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.

Impact of assisted reproductive technology on birth weight discordance in twins / 中国当代儿科杂志

OBJECTIVES@#To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT).@*METHODS@#A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis.@*RESULTS@#A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05).@*CONCLUSIONS@#ART is not associated with the risk of BWDT.

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Analysis of the impact of health management measures for entry personnel on imported Dengue fever in Guangdong Province, 2020-2022 / 中华流行病学杂志

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.

Patient-reported outcome measures and value-based medicine in paediatrics: a timely review

Healthcare delivery is moving towards a more personalised and patient-centric approach. There is now an appropriate emphasis on providing value in our healthcare system. Patient-reported outcome measures (PROMs) assess our patients' perceptions of the status of their health and quality of life, measured over a period of time. PROM is an integral component of a value-driven and value-based healthcare system and is key if we want to practise value-based medicine. In paediatrics and child health, PROMs, if implemented well with appropriate measurement tools that are regularly updated and validated in a self-learning healthcare ecosystem, will help to enhance personalised healthcare delivery and collectively improve the health of the community at large. This review covers the role of PROMs in paediatrics, as well as their role in value-based medicine.

Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort / 中华预防医学杂志

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

Analysis on characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive after discharge in Guangdong Province / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive in anal and/or throat swabs after discharge during the domestic imported epidemic stage in Guangdong Province in early 2020. Methods: The COVID-19 confirmed cases with the onset time before March 1, 2020 in Guangdong Province were collected to analyze the demographic data, epidemiological characteristics, and specimen collection and testing data after discharge. Logistic regression model was used for influencing factors analysis of re-positive cases. Results: A total of 1 286 COVID-19 confirmed cases were included, the M(Q1,Q3) of age was 44(32,58)years, 617 cases were male, 224 cases were re-positive in anal and/or throat swabs with the re-positive rate 17.42%. The M(Q1,Q3) of age of re-positive cases was 35(23, 50) years, which was younger than that of re-negative cases age was those 46(33, 59) years (P<0.001). With the increase of age, re-positive rate decreased (χ2trend=52.73, P<0.001). 85.27% (191/224) of re-positive cases were found in 14 d after discharge, the duration time of re-positive status was 13(7, 24) d, and 81.69% (183/224) of re-positive cases were re-tested negative in 28 d after re-positive date. No fever and other symptoms had been observed among re-positive cases during the whole follow-up. No secondary infectious cases had been found among close contacts after 14 d of centralized isolation and sampling screening. Univariate logistic regression model analysis revealed that the influencing factors of the re-positive cases included age, occupation, clusters, clinical types, and admission time. Multivariate logistic regression model analysis revealed that age was an independent risk factor. Conclusions: SARS-CoV-2 viral nucleic acid re-positive is found in COVID-19 confirmed cases after discharge in Guangdong Province. Most re-positive cases are confirmed among 14 d after discharge and re-test to negative among 28 d after re-positive date. Age is an risk factor for re-positive cases after discharge.

Advances in natural products that target the tumor microenvironment / 药学学报

The tumor microenvironment (TME), a dynamic and complex local environment, interacts with the tumor cells and is closely related to tumor growth, metastasis, immune escape and drug resistance. Thus, targeting the TME has been a worldwide focus in cancer therapy. Many natural products possess the advantages of multiple targets, multiple pathways and wide pharmacological functions, and are the main source of antitumor drugs. In recent years studies have found that some natural products had advantageous effects on the TME. In this review, we summarize the components and functions of the TME and some natural products that target the TME, with references to the drug therapy of cancer.

