Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

Characteristics of molecular classification in 52 endometrial cancer and atypical hyperplasia patients receiving fertility-sparing treatment

Objective To investigate the molecular classification of endometrial cancer(EC)and atypical endometrial hyperplasia(AEH)patients treated with fertility-sparing treatment(FST),and its relationship with clinicopathological factors and treatment efficacy.Methods:A total of 52EC and AEH patients who received FST and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2022,were retrospectively collected.We analyzed the relationship between molecular classification and clinicopathological factors and treatment outcomes.Results(1)Of the 52 patients,including 46EC and 6 AEH patients,42(80.8%)achieved complete remission(CR)after FST,with a median time to achieve CR of 9 months.Ten cases(23.8%)had recurrence.(2)Patients were distributed into 4 molecular subgroups as 39 cases(75%)of copy number low(CNL),7 cases(13.5%)of microsatellite instability-high(MSI-H),4 cases(7.7%)of POLE mutations(POLEmut),and 2 cases(3.8%)of copy number high(CNH).Patients with MSI-H subgroup had more family history of tumor(6/7),more with loss of expression of mismatch repair(MMR)protein(7/7),and higher expression level of Ki-67(3/3).(3)Patients with MSI-H subgroup had the lowest CR rate at 6 months(0/7,P=0.014),and survival analysis showed that such patients were less likely to achieve CR than those with CNL(P=0.022).For CNL patients,median 6-month CR rate was 40.6%.In addition,CR was obtained in 3(3/4)POLEmut patients and 2(2/2)CNH patients,respectively.Conclusions Molecular classification relates with the treatment response in patients with EC and AEH receiving FST.Patients with MSI-H subgroup have poor treatment efficacy,and patients with CNL need to be further divided to predict treatment benefit.There are also a few successful cases in POLEmut and CNH subtgroups,which needs further research.

Late effects of the treatment of childhood cancer

Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.

A novel solution treatment and aging for powder bed fusion-laser beam Ti-6Al-2Sn-4Zr-6Mo alloy:Microstructural and mechanical characterization

Ti-6Al-4Zr-2Sn-6Mo alloy is one of the most recent titanium alloys processed using powder bed fusion-laser beam(PBF-LB)technology.This alloy has the potential to replace Ti-6Al-4V in automotive and aerospace applications,given its superior mechanical properties,which are approximately 10%higher in terms of ultimate tensile strength(UTS)and yield strength after appropriate heat treatment.In as-built conditions,the alloy is characterized by the presence of soft orthorhombicα″martensite,necessitating a postprocessing heat treatment to decompose this phase and enhance the mechanical properties of the alloy.Usually,PBFed Ti6246 components undergo an annealing process that transforms theα″martensite into anα-βlamellar microstructure.The primary objective of this research was to develop a solution treatment and aging(STA)heat treatment tailored to the unique microstructure produced by the additive manufacturing process to achieve an ultrafine bilamellar microstructure reinforced by precipitation hardening.This study investigated the effects of various solution temperatures in theα-βfield(ranging from 800 to 875℃),cooling media(air and water),and aging time to determine the optimal heat treatment parameters for achieving the desired bilamellar microstructure.For each heat treatment condition,differentα-βmicrostructures were found,varying in terms of theα/βratio and the size of the primaryα-phase lamellae.Particular attention was given to how these factors were influenced by increases in solution temperature and how microhardness correlated with the percentage of the metastableβphase present after quenching.Tensile tests were performed on samples subjected to the most promising heat treatment parameters.A comparison with literature data revealed that the optimized STA treatment enhanced hardness and UTS by13%and 23%,respectively,compared with those of the annealed alloy.Fracture surface analyses were conducted to investigate fracture mechanisms.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Controversies around the treatment of peritoneal metastases of colorectal cancer

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Mechanism of cryorolling and aging treatment for enhancing corrosion properties of 2195 Al−Li alloy

The impact of cryorolling(CR)and room temperature rolling(RTR)followed by artificial aging on the corrosion characteristics of 2195 Al−Li alloy(AA2195)was studied.Transmission electron microscope,scanning electron microscope,optical microscope,intergranular corrosion experiment,and electrochemical experiment were used.Throughout different stages of aging treatment,the corrosion behavior of both CR and RTR samples exhibited a sequential progression of pitting corrosion,followed by intergranular corrosion,and then pitting corrosion again.The corrosion rates of both samples initially showed an increase,followed by a gradual stabilization over time.The size and density of T1 phase significantly influenced the corrosion performance of the alloy.During the peak aging and over-aging stages,the CR sample exhibited superior corrosion resistance to the RTR sample,attributed to its finer T1 phase.

