Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
Mutations in the liver/bone/kidney alkaline phosphatase(Alpl)gene cause hypophosphatasia(HPP)and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development.However,how and where Alp...Mutations in the liver/bone/kidney alkaline phosphatase(Alpl)gene cause hypophosphatasia(HPP)and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development.However,how and where Alpl acts in bone ageing is largely unknown.Here,we determined that ablation of Alpl induces prototypical premature bone ageing characteristics,including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16)and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs).Mechanistically,Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis.Then,the excessive extracellular ATP is,in turn,internalized by MSCs and causes an elevation in the intracellular ATP level,which consequently inactivates the AMPKαpathway and contributes to the cell fate switch of MSCs.Reactivating AMPKαby metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKαalterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.展开更多
Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections ...Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and ano-genital epithelia by high-risk展开更多
I read with interest the article entitled ＂Concurrent removal of intravitreal lens fragments afterphacoemulsification with pars plana vitrectomy prevents development of retinal detachment＂ by Chalam et al . In this ...I read with interest the article entitled ＂Concurrent removal of intravitreal lens fragments afterphacoemulsification with pars plana vitrectomy prevents development of retinal detachment＂ by Chalam et al . In this study, none of the patients developed retinal detachment （RD） during the one-year follow-up after concurrent removal lens fragments following phacoemulsification with pars plana vitrectomy （PPV）. The authors suggested that concurrent PPV for retained lens fragments after cataract surgery might prevent development of rhegmatogenous retinal detachment （RRD）, because early PPV prevents development of intraocular inflammation and inhibits vitreous contraction, a common cause of retinal tears and detachment.展开更多
Neutralizing CSF1 in vivo completely prevents ovariectomy （OVX）-induced bone loss in mice. There are two isoforms of CSF1, soluble （sCSF1）, and membrane-bound （mCSF1）, but their individual biological functions a...Neutralizing CSF1 in vivo completely prevents ovariectomy （OVX）-induced bone loss in mice. There are two isoforms of CSF1, soluble （sCSF1）, and membrane-bound （mCSF1）, but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout （K/O） and wild type （Wt） female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected （sCSF1 K/O）. Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density （BMD） between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of ＋0.1%, - 2.4%, and ＋2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.展开更多
Effects of two doses of the anti-diabetic drug, metformin （MF）, on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine （DMH）-induced colon tumor adenocarcinomas were ...Effects of two doses of the anti-diabetic drug, metformin （MF）, on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine （DMH）-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.展开更多
The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw(BRONJ)is the exposure of the necrotic jaw.Other clinical manifestations include jaw pain,swelling,abscess,and skin fistula,which seri...The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw(BRONJ)is the exposure of the necrotic jaw.Other clinical manifestations include jaw pain,swelling,abscess,and skin fistula,which seriously affect the patients’life,and there is no radical cure.Thus,new methods need to be found to prevent the occurrence of BRONJ.Here,a novel nanoparticle,t FNA-KLT,was successfully synthesized by us,in which the nanoparticle tetrahedral framework nucleic acid(tFNA)was used for carrying angiogenic peptide,KLT,and then further enhanced angiogenesis.TFNA-KLT possessed the same characteristics as tFNA,such as simple synthesis,stable structure,and good biocompatibility.Meanwhile,tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells.First,it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo.Then we apply tFNA-KLT to the prevention of BRONJ.The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis.In summary,the prepared novel nanoparticle,tFNA-KLT,was firstly synthesized by us.It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis,thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.展开更多
Objective To evaluate the role of β-irradiation with a liquid 188Re-filled balloon for limiting neointimal proliferation. Methods Balloon-overstretched injury was performed in the rabbit carotid artery, then ...Objective To evaluate the role of β-irradiation with a liquid 188Re-filled balloon for limiting neointimal proliferation. Methods Balloon-overstretched injury was performed in the rabbit carotid artery, then β-irradiation using the liquid 188Re-filled balloon was followed immediately, and the prescribed doses was 0, 15Gy or 20Gy at 0.5mm from the surface of vessel. All animals survived and were sacrificed at three weeks. Histopathologic analysis was performed. Results In the control group, the neointimal area was larger (0.40±0.04)mm 2, as compared with (0.23±0.06)mm 2 of the 15Gy irradiated group and (0.15±0.02)mm 2 in the 20Gy group (P<0.05). Conclusion The β-irradiation with a liquid 188Re-filled balloon is safe and effective.展开更多
Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to ...Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.展开更多
Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions a...Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions are being sought to transfer a large part of passengers and especially freight transport to(high-speed)rail,and efforts are moving towards electromobility,car-sharing,5G-connectivity,autonomous driving,MaaS(Mobility as a Service)-coordinated transport or hyperloop-type solutions.However,all these solutions have additional challenges and limitations.Solutions are not being searched where they really exist-in the mutual adaptation of road and rail vehicles and their deep cooperation.The ComplexTrans project shows that simply adapting the dimensions and functions of road and rail vehicles can eliminate(or at least significantly reduce)all the problems of existing land transport.The main features of the ComplexTrans system are sufficient parking spaces,reduction of urban and non-urban congestion,electric vehicles with unlimited range and cheaper than standard cars,cheaper and more accessible battery charging,“autonomous ride”,solving the overlap between passenger and freight rail transport and making it self-financing,transferring intercity freight transport to rail,replacing part of continental air transport and many others.The cost-effective and clustered individual transport and individualised public transport of the ComplexTrans system also bring very significant reductions in the risk of transmission of covid-19 and other contagious diseases during transport.展开更多
Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available....Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.展开更多
China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfall...China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfalls under global change is critical for effective disaster risk management.This study utilizes future typhoon track data simulated by the regional climate model version 4(RegCM4),combined with projected population and Gross Domestic Product(GDP)data for China’s coastal regions under three Shared Socioeconomic Pathways(SSPs:SSP1,sustainability;SSP2,middle of the road;SSP5,fossil-fueled development).We analyze typhoon impact zones for future periods(2030s,2050s,and 2090s)under Representative Concentration Pathways(RCPs:RCP2.6,RCP4.5,and RCP8.5,representing low,medium,and high greenhouse gas emission scenarios,respectively).Exposure levels for 2030,2050,and 2100 are calculated based on the annual average frequency of typhoon impacts during these periods,aiming to quantify the distribution characteristics of typhoon-affected population and GDP in China’s coastal regions.Key findings reveal two high-frequency typhoon im-pact zones:the Taiwan Strait region and the northern Qiongzhou Strait region.Furthermore,under RCP2.6,typhoon impacts may ex-tend to Liaoning,while RCP4.5 and RCP8.5 scenarios indicate potential impacts reaching further north to Heilongjiang.Under RCP4.5,Northeast China will experience the largest typhoon-affected area(43.800×10^(4) km^(2))by the 2030s.High population and GDP exposure concentrates in the Yangtze River Delta,the Pearl River Delta,and the Taiwan Strait coastal areas.Notably,Liaoning’s cumulative ex-posed population may exceed 0.100×10^(8) by 2030 and 2050 under RCP4.5 and RCP8.5 due to typhoon track migration.Given China’s location within the Western Pacific typhoon high-incidence region,the northward expansion of impacts will substantially escalate socio-economic exposure in mid-latitude regions previously at lower risk.These findings underscore the imperative for enhanced disaster pre-vention,mitigation strategies and targeted countermeasure research.展开更多
Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmenta...Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.展开更多
AIM:To conduct a systematic review and Meta-analysis to determine the differential effects of combined lutein and zeaxanthin supplementation on myopia prevention in teenagers.It also investigates the effects of supple...AIM:To conduct a systematic review and Meta-analysis to determine the differential effects of combined lutein and zeaxanthin supplementation on myopia prevention in teenagers.It also investigates the effects of supplements dosage,intervention duration,and geographical variation on intervention results.METHODS:A systematic search and screening of randomized controlled trials(RCTs)completed between 2014 and 2023 was undertaken using the PubMed,EMBASE,Cochrane Library,and Web of Science databases,in accordance with the PRISMA recommendations.The Cochrane risk of bias method was used to assess the quality of the studies.A Meta-analysis was performed using Stata 17.0 to calculate standardized mean differences(SMDs)and 95%confidence intervals(CIs).Subgroup analyses were performed to look at the effects of different doses,intervention periods,and geographic areas.Additionally,publication bias was assessed using Egger’s test.RESULTS:Ten studies including 1035 participants with myopia were analyzed.Supplementation with lutein and zeaxanthin resulted in a significant reduction in axial length elongation among adolescents in the intervention group(SMD=-0.40,P=0.001),an increase in macular pigment optical density(SMD=0.50,P=0.010),and an enhancement in visual sensitivity(SMD=0.53,P=0.008).Subgroup analyses revealed that participants receiving high doses and those undergoing intervention for more than 12mo exhibited significantly improved outcomes compared to those in the low-dose and short-term groups(high-dose vs low-dose:SMD=-0.41 vs-0.22,P=0.003;>12mo vs 6-12mo:SMD=-0.43 vs-0.23,P=0.004,respectively).Furthermore,Egger’s test indicated no significant publication bias(P=0.094).CONCLUSION:Combined lutein and zeaxanthin supplementation has a significant effect on myopia prevention in adolescents,with more pronounced benefits observed in high-dose and long-term interventions.The findings provide scientific evidence for its use as an adjunctive approach in myopia control.展开更多
BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehe...BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.展开更多
Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accom...Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.展开更多
With the intensification of population aging,knee and hip joint replacement surgeries have become core methods for treating end-stage joint diseases,with over a million cases performed globally each year.Postoperative...With the intensification of population aging,knee and hip joint replacement surgeries have become core methods for treating end-stage joint diseases,with over a million cases performed globally each year.Postoperative rehabilitation nursing,as a crucial aspect of enhancing surgical outcomes,reducing complications,and facilitating patients’return to normal life,has its scientific and effective protocols directly influencing patient prognosis.This article systematically reviews the core research findings on rehabilitation nursing after joint replacement surgery based on the concept of evidence-based medicine,aiming to provide references for the formulation of standardized and personalized rehabilitation nursing plans in clinical settings.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs a...Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.展开更多
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
基金financially supported by grants from the Nature Science Foundation of China(81620108007)National Key Research and Development Program of China(2016YFC1101400)+1 种基金Nature Science Foundation of China(31571532,31601099)National Institutes of Health,Department of Health and Human Services(R01DE017449 to S.S.)
