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Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering Research Center of Oral Biomaterials Chengdu 610041China Department of Head and Neck Oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment side effect

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side effects of different doses of ephedrine in rats with cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2010年第24期5卷 1883-1887页

作者： Ling Liu Liyun Lin Nong Xiao Yuxia Chen Siyuan Chen Rehabilitation Center Children's Hospital of Chongqing Medical University Chongqing 400014 China Ningbo Women & Children's Hospital Ningbo 315012 Zhejiang Province China

Ephedrine has a protective effect against cerebral ischemia,but its side effects limit its clinical *** from a previous study showed that 1.5 mg/kg per day ephedrine can promote motion recovery in rats following cerebral ischemia/reperfusion without significant side *** the present study,ephedrine at doses of 3.0,2.5 and 2.0 mg/kg was used to treat rats with cerebral ischemia/reperfusion and the effects of ephedrine on the heart,liver,kidney and cerebrum were *** showed that the blood pressure of rats with cerebral ischemia/reperfusion injury following ephedrine treatment was lower than in rats that recovered naturally from cerebral ischemia/reperfusion,but the pressure decreased with increasing doses of *** addition,serum aspartate transaminase,alkaline phosphatase and creatinine concentration in rats with cerebral ischemia/reperfusion injury following ephedrine treatment were greater than in rats that recovered naturally from cerebral ischemia/*** concentrations of these enzymes were decreased with increasing doses of ***-treated rats displayed hyperemia,degeneration and edema in the cerebrum,liver,heart and *** demonstrated that ephedrine exhibited side effects on the cerebrum,heart,liver and kidney in rats following cerebral ischemia/reperfusion in a dose-dependent manner.

关键词： cerebral ischemiaJreperfusion ephedrine side effect heart liver kidney cerebrum brain injury neural regeneration

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Clinical Efficacy of Acupuncture on the Morphine-related side effects in Patients Undergoing Spinal-epidural Anesthesia and Analgesia

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Chinese Journal of Integrative Medicine 2010年第1期16卷 71-74页

作者：蒋奕红江伟蒋雷鸣林高翔杨华谭毅熊威威 Department of Anesthesiology Hospital Affiliated to Guilin Medical College Department of Traditional Chinese Medicine Hospital Affiliated to Guilin Medical College Department of Urology Hospital Affiliated to Guilin Medical College

Objective： To investigate the effects of acupuncture on the morphine-related side effects （nausea, vomiting, itchiness and gastrointestinal disorders） in patients undergoing anesthesia and analgesia and try to find the clinical mechanism of acupuncture. Methods： Patients scheduled to have transurethral prostatic resection enrolled in the study （69 patients）, characterized as Grade Ⅱ or Ⅲ by the American Society of Anesthesiologists physical status classification, were randomly assigned to three groups, 23 patients in each group： the placebo group （control group）, non-anesthesia area （NAA） group, and the anesthesia area （AA） group. After spinal anesthesia, all patients received Patients Controlled Epidural Analgesia. The vital signs, bowel sounds, visual analogue scales, itchiness, nausea and vomiting, and time for first exhaust post operation were observed. Results： Altogether, nine cases were eliminated, three in each group. Finally, sixty cases completed this study, twenty in each group. There was a significant decrease of bowel sounds after morphine spinal anesthesia in the three groups. Compared with the control or AA group, the bowel sound recovered after acupuncture, the incidences of nausea and vomiting, itchiness, and time for first exhaust after operation decreased in the NAA group （P〈0.05）. There was a significant decrease of the incidence for itchiness in the NAA group compared with the control group （P〈0.05）. Conclusions： On the basis of this study, it is obviously seen that acupuncture could decrease the incidence of morphine-related side effects （nausea and vomiting, itchiness and gastrointestinal disorders） when the spinal cord conduct is normal. However, it decreases only the incidence of itchiness but not for gastrointestinal dysfunction when the spinal cord is blocked.

