Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

Efficacy of cetuximab combination with chemotherapy in non-small cell lung cancer first-line setting:the summary based on publications

Objective： The combination of cetuximab with standard chemotherapy was not widely studied though it was recommended by NCCN 2009 to apply in non-small cell lung cancer （NSCLC） first-line setting. The aim of this study was to summary the efficacy and safety profiles of all the NSCLC patients available in openly published papers treated with above mentioned regimens. Methods： The PubMed database was used to search all the papers on NSCLC associated with cetuximab treatment, and only the clinical trails applied cetuximab combined with doublets cytotoxic chemotherapy in first-line setting till to 30 November 2009 were collected. And the medians and their 95% CI of objective response rate （ORR）, progression free survival （PFS）, overall survival （OS）, and the common adverse events were calculated. Results： （1） Eight papers including 1032 patients were collected, and all cases were at advanced stage. （2） The ratio of male and female patients was 1.6, 50.1% patients were adenocarcinoma and 28.2% patients were squamous cell carcinoma （SCC）, 90.0% patients were PS = 0-1, and 78.2% patients were white ethnic. （3） The disease control rate （DCR）, ORR, PFS, and OS were 65.2% （95% CI： 60.7%-69.7%）, 33.2% （95% CI： 30.3%-36.1%）, 5.0 months （95% CI： 4.7-5.3） and 10.9 months （95% Cl： 9.6-12.2）, respectively. Conclusion： This is the first study to summarize the efficacy and safety profiles of cetuximab combined with chemotherapy in NSCLC first-line setting based on all available patients. The addition of cetuximab caused promising prognosis and acceptable side effects excepting higher incidence of neutropenia, and febrile neutropenia.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer:Gemcitabine monotherapy vs combination chemotherapy

BACKGROUND Combination chemotherapy(gemcitabine plus nab-paclitaxel and FOLFIRINOX)is widely used as the standard first-line treatment for pancreatic cancer.Considering the severe toxicities of combination chemotherapy,gemcitabine monotherapy(G mono)could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status.However,reports on the efficacy of G mono in patients older than 75 years are limited.AIM To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.METHODS We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono(n=45)or combination therapy(n=59)as a first-line treatment between 2011 and 2019.All patients were histologically diagnosed with ductal adenocarcinoma.Primary outcomes were progression-free survival and overall survival.We also analyzed subgroups according to age[65-74 years(elderly)and≥75 years(very elderly)].Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.RESULTS The baseline characteristics were significantly different between the two chemotherapy groups,especially regarding age,ratio of multiple metastases,tumor burden,and Eastern Cooperative Oncology Group performance status.After propensity score matching,the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients.In the elderly patients,the median progression-free survival(62 d vs 206 d,P=0.000)and overall survival(102 d vs 302 d,P=0.000)were longer in the combination chemotherapy group.However,in the very elderly patients,the median progression-free survival(147 d and 174 d,respectively,P=0.796)and overall survival(227 d and 211 d,respectively,P=0.739)were comparable between the G mono and combination chemotherapy groups.Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group,especially thromboembolism(G mono vs nab-paclitaxel vs FOLFIRINOX;8.9%vs 5.9%vs 28%,P=0.041),neutropenia(40.0%vs 76.5%vs 84.0%,P=0.000),and neuropathy(0%vs 61.8%vs 28.0%,P=0.006).CONCLUSION In elderly patients,combination therapy is more effective than G mono.However,G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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.

Advances in extracellular vesicle-based combination therapies for spinal cord injury

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.

Combination Activity of Standard Antituberculosis Drugs and Extracts of Medicinal Plants Commonly Used in Traditional Treatment of Tuberculosis in Uganda

Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

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.

Adaptive H_(∞)Filtering Algorithm for Train Positioning Based on Prior Combination Constraints

To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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.