Efficacy,safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart:A pilot study

BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Clinicopathological features and treatment of gastrointestinal schwannomas

BACKGROUND Gastrointestinal schwannomas(GIS)are rare neurogenic tumors arising from Schwann cells in the gastrointestinal tract.Studies on GIS are limited to small case reports or focus on specific tumor sites,underscoring the diagnostic and thera-peutic challenges they pose.AIM To comprehensively examine the clinical features,pathological characteristics,treatment outcomes,associated comorbidities,and prognosis of GIS.METHODS The study population included patients diagnosed with GIS at the First Affiliated Hospital,Zhejiang University School of Medicine,between June 2007 and April 2024.Data were retrospectively collected and analyzed from medical records,including demographic characteristics,endoscopic and imaging findings,treatment modalities,pathological evaluations,and follow-up information.RESULTS In total,229 patients with GIS were included,with a mean age of 56.00 years and a male-to-female ratio of 1:1.83.The mean tumor size was 2.75 cm,and most(76.9%)were located in the stomach.Additionally,6.6%of the patients had other malig-nant tumors.Preoperative imaging and endoscopy frequently misdiagnosed GIS as gastrointestinal stromal tumors.However,accurate preoperative diagnosis was achieved using endoscopic ultrasound-guided fine-needle aspiration combined with immunohistochemical analysis,in which S100 and SOX-10 markers were mostly positive.Smaller tumors were typically managed with endoscopic resection,while larger lesions were treated with surgical resection.Follow-up results showed that most patients experienced favorable outcomes.CONCLUSION Preoperative diagnosis of GIS via clinical characteristics,endoscopy,and imaging examinations remains challenging but crucial.Endoscopic therapy provides a minimally invasive and effective option for patients.

Scalable Ir‑Doped NiFe_(2)O_(4)/TiO_(2) Heterojunction Anode for Decentralized Saline Wastewater Treatment and H_(2) Production

Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2) production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2) overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell.In dilute(0.1 M)NaCl solutions,the NFI/TiO_(2) marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was confirmed.Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic contact.Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine.The scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.

Treatment of thymoma with low-dose glucocorticoids before surgery for significant tumor shrinkage: A case report

BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.

Pancreatic primitive neuroectodermal tumors:Clinical features,treatment,and influencing factors

BACKGROUND Data on clinical characteristics,treatment outcomes,and prognosis of pancreatic primitive neuroectodermal tumors(PNETs)are limited.AIM To analyze the clinical data of 30 patients with pancreatic PNETs to identify their clinical characteristics and factors associated with prognosis.METHODS We used the keywords"primary neuroectodermal tumor,""digestive tract,""pancreas,""pancreatic,"and"gastrointestinal,"individually or in combination,to collect data from a global database for all patients with pancreatic PNET to date.Univariate and Cox regression analyses were performed to identify prognostic factors for patient survival.RESULTS A total of 30 cases of pancreatic PNET were included in this study:15 males and 15 females with a mean age of 24 years.The main symptom was abdominal pain(73.3%),and the median tumor size was 7.85 cm.Twenty-four patients(80.0%)underwent surgery and nineteen patients received adjuvant therapy.Local metastasis was observed in 13 patients(43.3%),lymph node metastasis in 10 patients(33.3%),and distant metastasis in 6 patients(20.0%).Local recurrence was observed in 13 patients(43.3%).The median survival time of all patients was 29.4 months,and the overall estimated 1-year and 3-year survival rates were approximately 66.0%and 36.4%,respectively.Univariate analysis showed that chemotherapy(P=0.036),local metastasis(P=0.041),lymph node metastasis(P=0.003),distant metastasis(P=0.049),and surgical margins(P=0.048)were the prognostic factors affecting survival.Multivariate analysis revealed only lymph node metastasis(P=0.012)as a prognostic factor.CONCLUSION Pancreatic PNET is extremely rare,occurs in young adults,has no apparent sex predisposition,has a high rate of metastasis and early recurrence,and has a very poor prognosis.The diagnosis of pancreatic PNET requires a combination of clinical symptoms,pathologic features,immunohistochemistry,and cytogenetic analysis.Univariate analysis suggested that chemotherapy,metastasis,and surgical margins were prognostic factors affecting survival,and multivariate analysis suggested that lymph node metastasis is an important prognostic factor.Therefore,early diagnosis,early and extensive resection,and adjuvant chemoradiotherapy may help improve prognosis.

