Ultrasound contrast agent microbubbles combined with low frequency ultrasound named as low-frequency ultrasound-targeted microbubble destruction technology has become an effective and non-invasive anti-tumor therapy for deep tumors.It can enhance the efficacies of chemotherapy,gene therapy,immunotherapy,and anti-angiogenic therapy by improving cell membrane permeability and destroying tumor neovasculature.It can be applied to sonodynamic therapy and realize multimodal synergistic therapy on the basis of nanoparticles,which increases the anti-tumor efficiency and offers a promising target therapy for tumors.
Contrast Media ; Genetic Therapy ; Humans ; Microbubbles ; Neoplasms ; Ultrasonography

OBJECTIVETo observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.

METHODSEAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.

RESULTSCompared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).

CONCLUSIONSModel rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.

Animals ; Aorta ; Cell Proliferation ; Disease Models, Animal ; Hypertension ; physiopathology ; I-kappa B Proteins ; Interleukin-6 ; Leptin ; blood ; NF-KappaB Inhibitor alpha ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Wistar ; Suppressor of Cytokine Signaling Proteins ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha

Objective To compare the effects of vitrification with slow-freezing on the developmental ability of day 3 cleavage stage embryos.Methods Patients who had no less than 4 high quality embryos were included in this study.These embryos were cryopreserved using the methods of vitrification or slow-freezing.In the eryopreserved embryo transfer cycles,the embryos which were cryopreserved using one of the methods were chosen randomly.The developmental ability of embryos was compared between these two groups.Results A total of 80 patients were included in this study with 160 embryos.In the group of slow-freezing,73(91%)embryos were survived and achieved 15(38%)clinical pregnancies.Among these,3 were twins and the implantation rate was 25%(18/73).In the group of vitrification,71(89%)embryos were survived and achieved 19(48%)clinical pregnancies.Among these, 9 were twins and the implantation rate was 39%(28/71),which was significantly higher than the slow- freezing group(P

Objective To investigate the current status of coal-burning endemic fluorosis and the fluoride content in foods and drinking water in Hongya County,Sichuan Province.Methods Dental fluorosis and urinary fluoride were suveyed in children of 8～12 years old in two schools which repectively located in Gaomiao and Wawushan Town.The adults above 20 years old underwent clinical examination.At the same time,fifty adults above 20 years old in Garden Village were chosen to take forearm and calf X-ray films to find out the evidence of skeletal fluorosis.The content of fluoride in food such as bacon,corn,dry capsicum in Sanxing Village in Gaomiao Town and Futian Village in Wawushan Town as well as drinking water in five families in Sanxing Village were determined.Results The dental fluorosis rate of children was 40.76%(161/395),the dental fluorosis index was 0.86 in Gaomiao Town.The dental fluorosis rate of children was 14.36%(82/571),the dental fluorosis index was 0.31 in Wawushan Town.The medium value of the urine fluoride was 0.81 mg/L.ranged 0.16～3.89 mg/L.The positive rate oi the clinical examination of skeletal fluorosis was 5.27%(27/512),the X-rays detective rate was 4.00%(2/50).The medium value in bacon,corn,dry capsicum were 6.00,0.64,1.49 mg/kg.The averaged content of the fluoride in drinking water(0.14±0.06)mg/L of local household was within the eligible limitation.Conclusions It is currently a mild endemic disease in Hongya Country,its incidence is reduced apparently,pathogenetic environmental fluoride content is reduced.The main source of fluoride is from the preserved ham contaminated with fluoride,which is epidemiologically significant in endemic area of Hongya County.Defluoriding countermeasures should be taken in the endemic areas.

Three butylphthalide derivatives were isolated from the Rhizome of Ligusticum chuanxiong using a series of isolation and purification approaches including macroporous resin, ODS-A column, Sephadex LH-20 and preparative HPLC. These structures were elucidated based on extensive spectroscopic data (UV, IR, HR-ESI-MS and NMR) and identified as (3Z,3aE)-(6R,7R,2'S)-6-hydroxy-7-(2-carboxyl-2-hydroxyethylthio)-3-(2-hydroxybutylidene)-4,5,6,7-tetrahydro-phthalide (1), (3Z,3aZ)-3-butylidene-6,7-dihydroxy-4,5,6,7-tetrahydro-phthalide 7-O-α-D-glucopyranosyl-(1→2)-β-D-fructo-furanoside (2) and 3-(3-β-D-glucopyranosyloxy-butylidene)-7-hydroxy-phthalide (3).

