Effect of Electroacupuncture Added to Pelvic Floor Muscle Training in Women with Stress Urinary Incontinence: A Randomized Clinical Trial.

BACKGROUND: Pelvic floor muscle training (PFMT) is a first-line conservative therapy for stress urinary incontinence (SUI). Electroacupuncture (EA) has been used to treat SUI recently. OBJECTIVE: To compare the effectiveness of PFMT + EA versus PFMT + sham EA for SUI in women. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, randomized, controlled clinical trial was conducted at four hospitals in China involving 304 women with SUI from May 20, 2014 to November 21, 2017. Data were analyzed from April 20 to December 21, 2018. INTERVENTION: Participants were randomized to receive 8 wk of PFMT+ EA (n = 154) or PFMT + sham EA (n = 150). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the change in the amount of urine leakage measured on a 1-hr pad test. Student's t test, the χ2 test, and the Wilcoxon rank-sum test were used for data analysis. RESULTS AND LIMITATIONS: Among the 304 participants randomized, 286 completed the study. The mean age was 57.6 yr (standard deviation [SD] 8.9) for the PFMT + sham EA group and 57.2 yr (SD 9.1) for the PFMT + EA group. The mean urine leakage at baseline was 13.6 g for the PFMT + sham EA group and 13.9 g for the PFMT + EA group. After the 8-wk intervention, the PFMT + EA group had a greater decrease in mean urine leakage (-9.8 g) than the PFMT + sham EA group (-5.8 g) with a mean difference of 4.0 g (95% confidence interval [CI] 0.8-7.2). Significantly more patients experienced a ≥50% reduction in urine leakage and the mean number of incontinence episodes in 24 h in the PFMT + EA group than in the PFMT + sham EA group (26.3%, 95%CI 15.8-36.8%). The PFMT + EA group experienced better improvement in participant-reported SUI severity at 6 wk (p < 0.001) and 8 wk (p < 0.001) and self-evaluated therapeutic effects at 2-32 wk (p < 0.001) after the intervention. Lack of measurement of the amount of urine leakage during follow-up is a limitation. CONCLUSIONS: In this randomized clinical trial, 8-wk combined treatment with PFMT + EA led to a greater improvement in SUI symptoms and better outcomes than with PFMT + sham EA. PATIENT SUMMARY: We evaluated the effectiveness and safety of pelvic floor muscle training combined with electroacupuncture for stress urinary incontinence in women, Our results show that this is a promising therapeutic approach for the treatment of stress urinary incontinence.

Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis-associated Th17/Treg imbalance.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis-derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis-related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP-induced bone marrow-derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL-1ß release as well as the protein level of NLRP3, caspase-1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS-induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside-treated foecal bacterium into flora-depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.

Effect of Narrative Nursing on Family Resilience and Psychosocial Adaptation of Middle-Aged Patients with Breast Cancer.

Patients with breast cancer frequently experience psychological distress. This study aimed to investigate the effect of narrative nursing on middle-aged patients with breast cancer. In all, 82 patients with breast cancer admitted to the Affiliated Hospital of Nantong University were divided into two groups, namely, the observation group and the control group, by simple random sampling, with 41 cases in each group. The patients in both groups were treated with breast cancer surgery. Additionally, the control group received routine nursing, whereas the observation group received narrative nursing based on the control group. After 8 weeks of nursing, the SAS (self-rating anxiety scale) and SDS (self-rating depression scale) scores in the observation group were lower than those in the control group (P < 0.01). At the same time, the result of family hardiness showed that the patients with narrative nursing performed better in commitment, challenge, and control (P < 0.01). In conclusion, narrative nursing can alleviate the postoperative shame and negative emotions of patients with breast cancer and improve their quality of life.

Polyrhachis vicina Roger Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Through the EGR1/BACE1/APP Axis.