关键词： acupuncture spinal and epidural anesthesia morphine side effect

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side effects and tolerability of post-exposure prophylaxis with zidovudine, lamivudine, and lopinavir/ritonavir： a comparative study with HIV/AIDS patients

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Chinese Medical Journal 2014年第14期127卷 2632-2636页

作者： Cai Juan Xiao Jiang Zhang Qiang Capital Med Univ Dept Orthoped Beijing Ditan Hosp Beijing 100015 Peoples R China Capital Med Univ Ctr Infect Dis Beijing Ditan Hosp Beijing 100015 Peoples R China

Background In the era of highly active antiretroviral therapy （HAART）, the use of antiretrovirals as post-exposure prophylaxis （PEP） was the most important strategy for preventing occupational exposure to blood or fluids containing human immunodeficiency virus （HIV）. The objective of this study was to retrospectively evaluate the tolerability, safety, and side effects of a HAART regimen containing three antiretroviral drugs, consisting of zidovudine, lamivudine, and Iopinavir/ ritonavir, in healthcare personnel （HCP） who experienced occupational exposure to HIV. Methods The tolerability, safety, and side effects in 26 HCPs who experienced PEP and in 27 HIV/AIDS patients with HAART regimen, AZT＋3TC＋Lpv/r, were evaluated between January 2010 and December 2012. Results The most frequent clinical side effect was fatigue （in 23 cases, 88.5%）, and gastroenterological symptoms were the second most common side effects in HCP with PEP. Liver dysfunction was found in 10 cases （38.5%）, while drug rash was found in 18 cases （69.2%） after PEP. The prevalence of side effects in HCPs who experienced PEP was higher than that in HIV/AIDS patients P 〈0.05. One nurse （3.8%） experienced severe gastrointestinal symptoms, which led to withdrawal of PEP. No HIV infection was found during 6-month follow-up period. Conclusion HCPs who received occupational PEP with triple-drug regimen, AZT＋3TC＋Lpv/r, experienced different side effects, and the tolerability and safety of PEP regimen were good in this cohort. Chin Med J 2014;127 （14）： 2632-2636

关键词： post-exposure prophylaxis HIV/AIDS highly active antiretroviral therapy side effect

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Approach by Health Professionals to the side effects of Antihypertensive Therapy： Strategies for Improvement of Adherence

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Journal of Pharmacy and Pharmacology 2018年第4期6卷 340-349页

作者： Grazia Maria Guerra Heno Ferreira Lopes ELizangela Oliveira Freitast Fernanda Marciano Consolim-Colombo Patricia Silva Lessa4, Dante Marcelo Artigas Giorgi Luiz Aparecido Bortolloto Eduardo Moacyr Krieger Hypertension Unit Heart Institute of Hospital Clinical (InCor-HC FMUSP) School of Medicine University of Sao Paulo Sao Paulo 05403-000 SP Brazil Sao Camilo University Centers Sao Paulo 05022-000 SP Brazil Institute of Cancer of Sao Paulo State Sao Paulo 01246-000 SP Brazil Department of Electronics and Systems (DES-UFPE) Federal University of Pernambuco Recife 50670-901 PE Brazil

The aim was to determine whether complaints about side effects made by stage Ill hypertensive patients undergoing antihypertensive therapy lead to adequate blood pressure control. Forty-eight patients were monitored by a nurse every 15 days over the course of 180 days. At baseline, both groups presented similar SBP （systolic blood pressure）（GA, 196 （5）） mm Hg and GB, 189 （6） mm Hg） and DBP （diastolic blood pressure）（GA, 122 （3） mm Hg and GB, 121 （4） mm Hg）. On day 165, after a progressive decline in blood pressure levels, the two groups differed significantly from each other regarding SBP （GA, -16.9 （24） mm Hg and GB, -40.8 （31） mm Hg）. At the final follow-up, the patients were allocated to two groups： without complaints （GA） and with （GB） complaints about side effects. Complaining about side effects was a decisive factor for immediate nursing intervention and improved control over BP.

关键词： Nursing hypertension patient adherence side effect ambulatory blood pressure monitoring.