文摘Mutations in the liver/bone/kidney alkaline phosphatase(Alpl)gene cause hypophosphatasia(HPP)and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development.However,how and where Alpl acts in bone ageing is largely unknown.Here,we determined that ablation of Alpl induces prototypical premature bone ageing characteristics,including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16)and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs).Mechanistically,Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis.Then,the excessive extracellular ATP is,in turn,internalized by MSCs and causes an elevation in the intracellular ATP level,which consequently inactivates the AMPKαpathway and contributes to the cell fate switch of MSCs.Reactivating AMPKαby metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKαalterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.
基金supported by the Intramural Research Program of the National Institutes of HealthNational Cancer Institutethe Center for Cancer Research
文摘Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and ano-genital epithelia by high-risk
文摘I read with interest the article entitled ＂Concurrent removal of intravitreal lens fragments afterphacoemulsification with pars plana vitrectomy prevents development of retinal detachment＂ by Chalam et al . In this study, none of the patients developed retinal detachment （RD） during the one-year follow-up after concurrent removal lens fragments following phacoemulsification with pars plana vitrectomy （PPV）. The authors suggested that concurrent PPV for retained lens fragments after cataract surgery might prevent development of rhegmatogenous retinal detachment （RRD）, because early PPV prevents development of intraocular inflammation and inhibits vitreous contraction, a common cause of retinal tears and detachment.
基金supported by a grant from NIH(NIDDK DK045228)to KLIby the Yale Bone Center
文摘Neutralizing CSF1 in vivo completely prevents ovariectomy （OVX）-induced bone loss in mice. There are two isoforms of CSF1, soluble （sCSF1）, and membrane-bound （mCSF1）, but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout （K/O） and wild type （Wt） female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected （sCSF1 K/O）. Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density （BMD） between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of ＋0.1%, - 2.4%, and ＋2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.
基金supported in part by a grant from the Russian Foundation for Basic Research(Grant No.14-04-01653)
文摘Effects of two doses of the anti-diabetic drug, metformin （MF）, on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine （DMH）-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.
基金the National Key R&D Program of China(2019YFA0110600)the National Natural Science Foundation of China(81970916,81870746)the support of State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Oral&Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University。
文摘The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw(BRONJ)is the exposure of the necrotic jaw.Other clinical manifestations include jaw pain,swelling,abscess,and skin fistula,which seriously affect the patients’life,and there is no radical cure.Thus,new methods need to be found to prevent the occurrence of BRONJ.Here,a novel nanoparticle,t FNA-KLT,was successfully synthesized by us,in which the nanoparticle tetrahedral framework nucleic acid(tFNA)was used for carrying angiogenic peptide,KLT,and then further enhanced angiogenesis.TFNA-KLT possessed the same characteristics as tFNA,such as simple synthesis,stable structure,and good biocompatibility.Meanwhile,tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells.First,it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo.Then we apply tFNA-KLT to the prevention of BRONJ.The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis.In summary,the prepared novel nanoparticle,tFNA-KLT,was firstly synthesized by us.It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis,thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
文摘Objective To evaluate the role of β-irradiation with a liquid 188Re-filled balloon for limiting neointimal proliferation. Methods Balloon-overstretched injury was performed in the rabbit carotid artery, then β-irradiation using the liquid 188Re-filled balloon was followed immediately, and the prescribed doses was 0, 15Gy or 20Gy at 0.5mm from the surface of vessel. All animals survived and were sacrificed at three weeks. Histopathologic analysis was performed. Results In the control group, the neointimal area was larger (0.40±0.04)mm 2, as compared with (0.23±0.06)mm 2 of the 15Gy irradiated group and (0.15±0.02)mm 2 in the 20Gy group (P<0.05). Conclusion The β-irradiation with a liquid 188Re-filled balloon is safe and effective.
