The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvatio...Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.展开更多
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered ...Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit<sup><sup>®</sup></sup>) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNC...In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.展开更多
Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the...Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.展开更多
Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constru...Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.展开更多
Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 ant...Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。展开更多
Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with vene...Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.展开更多
Background: Vaginal discharge is one of the most common troubles faced by childbearing age women. About 20% - 25% of women who visit service of gynecology complain of vaginal discharge and leucorrhoea. Management of v...Background: Vaginal discharge is one of the most common troubles faced by childbearing age women. About 20% - 25% of women who visit service of gynecology complain of vaginal discharge and leucorrhoea. Management of vaginal discharge in low-income countries generally depends on syndromic approach, which limits the understanding of specific responsible agents. Thus targeted management is based on the identification of causal organism and targeting of therapy against it, while syndromic management is based on presence of high risk factors. Thus the oral combination kit (Azimyn FS Kit®) offers convenience of a one-day treatment compared to other multidose treatments, which will also ensure high patient adherence to treatment, thus increasing chances of desired results. Due to its widespread use, it is proposed to evaluate the effectiveness of this oral association kit therapy in management of vaginal discharge in the population of our milieu in the Democratic Republic of Congo (DRC) particularly those received in outpatient consultation in some medical facilities in city of Kinshasa. Expensive laboratory tests and the associated waiting period for result mean that patient remains without treatment while waiting for test results. Therefore, by adopting a syndromic management approach, patient’s eligibility for treatment will be decided based on abnormal vaginal discharge, their characteristics, severity and other presentations symptomatic. This approach will also avoid losing sight of patients during follow-up and will help to reduce financial burden for patients. Objectives: To determine the efficacy and safety of oral combination kit therapy containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultation in some medical facilities in the city of Kinshasa;to measure rate of recurrence of abnormal vaginal discharge in these patients. And to identify the adverse effects observed in these patients who received treatment with the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in outpatient consultation in some medical facilities in the city of Kinshasa. Methods: It will be a cross-sectional descriptive study. Sample size will be 319 women of childbearing age who consult the gynecology department with complaint of abnormal vaginal discharge and suspicion of vaginal infection, who agree to abstain from sex during treatment and who have given their written consent to use their personal and/or health data in the study. Conclusion: A study on clinical efficacy of oral combination therapy based on secnidazole, azithromycin and fluconazole is beneficial.展开更多
BACKGROUND The degree of psychological stress and the difficulty and efficacy of laparoscopic surgery differ in patients with pelvic abscesses after different durations of antiinfection treatment.AIM To compare and an...BACKGROUND The degree of psychological stress and the difficulty and efficacy of laparoscopic surgery differ in patients with pelvic abscesses after different durations of antiinfection treatment.AIM To compare and analyse the effects of different durations of anti-infective therapy on patients’preoperative psychological stress level and the clinical efficacy of laparoscopic surgery in patients with pelvic abscesses to offer a reference for the selection of therapy plans.METHODS A total of 100 patients with pelvic abscesses who were admitted to the Department of Gynecology of Suzhou Ninth Hospital affiliated to Soochow University(Suzhou Ninth People's Hospital)from January 2018 to December 2022 were retrospectively enrolled.According to the different durations of antiinfective therapy,they were divided into Group S(50 patients,received antiinfective therapy for 24-48 h)and Group L(50 patients,received anti-infective therapy for 48-96 h).Baseline data,state-trait anxiety score at admission and before surgery,self-rating anxiety scale(SAS)+self-rating depression scale(SDS)score,surgery time,adhesion grading score,intraoperative blood loss,presence or absence of intraoperative intestinal injury,ureteral injury or bladder injury,postoperative body temperature,length of hospital stay,and presence or absence of recurrence within 3 mo after surgery,chronic pelvic pain,incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction were compared between the S group and the L group.RESULTS There was no significant difference in the background data between the S group and the L group(P<0.05).There was no significant difference in the state-trait anxiety score or SAS+SDS score between the S group and the L group on admission(P<0.05).The state-trait anxiety score and SAS+SDS score of the S group were lower than those of Group L after receiving different durations of anti-infective therapy(P<0.05).There was no significant difference in the incidence of intestinal,ureteral or bladder injury between the S group and the L group(P<0.05).The surgery time of Group S was shorter than that of Group L,and the adhesion score and intraoperative blood loss volume were lower than those of Group L(P<0.05).There was no significant difference in the incidence of incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction between the S group and the L group(P<0.05).The postoperative body temperature of Group S was lower than that of Group L(P<0.05),and the hospital stay was shorter than that of Group L(P<0.05).The incidences of recurrence and chronic pelvic pain within 3 mo after surgery were lower than that of Group L(P<0.05).CONCLUSION Twenty-four to forty-eight hours of anti-infective therapy is better than 48-96 h of anti-infective therapy for patients with pelvic abscesses because the degree of psychological stress is lower,which is more conducive to achieving better outcomes after laparoscopic surgery.展开更多
Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different phar...Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic(PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties(e.g.,those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus,a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.展开更多