Clinical Observation on Effect of Toujie Quwen Granules in Treatment of COVID-19 / 中国实验方剂学杂志

Objective:To analyze the clinical efficacy of traditional Chinese medicine（TCM） Toujie Quwen granules in the treatment of coronavirs disease-2019（COVID-19） in the early stage, and its effect on relevant inflammatory index expression of COVID-19. Method:A total of 65 COVID-19 cases were diagnosed and divided into 2 groups: the treatment group （n=32） and the control group （n=33）. Before and after treatment，TCM syndrome score，WBC，LYM，LYM%，NEU%，PCT，CRP and D-dimer were compared. Result:After 10 days of treatment，the TCM syndrome score of the treatment group was significantly reduced（P<0.05），while the absolute value of lymphocyte was up-regulated，with statistically significant differences（P<0.05）， according to the inter-group comparison, there were statistically significant differences in the absolute value of LYM and NEU%（P<0.05）. There was no significant difference in WBC count and LYM%. The levels of CRP，PCT and D-dimer in the two groups were reduced after treatment，with statistically significant differences between two groups （P<0.05）. After treatment，the differences of CRP and PCT was statistically significant between both groups（P<0.05），but the difference in D-dimer was not statistically significant. There was no difference in the effect of chest CT examination between the both groups. Conclusion:The clinical syndrome and inflammatory particles of COVID-19 can be alleviated by early and timely use of Toujie Quwen granules.

Expression of Treg/Th17 Cells in Patients with HBV-ACLF in Different Traditional Chinese Medicine Syndrome " Yanghuang-Yinyanghuang-Yinhuang" / 中国实验方剂学杂志

Objective::To detect the expression levels of peripheral blood Treg/Th17 cells and related cytokines in patients with Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) with different traditional Chinese medicine (TCM) syndrome " Yanghuang-Yinyanghuang-Yinhuang" , in order to explore the cellular immunological characteristics of different TCM syndromes of liver failure. Method::The 32 cases of patients with HBV-ACLF in early, middle and late stages in line with the " Yanghuang-Yinyanghuang-Yinhuang" TCM syndrome grouping were selected. Flow cytometry was used to detect the frequency expression of Treg/Th17 cells in peripheral blood. The expression levels of interleukin-10(IL-10), transforming growth factor-β(TGF-β), interleukin-17A(IL-17A), tumor necrosis factor-α(TNF-α) and interleukin-23(IL-23) were detected by cytometric bead array (CBA). The expressions of transcription factor forkhead box P3(FoxP3) and retinoid-related orphan nuclear receptor-γt(ROR-γt) mRNA were detected by Real-time PCR. The SPSS 20.0 software was applied in data statistics and processing to analyze the expression characteristics of Treg/Th17 cells and related cytokines in patients with different TCM syndrome types of HBV-ACLF. Result::The patients with HBV-ACLF Yanghuang syndrome were mainly distributed in the early stage of liver failure, those with Yinyanghuang syndrome were mainly distributed in the middle stage, and those with Yinhuang syndrome were distributed in the late stage. From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the frequency of Treg and Th17 cells gradually increased, and the differences among the groups were statistically significant (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, Treg cytokines IL-10, TGF-β gradually increased, and the differences among the groups were statistically significant (P<0.05). Th17 cytokines IL-17A, TNF-α, IL-23 gradually increased, of which IL-17A were differences between Yanghuang syndrome and the Yinyanghuang syndrome, as well as Yanghuang syndrome and Yinhuang syndrome (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the expression of FoxP3 was gradually decreased, while that of ROR-γt was gradually increased, and the differences among the groups were statistically significant (P<0.01). Conclusion::There is a certain correlation between the different course of early, middle and late stages of HBV-ACLF and the distribution of TCM syndromes. The frequency of Treg and Th17 cells and the correlation of IL-17A, TGF-β and IL-10 with TCM syndrome differentiation are related, suggesting that Treg and Th17 cells have a certain reference value for the diagnosis of patients with HBV-ACLF and the syndrome differentiation of TCM syndromes.

Determination of Sugar,Fructose,Mannose and Glucose in Shenxiong Glucose Injection by UPLC-MS/MS / 中国实验方剂学杂志