Objective To investigate the effect of Ulinastatin on the delivery of cytokines in patients with septic shock.Methods It was a prospective and controlled clinical study.Seventy-eight patients with septic shock were randomly divided into control group and treatment group and thirty-nine in every group.Patients in treatment group received Ulinastatin 200 000 units intravenous everyday for 3 days,while those in control group received equal volume of normal saline as placebo.At different time points (at 24 th,48 th,72 th hour after start of treatment),the levels of tumor necrosis factor-alpha (TNF-?),interleukin-1 (IL-1),interleukin-6 (IL-6 ),interleukin-8 (IL-8) and superoxide dismutase (SOD) in serum were assayed.Results In comparison with control group,the levels of TNF-?,IL-1,IL-6,IL- 8 of treatment group decreased markedly (P＜0.05,P＜0.01) at different time points,whereas the level of SOD was higher markedly (P＜0.05,P＜0.01) at various time points.Conclusion Ulinastatin has protective effect on patients with septic shock through decreasing the levels of TNF-?,IL-1,IL-6,IL-8 and increasing in the level of SOD.

OBJECTIVETo investigate the pathogenesis of globozoospermia, fertilization ability of round-headed sperm, and the application value of assisted oocyte activation in intracytoplasmic sperm injection (ICSI) for the wives of glohozoospermia men.

METHODSWe collected oocytes from the wives of 2 globozoospermia patients and randomly divided them into two groups after ICSI to receive calcium ionophore A23187-activation and conventional treatment, respectively. We reviewed the relevant literature published at home and abroad, and discussed the etiology of globozoospermia, fertilization ability of round-headed sperm, and treatment options for this disease.

RESULTSQuality embryos were obtained in the A23187-activation group while no fertilized oocytes, oocyte cleavage, quality embryos, or blastular formation were found in the conventional treatment group. Both women achieved pregnancy and gave birth to healthy neonates after transfer of the quality embryos from the A23187-activation group.

CONCLUSIONCalcium ionophore A23187 can be applied to ICSI for the wives of globozoospermia men and bring about desirable clinical outcomes. Meanwhile, attention should be paid to its safety.

Calcimycin ; therapeutic use ; Calcium Ionophores ; therapeutic use ; Female ; Humans ; Infertility, Male ; drug therapy ; Male ; Oocytes ; Pregnancy ; Sperm Injections, Intracytoplasmic ; Spermatozoa ; abnormalities

The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.
Alkenes ; analysis ; Cell Culture Techniques ; Cells, Cultured ; Diterpenes ; analysis ; Molecular Structure ; Paclitaxel ; analysis ; Sitosterols ; analysis ; Taxoids ; analysis ; Taxus ; chemistry

Objective To observe the effects of Ginkgo biloba extract 50 (GBE50) on hemodynamics and myocardial tissue TNF-α pathway in rats with acute blood stasis syndrome; To discuss its mechanism of action. Methods A model of acute blood stasis syndrome was established by subcutaneous injection of epinephrine hydrochloride and ice bath. Male SD rats were divided randomly into normal group, model group and GBE50 group. After medicine was administrated by gavage for 11 days, the acute blood stasis model was established. The hemodynamic changes were observed in the next day. The expressions of TNF-α, TNFR1 and TNFR2 mRNA were detected by RT-PCR. The expressions of TNF-α, TNFR1 and TNFR2 protein were tested by radioimmunoassay and immunohistochemistry. Results The hemodynamics of the model group was lower than that of the normal group. Compared with model group, GBE50 could increase mLVSP, DP and decrease t-dp/dtmax(P<0.05). The protein expressions of TNF-α, TNFR1, and TNFR2 in GBE50 group were higher than those in model group, and TNFR2 mRNA expression increased significantly in GBE50 group (P<0.05). Conclusion GBE50 can ameliorate the decline of hemodynamics of rats with acute blood stasis syndrome, and regulate the myocardial TNF-α pathway. Increasing the expression of protective receptor TNFR2 may be one of the mechanisms of protecting cardiac function.

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.