Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as eit...Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.展开更多
Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,th...Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.展开更多
Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,...Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,064 patients were collected from 555 hospitals in 28 provinces of China.Results:Among 9,064 NHL patients,there were 5,241 males(57.8%)and 3,823 females(42.2%),with a male-to-female ratio of 1.37:1.Patients aged≥45 years accounted for 89.6%,with a mean age of 61.87±13.30 years.The predominant NHL subtypes were diffuse large B-cell lymphoma(DLBCL,45.2%),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL,19.8%),marginal zone lymphoma(MZL,13.9%),mantle cell lymphoma(MCL,9.7%),and central nervous system lymphoma(CNSL,4.3%).Combination therapy served as the primary treatment modality across all NHL subtypes.Conclusions:NHL in China demonstrates male predominance and primarily affects middle-aged and elderly populations,with combination chemotherapy remaining the mainstay therapeutic approach.展开更多
Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility...Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility,biodegradability,and the ability to modulate the tumor microenvironment.The main degradation products of magnesium alloys are magnesium ions(Mg^(2+)),hydrogen(H_(2)),and magnesium hydroxide(Mg(OH)_(2)).Magnesium ions can regulate tumor growth and metastasis by mediating the inflammatory response and oxidative stress,maintaining genomic stability,and affecting the tumor microenvironment.Similarly,hydrogen can inhibit tumorigenesis through antioxidant and anti-inflammatory properties.Moreover,Mg(OH)_(2) can alter the pH of the microenvironment,impacting tumorigenesis.Biodegradable magnesium alloys serve various functions in clinical applications,including,but not limited to,bonefixation,coronary stents,and drug carriers.Nonetheless,the anti-tumor mechanism associated with magnesium-based materials has not been thoroughly investigated.This review provides a comprehensive overview of the current state of magnesium-based therapies for cancer.It highlights the mechanisms of action,identifies the challenges that must be addressed,and discusses prospects for oncological applications.展开更多
Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by re...Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.展开更多
BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients ex...BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.展开更多
Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research o...Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.展开更多
Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives...Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.展开更多
Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve ...Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.展开更多
Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fis...Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.展开更多
Despite continuous efforts to improve the robustness of cardiac valve implants,neither bioprosthetic nor mechanical valves fulfill both hemodynamic and durability requirements.This study discussed novel flexible leafl...Despite continuous efforts to improve the robustness of cardiac valve implants,neither bioprosthetic nor mechanical valves fulfill both hemodynamic and durability requirements.This study discussed novel flexible leaflet designs,focusing on polymeric materials with proven hemocompatibility,such as polyether ether ketone,of much higher stiffness than native tissue,aiming at optimal valve implants.A biomimetic valve with a single-curvature belly-curve(B-C)was used as a reference for new design variants with a double-curvature B-C with varying radii.Soft(13.2 MPa)and stiff(2.4 GPa)leaflet materials and different thicknesses were studied using lean simulations and in vitro experiments under physiologic hemodynamic conditions.The performance was assessed using opening pressure(OP)and orifice area(OA).The latter was determined by a newly developed automatized image processing tool.Experimental trends are in agreement with simulations and demonstrated that a buckling-inspired double-curvature leaflet design significantly enhances the trileaflet valve opening behavior,which is particularly advantageous for stiffer leaflet materials.Compared to the reference,the best-performing variant showed an OP improvement of 47%and 44%based on simulations and experiments,respectively.In contrast,the achieved mean pressure differential was directly comparable to state-of-the-art bioprosthetic valves.The OA was slightly reduced for new variants but still in the satisfying range.展开更多
Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment reg...Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.展开更多