Objective: To establish a method for determining arabinose, mannose, fructopyranose and amylaceum in Shenxiong glucose injection by UPLC-MS/MS, so as to provide the basis for the scientific evaluation of the quality of Shenxiong glucose injection, and lay a foundation for the safe use of drugs in clinic. Method: Domestic GDX-403 solid-phase extraction column was used to purify Waters ACQUITY UPLC BEH Xbridge Amide column (2.1 mm×100 mm, 1.7 μm)at the column temperature of 35℃, and the mobile phase was 0.1% ammonia, 0.1% acetonitrile-0.1% ammonia water and water 85:15. The contents of arabinose, mannose, fructose and glucose in Shenxiong glucose injection were determined by UPLC-MS/MS with a flow rate of 0.3 mL·min-1. Result: A method was established to determine arabinose, mannose, fructopyranose and amylaceum in Shenxiong glucose injection. The concentration range of arabinose, mannose, fructopyranose and amylaceum showed a good linear relationship with the peak area, with a good repeatability and precision. Recoveries were 98.43%, 102.13%, 100.72%, 101.75%, and RSD were 2.4%, 1.3%, 3.1%, 2.7%. Arabinose and mannose content were stable in five batches of Shenxiong glucose injection. Conclusion: The method is simple and specific. Compared with the determination of total sugar, the method is more scientific and stable, and can be used for the quality control of Shenxiong glucose injection.

Suanzaoren Tang Exerts Neuroprotective Effect by Inhibiting Hippocampal Neuroinflammation in APP/PS1 Double Transgenic Mice / 中国实验方剂学杂志

Objective:To observe the effect of Suanzaoren Tang on hippocampal neuroinflammation in APP/PS1 mice and to explore its possible mechanism of neuroprotection. Method:The mice were randomly divided into blank group, model group, donepezil group(0.92 mg·kg-1), Suanzaoren Tang low and high-dose groups(12.96,25.92 g·kg-1). After 30 days of continuous administration in each group, pathological changes of dentate gyrus (DG) in hippocampus of mice in each group were observed by Nissl staining.The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum of each group were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of TNF-α and IL-1β in hippocampus of each group. The expression levels of glial fibrillary acidic protein (GFAP) and ionic calcium binding protein 1 (IBA1) in hippocampus of each group were detected by immunohistochemical staining (ICH) and Western blot. Result:Compared with blank group, the granule cells in DG region were unevenly arranged in model group, with obvious cell loss, and the nissl bodies in some neurons disappeared or condensed, serum TNF-α and IL-1β content significantly increased (Pα and IL-1β mRNA expression quantity significantly increased (PPα and IL-1β in the serum were decreased(PPα and IL-1β mRNA in the hippocampus were decreased(PPPPConclusion:Suanzaoren Tang can improve neuronal loss in APP/PS1 double transgenic mice, and its mechanism may be related to the regulation of hippocampal neuroinflammation in mice.

A new phenolic glycoside from honey-fried Eriobotrya japonica / 中国中药杂志

A total of twelve compounds were isolated from the ethyl acetate of the water extract of honey-fried Eriobotrya japonica through column chromatography over silica gel,Sephadex LH-20,RP-18,and preparative HPLC. Their structures were established by MS,1 D NMR and 2 D NMR data as japonicanoside A( 1),nerolidol-3-O-α-L-rhamnopyranosyl-( 1→2)-β-D-glucopyranoside( 2),nerolidol-3-O-α-L-rhamnopyranosyl-( l→4)-α-L-rhamnopyranosyl-( 1 → 2)-[α-L-( 4-trans-feruloyl)-rhamnopyranosyl-( 1 → 6) ]-β-D-glucopyranoside( 3),( +)-catechin( 4),(-)-epicatechin( 5),kaempferol 3-O-α-L-rhamnopyranoside( 6),quercitrin( 7),quercetin-3-O-β-D-galactopyranoside( 8),quercetin-3-O-β-glucopyranoside( 9),vanillin( 10),protocatechuic aldehyde( 11),and maltol( 12). Among them,1 is a new phenolic glycoside.

Chemical constituents from root barks of Dictamnus dasycarpus and their cytotoxic activities / 中国中药杂志

Nineteen compounds, including kihadanin D (1), obacunone (2), kihadanin A (3), kihadanin B (4), kihadanin C (5), limonin (6), evodol (7), fraxinellone (8), furo[2,3-b]quinolin-4-ol (9), preskimmianine (10), ifflaiamine (11), dictamnol (12), naringenin (13), diosmetin (14), wogonin (15), scopoletin (16), cleomiscosin A (17), apocynin (18), and methyl pyroglutamate (19), were isolated from the methanol extract of the root barks of Dictamnus dasycarpus by using various column chromatographies. Their chemical structures were extensively determined on basis of UV, IR, NMR, MS, and CD spectroscopic data analyses. Among them, 1 is a new limonoid, 9 was isolated from plant kingdom for the first time, 11, 13-14 and 17-19 were obtained from the genus Dictamnnus for the first time. Cytotoxicities of compounds 1-18 were tested, and the results indicated that 1 exhibited cytotoxicities against three human cancer cell lines MDA-MB-231, A549 and HT29 with IC₅₈ values of 16.22, 21.72 and 31.06 μmol·L⁻¹, respectively.

