The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are...The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.展开更多
This study aims to determine the environmental aspects and impacts of the phase relating to the operation of Manantali’s hydroelectric structures and facilities according to the requirements of the ISO 14001 version ...This study aims to determine the environmental aspects and impacts of the phase relating to the operation of Manantali’s hydroelectric structures and facilities according to the requirements of the ISO 14001 version 2015 standard. To do this, the mapping of the different work areas made it possible to identify all the activities within the framework of the farm. Based on the mapping, environmental measurements made including noise level, brightness, electric and magnetic fields, total particles, PM10, PM2.5, PM1 showed the work areas with the exposure limit values exceeded. The inventories of the waste produced show eighteen (18) types of waste, 67% of which are special industrial waste (SIW), 28% are ordinary industrial waste (OIW) and 5% are inert industrial waste (IIW). The identification and assessment of environmental aspects and impacts made it possible to determine sixteen (16) positive and negative significant environmental aspects (ESAs). The positive AES must be maintained, and for the negative ones, mitigation and mitigation measures must be put in place in order to manage them effectively. This will ultimately improve environmental management in the operation of hydroelectric structures and facilities.展开更多
Objective: Describe the psychosocial aspects of male infertility at the hospital of the Sino-Guinean Friendship. Patients and method: It is a prospective study of a descriptive type covering a period of 6 months. The ...Objective: Describe the psychosocial aspects of male infertility at the hospital of the Sino-Guinean Friendship. Patients and method: It is a prospective study of a descriptive type covering a period of 6 months. The study covered 17 patients, all received for a desire to conceive after at least one year of regular sexual intercourse without contraception. The data were collected from patient interviews using a pre-established questionnaire. Results: The average age of the patients was 32.07 years with extremes of 23 years and 42 years. During this study, 64.70% of patients were no longer participating in community ceremonies. The patients’ relationships with their spouse and family deteriorated in 52.94% and 47.06%, respectively. Conversely, relations with the family of origin remained unchanged in 70.59 percent of cases. The reduction in economic activity was by 13 patients (76.48%). Conclusion: Male infertility causes a real psychic earthquake in men with its corollaries of negative feelings. The rather complex moral repercussions of male infertility affect not only the individual, his/her partner, and family, but also economic activity.展开更多
Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin r...Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.展开更多
Aim: The objective of this research is to highlight the effectiveness of physical exercise and music therapy in older patients with Alzheimer’s disease (AD). Methods: Patients with a mild level of AD were included in...Aim: The objective of this research is to highlight the effectiveness of physical exercise and music therapy in older patients with Alzheimer’s disease (AD). Methods: Patients with a mild level of AD were included in this study, divided into the therapy group (TG;N = 30, aged 68 ± 3.2 years) and the control group (CG;N=30, aged 65 ± 2.6 years). The therapy group was enrolled in an exercise-training program (walking, resistance and balance exercises) combined with musical therapy for 10 weeks (three sessions of 60 minutes per week). The Control group was instructed to follow their daily rhythm of life (e.g., rest, reading) under the same conditions. The intervention program was enrolled under the supervision of;one psychologist;a neurologist;two music therapists, and two physiotherapists, all belonging to the same hospital unit. After 10 weeks of participation in the combined program, cognitive parameters were improved in the therapy group measured with the Behavior Pathology in Alzheimer Disease (BEHAVE-AD), (p < 0.05) for activity disturbance, diurnal rhythm disturbances, anxieties and phobias, affective disturbance. The percentage range of improvements is 1.07% to 2.96%. Results: Our results demonstrate that physical exercise combined with music therapy improves cognitive function in patients with Alzheimer’s disease. Conclusions: Physical exercise and music therapy are beneficial combined treatments for improving life quality in older patients. This approach may be useful to help patients with a mild level of Alzheimer’s disease improve their behavioral and psychological parameters.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
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
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
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
Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Not...Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative res...Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.展开更多
Background:Social distancing may affect athletes,training,causing negative effects on mental and physical health.Objective:This study therefore aimed to characterize the perception of Brazilian athletes about their ph...Background:Social distancing may affect athletes,training,causing negative effects on mental and physical health.Objective:This study therefore aimed to characterize the perception of Brazilian athletes about their physical and psychosocial aspects,sleep quality and coping strategies during the quarantine of the coronavirus disease 2019(COVID-19)pandemic.Methods:This was a cross-sectional study with online survey,performed with Brazilian athletes(amateur and professional)over 18 years.The main outcomes measures assessed were physical and psychosocial aspects,sleep quality and coping strategies.Results:A total of 214 athletes were included.The average weekly hours of training during the quarantine was 4.71±3.71 h,of which 64.5%athletes(138/214)were oriented by medical staff during training.For 52.8%(113/214)of athletes,training intensity during the quarantine was different/very different from the intensity before the quarantine.79.4%athletes(170/214)reported moderate to extreme difficulties in keeping the same level of training during the quarantine.77.1%athletes(165/214)had moderate to extreme anxiety and each of the athletes had concern about his or her athletic career future,including return to the sport.72.9%athletes(156/214)reported change in sleep schedule during the quarantine period.Conclusion:The quarantine period during COVID-19 pandemic negatively affected the athlete^perception about training routine,since athletes reported reduction in training hours and training intensity.Overall,the athletes reported that they were moderately to extremely anxious.They also had concerns about their career in the future,as well as concerns regarding return to sport.展开更多
Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safet...Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.展开更多
BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential thera...BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.展开更多
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82071199 and 81871117)the Natural Science Foundation of Jiangsu Province(Grant No.BK20230057)Shandong Postdoctoral Innovative Talents Program(Grant No.SDBX2023056).