The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the ...The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the urban space.In this paper,we use metro smart card data from two Chinese metropolises,Shanghai and Shenzhen.Five metro mobility indicators are introduced,and association rules are established to explore the mobility patterns.The proportion of people entering and exiting the station is used to measure the jobs-housing balance.It is found that the average travel distance and duration of Shanghai passengers are higher than those of Shenzhen,and the proportion of metro commuters in Shanghai is higher than that of Shenzhen.The jobs-housing spatial relationship in Shenzhen based on metro travel is more balanced than that in Shanghai.The fundamental reason for the differences between the two cities is the difference in urban morphology.Compared with the monocentric structure of Shanghai,the polycentric structure of Shenzhen results in more scattered travel hotspots and more diverse travel routes,which helps Shenzhen to have a better jobs-housing balance.This paper fills a gap in comparative research among Chinese cities based on transportation big data analysis.The results provide support for planning metro routes,adjusting urban structure and land use to form a more reasonable metro network,and balancing the jobs-housing spatial relationship.展开更多
Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness...Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness raised concerns about the prevalence of the diseases among the youth population, and motivated the SVG Retired Nurses Association (SVGRNA) to collaborate with the Mustique Charitable Trust (MCT) to conduct the “Be Healthy: Know Your Numbers” research project among college-age students. The tri-fold purpose of the project was to determine the prevalence of high blood pressure and blood sugar levels among the college-aged population in Savageries, the awareness of the youths about the causal factors of the diseases, and encourage healthy lifestyle among the demographic. For this mixed-method research project, both quantitative and qualitative data were gathered from a sample of 851 students;306 were males and 545 were females. The results revealed that a significantly high number of students were diabetic and hypertensive, or were at high risk of getting the diseases on account of their poor dietary and lifestyle practices. The highest readings for both diseases were seen among the males. At the onset of the research, the students were largely apathetic toward the diseases. However, there was noticeable attitudinal change, and demonstrable willingness to make the needed lifestyle changes. The study concluded that mitigating the risks of hypertension and diabetes within the youth community in St. Vincent and the Grenadines will be achieved through education about the causal factors and implications of the diseases, as well as through targeted interventions delivered by a wide cross-section of stakeholders.展开更多
Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study desi...Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.展开更多
Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling o...Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood.Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.展开更多
基金supported by the Rainwater Charitable Foundation。
文摘Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.
文摘Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
文摘Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,064 patients were collected from 555 hospitals in 28 provinces of China.Results:Among 9,064 NHL patients,there were 5,241 males(57.8%)and 3,823 females(42.2%),with a male-to-female ratio of 1.37:1.Patients aged≥45 years accounted for 89.6%,with a mean age of 61.87±13.30 years.The predominant NHL subtypes were diffuse large B-cell lymphoma(DLBCL,45.2%),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL,19.8%),marginal zone lymphoma(MZL,13.9%),mantle cell lymphoma(MCL,9.7%),and central nervous system lymphoma(CNSL,4.3%).Combination therapy served as the primary treatment modality across all NHL subtypes.Conclusions:NHL in China demonstrates male predominance and primarily affects middle-aged and elderly populations,with combination chemotherapy remaining the mainstay therapeutic approach.
文摘Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility,biodegradability,and the ability to modulate the tumor microenvironment.The main degradation products of magnesium alloys are magnesium ions(Mg^(2+)),hydrogen(H_(2)),and magnesium hydroxide(Mg(OH)_(2)).Magnesium ions can regulate tumor growth and metastasis by mediating the inflammatory response and oxidative stress,maintaining genomic stability,and affecting the tumor microenvironment.Similarly,hydrogen can inhibit tumorigenesis through antioxidant and anti-inflammatory properties.Moreover,Mg(OH)_(2) can alter the pH of the microenvironment,impacting tumorigenesis.Biodegradable magnesium alloys serve various functions in clinical applications,including,but not limited to,bonefixation,coronary stents,and drug carriers.Nonetheless,the anti-tumor mechanism associated with magnesium-based materials has not been thoroughly investigated.This review provides a comprehensive overview of the current state of magnesium-based therapies for cancer.It highlights the mechanisms of action,identifies the challenges that must be addressed,and discusses prospects for oncological applications.
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by the U.S.Department of Defense(W81XWH-09-2-0194 for the pilot phase)the Canadian Institutes of Health Research(MCT-94834 for the pilot phase and 14238 for the definitive phase).
文摘Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.
文摘BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.
基金Supported by The China Scholarship Council,No.202308420035.
文摘Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.
文摘Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.
文摘Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.
文摘Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.