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 a...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.展开更多
Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report an...Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma. The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited. The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.展开更多
OBJECTIVE: To evaluate the efficacy of α-lipoic acid(ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy(DPN). DATA SOURCES: The electronic databases of Pub Med, Medline,...OBJECTIVE: To evaluate the efficacy of α-lipoic acid(ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy(DPN). DATA SOURCES: The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were(diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND(α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat. DATA SELECTION: All of the eligible studies met the following inclusion criteria:(1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.(2) The minimum duration of treatment was 2 weeks.(3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.(4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES: The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity(MNCV), median sensory nerve conduction velocity(SNCV), peroneal MNCV and peroneal SNCV.RESULTS: Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies(RR = 1.29, 95% CI: 1.21–1.38; RR = 1.43, 95% CI: 1.34–1.54, respectively). ALA plus epalrestat combination therapy also significantly improved median MNCV(WMD = 5.41, 95% CI: 2.07–8.75), median SNCV(WMD = 5.87, 95% CI: 1.52–10.22), peroneal MNCV(WMD = 5.59, 95% CI: 2.70–8.47) and peroneal SNCV(WMD = 4.57, 95% CI: 2.46–6.68).CONCLUSION: ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.展开更多
AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combin...AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.展开更多
AIM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount...AIM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC.METHODS: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system.RESULTS: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups.In PEI-RFA, enlargement of coagulated necrosis was admitted in 3 dimensions and the amount of energy requirement per unit volume of coagulated necrosis was negatively correlated with the amount of ethanol injected into HCC.CONCLUSION: These results suggest that, compared to RFA alone, PEI-RFA enables to induce comparable coagulated necrosis with smaller energy requirement, and that PEI-RFA is likely to be less invasive than RFA alone irrespective of inducing enhanced coagulated necrosis.Thus, simple prior injection of ethanol may make RFA treatment more effective and less invasive for the treatment of patients with HCC.展开更多
The introduction of oral phosphodiesterase-5 inhibitors (PDE51s) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction...The introduction of oral phosphodiesterase-5 inhibitors (PDE51s) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE51 monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE51 therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE51 plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.展开更多
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
文摘Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit<sup><sup>®</sup></sup>) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
基金Zanjan University of Medical Sciences supported the present study(Grant Number:A-12-1244-18).
文摘In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.
基金supported by the National Key Research and Development Programs of China(Grant No.2018YFA0209700)National Natural Science Foundation of China(Grant No.22077073)+1 种基金Frontiers Science Center for New Organic Matter,Nankai University(Grant No.63181206)the Fundamental Research Funds for the Central Universities,Nankai University(Grant No.63206015)。
文摘Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.
基金financial supports from National Natural Science Foundation of China(32000992,21977081,32101124)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001)+1 种基金Wenzhou Medical University(KYYW201901)Zhejiang Qianjiang Talent Plan(QJD20020224)
文摘Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.
文摘Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。
文摘Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.
文摘Background: Vaginal discharge is one of the most common troubles faced by childbearing age women. About 20% - 25% of women who visit service of gynecology complain of vaginal discharge and leucorrhoea. Management of vaginal discharge in low-income countries generally depends on syndromic approach, which limits the understanding of specific responsible agents. Thus targeted management is based on the identification of causal organism and targeting of therapy against it, while syndromic management is based on presence of high risk factors. Thus the oral combination kit (Azimyn FS Kit®) offers convenience of a one-day treatment compared to other multidose treatments, which will also ensure high patient adherence to treatment, thus increasing chances of desired results. Due to its widespread use, it is proposed to evaluate the effectiveness of this oral association kit therapy in management of vaginal discharge in the population of our milieu in the Democratic Republic of Congo (DRC) particularly those received in outpatient consultation in some medical facilities in city of Kinshasa. Expensive laboratory tests and the associated waiting period for result mean that patient remains without treatment while waiting for test results. Therefore, by adopting a syndromic management approach, patient’s eligibility for treatment will be decided based on abnormal vaginal discharge, their characteristics, severity and other presentations symptomatic. This approach will also avoid losing sight of patients during follow-up and will help to reduce financial burden for patients. Objectives: To determine the efficacy and safety of oral combination kit therapy containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultation in some medical facilities in the city of Kinshasa;to measure rate of recurrence of abnormal vaginal discharge in these patients. And to identify the adverse effects observed in these patients who received treatment with the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in outpatient consultation in some medical facilities in the city of Kinshasa. Methods: It will be a cross-sectional descriptive study. Sample size will be 319 women of childbearing age who consult the gynecology department with complaint of abnormal vaginal discharge and suspicion of vaginal infection, who agree to abstain from sex during treatment and who have given their written consent to use their personal and/or health data in the study. Conclusion: A study on clinical efficacy of oral combination therapy based on secnidazole, azithromycin and fluconazole is beneficial.