Memory deficits and loss are the earliest and most prominent features of Alzheimer's disease (AD). This study was aimed to clarify the mechanistic basis of an active fraction of Polyrhachis vicina Roger (AFPR) on the memory abilities of AD rat models, which involves early growth response 1 (EGR1) expression and ß-secretase 1 (BACE1)-mediated deposition of amyloid ß peptide (Aß). An AD rat model was developed by Aß25-35, which was further treated with AFPR alone or in combination with lentiviral EGR1. The Morris water maze test and HE and Fluoro-Jade C staining were adopted to observe the memory behaviors, hippocampus neuron morphology, and Aß deposition. Aß25-35-induced SK-N-SH and HT22 neurons were subjected to AFPR for in vitro experiments on neuronal viability and apoptosis. AFPR improved the impaired memory function, preserved the neuron structure, and suppressed Aß deposition in AD rat models. Further, the expression of APP pathway-related proteins was downregulated by AFPR in both rat and cellular models. Moreover, AFPR inhibited the Aß25-35-induced neuronal apoptosis. AFPR suppressed the expression of EGR1, downregulated the BACE1 expression via impeding the binding of EGR1 to the BACE1 promoter, and thus blocked the activation of the APP signaling, ultimately protecting neurons. Notably, the aforementioned effects of AFPR were in a concentration-dependent manner; among three doses, 3.65, 15.6, and 30 mg/(kg·d), high-dose AFPR exhibited the most appreciable effects. In conclusion, AFPR inhibited the BACE1 expression by repressing the binding of EGR1 to the promoter of BACE1, thereby suppressing the Aß deposition and improving the memory function of AD rats.

[Acupuncture combined with western medication in treatment of type 2 diabetes mellitus with angina pectoris of coronary heart disease: a randomized controlled study].

OBJECTIVE: To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication. METHODS: A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet ß cell function [homeostasis model assessment-ß (HOMA-ß), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups. RESULTS: After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all lower than those in the medication group (P<0.05). The values of HOMA-ß, ISI, CO and LVEF after treatment were higher than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all higher than those in the medication group (P<0.05). The total effective rate was 93.8% (60/64) in the acupuncture plus medication group, higher than 79.4% (50/63) in the medication group (P<0.05). CONCLUSION: The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet ß cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.

CoQ10 improves meiotic maturation of pig oocytes through enhancing mitochondrial function and suppressing oxidative stress.

Coenzyme Q10 (CoQ10) is essential to many fundamental biological processes. However, the effect of CoQ10 on meiotic maturation of pig oocytes still remains elusive. In the present study we aimed to understand the effects of CoQ10 on porcine oocyte maturation, by supplementing different concentrations of CoQ10 (25, 50 and 100 µM) into the maturation medium. We showed that CoQ10 at 50 µM had better capacity to promote the nuclear maturation of pig oocytes derived from both small and large antral follicles. Though the cleavage and blastocyst rates of parthenotes stayed stable, 50 µM CoQ10 treatment could accelerate the development of parthenotes to blastocyst stage, and increase the average cell number of blastocyst. For cumulus-oocyte complexes from large antral follicles categorized by the brilliant cresyl blue (BCB) test, 50 µM CoQ10 treatment could specifically promote the nuclear maturation of poor-quality oocytes in the BCB-negative group. Mitochondrial function of oocytes treated by 50 µM CoQ10 could be boosted, through increasing the levels of mitochondrial membrane potential, ATP production and CoQ6, and changing the pattern of mitochondrial distribution as well. Moreover, 50 µM CoQ10 treatment suppressed the level of reactive oxygen species and reduced the percentage of oocytes with early apoptosis signal. Taken together, CoQ10 could improve the meiotic maturation of pig oocytes, especially for poor-quality oocytes, mainly through enhancing mitochondrial function and suppressing oxidative stress to reduce apoptosis.

Disturbance in biosynthesis of arachidonic acid impairs the sexual development of the onion blight pathogen Stemphylium eturmiunum.