Chemical and cytotoxic constituents of Zanthoxylum nitidum / 中国中药杂志

Ten compounds were isolated from the methanol extract of Zanthoxylum nitidum through silica gel, Sephadex LH-20, RP-18 and HPLC chromatography techniques. Their structures were elucidated by the MS and NMR spectra as zanthonitidine B(1), cyclo-(Leu-Leu-Leu-Leu-Ile)(2),6S-10-O-demethylbocconoline(3), liriodenine(4), isoplatydesmine(5), 5, 5'-dimethoxylariciresinol(6), syringaresinol (7), episyringaresinol (8), marmesin (9) and syringaldehyde (10). Among them,1 is a new alkaloid,2 is a cyclopentapeptide isolated from plant kingdom for the first time, and 3 is from the genus Zanthoxylum for the first time. Compounds 3 and 4 exhibited cytoxoxicity against three human cancer cell lines HT29, A549 and MDA-MB-231 with IC₅₈ values of 27.37, 24.10, 33.58 μmol·L⁻¹ and 9.12,6.05, 11.35 μmol·L⁻¹, respectively.

Mass spectrometry guided strategy based on feature fragment ions for guided-separation on quinoline alkaloids from root barks of Dictamnus dasycarpus / 中国中药杂志

The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.

Chemical constituents from roots and rhizomes of Rubia oncotricha and their cytotoxic activities / 中国中药杂志

Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time. Cytotoxic and nematicidal activities of all these compounds were evaluated, and the results showed that only 4, 6, 11 and 12 exhibited cytotoxicities against A549, SGC-7901 and HeLa cancer cell lines. The IC₅₀ of 6 were 19.42, 2.74, 8.07 μmol·L⁻¹, respectively.

Network pharmacology deciphering multiple mechanisms of volatiles of Wendan granule for treatment of senile dementia / 中国药理学与毒理学杂志

OBJECTIVE To explore the mechanisms of the volatiles of Wendan granule for the treatment of senile dementia,network pharmacology method integrating absorption,distribution,metab-olism, and excretion (ADME) screening, target fishing, network constructing, pathway analyzing, and correlated diseases prediction was applied. METHODS Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2%,and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and then the corresponding targets, genes, pathways and diseases were predicted according to the data provided by TCMSP,DrugBank,Uniport and the Database for Annotation,Visualization and Integrated Discovery(DAVID).The related pathways and correlation analysis were explored by the Kyoto Encyclo-pedia and Genomes (KEGG) database. Finally, the networks of compound-target, target-pathway and pathway-disease of WDG were constructed by Cytoscape software. RESULTS Twelve compounds interacted with 49 targets, of which top three targets were Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), Prostaglandin G/H synthase 2 (PGHS-2) and Sodium-dependent noradrenaline transporter.Interestingly,these targets were highly associated with depression,insomnia and Alzheimer′s disease that mainly corresponded to mental and emotional illnesses. CONCLUSION The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of volatiles of WDG for relieving senile dementia related syndromes,which will also facilitate the application of traditional Chinese medicine in modern medicine,as well as follow-up studies such as upgrading the quality stan-dard of clinical medicine and novel drug development.