文摘The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.
文摘This study aims to determine the environmental aspects and impacts of the phase relating to the operation of Manantali’s hydroelectric structures and facilities according to the requirements of the ISO 14001 version 2015 standard. To do this, the mapping of the different work areas made it possible to identify all the activities within the framework of the farm. Based on the mapping, environmental measurements made including noise level, brightness, electric and magnetic fields, total particles, PM10, PM2.5, PM1 showed the work areas with the exposure limit values exceeded. The inventories of the waste produced show eighteen (18) types of waste, 67% of which are special industrial waste (SIW), 28% are ordinary industrial waste (OIW) and 5% are inert industrial waste (IIW). The identification and assessment of environmental aspects and impacts made it possible to determine sixteen (16) positive and negative significant environmental aspects (ESAs). The positive AES must be maintained, and for the negative ones, mitigation and mitigation measures must be put in place in order to manage them effectively. This will ultimately improve environmental management in the operation of hydroelectric structures and facilities.
文摘Objective: Describe the psychosocial aspects of male infertility at the hospital of the Sino-Guinean Friendship. Patients and method: It is a prospective study of a descriptive type covering a period of 6 months. The study covered 17 patients, all received for a desire to conceive after at least one year of regular sexual intercourse without contraception. The data were collected from patient interviews using a pre-established questionnaire. Results: The average age of the patients was 32.07 years with extremes of 23 years and 42 years. During this study, 64.70% of patients were no longer participating in community ceremonies. The patients’ relationships with their spouse and family deteriorated in 52.94% and 47.06%, respectively. Conversely, relations with the family of origin remained unchanged in 70.59 percent of cases. The reduction in economic activity was by 13 patients (76.48%). Conclusion: Male infertility causes a real psychic earthquake in men with its corollaries of negative feelings. The rather complex moral repercussions of male infertility affect not only the individual, his/her partner, and family, but also economic activity.
文摘Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.
文摘Aim: The objective of this research is to highlight the effectiveness of physical exercise and music therapy in older patients with Alzheimer’s disease (AD). Methods: Patients with a mild level of AD were included in this study, divided into the therapy group (TG;N = 30, aged 68 ± 3.2 years) and the control group (CG;N=30, aged 65 ± 2.6 years). The therapy group was enrolled in an exercise-training program (walking, resistance and balance exercises) combined with musical therapy for 10 weeks (three sessions of 60 minutes per week). The Control group was instructed to follow their daily rhythm of life (e.g., rest, reading) under the same conditions. The intervention program was enrolled under the supervision of;one psychologist;a neurologist;two music therapists, and two physiotherapists, all belonging to the same hospital unit. After 10 weeks of participation in the combined program, cognitive parameters were improved in the therapy group measured with the Behavior Pathology in Alzheimer Disease (BEHAVE-AD), (p < 0.05) for activity disturbance, diurnal rhythm disturbances, anxieties and phobias, affective disturbance. The percentage range of improvements is 1.07% to 2.96%. Results: Our results demonstrate that physical exercise combined with music therapy improves cognitive function in patients with Alzheimer’s disease. Conclusions: Physical exercise and music therapy are beneficial combined treatments for improving life quality in older patients. This approach may be useful to help patients with a mild level of Alzheimer’s disease improve their behavioral and psychological parameters.
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 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.
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.
文摘Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
基金the Specific Research Project of Guangxi for Research Bases and Talents,No.GuiKe AD22035057the National Natural Science Foundation of China,No.82060510 and No.82260569.
文摘Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.
文摘Background:Social distancing may affect athletes,training,causing negative effects on mental and physical health.Objective:This study therefore aimed to characterize the perception of Brazilian athletes about their physical and psychosocial aspects,sleep quality and coping strategies during the quarantine of the coronavirus disease 2019(COVID-19)pandemic.Methods:This was a cross-sectional study with online survey,performed with Brazilian athletes(amateur and professional)over 18 years.The main outcomes measures assessed were physical and psychosocial aspects,sleep quality and coping strategies.Results:A total of 214 athletes were included.The average weekly hours of training during the quarantine was 4.71±3.71 h,of which 64.5%athletes(138/214)were oriented by medical staff during training.For 52.8%(113/214)of athletes,training intensity during the quarantine was different/very different from the intensity before the quarantine.79.4%athletes(170/214)reported moderate to extreme difficulties in keeping the same level of training during the quarantine.77.1%athletes(165/214)had moderate to extreme anxiety and each of the athletes had concern about his or her athletic career future,including return to the sport.72.9%athletes(156/214)reported change in sleep schedule during the quarantine period.Conclusion:The quarantine period during COVID-19 pandemic negatively affected the athlete^perception about training routine,since athletes reported reduction in training hours and training intensity.Overall,the athletes reported that they were moderately to extremely anxious.They also had concerns about their career in the future,as well as concerns regarding return to sport.
基金The work was financially supported by the National Natural Science Foundation of China(No.52173135,22207024)Jiangsu Specially Appointed Professorship,Leading Talents of Innovation and Entrepreneurship of Gusu(ZXL2022496)the Suzhou Science and Technology Program(SKY2022039).
文摘Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.
文摘BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