The formation of sexual fruiting bodies for plant pathogenic fungi is a key strategy to propagate their progenies upon environmental stresses. Stemphylium eturmiunum is an opportunistic plant pathogen fungus causing blight in onion. This self-fertilizing filamentous ascomycete persists in the soil by forming pseudothecia, the sexual fruiting body which helps the fungus survive in harsh environments. However, the regulatory mechanism of pseudothecial formation remains unknown. To uncover the mechanism for pseudothecial formation so as to find a practical measure to control the propagation of this onion pathogen, we tentatively used DNA methyltransferase inhibitor 5-azacytidine (5-AC) to treat S. eturmiunum. 5-AC treatment silenced the gene-encoding monoacylglycerol lipase (magl) concomitant with the presence of the inheritable fluffy phenotype and defectiveness in pseudothecial development. Moreover, the silence of magl also resulted in a reduction of arachidonic acid (AA) formation from 27 ± 3.1 µg/g to 9.5 ± 1.5 µg/g. To correlate the biosynthesis of AA and pseudothecial formation, we created magl knockdown and overexpression strains. Knockdown of magl reduced AA to 11 ± 2.4 µg/g, which subsequently disabled pseudothecial formation. In parallel, overexpression of magl increased AA to 37 ± 3.4 µg/g, which also impaired pseudothecial formation. Furthermore, exogenous addition of AA to the culture of magl-silenced or magl knockdown strains rescued the pseudothecial formation but failed in the gpr1 knockdown strain of S. eturmiunum, which implicates the involvement of AA in signal transduction via a putative G protein-coupled receptor 1. Thus, AA at a cellular level of 27 ± 3.1 µg/g is essential for sexual development of S. eturmiunum. Disturbance in the biosynthesis of AA by up- and down-regulating the expression of magl disables the pseudothecial development. The specific requirement for AA in pseudothecial development by S. eturmiunum provides a hint to curb this onion pathogen: to impede pseudothecial formation by application of AA.

Ascorbic acid induces global epigenetic reprogramming to promote meiotic maturation and developmental competence of porcine oocytes.

L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 µM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes. AA2P treatment caused methylation erasure in mature oocytes on nucleic acids (5-methylcytosine (5 mC) and N 6 -methyladenosine (m6A)) and histones (Histone H3 trimethylations at lysines 27, H3K27me3), but establishment of histone H3 trimethylations at lysines 4 (H3K4me3) and 36 (H3K36me3). During the global methylation reprogramming process, levels of TET2 (mRNA and protein) and Dnmt3b (mRNA) were significantly elevated, but simultaneously DNMT3A (mRNA and protein), and also Hif-1α, Hif-2α, Tet3, Mettl14, Kdm5b and Eed (mRNA) were significantly inhibited. Our findings support that ascorbic acid can reprogram the methylation status of not only DNA and histone, but also RNA, to improve pig oocyte maturation and developmental competence.

Novel Phellodendri Cortex (Huang Bo)-derived carbon dots and their hemostatic effect.

AIM: To explore the hemostatic effect of Phellodendri Cortex-derived carbon dots. MATERIALS & METHODS: Transmission electron microscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, fluorescence spectroscopy, x-ray photoelectron spectroscopy and a cell counting kit-8 assay were studied. Hemostatic effect of Phellodendri Cortex Carbonisatus-carbon dots (PCC-CDs) was studied in mouse bleeding models. To explore their related hemostatic mechanism, coagulation parameters and platelets were measured. RESULTS: The PCC-CDs ranged in diameter from 1.2 to 4.8 nm and had a quantum yield of 9.62%. They exhibited no toxicity up to concentrations of 1000 µg/ml. After administration, mice had a significantly shortened bleeding time and coagulation parameters and platelets significantly increased. CONCLUSION: These results showed the definite hemostatic effect of PCC-CDs.

Novel carbon dots derived from Schizonepetae Herba Carbonisata and investigation of their haemostatic efficacy.