Effects of Alcohol Dependence or Withdrawal on Median Effective Dose of Propofol in Rats / 中国药房

OBJECTIVE:To determine the median effective dose (ED50) of propofol with single intravenous injection in alcohol dependence or withdrawal model rats,and to observe the anaesthetic effect of 2-fold ED50 propofol. METHODS:Fifty SD rats were divided into drinking group(n＝23)and control group(n＝27)based on whether the consumption of alcohol was greater than 3.0 g/(kg·d). Drinking group continued to drink freely and intermittently to establish alcohol dependence model. Control group was only given drinking water for ethanol elution 16 rats were randomly selected from each group to determine ED50 of propofol with single intravenous injection by sequential method,and initial dose was 6.02 mg/kg. After eluting for a week,alcohol dependence rats stopped drinking for 24 hours and had alcohol withdrawal symptoms to establish alcohol withdrawal model. ED50 of propofol in alcohol withdrawal group and control group were determined with same method. After eluting for a week,anaesthetic effect [disappearance time and reappearance time of forepaw righting reflex(FRR),time of activity complete recovery] of 2-fold ED50 propofol with single intravenous injection were observed in alcohol dependence group,alcohol withdrawal group and control group,and corresponding time point and the frequency of respiration before administration were also observed. Changes of liver function indexes(serum albumin,alanine transaminase,total bilirubin,γ glutamyl transaminopeptidase)and liver histomorphology were observed 48 h after medication,10 in each group. RESULTS:ED50 of propofol in alcohol dependence model rats was 9.563 mg/kg,which was higher than 5.623 mg/kg of control group. ED50 of propofol in alcohol withdrawal model rats was 4.086 mg/kg,which was lower than 5.297 mg/kg of control group. Compared with control group,reappearance time of FRR was prolonged significantly in alcohol dependence group and alcohol withdrawal group (P＜0.05). There was no statistical significance in disappearance time of FRR or activity complete recovery time (P＞0.05). The frequency of respiration during FRR disappearance was lower than before propofol injection,FRR reappearance and activity complete recovery (P＜0.01). After intravenous injection of 2-fold ED50 propofol,reappearance time of FRR in alcohol dependence group and alcohol withdrawal group were longer than control group(P＜0.05)；the alcohol dependence group was longer than the alcohol withdrawal group(P＜0.05).The time of activity complete recovery in alcohol dependence group was longer than control group and alcohol withdrawal group (P＜0.05). The frequency of respiration in 3 groups during FRR disappearance were all lower than before propofol injection,FRR reappearance and activity complete recovery(P＜0.01). There was no significant difference in the change of liver function indexes or liver histomorphology. CONCLUSIONS:ED50 of propofol is increased in alcohol dependence rats,while ED50 of propofol is decreased in alcohol withdrawal rats. 2-fold ED50 of propofol has no significant toxicity to liver function.

Relationship between serum cystatin C and cognitive impairment in patients with acute cerebral infarction / 中华行为医学与脑科学杂志

Objective To explore the correlation between serum cystatin C (CysC) and cognitive function and executive function in patients with acute cerebral infarction.Methods A total of 103 patients with acute cerebral infarction were selected in clinical research.Based on the Montreal cognitive assessment scale (MoCA),patients were divided into cognitive impairment group and normal cognitive group.The levels of serum CysC and MoCA subtypes were compared between the two groups,and the correlation between cystatin C and cognitive function was analyzed.According to the level of serum CysC,the patients were divided into low-level group and middle-high level group.The relationship between CysC and executive function was further investigated by Stroop test.Results CysC was a risk factor of cognitive impairment in the acute phase after cerebral infarction (OR=8.855,95％CI=1.674-46.841,P=0.010),and the level of CysC was negatively correlated with MoCA score (r=-0.509,P=0.001).In each of the MoCA subproject,the scores of the cognitive impairment group (clock drawing:0 (0,1),connection:0 (0,0),copying the cube:0 (0,0)) were lower in clock drawing,connection,and copying the cube than that of the normal cognitive group(clock drawing:3 (2,3),connection:1 (0,1),copying the cube:1 (1,1)) (P＜ 0.05).The difference of task C between low-level CysC group and middle-high level group was statistically significant(P＜0.05).The level of CysC was negatively correlated with amount of interference in correct response(r=-0.471,P＜0.05),and positively correlated with amount of interference in reacting time(r=0.796,P＜0.05).Conclusion Serum CysC is a risk factor of cognitive impairment in acute cerebral infarction.The higher the level of CysC,the more serious cognitive impairment,and cognitive impairment mainly manifested as executive function impairment.