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| 1 | De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis显示文摘AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality. | Jiang-Shan Lian Lin-Yan Zeng Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang Liang Yu Jian-Hua Hu Ying-Feng Lu Ling Zheng Lan-Juan Li Yi-Da Yang | 2013 | World Journal of Gastroenterology2013，19，37： | 36 |
| 2 | Transcatheter arterial chemoembolization followed by immediate radiofrequency ablation for large solitary hepatocellular carcinomas显示文摘AIM: To assess the technical safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA) for large hepatocellular carcinomas (HCC) (maximum diameter ≥ 5 cm). METHODS: Individual lesions in 18 patients with HCCs (mean maximum diameter: 7.5 cm; range: 5.1-15.5 cm) were treated by TACE combined with percutaneous RFA between January 2010 and June 2012. All of the patients had previously undergone one to four cycles of TACE treatment. Regular imaging and laboratory tests were performed to evaluate the rate of technical success, technique-related complications, local-regional tumor responses, recurrence-free survival time and survival rate after treatment.RESULTS: Technical success was achieved for all 18 visible HCCs. Complete response (CR) was observed in 17 cases, and partial response was observed in 1 case 1 mo after intervention. The CR rate was 94.4%. Local tumors were mainly characterized by coagulative necrosis. During follow-up (2-29 mo), the mean recurrencefree survival time was 16.8 ± 4.0 mo in 17 cases of CR. The estimated overall survival rate at 6, 12, and 18 mo was 100%. No major complications were observed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood of 17 patients transiently increased on the third day after treatment (ALT 200.4 ± 63.4 U/L vs 24.7 ± 9.3 U/L, P < 0.05; AST 228.1 ± 25.4 U/L vs 32.7 ± 6.8 U/L, P < 0.05). Severe pain occurred in three patients, which was controlled with morphine and fentanyl. CONCLUSION: TACE combined with immediate RFA is a safe and effective treatment for large solitary HCCs. Severe pain is a major side effect, but can be controlled by morphine. | Zhi-Jun Wang Mao-Qiang Wang Feng Duan Peng Song Feng-Yong Liu Zhong-Fei Chang Yan Wang Jie-Yu Yan Kai Li | 2013 | World Journal of Gastroenterology2013，19，26： | 24 |
| 3 | Radiofrequency deep hyperthermia combined with chemotherapy in the treatment of advanced non-small cell lung cancer显示文摘Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January 2014.The patients were divided into HCT and chemotherapy(CT)groups.The HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Also,it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients. | Wen-Hui Yang Jun Xie Zhi-Yong Lai Mu-Dan Yang Ge-Hong Zhang Yuan Li Jian-Bing Mu Jun Xu | 2019 | Chinese Medical Journal2019，，8： | 15 |
| 4 | Chinese Medicine as Complementary Therapy for Female Infertility显示文摘Chinese medicine(CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment. | XIA du-feng Yoshinori Inagaki ZHANG Jian-feng WANG Ling SONG Pei-pei | 2017 | Chinese Journal of Integrative Medicine2017，23，4： | 14 |
| 5 | Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials显示文摘BACKGROUND:It has been demonstrated that only a minority of patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB) obtain a sustained response after either interferon(IFN) or nucleos(t)ide analogue monotherapy.Therefore,combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients.We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon(CON-IFN) and pegylated interferon(PEG-IFN) for HBeAg-negative CHB patients.DATA SOURCES:A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches(MEDLINE,OVID,EMBASE,the Cochrane Library Clinical Trials Registry,and the Chinese Medical Database),manual searches,and contact with experts.Sustained virological and biochemical responses were defined as primary efficacy measures.We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups.RESULTS:No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs.26.7%,odds ratio(OR)=0.98,95% confidence interval(CI) 0.65-1.50,P=0.94,and 41.8% vs.40.3%,OR=1.13,95% CI 0.78-1.65,P=0.51,respectively],though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs.30.0%,OR=0.16,95% CI 0.076-0.33,P<0.001].However,data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs.6.6%,OR=3.42,95% CI 1.71-6.84,P<0.001 and 60.0% vs.44.2%,OR=1.88,95% CI 1.23-2.85,P=0.003,respectively].CONCLUSIONS:Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine.Combination of PEG-IFN and lamivudine might increase the sustained response,and further clinical trials are needed for confirmation. | Shi, Yu Wu, Yi-Hua Shu, Zhe-Yue Zhang, Wan-Jun Yang, Jun Chen, Zhi | 2010 | Hepatobiliary & Pancreatic Diseases International2010，9，5： | 12 |
