Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia.

CONTEXT: Obstructive sleep apnoea (OSA) causes chronic intermittent hypoxia (CIH), which results in mitochondrial dysfunction and generates reactive oxygen species (ROS) in the heart. Excessive free iron could accelerate oxidative damage, which may be involved in this process. Banxia-Houpu decoction (BHD) was reported to improve the apnoea hypopnoea index in OSA patients, but the specific mechanism was still unclear. OBJECTIVE: To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function. MATERIALS AND METHODS: C57BL/6N mice were randomly divided into control, CIH and BHD groups. Mice were exposed to CIH (21 - 5% O2, 20 times/h, 8 h/d) and administered BHD (3.51, 7.01 and 14.02 g/kg, intragastrically) for 21 d. Cardiac and mitochondrial function, iron levels, apoptosis and mitophagy were determined. RESULTS: BHD (7.01 g/kg) significantly improved cardiac dysfunction, pathological change and mitochondrial structure induced by CIH. BHD increased the Bcl-2/Bax ratio (1.4-fold) and inhibited caspase 3 cleavage in CIH mice (0.45-fold). BHD activated mitophagy by upregulating Parkin (1.94-fold) and PINK1 (1.26-fold), inhibiting the PI3K-AKT-mTOR pathway. BHD suppressed ROS generation by decreasing NOX2 (0.59-fold) and 4-HNE (0.83-fold). BHD reduced the total iron in myocardial cells (0.72-fold) and mitochondrial iron by downregulating Mfrn2 (0.81-fold) and MtFt (0.78-fold) proteins, and upregulating ABCB8 protein (1.33-fold). Rosmarinic acid, the main component of Perilla Leaf in BHD, was able to react with Fe2+ and Fe3+ in vitro. DISCUSSION AND CONCLUSIONS: These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

Diagnosis and treatment of pleomorphic rhabdomyosarcoma of the uterus: a rare case report and review of the literature.

Pleomorphic rhabdomyosarcomas of the uterus (PRMSu) is a rare malignant tumor of the female genital tract. Accurate diagnosis and effective treatment of PRMSu are important. We report an 81-year-old woman who was diagnosed with PRMSu. She had an extremely unusual presentation of secondary dyspnea because of an extremely large uterus (26.0 cm). Pelvic magnetic resonance imaging showed rare severe enlargement and intrauterine filling with tumor tissue, and she was initially diagnosed with uterine leiomyosarcoma. The patient underwent hysterectomy, as well as bilateral salpingo-oophorectomy and omentectomy, and was finally confirmed as having PRMSu by histopathology combined with immunohistochemistry. We performed a systematic review of the literature between 1982 and 2020 and focused on different treatment strategies and prognosis of PRMSu. A retrospective review of 28 cases was conducted and survival analysis was estimated by using the Kaplan-Meier method. We found that the accuracy of diagnosis of PRMSu completely depends on histopathology and immunohistochemistry because of no special clinical symptoms, no sensitive tumor markers, and no special imaging findings. Although there is no standardized approach for treating this rare disease, the treatment strategy of a surgical operation combined with adjuvant chemotherapy appears to be the best choice.

[Correlation study on non-volatile ingredients of Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS].

To establish the method for determining non-volatile ingredients of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isochlorogenic acid A, rosmarinic acid, ferulic acid, rutin, luteoloside, isoquercitrin, hesperidin, diosmin, diosmetin, luteolin, acacetin and linarin in Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS, and analyze the correlation of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces. Shim-pack GIST C_(18) column(2.1 mm×100 mm, 2 µm) was adopted with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution at the flow rate of 0.4 mL·min~(-1). The column temperature was set at 35 ℃. The quantitative analysis was performed using the electrospray ionization source and the multiple reaction monitoring. The linear relationship, resolution, repeatability and recovery of the 16 chemical components all met the requirements. The 16 non-volatile ingredients in traditional herbal pieces of Menthae Haplocalycis Herba could be tracked in formula granules. There were certain differences of the 16 chemical components among Menthae Haplocalycis Herba formula granules of different manufacturers and traditional herbal pieces of different producing areas. The UPLC-MS/MS method was simple, rapid and accurate, and could be used for the quality control of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces.