Schizonepetae Herba Carbonisata (SHC) has been used in traditional Chinese medicine (TCM) to treat haemorrhagic diseases for more than 1000 years. However, little information is available on its haemostatic components and mechanism. In this study, we developed novel water-soluble carbon dots (CDs) in aqueous extracts of SHC for the first time and a modified pyrolysis method was used to prepare the SHC using Schizonepetae Herba (SH) as the sole precursor. The SHC-CDs were characterized using transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis) and fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and high-performance liquid chromatography (HPLC). Furthermore, the CDs with a quantum yield (QY) around 2.26% exhibited no toxicity within approximately 0.84 mg/mL in the CCK-8 assay. More interestingly, tail haemorrhaging and liver haemorrhaging experiments showed that CDs-treated mice had significantly shorter bleeding time than did normal saline (NS)-treated control group. Coagulation assays suggested that SHC-CDs could stimulate the extrinsic blood coagulation system and activate the fibrinogen system. These results suggested that SHC-CDs possess a remarkable haemostatic property, which provides evidence to support the further investigation of the considerable potential and effective material basis of TCM.

Hemostatic bioactivity of novel Pollen Typhae Carbonisata-derived carbon quantum dots.

BACKGROUND: Pollen Typhae Carbonisata (PTC) is a type of calcined herb drug that has been used as a hemostatic medicine to promote hemostasis for thousands of years. In this study, we discovered and separated novel water-soluble carbon quantum dots (CQDs, named PTC-CQDs) from aqueous extracts of PTC. These PTC-CDs were characterized using transmission electron microscopy (TEM) and high-resolution TEM, as well as Fourier transform infrared, ultraviolet-visible, and fluorescence spectroscopy. Then, we assessed the anti-hemorrhagic effects and related hemostatic mechanisms of the obtained PTC-CQDs. RESULTS: The PTC-CQDs separated from PTC are spherical, monodisperse, and have a narrow size distribution between 2 and 8 nm. In the pharmacology experiment, remarkable anti-hemorrhage effects of PTC-CQDs were revealed. Additionally, the rats showed a profound decrease in activated partial thromboplastin time and increase in fibrinogen and PLT after PTC-CQDs treatment. CONCLUSIONS: These results indicated the explicit hemostasis effect of PTC-CQDs, which not only provided a new idea for the material research of PTC, but have also provided new insights into potential biomedical and healthcare applications of CQDs in the field of haemorrhage control and laid a solid foundation for future drug discovery.

Novel carbon quantum dots from egg yolk oil and their haemostatic effects.

In this study, the properties of egg yolk oil (EYO) were investigated. Water extraction, dialysis, and ultrafiltration were used to extract and purify EYO, and microscopy, spectrophotometry, and chromatography were used to identify carbon dots (CDs) present in EYO (EYO CDs). Morphology analyses demonstrated that CDs were almost spherical, with an average size of <10 nm, a lattice spacing of 0.267 nm, and a composition of mainly C, O, and Fe. The solution showed bright blue fluorescence at 365 nm. Tail haemorrhaging and liver haemorrhaging experiments showed that CD-treated mice had significantly shorter bleeding times than did control mice. Coagulation assays suggested that EYO CDs stimulate the intrinsic blood coagulation system and activate the fibrinogen system. Thus, EYO CDs possess the ability to activate haemostasis, which may lead to further investigations of this ingredient of traditional Chinese medicine.

Effects of oil extracts of Eupatorium adenophorum on Phytophthora capsici and other plant pathogenic fungi in vitro.

The antifungal activity of oils extracted from Eupatorium adenophorum was tested against five phytopathogens in vitro. Oil extracts inhibited the mycelial growth of Phytophthora capsici which causes phytophthora blight in pepper. The minimum inhibitory concentration of oils against P. capsici was 500µg/ml after 7days incubation. At the ultrastructural level, oil extracts caused complete disorganization of intracellular organelles, cytoplasm depletion, disruption of cytoplasmic membranes and the cell wall. Membrane permeability increased with the increasing concentration of oil extracts. These results suggested that these oil extracts exhibited multiple modes of action including disruption of the cell membrane system. Furthermore, oil extracts combined with synthetic fungicides synergistically inhibited mycelial growth of P. capsici, which creates the possibility of reducing fungicide concentration needed to successfully control phytophthora blight in commercial pepper production. This study's use of multiple methods of analysis has increased our understanding of the mode of action of E. adenophorum oil extracts against P. capsici.

Development of Fluorescence-Linked Immunosorbent Assay for Icariin.