| 6 | Immunotherapy of hepatocellular carcinoma: strategies for combinatorial intervention显示文摘Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients with early-stage HCC develop recurrence by the time of follow-up.Immunotherapeutic intervention has emerged as a novel,effective treatment to delay the progression of aggressive tumors and suppress tumor recurrence and metastasis.However,few clinical immunotherapy trials have been conducted in HCC patients,and there is an unmet need for novel therapeutic strategies.The combination of conventional treatments with specific immunotherapeutic approaches may dramatically improve the efficacy of HCC treatment and the clinical outcome of HCC patients.In this review,we briefly summarize immunotherapy strategies and discuss new advances in combined immunotherapeutic approaches for the treatment of patients with liver cancer. | Mengxin Tian Yinghong Shi Weiren Liu Jia Fan | 2019 | Science China(Life Sciences)2019，62，9： | 12 |
| 7 | Intermediate hepatocellular carcinoma: How to choose the best treatment modality?显示文摘Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma(HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large(> 5 cm) solitary HCC should be firstly considered for liver resection(LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization(TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization(TARE)-plus percutaneous ablation] is 'a priori' preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases(patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be 'patient-tailored' and made by a multidisciplinary team. | Giovan Giuseppe Di Costanzo Raffaella Tortora | 2015 | World Journal of Hepatology2015，7，9： | 12 |
| 8 | High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care显示文摘Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be studied.Building on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study Xue Bi Jing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi Jing.Collectively, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations. | Jian Li Olajide E.Olaleye Xuan Yu Weiwei Jia Junling Yang Chuang Lu Songqiao Liu Jingjing Yu Xiaona Duan Yaya Wanga Kai Dong Rongrong He Chen Cheng Chuan Li | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 10 |
| 9 | Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients:A Randomized Controlled 48-Week Trial显示文摘Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263). | LI Xiao-ke ZHANG Ming-xiang SHAO Feng-zhen ZHOU Da-qiao XUE Jing-dong LIU Tie-jun CHI Xiao-ling LU Bing-jiu WANG Xian-bo LI Qin LI Jun MAO De-wen YANG Hua-sheng YANG Hong-zhi ZHAO Wen-xia LI Yong ZHANG Guo-liang ZHAO Yi-ming ZOU Jian-dong LIU Meng-yang ZHANG Ke-ke YANG Xian-zhao GAN Da-nan LI Ying ZHANG Peng LI Zhi-guo LI Shuo YE Yong-an | 2020 | Chinese Journal of Integrative Medicine2020，26，5： | 9 |
| 10 | Two-dimensional metal-organic-framework as a unique theranostic nano-platform for nuclear imaging and chemo-photodynamic cancer therapy显示文摘Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications.Herein,2D NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG).Compared to their particulate counterpart,such 2D NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production,promising for chemotherapy and photodynamic therapy (PDT),respectively.Utilizing the porphyrin structure of TCPP,our 2D NMOFs could be labeled with a diagnostic radioisotope,99mTc,for single photon emission computer tomography (SPECT) imaging,which reveals efficient tumor homing of those 2D NMOFs upon intravenous injection.While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT,such 2D NMOFs show efficient biodegradation and rapid renal clearance.Our work presents the great promise of 2D NMOFs for nanomedicine applications. | Wenjun Zhu Yu Yang Qiutong Jin Yu Chao Longlong Tian Jingjing Liu Ziliang Dong Zhuang Liu | 2019 | Nano Research2019，12，6： | 9 |