[Comparison of eleven active components in Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicero japonica by UPLC].

This present study aims to establish a UPLC method for simultaneously determining eleven components such as new chlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,artichoke,isochlorogenic acid A,isochlorogenic acid B,isochlorogenic acid C,rutin,hibisin and loganin in Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica and comparing the differences in the contents of phenolic acids,flavonoids and iridoid glycosides of Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.The method was carried out on an ACQUITY UPLC BEH C18column(2.1 mm×100 mm,1.7 µm) by a gradient elution using acetonitrile and 0.1% phosphoric acid.The flow rate was 0.3 mL·min-1.The column temperature was maintained at 30 ℃.The sample room temperature was 8 ℃.The wavelength was set at 326 nm for new chlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,artichoke,isochlorogenic acid A,isochlorogenic acid B and isochlorogenic acid C,352 nm for rutin and lignin,and 238 nm for loganin.The injection volume was 1 µL.The eleven components has good resolution and was separated to baseline.Each component had a wide linear range and a good linear relationship(r≥0.999 6),the average recovery rate(n=9) was 98.96%,100.7%,97.24%,97.06%,99.53%,96.78%,98.12%,95.20%,95.12%,100.2%,98.61%and with RSD was 2.5%,1.4%,1.9%,2.1%,1.7%,1.9%,1.6%,2.0%,1.4%,2.2%,2.0%,respectively.Based on the results of the content determination,the chemometric methods such as cluster analysis and principal component analysis were used to compare the Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.The results showed that Lonicerae Japonicae Flos and leaves of Lonicera japonica were similar in the chemical constituents,but both showed chemical constituents difference compored to Lonicerae Japonicae Caulis.The established multi-component quantitative analysis method can provide a reference for the quality control of Lonicerae Japonicae Flos,Lonicerae Japonicae Caulis and leaves of Lonicera japonica.

Clinical features and early treatment effects in intermediate risk and poor risk acute myeloid leukemia with EVI1 positive / 北京大学学报(医学版)

Objective:To investigate the clinical biological characteristics of EVI1 positive acute myeloid leukemia (AML) and its effect on early chemotherapy.Methods:The clinical and biological characteristics of 33 AML patients with EVI1 positive were retrospectively analyzed in 361 AML patients who were diagnosed and treated in our institute from March 2015 to July 2016,and the clinical and biological features,and rates of the induced remission were compared between the intermediate risk and poor risk with EVI1 positive AML,moreover,the influential factors on complete remission (CR) were analyzed.The expression of EVI1/ABL was tested in 32 healthy donors to confirm the abnormal threshold of EVI1 expression.Results:The definition of EVI1 positive was that the quantitative expression of EVI1/ABL was more than 8.0％.The 33 AML patients with EVI1 positive were found in 361 newly diagnosed AML patients,in which the female and male patients were 17 and 16 respectively,the median age was 45 (18-67) years,with a median follow-up of 6.6 (0.7-13.2) months.Intermediate karyotype was found in 17 patients (including 9 patients with normal karyotypes,1 patient with + 8);unfavorable karyotype was found in 14 patients [including 7 patients with-7/7q-,4 patients with t (v;11q23),3 patients with inv (3)/t (3;3),and 2 patients without mitotic figures].The rate of CR in the first induction chemotherapy was 42.4％,and the rate of total CR was 60.6％.According to the NCCN,16 intermediate risk patients and poor risk patients were divided,without favorable risk patients.The rate of CR in the first induction chemotherapy were 68.8％ and 17.6％ (P =0.005) in the intermediate risk and poor risk respectively,that of total CR were 81.3％ and 41.2％ (P =0.032),and the rates of relapse were 7.7％ and 14.3％.Univariable analysis revealed that unfavorable karyotype could affect the rate of CR in the first reduction chemotherapy and that of total CR (P =0.004,0.029).The poor risk patients had higher mortality (41.2％ vs.6.3％,P =0.039) and lower overall survival (OS) (P =0.012).Conclusion:EVI1 may be not an independent prognostic factor for the AML patients considering the appearance in the intermediate and poor risk patients.It predicts poor outcome in the EVI1 positive AML patients who have unfavorable karyocytes,such as-7/7q-,t (v;11 q23),and inv (3)/t (3;3),and also a low rate of both CR in the first induction chemotherapy and total CR.It also has a low rate of long-term survival and high mortality in the AML patients with EVI1 positive,who may benefit from allogeneic bone marrow transplantation as soon as possible.

