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.

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.

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.

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.

Efficacy of capecitabine and oxaliplatin regimen for extrahepatic metastasis of hepatocellular carcinoma following local treatments

AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer

AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the patients.METHODS:Sixty-four patients(median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy.Each patient received at least two cycles of treatment.The efficacy,side effects and patient survival were evaluated.RESULTS:The partial response(PR) rate was 43.8%(28/64).Stable disease(SD) rate was 47.9%(26/64),and disease progression rate was 15.6%(10/64).The clinical benefit rate(PR + SD) was 84.4%.The main toxicities were leukopenia(50.0%),nausea and vomiting(51.6%),diarrhea(50.0%),stomatitis(39.1%),polyneuropathy(37.5%) and hand-foot syndrome(37.5%).No grade 4 event in the entire cohort was found.The median progression-free survival was 4 mo,median overall survival was 10 mo(95% CI:8.3-11.7 mo),and the 1-and 2-year survival rates were 38.1% and 8.2%,respectively.High Karnofsky index,single metastatic lesion and response to the regimen indicated respectively good prognosis.CONCLUSION:Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients.The regimen has improved the survival moderately and merits further studies.

The short-time effects of chemotherapy with combinations of hydroxycamptothecine and oxaliplatin in treatment of advanced colorectal cancer

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.

Arterioportal shunt incidental to treatment with oxaliplatin that mimics recurrent gastric cancer

Arterioportal shunt(APS) is an organic communication between the hepatic arterial system and the portal venous system. The APS is one of the major causes of transient hepatic attenuation differences on dynamic computed tomography(CT) or magnetic resonance imaging(MRI). This condition is usually associated with trauma,liver cirrhosis,and malignancies of the liver. However,there has been no report about oxaliplatininduced APS. A 41-year-old male was diagnosed with Stage ⅢB gastric cancer. The patient initially underwent neoadjuvant chemotherapy with capecitabine and oxaliplatin After 3 cycles of therapy,the mass had markedly decreased,and a total gastrectomy with splenectomy was performed. Since the malignancy was locally invasive,the patient was continued on the same regimen of the adjuvant chemotherapy. After 3 more cycles,a computed tomography revealed a 1 cm sized arterial-enhancing nodule in the right lobe of the liver. An MRI revealed an arterial enhancing lesion,and a positron emission tomography CT scan showed a hypermetabolic lesion in the same portion of the liver. We tried to perform a liver biopsy; however,an ultrasonography could not detect any mass. A presumptive diagnosis of an APS due to a recurred cancer was made. We found a similar but slightly different case report of an oxaliplatin-induced liver injury,mimicking a metastatic tumor on an MRI. Based on a prior report,the patient was continuedon treatment with adjuvant chemotherapy following discontinuation of oxaliplatin. After 2 cycles,the arterial enhancing liver mass resolved,supporting the final diagnosis of an APS,related to oxaliplatin-induced sinusoidal injury. The patient has not experienced any a relapse after two years of additional follow up recurrent gastric cancer upon interpretation of multiple imaging modalities.

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.

A Multicenter Cohort Study for XELOX (Capecitabine, Leucovorin plus Oxaliplatin) Therapy as First-Line Treatment in Elderly Patients with Unresectable Colorectal Cancer

Oxaliplatin-based chemotherapy with bevacizumab is now widely used for colorectal cancer patients. This study evaluated the efficacy and tolerability of XELOX (capecitabine + oxaliplatin + leucovorin combined) therapy with or without bevacizumab in elderly patients. One hundred and seven patients, consisting of 52 elderly (>70 years of age) and 55 non-elderly, with unresectable colorectal cancer were enrolled in this multicenter cooperative group study using a database between October 2009 and March 2012. We evaluated the outcomes in terms of the median time to treat failure (TTF), overall response rate (ORR), disease control rate (DCR) and tolerability in both age groups. The median TTF for the XELOX + bevacizumab regimen was 7.1 months in the non-elderly group and 8.1 months in the elderly group (p = 0.838). There was no significant difference in TTF between the two groups. The ORR and DCR in the non-elderly group were 30.8% and 73.1%, respectively. In the elderly group, the ORR was 40.0% and the overall DCR was 90.0%. No severe or uncontrollable adverse events were observed in the two groups. These data indicated that the XELOX chemotherapy with or without bevacizumab has an equivalent efficacy in both groups, without increasing the adverse events even in the elderly population.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Treatment of Chronic Oxaliplatin-Induced Peripheral Neuropathy: A Systematic Review

Introduction: Oxaliplatin is a platinum-derivative chemotherapeutic agent used in digestive tumours, in the adjuvant and metastatic setting. Oxaliplatin can cause a chronic peripheral sensory neuropathy which impacts the quality of life and is dose limiting. To date, no therapeutic strategies have proved effective in the treatment of oxaliplatin-induced peripheral neuropathy (OIPN). Methods: A computerized search of the literature on PubMed database was performed. Publisher original articles were included if they focused on treatment of peripheral neuropathy among patients submitted to oxaliplatin. Eleven out of 242 reviewed papers met our inclusion criteria and were subjected to a 19-item quality checklist. Results: The included studies differed with respect to study design, patient population and sample size, neuropathic symptoms assessment and efficacy measure. Most studies had an adequate quality. Ten trials tested one drug, and one pilot study tested a non-pharmacological treatment—the neurofeedback. Of these, 3 trials included only patients submitted to oxaliplatin-based chemotherapy. Duloxetine showed moderate efficacy in 3 trials. Topical treatment with capsaicin or 10% amitriptyline was promisors in 2 single-arm trials with a few samples. Conclusion: In the last decade, there wasn’t an improvement in the treatment of chronic OIPN. The duloxetine is the unique drug with moderate efficacy on the treatment of OIPN. There is insufficient evidence to support a recommendation for any other treatment.

Observe the efficacy of the air wave pressure therapeutic equipment in treatment of oxaliplatin nerve toxicity

Objective： The aim of this study was to observe the efficacy of air wave pressure therapeutic equipment in pre- vention of oxaliplatin-inducted neurotoxicity. Methods： Forty-five patients with colorectal cancer were randomly divided into treatment group and control group, treatment group were given the treatment of air wave pressure therapeutic equipment during chemotherapy with oxaliplatin, the control group were given preventive treatment, the oxaliplatin-inducted neurotoxicity was evaluated after each cycle of chemotherapy. Evaluate the chemotherapy efficacy after the third cycle and sixth cycle of chemotherapy. Results： The treatment group have lower incidence of peripheral nerve toxicity than the control group, the difference was statistically significant （X2= 13.93; P 〈 0.01）. Chemotherapy effect between the 2 groups was no significant difference （P 〉 0.05）. Conclusion： Treatment with air wave pressure therapeutic equipment can reduce the incidence of peripheral nerve toxicity during oxaliplatin chemotherapy.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei

BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.