| 11 | Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study显示文摘AIM:To investigate efficacy and safety of vildagliptin compared to other oral antidiabetics in clinical practice in Germany.METHODS:In this prospective,open,observational study,patients with type 2 diabetes mellitus(T2DM) previously on oral monotherapy were selected by their treating physician to receive either vildagliptin addon to metformin(cohort 1),vildagliptin+metformin single-pill combination(SPC)(cohort 2)or another dual combination therapy with oral antidiabetic drugs(OADs)(cohort 3).According to routine clinical practice,interim examinations occurred every 3 mo:at baseline,after approximately 3 mo and after approximately 6 mo.Parameters documented in the study included demographic and diagnostic data,history of T2DM,data on diabetes control,vital signs,relevant prior and concomitant medication and disease history.Efficacy was assessed by changes in HbA1c and fasting plasma glucose(FPG)3 mo and 6 mo after initiation of dual combination therapy.Safety was assessed by adverseevent reporting and measurement of specific laboratory values(serum creatinine,total bilirubin,alanine aminotransferase,aspartate aminotransferase,creatine kinase).RESULTS:Between October 2009 and January 2011,a total of 3881 patients were enrolled in this study.Since 47 patients were withdrawn due to protocol violations,3834 patients were included in the statistical analysis.There were no relevant differences between the three cohorts concerning age,body weight and body mass index.Average diabetes duration was approximately 6 years and mean HbA1c was between 7.6%and 7.9% at baseline.Antidiabetic treatment was recorded in 3648 patients.Patients were treated with vildagliptin add-on to metformin(n=603),vildagliptin+metformin(SPC)(n =2198),and other oral OADs including combinations of metformin with sulfonylurea(n=370),with glitazones(n =123),other dipeptidyl peptidase-4 inhibitors(n=99).After 6 mo of treatment,the absolute decrease in HbA1c(mean±SE)was significantly more pronounced in patients receiving vildagliptin add-on to metformin(-0.9% ±0.04%)and vildagliptin+metformin(SPC)(-0.9%± 0.03%)than in patients receiving other OADs(-0.6% ±0.04%;P<0.0001).In addition,significant cohort differences were observed for the improvement in FPG after 6 mo treatment(vildagliptin add-on to metformin:-291 mg/L±18.3 mg/L;vildagliptin+metformin(SPC):-305 mg/L±9.6 mg/L;other antidiabetic drugs:-209 mg/L±14.0 mg/L for(P<0.0001).Moderate decreases in body weight(absolute difference between last control and baseline:mean±SE)were observed for patients in all cohorts(vildagliptin add-on to metformin:-1.4 kg ±0.17 kg;vildagliptin+metformin(SPC):-1.7 kg± 0.09 kg;other OADs:?0.8 kg±0.13 kg).No significant differences in adverse events(AEs)and other safety measures were observed between the cohorts.When performing an additional analysis by age(patients<65 years vs patients≥65 years),there was no relevant difference in the most common AEs between the two age groups and the AE profile was similar to that of the overall patient population.CONCLUSION:Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients. | Matthias Blüher Ira Kurz Simone Dannenmaier Markus Dworak | 2012 | World Journal of Diabetes2012，3，9： | 9 |
| 12 | Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer显示文摘Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target(m TOR), inhibition of which could result in autophagic cell death(ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin(RAP) into 7 pep-modified PEG-DSPE polymer micelles(7 pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor(Tf R). Cytotoxic paclitaxel(PTX)-loaded micelle(7 pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake in vitro and more tumor accumulation of micelles in vivo, 7 pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7 pep-M-PTX. Mechanism study further revealed that 7 pep-M-RAP and 7 pep-MPTX used in combination provided enhanced efficacy through induction of both apoptosis-and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality. | Dong Mei Binlong Chen Bing He Haibin Liu Zhiqiang Lin Jialiang Lin Xiaoyan Zhang Ning Sun Libo Zhao Xiaoling Wang Qiang Zhang | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 8 |