基金provided by Board of the Swiss Federal Institutes of TechnologyUniversitat Zürichthe Laboratory of Composite Materials and Adaptive structures。
文摘Despite continuous efforts to improve the robustness of cardiac valve implants,neither bioprosthetic nor mechanical valves fulfill both hemodynamic and durability requirements.This study discussed novel flexible leaflet designs,focusing on polymeric materials with proven hemocompatibility,such as polyether ether ketone,of much higher stiffness than native tissue,aiming at optimal valve implants.A biomimetic valve with a single-curvature belly-curve(B-C)was used as a reference for new design variants with a double-curvature B-C with varying radii.Soft(13.2 MPa)and stiff(2.4 GPa)leaflet materials and different thicknesses were studied using lean simulations and in vitro experiments under physiologic hemodynamic conditions.The performance was assessed using opening pressure(OP)and orifice area(OA).The latter was determined by a newly developed automatized image processing tool.Experimental trends are in agreement with simulations and demonstrated that a buckling-inspired double-curvature leaflet design significantly enhances the trileaflet valve opening behavior,which is particularly advantageous for stiffer leaflet materials.Compared to the reference,the best-performing variant showed an OP improvement of 47%and 44%based on simulations and experiments,respectively.In contrast,the achieved mean pressure differential was directly comparable to state-of-the-art bioprosthetic valves.The OA was slightly reduced for new variants but still in the satisfying range.
文摘Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
基金National Key R&D Program of China(No.2019YFB2103102)Hong Kong Polytechnic University(No.CD06,P0042540)。
文摘The advent of the big data era has provided many types of transportation datasets,such as metro smart card data,for studying residents’mobility and understanding how their mobility has been shaped and is shaping the urban space.In this paper,we use metro smart card data from two Chinese metropolises,Shanghai and Shenzhen.Five metro mobility indicators are introduced,and association rules are established to explore the mobility patterns.The proportion of people entering and exiting the station is used to measure the jobs-housing balance.It is found that the average travel distance and duration of Shanghai passengers are higher than those of Shenzhen,and the proportion of metro commuters in Shanghai is higher than that of Shenzhen.The jobs-housing spatial relationship in Shenzhen based on metro travel is more balanced than that in Shanghai.The fundamental reason for the differences between the two cities is the difference in urban morphology.Compared with the monocentric structure of Shanghai,the polycentric structure of Shenzhen results in more scattered travel hotspots and more diverse travel routes,which helps Shenzhen to have a better jobs-housing balance.This paper fills a gap in comparative research among Chinese cities based on transportation big data analysis.The results provide support for planning metro routes,adjusting urban structure and land use to form a more reasonable metro network,and balancing the jobs-housing spatial relationship.
文摘Among the adult population in St. Vincent and the Grenadines (SVG), there is a marked prevalence of diabetes and hypertension;diseases that pose significant public health, and socio-economic challenges, This awareness raised concerns about the prevalence of the diseases among the youth population, and motivated the SVG Retired Nurses Association (SVGRNA) to collaborate with the Mustique Charitable Trust (MCT) to conduct the “Be Healthy: Know Your Numbers” research project among college-age students. The tri-fold purpose of the project was to determine the prevalence of high blood pressure and blood sugar levels among the college-aged population in Savageries, the awareness of the youths about the causal factors of the diseases, and encourage healthy lifestyle among the demographic. For this mixed-method research project, both quantitative and qualitative data were gathered from a sample of 851 students;306 were males and 545 were females. The results revealed that a significantly high number of students were diabetic and hypertensive, or were at high risk of getting the diseases on account of their poor dietary and lifestyle practices. The highest readings for both diseases were seen among the males. At the onset of the research, the students were largely apathetic toward the diseases. However, there was noticeable attitudinal change, and demonstrable willingness to make the needed lifestyle changes. The study concluded that mitigating the risks of hypertension and diabetes within the youth community in St. Vincent and the Grenadines will be achieved through education about the causal factors and implications of the diseases, as well as through targeted interventions delivered by a wide cross-section of stakeholders.
文摘Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.
基金supported by the Bayerische Forschungsstiftung to B.K.the Deutsche Forschungsgemeinschaft (CRC1181 to G.K.and G.S.+3 种基金SCHE 2062/1-1 to C.S.)funded by the Wellcome Trust Investigator Award (107964/Z/15/Z)the UK Dementia Research Institutefunded by BBSRC Discovery Fellowship (BB/T009543/1)。
文摘Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood.Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.