[An overview of effects of traditional medicine on pharmacokinetics of western medicine].

Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem. Herb-drug interactions have been extensively investigated worldwide, and there is an increasing concern about the clinical herb-drug interaction. In this review we introduced the current progress in the herb-drug interactions including evidence-based clinical studies and establishment of levels of evidence for herb-drug interaction; and in the related mechanisms including the induction and inhibition of metabolic enzymes, inhibition and induction of transport and efflux proteins, alteration of gastrointestinal functions, and alteration in renal elimination. We also analyzed both the achievements and the challenges faced in the concomitant administration of traditional Chinese medicine and western medicine.

(-)Doxazosin is a necessary component for the hypotensive effect of (±)doxazosin during long-term administration in conscious rats.

AIM: Doxazosin is a racemic mixture of (-)doxazosin and (+)doxazosin that is currently used as an add-on therapy for hypertension. In this study we investigated the contribution of each enantiomer to the hypotensive action of long-term administration of (±)doxazosin in conscious rats. METHODS: Blood pressure of conscious SD rats was measured using a volume pressure recording system. The rats were orally administered (-)doxazosin, (+)doxazosin, or (±)doxazosin (8 mg·kg(-1)·d(-1)) for 12 weeks. Plasma concentrations of the agents were analyzed with HPLC. The effect of the agents on α1-adrenoceptor was examined in isolated rat caudal artery preparations. RESULTS: Treatment of conscious rats with a single dose of (±)doxazosin (8 mg/kg) did not affected DBP and MBP, but significantly decreased SBP by 11.9% 4 h after the administration. Long-term treatment of conscious rats with (±)doxazosin significantly decreased SBP, DBP and MBP with a maximal decrease of SBP by 29.3% 8 h after the last administration. The rank order of the hypotensive actions caused by long-term treatment in conscious rats was (±)doxazosin>(+)doxazosin>>(-)doxazosin. However, the pKB values for inhibiting NA-induced contraction of isolated rat caudal artery were (+)doxazosin (8.995)>(±)doxazosin (8.694)>(-)doxazosin (8.032). The plasma concentrations of (-)doxazosin, (+)doxazosin, and (±)doxazosin were 18.26±3.55, 177.11±20.66, and 113.18±13.21 ng/mL, respectively, 8 h after the last administration of these agents. CONCLUSION: Long-term treatment with (±)doxazosin produces potent hypotensive action in conscious rats that seems to result from synergic interaction of the two enantiomers.

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats, dogs and humans in vitro.

AIM: (±)Doxazosin is a long-lasting inhibitor of α1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. METHODS: Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. RESULTS: Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [(-)doxazosin: 89.4%-94.3%; (+)doxazosin: 90.9%-95.4%]. (+)Doxazosin exhibited significantly higher protein binding capacities than (-)doxazosin in all the three species, and the difference in the bound concentration (Cb) between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog>human>rat. CONCLUSION: (-)Doxazosin and (+)doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.

[Determination of doxazosin enantiomers in rat plasma and investigation of their chiral inversion].

The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.8 mL x min(-1) was done. The fluorescence detection was set at lambda(Ex) = 255 nm and lambda(Em) = 385 nm. Prazosin was used as the internal standard. (-) Doxazosin or (+) doxazosin added into rat plasma in vitro was determined after incubating in 37 degrees C water bath for 2, 5 and 10 days. (-) Doxazosin or (+) doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng x mL(-1). The average recovery for (-) doxazosin was 99.5% with RSD 3.6%, and for (+) doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between (-) doxazosin and (+) doxazosin in the rat.