| 13 | Study on effect of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema显示文摘Objective:To study the effects of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema.Methods:DNCB acetone solution was used to sensitize the skin of back and ears of 36 rats in order to establish chronic eczema model.A total of 36 rats were divided into four groups of 9 randomly including oral medicine group,external inunctum group,combination therapy group,and model control group respectively.Besides,the blank group of 4 healthy rats were set.The oral medicine group was given Traditional Chinese Medicine Jianpi Chushi decoction [(Poria cocos,Chinese yam,Cortex dictamni,Zaocys dhumnade,Rhizoma atractylodis,Pericarpium citri reticulatae,Scutellaria baicalensis,Radix Sophorae Flavescentis,Raw Radix Paeoniae Alba,Licorice roots(Northwest Origin)] by gastric infusion(1.6 g/m L·5 m L/d); the external inunctum group was given Qingpeng ointment on the skin,the combination therapy group was given Jianpi Chushi decoction by gastric infusion and Qingpeng ointment combination therapy.The model control group was given normal saline(NS) of the same volume by gastric infusion and vaseline on skin.Continuous administration 15 d and stopped for 3 d.The thickness difference and weight difference of left and right ear of every group were measured and the degree of ear swelling were evaluated.The CD4^+ and CD8^+ content and the IL-2,IL-4 level of serum were detected,and the inflammatory cells counts of back skin were recorded.Results:After treatment,the degree of ear swelling of oral medicine group,external inunctum group and combination therapy group significant decreased compared with model control group(P<0.05).The CD4^+,CD8^+ cell content and IL-2 level of oral medicine group,external inunctum group,combination therapy group and model control group significant decreased compared with blank group,and IL-2 level and the inflammatory cells count increased.After 15 d of treatment,the CD4^+,CD8^+ cell content and IL-2 level of serum of oral medicine group,external inunctum group and combination therapy group raised and the IL-4 level and the inflammatory cells count had significant decreased compared with model control group,and the effect of combination therapy group was more obvious(P<0.05).Conclusions:Qral Jianpi Chushi decoction could treat chronic eczema effectively,and oral Chinese medicine combined with ointment could enhance and speed up the efficacy. | Hui-Lei Wan Hui-Zhi Chen Xiu-Qin Shi | 2016 | Asian Pacific Journal of Tropical Medicine2016，9，9： | 8 |
| 14 | Antitumor effect of axitinib combined with dopamine and PKPD modeling in the treatment of human breast cancer xenograft显示文摘Rising evidence has shown the development of resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors in the practices of cancer therapy. It is reported that the efficacy of axitinib (AX), a VEGFR inhibitor, is limited in the treatment of breast cancer as a single agent or in combination with other chemotherapeutic drugs due to the probability of rising population of cancer stem-like cells (CSCs) caused by AX. The present study evaluated the effect of dopamine (DA) improving AX’s efficacy on MCF-7/ADR breast cancer in vitro and in vivo, and developed a pharmacokinetic-pharmacodynamic (PK-PD) model describing the in vivo experimental data and characterizing the interaction of effect between AX and DA. The results showed that AX up-regulated the expression of breast CSC (BCSC) markers (CD44^+/CD24^-/low) in vivo, and DA significantly synergized the inhibitory effect on tumor growth by deducting the BCSC frequency. The PK-PD model quantitatively confirmed the synergistic interaction with the parameter estimate of interaction factor ψ 2.43. The dose regimen was optimized as 60mg/kg AX i.g. b.i.d. combined with 50mg/kg DA i.p. q3d in the simulation study on the basis of the PK-PD model. The model where DA synergistically enhances the effect of AX in an all-or-none manner provides a possible solution in modeling the agents like DA. Moreover, the outcome of AX and DA combination therapy in MCF-7/ADR breast cancer provided further insight of co-administering DA in the treatment of the possible CSC-causing AX-resisting breast cancer. And this combination therapy has the prospect of clinical translation. | Yuan-heng Ma Si-yuan Wang Yu-peng Ren Jian Li Ting-jie Guo Wei Lu Tian-yan Zhou | 2019 | Acta Pharmacologica Sinica2019，40，2： | 7 |
