Topical Delivery of Modified Da-Cheng-Qi Decoction () Using Low-Frequency Ultrasound Sonophoresis for Refractory Metastatic Malignant Bowel Obstruction: An Open-Label Single-Arm Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design.@*METHODS@#Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators.@*RESULTS@#Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed.@*CONCLUSION@#Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

Synergistic Anti-tumor Mechanisms of Low-frequency Ultrasound-targeted Microbubble Destruction:Mechanisms and Application / 中国医学科学院学报

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.

Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.

Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.

Clinical effect of low frequency ultrasound combined with high frequency ultrasound in the diagnosis of gallbladder polypoid lesions / 中国综合临床

Objective To explore the clinical effect of low frequency ultrasound combined with high frequency ultrasound in the diagnosis of polypoid lesions of gallbladder,and to provide reference for clinical diagnosis. Methods From January 2013 to January 2017,87 patients with gallbladder polypoid lesions in Hankou Hospital were selected as the subjects,all the patients were checked by low frequency ultrasound and high frequency ultrasound,the results were compared with postoperative pathological findings. The diagnostic effect were compared between the low frequency ultrasound and low frequency ultrasound combined with high frequency ultrasound,and the consistency between the two inspection methods and postoperative pathological results was analyzed. Results The postoperative pathological report showed that among the 87 patients,59 cases ( 67. 82%) had gallbladder polyp, 6 cases ( 6. 90%) had adenomyosis, 10 cases ( 11. 49%) had gallbladder adenoma, 12 ( 13. 79%) had small nodular gallbladder cancer, 65 ( 86. 67%) had benign polypoid lesions,73 (97. 33%) had low frequency ultrasound combined with high frequency ultrasound. The accuracy of combined high-frequency ultrasound in the diagnosis of benign gallbladder polypoid lesions was significantly higher than that of low frequency ultrasound (χ2＝5. 797,P＜0. 05); the specificity and positive predictive value of combined low frequency ultrasound and high frequency ultrasound in the diagnosis of benign gallbladder polypoid lesions were significantly higher than those of low frequency ultrasound(90. 00%and 41. 18%,97. 33% and 86. 67%) . The difference was statistically significant ( χ2 ＝6. 217, 5. 797, P＝0. 013,0. 016). Conclusion Compared with low frequency ultrasound,low frequency ultrasound combined with high frequency ultrasound improves the differential diagnosis effect of gallbladder polypoid lesions,which is worthy of clinical attention.

Eucerin impedes transdermal insulin delivery by sonophoresis in rats.

The present study was designed to evaluate the effect of low-frequency ultrasound on transdermal delivery of insulin as an ointment. This was conducted in the proceeding of a previously published paper by the authors. Forty-two Wistar rats were randomly divided into 7 groups including one control and six experimental groups with six rats in each group. An ointment of insulin was prepared and applied (alone and with low-frequency ultrasound) on the skin of animals. In all the groups, blood samples were collected from the tail vein of the animals every 15 minutes of the whole 90-minute experimental period. The changes of blood glucose levels with time were assessed in the groups. The results of this study showed that the exposure of the insulin ointment to low-frequency ultrasound for a period of 60 minutes significantly decreased its potency in lowering the blood glucose levels. We conclude that eucerin impedes transdermal insulin delivery by sonophoresis in rats. We suggest that the lowering effect of ultrasound on the penetration ability of insulin is probably due to its effect on the specific molecular structure formed between the insulin and the ointment base after its preparation. However, further studies are needed in order to more precisely identify the involving mechanisms.

Effect of Low Frequency Ultrasound on Carotid Plaque / 中国康复理论与实践

@#Objective To observe the effects of low frequency ultrasound on carotid artery plaque and artery stenosis. Methods 156 patients with carotid atherosclerosis were divided into treatment group (n=80) and control group (n=76). The control group was administered routine medicine, while the treatment group accepted low frequency ultrasound therapy in addition. The size and shape of carotid artery plaque, severity of stenosis and the level of lipid were observed before and after treatment, and the side-effects were recorded. Results The intima-media thickness (IMT), diameter of plaque, plaque score decreased after treatment in both groups, and decreased more in the treatment group than in the control group (P<0.05); while the frequence of moderate stenosis and severe stenosis was less (P<0.05). The levels of low density lipoprotein- cholesterol and total cholesterol decreased in both groups after treatment (P<0.05), and decreased more in the treatment group than in the control group (P<0.05). No serious side-effect was observed. Conclusion Low frequency ultrasound can reduce the atherosclerotic plaques in carotid artery and relieve the stenosis.