We have been looking for a faster and simpler method for traditional Chinese medicine and natural product assay. In this study, we developed a fluorescent immunoassay approach to detect icariin (ICA) using a fluorescently labelled monoclonal antibody. The ICA-specific antibody was purified by the caprylic acid-ammonium sulphate method and then labelled with rhodamine B isothiocyanate (RBITC). Subsequently, an indirect competitive fluorescence-linked immunosorbent assay (icFLISA) was developed to detect ICA using RBITC-labelled anti-ICA MAbs. The RBITC-labelled monoclonal antibody was highly specific for ICA. The fluorescence assay demonstrated an effective ICA measurement range of 1.28 ng/mL to 20 µg/mL (R2 = 0.9946) with relative standard deviations below 10% for both intra-assay and inter-assay repeatability and precision. This icFLISA for ICA is simple, rapid, and sensitive, with a 20-fold greater linear range and a 10-fold lower limit of detection than with the previously developed indirect competitive enzyme-linked immunosorbent assay (ELISA). Thus, this study establishes a useful method for detecting ICA, enabling in vivo visualization research. In the future, FLISA can be also used to assay the concentrations of ICA in biological samples, as well as to investigate the pharmacokinetics of ICA in different tissues to explore the targets of ICA in vivo.

Oils extracted from Eupatorium adenophorum leaves show potential to control Phythium myriotylum in commercially-grown ginger.

Oils extracted from the leaves of Eupatorium adenophorum were tested in vitro and in vivo against the soilborne pathogen Pythium myriotylum which causes soft rot, a devastating disease of commercial ginger production in China. Twelve compounds accounting for 99.15% of the total oil composition were identified by GC-MS. The major components were 10Hß-9-oxo-agerophorone (37.03%), 10Hα-9-oxo-agerophorone (37.73%) and 9-oxo-10, 11-dehydro-agerophorone (23.41%). Antifungal activity was tested by the poisoned food technique against P. myriotylum, indicating minimum inhibitory concentrations of 100µg/ml after 7 days incubation. In addition, the oil extracts greatly inhibited the formation of both wet and dry mycelial biomass. The combination of E. adenophorum oil extracts and synthetic fungicides showed a strong synergistic effect, inhibiting the mycelial growth in in vitro assays. The synergistic effect of oil extracts with fungicides could allow fungicides to be used at reduced rates in the future which has environmental advantages. Oil extracts applied at 160 and 200µg/ml concentrations to ginger rhizomes before inoculation with P. myriotylum significantly reduced the infection rate in ginger. Examination by light and transmission electron microscopy revealed that oil extracts caused swelling of the hyphae, disruption of the cell wall, degradation of the cytoplasmic organelles and shortening of the cytoplasmic inclusion. These results suggested that the plasma membrane and endomembrane systems of P. myriotylum were severely damaged by the oil extracts of E. adenophorum which offer significant potential for use as a fungicide to control P. myriotylum.

A sensitive and specific indirect competitive enzyme­linked immunosorbent assay for the detection of icariin.

In the present study, a novel monoclonal antibody (MAb) specific for icariin (ICA) was prepared and characterized. A hybridoma­secreting MAb against icariin was produced by fusing splenocytes immunized with an ICA­bovine serum albumin conjugate with a hypoxanthine­aminopterin­thymidine­sensitive mouse myeloma SP2/0 cell line. The antibody showed high specificity for ICA with almost no cross­reactivity against the majority of structurally­related chemicals. Subsequently, an indirect competitive enzyme­linked immunosorbent assay (ELISA) for ICA was established and characterized. In this assay, an effective measuring range of 10­1,000 ng/ml of ICA (R2=0.9828) was detected. Intra­ and inter­assay repeatability and precision were achieved with a relative standard deviation (RSD) of <10%. A mean recovery of 95­115% was obtained, with an RSD of <10%. In addition, the levels of ICA in traditional Chinese herbal prescriptions were determined, and correlation between the ELISA and high­performance liquid chromatography analyses of total ICA was obtained. These results demonstrated that a reliable ELISA method had been successfully developed to determine ICA in traditional Chinese herbs and may contribute to further clinical investigations.