Evaluation of soil erosion vulnerability in Hubei Province of China using RUSLE model and combination weighting method

Soil erosion has been recognized as a critical environmental issue worldwide.While previous studies have primarily focused on watershed-scale soil erosion vulnerability from a natural factor perspective,there is a notable gap in understanding the intricate interplay between natural and socio-economic factors,especially in the context of spatial heterogeneity and nonlinear impacts of human-land interactions.To address this,our study evaluates the soil erosion vulnerability at a provincial scale,taking Hubei Province as a case study to explore the combined effects of natural and socio-economic factors.We developed an evaluation index system based on 15 indicators of soil erosion vulnerability:exposure,sensitivity,and adaptability.In addition,the combination weighting method was applied to determine index weights,and the spatial interaction was analyzed using spatial autocorrelation,geographical temporally weighted regression and geographical detector.The results showed an overall decreasing soil erosion intensity in Hubei Province during 2000 and 2020.The soil erosion vulnerability increased before 2000 and then.The areas with high soil erosion vulnerability were mainly confined in the central and southern regions of Hubei Province(Xiantao,Tianmen,Qianjiang and Ezhou)with obvious spatial aggregation that intensified over time.Natural factors(habitat quality index)had negative impacts on soil erosion vulnerability,whereas socio-economic factors(population density)showed substantial spatial variability in their influences.There was a positive correlation between soil erosion vulnerability and erosion intensity,with the correlation coefficients ranging from-0.41 and 0.93.The increase of slope was found to enhance the positive correlation between soil erosion vulnerability and intensity.

LociScan,a tool for screening genetic marker combinations for plant variety discrimination

To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.

A Clinical Study to Assess the Effectiveness of Oral Combination Kit Therapy in Syndromic Management of Abnormal Vaginal Discharge (FEMINE Study) in Kinshasa, Democratic Republic of Congo

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®) 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® 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® 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.

Orthogonal matrix of polarization combinations:concept and application to multichannel holographic recording

Orthogonal matrices have become a vital means for coding and signal processing owing to their unique distributional properties.Although orthogonal matrices based on amplitude or phase combinations have been extensively explored,the orthogonal matrix of polarization combinations(OMPC)is a novel,relatively unexplored concept.Herein,we propose a method for constructing OMPCs of any dimension encompassing 4n(where n is 1,2,4,8,…)mutually orthogonal 2ncomponent polarization combinations.In the field of holography,the integration of polarization multiplexing techniques with polarization-sensitive materials is expected to emerge as a groundbreaking approach for multichannel hologram multiplexing,offering considerable enhancements in data storage capacity and security.A multidimensional OMPC enables the realization of multichannel multiplexing and dynamical modulation of information in polarization holographic recording.Despite consolidating all information into a single position within the material,we effectively avoided extraneous crosstalk during the reconstruction process.Our results show that achieving four distinct holographic images individually and simultaneously depends on the polarization combination represented by the incident wave.This discovery opens up a new avenue for achieving highly holographic information storage and dynamically displayed information,harnessing the potential of OMPC to expand the heretofore limited dimensionality of orthogonal polarization.

Pathogenicity Analysis on Magnaporthe oryzae from Hybrid Combination Wuyou 308

Eighteen blast isolates were obtained from hybrid combination Wuyou308 using the Magnaporthe oryzae pathogen isolation method.Race identification of these isolates was conducted based on seven Chinese blast differentials and 11 blast monogenic lines.The results indicated that the isolates were identified as the races of ZB13,ZB15 and ZC13,accounting for 66.67%,27.78%,5.56%,respectively,and the resistance genes including Pi-ta2 and Pi-sh,Pi-i were highly susceptible to these isolates,while the resistance genes like Pi-kh,Pi-1,Pi2,Pi-9 and Pi-50 showed good resistance to tested pathogens.All isolates were compatible to the original rice hybrid Wuyou308.Three isolates including GDHY-308-1401 were used for testing their pathogenicity to 45 local varieties.The results demonstrated that 13 varieties appeared highly susceptible to the tested isolates,accounting for 28.89%;two varieties appeared moderately susceptible to the tested isolates,accounting for 4.44%;30 varieties showed moderately/highly resistance,accounting for 66.67%.Among them,some of new hybrid combinations such as Wufengyou 9802,Wuyou 613,Wuyou 1179 showed good resistance to the inoculated strains,and they were recommended to be candidates in the rice region where Wuyou308 showed susceptibility.

Exploring combination therapy centered on targeted immunotherapy for advanced hepatocellular carcinoma:a beacon of hope

Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.