| 15 | One-pot photoreduction to prepare NIR-absorbing plasmonic gold nanoparticles tethered by amphiphilic polypeptide copolymer for synergistic photothermal-chemotherapy显示文摘We developed one-pot photoreduction strategy to prepare near infrared light(NIR)-absorbing plasmonic gold nanoparticles(Au NPs) tethered by amphiphilic polypeptide copolymer poly(L-cysteine)-b-poly(ethylene oxide)(PLC-b-PEO). The PLC-b-PEO@Au NPs possessed strong NIR absorption at 700–1100 nm and ultrahigh photothermal conversion efficiency of 62.1%. Upon the NIR irradiation(808nm,2 W/cm^2,5 min), the PLC-b-PEO@Au NPs(1mg/mL) sharply attained an elevation of 30.8℃ and the hyperthermia effect could efficiently kill cancer cells in vitro. As for the PT-CT treatment, the doxorubicin(DOX)-loaded nanoparticles of DOX-PLC-b-PEO@Au NPs gave a combination index of 0.9 compared to single chemotherapy(CT) or photothermal therapy(PT), demonstrating a synergistic effect. | Siqi Yang Linzhu Zhou Yue Su Rong Zhang Chang-Ming Dong | 2019 | Chinese Chemical Letters2019，30，1： | 6 |
| 16 | Insulin plus incretin:A glucose-lowering strategy for type 2-diabetes显示文摘There are many advantages of combining incretin therapy[glucagon-like peptide-1(GLP-1)receptor agonists and dipeptidyl peptidase-4(DPP-4)inhibitors]with insulin therapy as a glucose-lowering strategy in type2 diabetes.One important advantage is the complementary mode of the mechanistic action of incretin and insulin therapy.Another advantage is the reduction in risk of hypoglycemia and weight gain when adding incretin therapy to insulin.Several clinical trials have studied the addition of GLP-1 receptor agonists[exenatide BID(twice daily),lixisenatide,albiglutide]or DPP-4inhibitors(vildagliptin,sitagliptin,saxagliptin,alogliptin,linagliptin)to ongoing insulin therapy or adding insulin to ongoing therapy with a GLP-1 receptor agonist(liraglutide).These studies show improved glycemia in the presence of limited risk for hypoglycemia and weight gain with the combination of incretin therapy with insulin.This article reviews the background and clinical studies on this combination. | Bo Ahrén | 2014 | World Journal of Diabetes2014，5，1： | 5 |
| 17 | Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure显示文摘In advanced heart failure(HF), chronic inotropic therapy with intravenous milrinone, a phosphodiesterase Ⅲ inhibitor, is used as a bridge to advanced management that includes transplantation, ventricular assist device implantation, or palliation. This is especially true when repeated attempts to wean off inotropic support result in symptomatic hypotension, worsened symptoms, and/or progressive organ dysfunction. Unfortunately, patients in this clinical predicament are considered hemodynamically labile and may escape the benefits of guidelinedirected HF therapy. In this scenario, chronic milrinone infusion may be beneficial as a bridge to introduction of evidence based HF therapy. However, this strategy is not well studied, and in general, chronic inotropic infusion is discouraged due to potential cardiotoxicity that accelerates disease progression and proarrhythmic effects that increase sudden death. Alternatively, chronic inotropic support with milrinone infusion is a unique opportunity in advanced HF. This review discusses evidence that long-term intravenous milrinone support may allow introduction of beta blocker(BB) therapy. When used together, milrinone does not attenuate the clinical benefits of BB therapy while BB mitigates cardiotoxic effects of milrinone. In addition, BB therapy decreases the risk of adverse arrhythmias associated with milrinone. We propose that advanced HF patients who are intolerant to BB therapy may benefit from a trial of intravenous milrinone as a bridge to BB initiation. The discussed clinical scenarios demonstrate that concomitant treatment with milrinone infusion and BB therapy does not adversely impact standard HF therapy and may improve left ventricular function and morbidity associated with advanced HF. | Abhishek Jaiswal Vinh Q Nguyen Thierry H Le Jemtel Keith C Ferdinand | 2016 | World Journal of Cardiology2016，8，7： | 4 |