Advances in radiotherapy in the treatment of esophageal cancer

Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life.Traditional radiotherapy techniques have been enhanced by the integration of advanced imaging and precision targeting technologies,such as intensity-modulated radiotherapy and proton therapy,which allow for more accurate tumor targeting while minimizing damage to surrounding healthy tissues.Additionally,combining radiotherapy with immunotherapy has shown promising results,leveraging the body’s im-mune response to enhance the effectiveness of cancer treatment.Studies have also highlighted the benefits of neoadjuvant chemoradiation followed by surgical resection,which has been associated with improved overall survival rates com-pared to radiotherapy alone.These innovations are paving the way for more effe-ctive and personalized treatment strategies,offering new hope for patients with esophageal cancer.

Variations in quantifying patient reported outcome measures to estimate treatment effect

In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.

Risk factors,monitoring,and treatment strategies for early recurrence after rectal cancer surgery

Early recurrence(ER)following surgery for rectal cancer is a significant factor impacting patient survival rates.Tsai et al identified age,preoperative neoadjuvant therapy,length of hospital stay,tumour location,and pathological stage as factors influencing the risk of ER.Postoperative monitoring for ER should encompass a thorough medical history review,physical examination,tumour marker testing,and imaging studies.Additionally,noninvasive circulating tumour cell DNA testing can be utilized to predict ER.Treatment strategies may involve radical surgery,radiation therapy,chemotherapy,and immunotherapy.Through a comprehensive analysis of risk factors,the optimization of monitoring methods,and the development of personalized treatment strategies,it is anticipated that both the efficacy of treatment and the quality of life for rectal cancer patients with postoperative recurrence can be significantly improved.

Addressing social function in the treatment of depression:A call for holistic approaches

This article discusses the importance of addressing social functioning impairment in patients with residual depressive symptoms,as highlighted in the study by Liao et al.The authors showed that social dysfunction persists in many patients despite symptom remission.This observation calls for a shift in depression treatment strategies,with an emphasis on integrating social functioning as a key treatment goal.This article suggests targeted interventions that focus on both symptomatic relief and the restoration of social function.

SEIR Mathematical Model for Influenza-Corona Co-Infection with Treatment and Hospitalization Compartments and Optimal Control Strategies

The co-infection of corona and influenza viruses has emerged as a significant threat to global public health due to their shared modes of transmission and overlapping clinical symptoms.This article presents a novel mathematical model that addresses the dynamics of this co-infection by extending the SEIR(Susceptible-Exposed-Infectious-Recovered)framework to incorporate treatment and hospitalization compartments.The population is divided into eight compartments,with infectious individuals further categorized into influenza infectious,corona infectious,and co-infection cases.The proposed mathematical model is constrained to adhere to fundamental epidemiological properties,such as non-negativity and boundedness within a feasible region.Additionally,the model is demonstrated to be well-posed with a unique solution.Equilibrium points,including the disease-free and endemic equilibria,are identified,and various properties related to these equilibrium points,such as the basic reproduction number,are determined.Local and global sensitivity analyses are performed to identify the parameters that highly influence disease dynamics and the reproduction number.Knowing the most influential parameters is crucial for understanding their impact on the co-infection’s spread and severity.Furthermore,an optimal control problem is defined to minimize disease transmission and to control strategy costs.The purpose of our study is to identify the most effective(optimal)control strategies for mitigating the spread of the co-infection with minimum cost of the controls.The results illustrate the effectiveness of the implemented control strategies in managing the co-infection’s impact on the population’s health.This mathematical modeling and control strategy framework provides valuable tools for understanding and combating the dual threat of corona and influenza co-infection,helping public health authorities and policymakers make informed decisions in the face of these intertwined epidemics.