Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic ...Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.展开更多
Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospecti...BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and par...Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual...Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.展开更多
X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.Howev...X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.展开更多
Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, ...Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.展开更多
Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and M...Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and Materials: The DFR-TSET combined the Stanford 6-field and McGill rotational methods. Dual 6 MeV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (MOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.展开更多
The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a highe...The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.展开更多
Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplem...Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse events.Results The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 years.Before RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/L.The patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing obesity.All patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG.No improvement in weight gain was observed upon RCS supplementation.Mild diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The thera...The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.展开更多
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is...Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.展开更多
Introduction: Cotrimoxazole Prophylactic Therapy (CPT) compliance lowers the risk of opportunistic infections and other Acquired Immune Deficiency Syndrome (AIDS)-related diseases. The aim of this study was to examine...Introduction: Cotrimoxazole Prophylactic Therapy (CPT) compliance lowers the risk of opportunistic infections and other Acquired Immune Deficiency Syndrome (AIDS)-related diseases. The aim of this study was to examine factors that influence compliance with CPT among HIV patients in the Care and Treatment Clinic (CTC) at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Methods: A descriptive cross-sectional study was conducted at the BMC between April 1, 2021, and June 30, 2021. Data were collected using face-to-face interviews and a semi-structured questionnaire. Data are presented in frequency, percentages, and cross-tabulation tables. A P-value of less than 0.05 was considered statistically significant. Results: The prevalence of compliance with CPT by self-reported measurement was 158 (63.7%). Most CPT-compliant participants were more likely to have a spouse who is familiar with CPT, have a family member who is aware of their HIV status, and be aware of the benefits of CPT. The majority of participants who complied with CPT were more likely to have experienced counseling during refill, felt that the length of time spent seeing doctors for treatment was reasonable, and received accurate information from them. Conclusion: Most adult HIV patients attending CTC at BMC were reported to be in compliance with CPT. These findings suggest that improving social support and patient-provider communication may be effective strategies for improving compliance with CPT among HIV patients.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
基金supported by the National Natural Science Foundation of China,No.31960120Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(both to ZW).
文摘Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
基金Supported by the Natural Science Foundation of Fujian Province,No.2020J011087 and No.2022J011025Medical Innovation Project of Fujian Provincial Health Commission,No.2020CXA006and Zhuhai Science and Technology Project,No.20181117E030040.
文摘BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.
基金supported by the National Natural Science Foundation of China(U22A20383,82003668)the Natural Science Foundation of Zhejiang Province(LD22H300002,LQ21H300002)Ningbo Technology Innovation 2025 Major Special Project(2022Z150).
文摘Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
文摘Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.
基金funded by the National Natural Science Foundation of China (Nos.81771972,52171243,and 52371256)the National Key Research and Development Program of China (No.2017YFC0107405).
文摘X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.
基金supported by the National Natural Science Foundation of China (No. 82003311, No. 82061148016, No. 82230057 and No. 82272859)National Key R&D Program of China (No. 2022YFC2505101)+2 种基金Sun Yat-Sen Clinical Research Cultivating Program (No. SYS-Q202004)Beijing Medical Award Foundation (No. YXJL2020-0941-0760)Guangzhou Science and Technology Program (No. 202102010272 and No. 202201020486)。
文摘Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.
文摘Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and Materials: The DFR-TSET combined the Stanford 6-field and McGill rotational methods. Dual 6 MeV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (MOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.
文摘The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.
基金supported by the National High Level Hospital Clinical Research Fund(2022-PUMCH-A-146)the National Natural Science Foundation of China(72074222)the Na-tional Key Research and Development Program of China(2020YFC2005005).
文摘Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse events.Results The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 years.Before RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/L.The patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing obesity.All patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG.No improvement in weight gain was observed upon RCS supplementation.Mild diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.
文摘Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.
文摘Introduction: Cotrimoxazole Prophylactic Therapy (CPT) compliance lowers the risk of opportunistic infections and other Acquired Immune Deficiency Syndrome (AIDS)-related diseases. The aim of this study was to examine factors that influence compliance with CPT among HIV patients in the Care and Treatment Clinic (CTC) at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Methods: A descriptive cross-sectional study was conducted at the BMC between April 1, 2021, and June 30, 2021. Data were collected using face-to-face interviews and a semi-structured questionnaire. Data are presented in frequency, percentages, and cross-tabulation tables. A P-value of less than 0.05 was considered statistically significant. Results: The prevalence of compliance with CPT by self-reported measurement was 158 (63.7%). Most CPT-compliant participants were more likely to have a spouse who is familiar with CPT, have a family member who is aware of their HIV status, and be aware of the benefits of CPT. The majority of participants who complied with CPT were more likely to have experienced counseling during refill, felt that the length of time spent seeing doctors for treatment was reasonable, and received accurate information from them. Conclusion: Most adult HIV patients attending CTC at BMC were reported to be in compliance with CPT. These findings suggest that improving social support and patient-provider communication may be effective strategies for improving compliance with CPT among HIV patients.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.