Effect of Low Frequency Ultrasound on Carotid Plaque / 中国康复理论与实践

Objective To observe the effects of low frequency ultrasound on carotid artery plaque and artery stenosis. Methods 156 pa-tients with carotid atherosclerosis were divided into treatment group (n=80) and control group (n=76). The control group was administered routine medicine, while the treatment group accepted low frequency ultrasound therapy in addition. The size and shape of carotid artery plaque, severity of stenosis and the level of lipid were observed before and after treatment, and the side-effects were recorded. Results The intima-media thickness (IMT), diameter of plaque, plaque score decreased after treatment in both groups, and decreased more in the treat-ment group than in the control group (P<0.05);while the frequence of moderate stenosis and severe stenosis was less (P<0.05). The levels of low density lipoprotein-cholesterol and total cholesterol decreased in both groups after treatment (P<0.05), and decreased more in the treatment group than in the control group (P<0.05). No serious side-effect was observed. Conclusion Low frequency ultrasound can reduce the atherosclerotic plaques in carotid artery and relieve the stenosis.

Biology effect research of dihydroartemisinin induce the apoptosis in PC-3 cell lines of prostate cancer enhanced by low frequency ultrasound / 重庆医学

Objective To study the enhancement effects of the low frequency ultrasound to the apoptosis induced by dihydroar-temisinin in the transplantation human prostate cancer PC-3 cells in nude mice ,and to explore the underlying action mechanism . Methods Prostate cancer PC-3 cells were transplanted into 20 nude mice to establish the solid tumor mode .These nude mice were randomly divided into 4 groups with 5 mice in each group :control group ,dihydroartemisinin group ,ultrasound group and ultrasound+ dihydroartemisinin group .After 13 days and 7 times drug administration ,The positive products of Bcl-2 ,Bax ,VEGF ,Caspase-3 and CHOP were tested by immunohistochemical method .Results The tumor volume were larger in control group and ultrasound group through observed by tumor contour ,and there were liquefication and necrosis region after incised the tumor tissue .Immuno-histochemical examination revealed that the positive products of Bcl-2 and VEGF were decreased in ultrasound+DHA group ,DHA group and ultrasound group .Immunohistochemical examination revealed that the positive products of Bax 、Caspase-3 and CHOP were significantly increased in ultrasound+DHA group ,DHA group and ultrasound group .Conclusion The low frequency ultra-sound can′t cause obvious damage to the normal cell ,which could causing the change of the positive products in transplantation hu-man prostate cancer PC-3 cells .The results show that DHA has this action alone ,the ultrasound may enhance the apoptosis of PC-3 cells induced by DHA.

Radiofrequency ablation combined with low frequency ultrasound radiation with microbubble for the treatment of malignant liver neoplasms / 中华消化外科杂志

Objective To investigate the clinical efficacy and safety of radiofrequency ablation (RFA)combined with low frequency ultrasound radiation with microbubble for the treatment of malignant liver neoplasms.Methods The clinical data of 25 patients with malignant liver neoplasms who received RFA combined with low frequency ultrasound radiation with microbubble at the Kunming General Hospital from January 2010 to June 2011 were retrospectively analyzed.RFA was firstly performed with ultrasonic guidance,and then low frequency ultrasound radiation with microbubble was performed according to the results of ultrasound contrast examination 1 week after RFA.Ultrasound contrast examination was performed and the hepatic function and serum alpha fetoprotein (AFP) were assayed before operation,3 and 6 months after operation,respectively.All data were analyzed using the t test or chi-square test.Results The gross tumor volumes of 16 patients reduced by 30％ at 3 months after operation when compared with that before operation.The gross tumor volumes of 17 patients reduced by 50％ at 6 months after operation when compared with that before operation.The gross tumor volume of 7 patients reduced,but tissues surrounding tumors showed the signal of bloodstream.The gross tumor volume of 1 patient did not reduce.The levels of aspartate aminotransferase (AST),total bilirubin (TBil) and alpha fetoprotein (AFP) at 3 months after operation were significantly lower than those before operation (t =23.51,13.79,257.07,P ＜0.05).The levels of alanine aminotransferase (ALT),AST,TBil and AFP at 6 months after operation were significantly lower than those before operation (t =5.67,27.19,21.02,333.46,P ＜ 0.05).No local recurrence was detected during a follow-up of 6 months.The scores of quality of life (QOL) were very good in 21 (84.0％) patients,good in 2 (8.0％) patients,fair in 1 (4.0％) patient and poor in 1 (4.0％) patient.The scores of Karnofsky (KPS)were improved in 19 (76.0％) patients,stable in 5 (20.0％) patients and aggravated in 1 (4.0％) patient.There were significant differences in QOL and KPS between pre-and postoperation (x2=41.600,18.960,P ＜0.05).Conclusion RFA combined with low frequency ultrasound radiation with microbubble is effective in reducing the tumor size and protect the hepatic function for patients with malignant liver neoplasms.