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Analysis of Serum Antibody Level after COVID-19 Vaccine and side effects after Vaccine

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Advances in Infectious Diseases 2023年第2期13卷 249-262页

作者： Hiromi Nagashima Shinji Chiba Shinnosuke Oura Itaru Fujimura Masachika Akiyama Yu Utsumi Hironori Sakai Wataru Hojo Takuya Iwabuchi Makoto Maemondo Department of Internal Medicine Division of Pulmonary Medicine Iwate Medical University Yahaba Japan R&D Cellspect Co. Ltd. Morioka Japan Department of Medicine Division of Pulmonary Medicine Jichi Medical University Shimotsuke Japan

Background: COVID-19 has caused a large number of deaths, in the elderly. In this situation, vaccines have been considered the main strategy to combat COVID-19 and were developed worldwide in 2020. One problem with COVID-19 vaccination is side effects after vaccination. In this report, we identify the relationship between side effects and elevation of antibodies as determined by monitoring several kinds of antibodies against COVID-19. Objective: We investigated whether the antibody level changed depending on side effects after COVID-19 vaccination. Methods: Healthy volunteers, who received two vaccinations between 10 March and 7 May 2021, were collected for this study. Information including age, gender, smoking history, medical history including allergies and side reactions after vaccination was obtained by questionnaire. Serum levels of antibodies of IgG and IgM against each S1, SP, and NP antigens of COVID-19 were evaluated frequently for 3 - 4 months after the first vaccination. Result: Ten employees working at Iwate Medical University were evaluated in this study. side effects were observed in 7 of 10 patients, and grade 2 side effects in all 3 patients with a history of allergic disease. Serum S1 and SP IgG were elevated sufficiently in all patients. In all patients, IgG antibody titers fell below the cutoff point in approximately 3 months. No cases had elevated NP antibodies. SP IgM was elevated in three cases;all three cases with elevated IgM had allergic disease and the degree of side effects was relatively higher. Subjects with long-lasting elevated SPIgM were observed. Conclusion: S1 IgG and SP IgG exceeded the cutoff in all subjects after vaccination but decreased below the cutoff in all subjects within 4 months, regardless of side effects or allergic history. On the other hand, elevated SPIgM was suspected to be related to side effects and history of allergies, and cases with persistent elevation of SPIgM were observed.

关键词： COVID-19 Vaccination History of Allergic Disease side effect S1 IgG SP IgG SP IgM

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Clinical Observation on side effects of Various Tripterygium Wilfordii Preparations

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Chinese Journal of Integrative Medicine 1999年第3期5卷 171-175页

作者：周嘉陵朱琦杨晓凌张芳 Guanghua Hospital of Integrated Traditional Chinese and Western Medicine 200052 Shanghai

Objective: To observe the side effects of various Tripterygium wilfordii (TW) preparations in treating rheumatoid arthritis (RA). Methods: The total of 271 patients with RA were treated with various TW preparations to observe the occurrence of side effects. Results: The influence on reproductive system with TW preparations extracted from the TW leaves (Leino ester tablet, LE) was milder than that extracted from the roots (TW tablets and TW polyglycoside tablets, TWP). In the TWP group, the rate of side effect of 60 mg daily was higher than that of 30 mg daily, P effects on digestive system and irregular menstruation occurred before 50 years in age, while it was kidney impairment after the age of 50. Those side effects occurred within the first ten years in long term application. The side effects of TWP produced in the Damp Heat Stagnation type of RA was much lower than Liver and Kidney Yin Deficiency type of RA, P <0.05. Conclusion: TW Leino ester tablet is indicated for young woman, and small dosage of TWP tablet is indicated for maintenance therapy, particularly to the Damp Heat type of RA.

关键词： Tripterygium wilfordii preparation rheumatoid arthritis side effect

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Evidence against the participation of a pharmacokinetic interaction in the protective effect of single-dose curcumin against gastrointestinal damage induced by indomethacin in rats

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Journal of Integrative Medicine 2017年第2期15卷 151-157页

作者： Liliana Zazueta-Beltran Lorena Medina-Aymerich Nadia Estela Diaz-Triste Aracely Evangelina Chavez-Pina GUberto Castaneda-Hernandez Leticia Cruz-Antonio Department of Pharmacology Center for Research and Advanced Studies of the National Polytechnic Institute 07360 Mexico City Mexico Laboratory of Pharmacology Institutional Program in Molecular Biomedicine National School of Medicine and Homeopathy of the National Polytechnic Institute Academic Area of Medicine of the Institute of Health Sciences 07320 Mexico City Mexico Superior Studies Faculty of Zaragoza Universidad National Autonomous of Mexico 09230 Mexico City Mexico