文摘BACKGROUND The degree of psychological stress and the difficulty and efficacy of laparoscopic surgery differ in patients with pelvic abscesses after different durations of antiinfection treatment.AIM To compare and analyse the effects of different durations of anti-infective therapy on patients’preoperative psychological stress level and the clinical efficacy of laparoscopic surgery in patients with pelvic abscesses to offer a reference for the selection of therapy plans.METHODS A total of 100 patients with pelvic abscesses who were admitted to the Department of Gynecology of Suzhou Ninth Hospital affiliated to Soochow University(Suzhou Ninth People's Hospital)from January 2018 to December 2022 were retrospectively enrolled.According to the different durations of antiinfective therapy,they were divided into Group S(50 patients,received antiinfective therapy for 24-48 h)and Group L(50 patients,received anti-infective therapy for 48-96 h).Baseline data,state-trait anxiety score at admission and before surgery,self-rating anxiety scale(SAS)+self-rating depression scale(SDS)score,surgery time,adhesion grading score,intraoperative blood loss,presence or absence of intraoperative intestinal injury,ureteral injury or bladder injury,postoperative body temperature,length of hospital stay,and presence or absence of recurrence within 3 mo after surgery,chronic pelvic pain,incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction were compared between the S group and the L group.RESULTS There was no significant difference in the background data between the S group and the L group(P<0.05).There was no significant difference in the state-trait anxiety score or SAS+SDS score between the S group and the L group on admission(P<0.05).The state-trait anxiety score and SAS+SDS score of the S group were lower than those of Group L after receiving different durations of anti-infective therapy(P<0.05).There was no significant difference in the incidence of intestinal,ureteral or bladder injury between the S group and the L group(P<0.05).The surgery time of Group S was shorter than that of Group L,and the adhesion score and intraoperative blood loss volume were lower than those of Group L(P<0.05).There was no significant difference in the incidence of incision infection,dysmenorrhea,menstrual disorder or intestinal obstruction between the S group and the L group(P<0.05).The postoperative body temperature of Group S was lower than that of Group L(P<0.05),and the hospital stay was shorter than that of Group L(P<0.05).The incidences of recurrence and chronic pelvic pain within 3 mo after surgery were lower than that of Group L(P<0.05).CONCLUSION Twenty-four to forty-eight hours of anti-infective therapy is better than 48-96 h of anti-infective therapy for patients with pelvic abscesses because the degree of psychological stress is lower,which is more conducive to achieving better outcomes after laparoscopic surgery.
基金supported by the grants from the National Basic Research Program of China(Grant No.973 Program 2014CB931900,2013CB932503)National Natural Science Foundation of China(Grant No.81373357,81422048,81673382,81521005)
文摘Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic(PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties(e.g.,those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus,a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.
基金supported by grants from the Major State Basic Research Development Program (973) (No. 2007CB512905)the National Natural Science Foundation of China (No. 30771918)the Major State S&T Projects of China (11th Five-Year) (2008ZX10002-007)
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.
基金supported by the Wu Jieping Medical Foundation Grant (No. 320.6750.11074)
文摘Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma. The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited. The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.
基金supported by the National Natural Science Foundation of China,No.81370165a grant from the Public Benefit Technology and Society Development Program of Zhejiang Province of China,No.2015C33309+2 种基金a grant from the Ningbo Science and Technology Innovation Team Program in China,No.2014B82002,2015B11050a grant from the Ningbo Science and Technology Project in China,No.2015A610217the Fang Runhua Fund of Hong Kong,K.C.Wong Magna Fund in Ningbo University
文摘OBJECTIVE: To evaluate the efficacy of α-lipoic acid(ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy(DPN). DATA SOURCES: The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were(diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND(α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat. DATA SELECTION: All of the eligible studies met the following inclusion criteria:(1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.(2) The minimum duration of treatment was 2 weeks.(3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.(4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES: The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity(MNCV), median sensory nerve conduction velocity(SNCV), peroneal MNCV and peroneal SNCV.RESULTS: Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies(RR = 1.29, 95% CI: 1.21–1.38; RR = 1.43, 95% CI: 1.34–1.54, respectively). ALA plus epalrestat combination therapy also significantly improved median MNCV(WMD = 5.41, 95% CI: 2.07–8.75), median SNCV(WMD = 5.87, 95% CI: 1.52–10.22), peroneal MNCV(WMD = 5.59, 95% CI: 2.70–8.47) and peroneal SNCV(WMD = 4.57, 95% CI: 2.46–6.68).CONCLUSION: ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.
文摘AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.
文摘AIM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC.METHODS: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system.RESULTS: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups.In PEI-RFA, enlargement of coagulated necrosis was admitted in 3 dimensions and the amount of energy requirement per unit volume of coagulated necrosis was negatively correlated with the amount of ethanol injected into HCC.CONCLUSION: These results suggest that, compared to RFA alone, PEI-RFA enables to induce comparable coagulated necrosis with smaller energy requirement, and that PEI-RFA is likely to be less invasive than RFA alone irrespective of inducing enhanced coagulated necrosis.Thus, simple prior injection of ethanol may make RFA treatment more effective and less invasive for the treatment of patients with HCC.
文摘The introduction of oral phosphodiesterase-5 inhibitors (PDE51s) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE51 monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE51 therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE51 plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.