Enhancing cytotoxicity of Mitoxantrone on human breast cancer cell with microbubble contrast during low-frequency ultrasound exposure / 中国医学影像技术

Objective To investigate the antitumor effect and its mechanism of microbubble contrast combined with Mitoxantrone exposed to low-frequency ultrasound on human breast cancer cell MCF-7. Methods MTT method was applied to examine the growth inhibition of MCF-7 treated with Mitoxantrone. MCF-7 cells were randomly divided into 4 groups:Mitoxantrone group (group D), ultrasound+Mitoxantrone group (group U+D), ultrasound+microbuble +Mitoxantrone group (group U+M+D) and control group (group C). The cytoactive of each group was examined with MTT. The intracellular drug content in each group was measured with high performance liquid chromatography. The morphology of MCF-7 cells apoptosis was observed with transmission electron microscopy (TEM). Results The IC_(50) of Mitoxantrone was 2.87 μg/ml. The differences of cytoactive among all groups were significant (P<0.05). The intracellular drug content of group U+M+D was higher than that of group U+D, and the latter was higher than that of group D. The morphological changes of apoptosis were observed with TEM. Conclusion Low-frequency ultrasound can promote intracellular drug content as to enhance the sensitivity of chemotherapy drugs on tumor cells, and this effect can be enhanced by microbubble contrast exposure to low-frequency ultrasound.

Low Frequency Ultrasound Triggering Drug Release from Improved PLGA Microcapsules in Vitro / 中国康复理论与实践

@# Objective To study the effect of low frequency on drug release from improved PLGA microcapsules, and investigate the possibility of utilizing PLGA microcapsules as the carrier of ultrasound targeted drug delivery system to deliver drug into brain. Methods Doxorubicin loaded poly (D,L lactic-co-glycolic acid) (PLGA) microcapsules were prepared via double emulsion solvent evaporate method and coated with either chitosan or gelatin. In vitro drug release profile and the drug release rate under the exposure of low frequency pulsed ultrasound (25 kHz) and continuous wave ultrasound (35.1 kHz) were assayed. Results The coating with chitosan or gelatin can depress the burst of drug release. The drug release rate from uncoated and chitosan-coated microcapsules did not changed with the exposure of ultrasound, and the rate of gelatin-coated microcapsules did increased. The effect of pulsed ultrasound was stronger than that of continuous ultrasound. Conclusion The drug release from gelatin-coated PLGA microcapsules can be controlled and triggered by 25 kHz pulsed ultrasound, which may be a potent carrier of targeting drugs into brain.

Transdermal enhancement of low-frequency ultrasound / 医疗卫生装备

The transdermal enhancement of ultrasound was discovered 50 years ago.The advantages of low-frequency ultrasound in enhancing the transdermal transport of molecule were discovered in 40 years' study.Because the cavitation is easier to happen in lower frequency ultrasound,the transdermal enhancement of low-frequency ultrasound is higher.The inertial cavitations near the surface of skin play important roles in the transdermal enhancement of low-frequency ultrasound.There are many studies about the effects of the parameters of ultrasound on the transdermal enhancement of low-frequency ultrasound,but there are fewer studies about the effects of other factors.The transdermal enhancement of low-frequency ultrasound has been used for transdermal drug delivery.There are many studies about the transdermal monitoring of glucose and other analytes using low-frequency ultrasound.Many opportunities and challenges lie ahead.

The therapeutic effects of low frequency ultrasound enhanced thrombolysis on acute cerebral infarction in rats / 中华物理医学与康复杂志

Objective To observe the therapeutic effects of low frequency ultrasound enhanced thrombolysis (LFUET) on acute cerebral infarction (ACI) in rats.Methods The ACI animal models were established by injec- ting auto-thrombus into the rats' left middle cerebral arteries.They were then treated with urokinase,and received transcranial LFUET treatment at the same time.Nervous system functioning was assessed using NSS,and infarct vol- umes (IVs) were measured through tetrazolium chloride (TTC) staining.Results The NSS scores in the large- dose urokinase group (LDU group),the ultrasound plus small-dose urokinase group (USMU group) and in the in- farct group (Ⅰgroup) at 24 h after treatment were significantly lower than those before treatment.IVs in the two treat- ment groups are lower than those in theⅠgroup,but there was no significant difference between the LDU group and USMU group volumes.Conclusion LFUET can accelerate the recovery of nervous system function in rats after ACI,minimize IVs,and reduce the required dosage of urokinase.

The effects of low frequency ultrasound on the proliferation and apoptosis of smooth muscle cells in carotid atherosclerosis / 中华物理医学与康复杂志

Objective To investigate the effects of low frequency ultrasound (LFU) on the proliferation and apoptosis of smooth muscle cells (SMCs) in rabbits with carotid atherosclerosis(CA).Methods CA models were established in 30 New Zealand rabbits using a high fat diet and air-drying.They were randomly divided into a control group and four LFU groups:group A received 0.5 W/cm~2 LFU for 5 min/d,group B 0.5 W/cm~2 for 10 min/d, group C 1 W/cm~2,5 min/d,and group D 1 W/cm~2,10 min/d.The rabbits' carotid arteries were autopsied after 20 d of the LFU treatment.The expression of PCNA and TUNEL staining were used to explore the proliferation and apopto- sis of SMCs,and the proliferation rates (PRs) and apoptosis rates (ARs) were calculated.Results Compared with the control group,the PRs in groups B,C and D were significantly lower,while the ARs in groups B,C and D were significantly higher.There was no significant difference in ARs or PRs among groups B,C and D.Con- clusion LFU can induce SMC apoptosis and inhibit SMC proliferation in rabbits with CA.