[Advance in studies on long-circulating tumor targeted compound preparations].

Tumor has long been a hard-nut problem in the world medical field. The effect of the conventional drugs is very limited because of the intervention of multiple micro-environmental factors during the occurrence and progression of tumors. With the characteristics of high efficiency, low toxicity and multi-targets synergistic effect, the long-circulating tumor targeted compound preparations show its unique advantages in improving tumor microenvironment and enhancing the therapeutic effect of treatment, thus it has gradually become a hotspot of studies both at home and abroad. Through consulting a great number of professional literatures at home and abroad in recent years, the authors summarized the current studies in vitro and in vive on long-circulating tumor targeted compound preparations in different carriers, in the expectation of providing new ideas and methods for the development of long-circulating tumor targeted compound preparations.

Novel linear and step-gradient counter-current chromatography for bio-guided isolation and purification of cytotoxic podophyllotoxins from Dysosma versipellis (Hance).

Dysosma versipellis (Hance) is a famous traditional Chinese medicine for the treatment of snakebite, weakness, condyloma accuminata, lymphadenopathy, and tumors for thousands of years. In this work, four podophyllotoxin-like lignans including 4'-demethylpodophyllotoxin (1), α-peltatin (2), podophyllotoxin (3), ß-peltatin (4) as major cytotoxic principles of D. versipellis were successfully isolated and purified by several novel linear and step gradient counter-current chromatography methods using the systems of hexane/ethyl acetate/methanol/water (4:6:3:7 and 4:6:4:6, v/v/v/v). Compared with isocratic elution, linear and step-gradient elution can provide better resolution and save more time for the separation of photophyllotoxin and its congeners. Their cytotoxicities were further evaluated and their structures were validated by high-resolution electrospray TOF MS and nuclear magnetic resonance spectra. All components showed potent anticancer activity against human hepatoma cells HepG2.

Effects of HMG-CoA reductase inhibitor on experimental autoimmune myocarditis.

PURPOSE: Myocarditis is an acute inflammatory disease of the heart and is often a precursor of dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. The purpose of this study was to investigate the therapeutic role of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on the development of EAM. METHODS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with murine cardiac α-myosin heavy chain (MyHc-α(614-629) [Ac-SLKLMATLFSTYASAD-OH]). High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) rosuvastatin or vehicle was administered orally by gastric gavage to mice with EAM from day 0 to day 21 after immunization. On day 21 after immunization, echocardiography was carried out and the severity of myocarditis was detected by histopathological evaluation. Levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured by ELISA. Histopathology was performed using haematoxylin and eosin. With apoptosis examined by Tunel, the expression of active caspase-3 in myocardium was investigated by immunohistochemistry. RESULTS: Rosuvastatin attenuated the histopathological severity of myocarditis. Cardiac function was improved in the two rosuvastatin-treated groups compared to the non-treated EAM group (LVFS: high-dose rosuvastatin group [group H], 0.38 ± 0.10%; low-dose rosuvastatin group [group L], 0.34 ± 0.06%; non-treated EAM group [group N], 0.29 ± 0.07%. LVEF: group H, 0.80 ± 0.09%; group L, 0.71 ± 0.07%; group N, 0.68 ± 0.07%). Furthermore, treatment with rosuvastatin decreased the expression levels of TNF-α (group H, 65.19 ± 7.06 pg/ml; group L, 108.20 ± 5.28 pg/ml; group N, 239.34 ± 11.65 pg/ml) and IL-6 (group H, 14.33 ± 2.15 pg/ml; group L, 19.67 ± 3.04 pg/ml; group N, 40.39 ± 7.17 pg/ml). The rates of expression of active Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology. CONCLUSIONS: These results demonstrate that administration of rosuvastatin can ameliorate EAM progression, inhibit apoptosis of cardiomyocytes, and preserve cardiac output, and they also suggest rosuvastatin may be a promising novel therapeutic strategy for the clinical treatment of myocarditis.