending and descending. Because spleen-stomach's ascending and descending disorder is consistent with symptoms of intestinal flora imbalance, intestinal flora is closely related to spleen-stomach's ascending and descending in TCM. Based on modern intestinal micro-ecosystem, this paper expounds theoretical basis for treatment of NAFLD based on relationship between spleen-stomach's ascending and descending in TCM, and on that basis, ideas of prescription and medication for NAFLD were put forward, mainly including: invigorating spleen and replenishing Qi and ascending clearity, regulating Qi-flowing and regulating stomach and descending turbidity, resolving phlegm, activating blood circulation and dissipating accumulation, and dominant role in coordinating spleen-stomach's ascending and descending and intestinal microecology is highlighted in treatment of NAFLD. Soothing liver and regulating Qi, dispersing and descending lung-Qi, ascending clearity and descending turbidity, and warming and activating kidney-Yang, synergistic factors for onset of NAFLD were taken into account to promote spleen-stomach's ascending and descending functions, and therapeutic effect shall be considered from perspective of intestinal microecology. After retention enema with Chinese herbs, transporting function of large intestine might be activated to help stomach-Qi descending and coordinate spleen-stomach's ascending and descending, and intestinal microecological mechanism of drug delivery channel intervening NAFLD may be studied based on 16s rDNA gene pathway. With deepening of research on intestinal flora, relationship between it and spleen-stomach's ascending and descending and NAFLD will be further revealed, which not only inherits China's long history of applying spleen-stomach's ascending and descending to treat liver diseases, but also expand perspective of regulating intestinal microecolog(intestinal flora) in treatment of NAFLD.

Clinical Efficacy of Modified Sanzi Yangqintang and Colon Hydrotherapy on Treatment of Non-alcoholic Fatty Liver Disease with Phlegm-dampness / 中国实验方剂学杂志

Objective::To explore the clinical efficacy of modified Sanzi Yangqintang combined with colon hydrotherapy in the treatment of non-alcoholic fatty liver disease (NAFLD) with phlegm-dampness. Method::Totally 100 patients with NAFLD were selected and randomly divided into treatment group (50 cases) and control group (50 cases). Both groups were orally given silybin and glycyrrhizic acid diamine capsules.The treatment group was also added with modified Sanzi Yangqintang and colon hydrotherapy.The treatment lasted for 7 days.The control group was also added with saline colon hydrotherapy.Main traditional Chinese medicine (TCM) syndrome scores and liver function indexes before and after treatment [alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamate transpeptidase (GGT)], blood lipid routine [cholesterol (TCH), triglyceride (TG)], inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], FibroScan measurement [liver stiffness measurement (LSM), controlled attenuation parameters (CAP)], uric acid and body weight changes were observed.Adverse reactions were observed, and the patient's medication safety was evaluated. Result::TCM syndrome score, liver enzyme index, blood lipid index, inflammatory factor index, FibroScan CAP, uric acid and body weight of the two groups were significantly reduced than those before treatment(P<0.05, P<0.01) .There was no significant difference in liver enzymes, TCH, IL-6 and LSM between treatment group and control group.And TCM syndrome scores, UA, TNF-α, FibroScan CAP decreased were significantly different from control group (P<0.05). Conclusion::Modified Sanzi Yangqintang combined with colon hydrotherapy can not only alleviate NAFLD with phlegm-dampness symptoms, but also significantly reduce triglyceride, tumor necrosis factor and FibroScan CAP and body mass, with certain clinical efficacy in a short term.

Patrinia scabiosaefolia Inhibits Growth of 5-FU-Resistant Colorectal Carcinoma Cells via Induction of Apoptosis and Suppression of AKT Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of ethanol extract of Patrinia scabiosaefolia (EEPS) on chemo-resistance of colorectal cancer cells (CRC) and explore the possible molecular mechanisms.@*METHODS@#5-fluorouracil (5-FU)-resistant human colorectal carcinoma cell line (HCT-8/5-FU) and its parental cells HCT-8 were treated with EEPS (0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU (0, 100, 200, 400, 800 or 1600 μmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the cell viability. Cell density was observed by phase-contrast microscope, cell counting and colony formation assay were used to determine the cell proliferation of HCT-8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was determined by Hoechst staining. Western-blot was performed to detect the phosphorylation of AKT as well as the protein expression level of B-cell CLL/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).@*RESULTS@#Compared with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were resistant to 5-FU treatment (P0.05). Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS treatment significantly reduced cell density, cell number, inhibited cell survival (P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and 2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and Bcl-2 protein expression, and increased the expression of Bax protein (P<0.05).@*CONCLUSION@#EEPS is a promising therapeutic agent that may overcome chemo-resistance in cancer cells, likely through suppression of the AKT pathway and promotion of cancer cell apoptosis.

Effect of Manual and Machine Decocting on Chemical Constituents in Bazhentang Based on Non-targeted Metabolomics / 中国实验方剂学杂志

Objective: To evaluate the effect of manual decocting and machine decocting on the chemical constituents in Bazhentang based on non-targeted metabolomics, and to find the differential chemical constituents of these two decocting methods. Method: Bazhentang was boiled by standardized manual decocting and machine decocting methods,respectively. Orthogonal partial least square-discriminate analysis(OPLS-DA) and other multivariate statistical methods, combined with variable importance in the projection(VIP) value and t-test, were employed to analyze the effect of two decocting methods on the chemical constituents in Bazhentang. The differential chemical constituents were analyzed by UPLC-LTQ-Orbitrap MS under positive and negative ion modes,mobile phase was acetonitrile-0.1%formic acid aqueous solution for gradient elution,the scanning range was m/z 50-1 500. Result: Under the positive and negative ion modes of high-resolution mass spectrometry, a total of 87 differential components were found,40 of them were identified according to the mass spectrometry data and literature reports, including senkyunolide A, glycyrrhizin, ferulic acid, etc. Conclusion: Based on the analysis of color and chemical compositions of Bazhentang, there are obvious differences between the standardized manual decocting and machine decocting. If the advantages of these two methods are combined,a standardized decoction process can be established on the basis of maintaining the advantages of manual decocting, the effectiveness of traditional Chinese medicine decoction will be maximized and it will be convenient for patients to take it.