| 18 | 1,3-Bis(2-chloroethyl)-1-nitrosourea enhances the inhibitory effect of Resveratrol on 5-fluorouracil sensitive/resistant colon cancer cells显示文摘AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination treatment.METHODS:We established and characterized a 5-FU resistance(5-FU-R)cell line derived from continuous exposure(25μmol/L)to 5-FU for 20 wk in 5-FU sensitive HCT-116 cells.The proliferation and expression of different representative apoptosis and anti-apoptosis markers in 5-FU sensitive and 5-FU resistance cells were measured by the MTT assay and by Western blotting,respectively,after treatment with Resveratrol(Res)and/or 1,3-Bis(2-chloroethyl)-1-nitrosourea(BCNU).Apoptosis and cell cycle arrest was measured by 4',6'-diamidino-2-phenylindole hydrochloride staining and fluorescence-activated cell sorting analysis,respectively.The extent of DNA damage was measured by the Comet assay.We measured the visible changes in the DNA damage/repair cascade by Western blotting.RESULTS:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent manner.Combined application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual treatment.In addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive cells.We established a 5-FU resistance cell line(5-FU-R)from 5-FU-sensitive HCT-116(mismatch repair deficient)cells that was not resistant to other chemotherapeutic agents(e.g.,BCNU,Res)except 5-FU.The 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT assay.There was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU treatment.This resistant cell line overexpressed anti-apoptotic[e.g.,AKT,nuclear factorκB,FLICE-like inhibitory protein),DNA repair(e.g.,DNA polymerase beta(POL-β),DNA polymerase eta(POLH),protein Flap endonuclease 1(FEN1),DNA damage-binding protein 2(DDB2)]and 5-FU-resistance proteins(thymidylate synthase)but under expressed pro-apoptotic proteins(e.g.,DAB2,CK1)in comparison to the parental cells.Increased genotoxicity and apoptosis were observed in resistant cells after combined application of BCNU and Res in comparison to untreated or parental cells.BCNU increased the sensitivity to Res of 5-FU resistant cells compared with parental cells.Fifty percent cell death were noted in parental cells when 18μmol/L of Res was associated with fixed concentration(20μmol/L)of BCNU,but a much lower concentration of Res(8μmol/L)was needed to achieve the same effect in 5-FU resistant cells.Interestingly,increased levels of adenomatous polyposis coli and decreased levels POL-β,POLH,FEN1 and DDB2 were noted after the same combined treatment in resistant cells.CONCLUSION:BCNU combined with Res exerts a synergistic effect that may prove useful for the treatment of colon cancer and to overcome drug resistance. | Dipon Das Ranjan Preet Purusottam Mohapatra Shakti Ranjan Satapathy Chanakya Nath Kundu | 2013 | World Journal of Gastroenterology2013，19，42： | 4 |
| 19 | Preparation and evaluation of paclitaxel and Brucea javanica oil core-matched nanoemulsions to treat cancer in vitro and in vivo显示文摘Objective: Developed the core-matched nanoemulsions(CMNEs) to co-delivery paclitaxel-oleic acid(PTXOA) prodrug and Brucea javanica oil(BJO) for increasing the antitumor effect.Methods: Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology(CMT) were evaluated in vitro and in vivo.Results: The PTX-OA/BJO CMNEs were of nanoscale particle size(108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline(P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPOⅡ.Conclusion: Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity. | Shu-qing Cao Kuan-yun Zhang Xia Yan Yan Ma | 2018 | Chinese Herbal Medicines2018，10，3： | 4 |
| 20 | Influence of As_2O_3 combined with ginsenosides Rg3 on inhibition of lung cancer NCI-H1299 cells and on subsistence of nude mice bearing hepatoma显示文摘Objective:To study the effect of arsenic trioxide(As_2O_3)combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of(As_2O_3)combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As_2O_3 group.Rg3 group and As_2O_3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)%and(82.67±5.43)%,respectively.Inhibition rate of tumor cell in As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)%and(42.65±3.55)%of the original,tumor volume of saline group was 1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment. | Jian-Bo Che Zhong-Hua Liu Hong-Bing Ma Yong Li Hui Zhao Xiao-Hui Li Wei-Chao Liu Gong-Ning Shi | 2014 | Asian Pacific Journal of Tropical Medicine2014，7，10： | 3 |
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