OBJECTIVE： To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin. METHODS： Wistar rats orally received single dose of indomethacin （30 mg/kg） with and without curcumin （30 mg/kg）; gastric injury was evaluated by determining the total damaged area. Additional groups of rats received an oral single dose of indomethacin （30 mg/kg） or its prodrug acemetacin （34.86 mg/kg） in the presence or absence of curcumin （30 mg/kg）. Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography Plasma concentration-against-time curves were constructed, and bioavailability parameters, maximal concentration （Cmax） and area under the curve to the last sampling time （AUC0_t） were estimated. RESULTS： Concomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage compared to indomethacin alone. However, co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug. CONCLUSION： Curcumin exhibits a protective effect against indomethacin-induced gastric damage, but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug, indomethacin. Data thus suggest that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection.

关键词： indomethacin curcumin acemetacin bioavailability damage, ggastrointestinal side effect drugs, Chinese herbal

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Salvia miltiorrhiza: Traditional medicinal uses, chemistry, and pharmacology

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Chinese Journal of Natural Medicines 2015年第3期13卷 163-182页

作者： SU Chun-Yan MING Qian-Liang RAHMAN Khalid HAN Ting QIN Lu-Ping Department of Pharmacognosy School of Pharmacy Second Military Medical University Institute of Medicinal Plant Development Chinese Academy of Medical Science and Peking Union Medical College Department of Pharmacognosy School of Pharmacy Third Military Medical University Faculty of Science School of Pharmacy and Biomolecular Sciences Liverpool John Moores University

Salvia miltiorrhiza Bunge(SM) is a very popular medicinal plant that has been extensively applied for many years to treat various diseases, especially coronary heart diseases and cerebrovascular diseases, either alone or in combination with other Chinese plant-based medicines. Although a large number of studies on SM have been performed, they are scattered across a variety of publications. The present review is an up-to-date summary of the published scientific information about the traditional uses, chemical constituents, pharmacological effects, side effects, and drug interactions with SM, in order to lay the foundation for further investigations and better utilization of SM. SM contains diverse chemical components including diterpenoid quinones, hydrophilic phenolic acids, and essential oils. Many pharmacological studies have been done on SM during the last 30 years, focusing on the cardiovascular and cerebrovascular effects, and the antioxidative, neuroprotective, antifibrotic, anti-inflammatory, and antineoplastic activities. The research results strongly support the notion that SM has beneficial therapeutic properties and has a potential of being an effective adaptogenic remedy.

关键词： Danshen Cardiovascular diseases Antitumor side effect Review

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Selectivity of Three Miticides to Spider Mite Predator,Phytoseius plumifer(Acari:Phytoseiidae) Under Laboratory Conditions

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Agricultural Sciences in China 2009年第3期8卷 326-331页

作者： Ahmad Nadimi Karim Kamali Masoud Arbabi Fateme Abdoli Department of Entomology Tarbiat Modares University Department of Agricultural Research Zoology Iranian Plant Protection Research Institute Department of Biology Guilan University

The predatory mite, Phytoseius plumifer （Canestrini ＆ Fanzago）, is one of the most abundant natural enemies and efficient predator of phytophagous mites in Iran. The miticides hexythiazox （Nisorun, EC 10%）, fenpyroximate （Ortus, SC 5%）, and abamectin （Vertimec, EC 1.8%） were tested in the laboratory for their side effects on P. plumifer. The miticides were applied at the highest field recommended concentration （N） to detached leaves using a Potter Tower to deposit 2 mg spray solution per cm2. Percent predator mortality was evaluated from the protonymph up to the adult stage including the first five days of the oviposition period. Analysis of data showed that the total effect values of hexythiazox were below the lower threshold, and thus it could be considered to be a harmless miticide to P. plumifer. In contrast, the total effects of fenpyroximate and abamectin were found harmful to the predatory mite at the highest field recommended concentrations.

关键词： Phytoseius plumifer selectivity side effect miticide predatory mite

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