基金supported by grants from the Ministerio de Economia y Competitividad(BFU2013-43458-R)Junta de Andalucia(P12-CTS-1694 and Proyexcel-00422)to ZUK。
文摘Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.
基金This research is partly supported by project SGS-2019-001The 3-D visualisations were prepared by students of University of West Bohemia or by professional designers.
文摘Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions are being sought to transfer a large part of passengers and especially freight transport to(high-speed)rail,and efforts are moving towards electromobility,car-sharing,5G-connectivity,autonomous driving,MaaS(Mobility as a Service)-coordinated transport or hyperloop-type solutions.However,all these solutions have additional challenges and limitations.Solutions are not being searched where they really exist-in the mutual adaptation of road and rail vehicles and their deep cooperation.The ComplexTrans project shows that simply adapting the dimensions and functions of road and rail vehicles can eliminate(or at least significantly reduce)all the problems of existing land transport.The main features of the ComplexTrans system are sufficient parking spaces,reduction of urban and non-urban congestion,electric vehicles with unlimited range and cheaper than standard cars,cheaper and more accessible battery charging,“autonomous ride”,solving the overlap between passenger and freight rail transport and making it self-financing,transferring intercity freight transport to rail,replacing part of continental air transport and many others.The cost-effective and clustered individual transport and individualised public transport of the ComplexTrans system also bring very significant reductions in the risk of transmission of covid-19 and other contagious diseases during transport.
文摘Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.
基金Under the auspices of National Key Research and Development Program of China(No.2017YFA0604902,2024YFF1306802)Natural Science Foundation of Fujian Province(No.2022J01497)Open Project of the Strait Meteorology Laboratory(No.2025KF03)。
文摘China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfalls under global change is critical for effective disaster risk management.This study utilizes future typhoon track data simulated by the regional climate model version 4(RegCM4),combined with projected population and Gross Domestic Product(GDP)data for China’s coastal regions under three Shared Socioeconomic Pathways(SSPs:SSP1,sustainability;SSP2,middle of the road;SSP5,fossil-fueled development).We analyze typhoon impact zones for future periods(2030s,2050s,and 2090s)under Representative Concentration Pathways(RCPs:RCP2.6,RCP4.5,and RCP8.5,representing low,medium,and high greenhouse gas emission scenarios,respectively).Exposure levels for 2030,2050,and 2100 are calculated based on the annual average frequency of typhoon impacts during these periods,aiming to quantify the distribution characteristics of typhoon-affected population and GDP in China’s coastal regions.Key findings reveal two high-frequency typhoon im-pact zones:the Taiwan Strait region and the northern Qiongzhou Strait region.Furthermore,under RCP2.6,typhoon impacts may ex-tend to Liaoning,while RCP4.5 and RCP8.5 scenarios indicate potential impacts reaching further north to Heilongjiang.Under RCP4.5,Northeast China will experience the largest typhoon-affected area(43.800×10^(4) km^(2))by the 2030s.High population and GDP exposure concentrates in the Yangtze River Delta,the Pearl River Delta,and the Taiwan Strait coastal areas.Notably,Liaoning’s cumulative ex-posed population may exceed 0.100×10^(8) by 2030 and 2050 under RCP4.5 and RCP8.5 due to typhoon track migration.Given China’s location within the Western Pacific typhoon high-incidence region,the northward expansion of impacts will substantially escalate socio-economic exposure in mid-latitude regions previously at lower risk.These findings underscore the imperative for enhanced disaster pre-vention,mitigation strategies and targeted countermeasure research.
文摘Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.
文摘AIM:To conduct a systematic review and Meta-analysis to determine the differential effects of combined lutein and zeaxanthin supplementation on myopia prevention in teenagers.It also investigates the effects of supplements dosage,intervention duration,and geographical variation on intervention results.METHODS:A systematic search and screening of randomized controlled trials(RCTs)completed between 2014 and 2023 was undertaken using the PubMed,EMBASE,Cochrane Library,and Web of Science databases,in accordance with the PRISMA recommendations.The Cochrane risk of bias method was used to assess the quality of the studies.A Meta-analysis was performed using Stata 17.0 to calculate standardized mean differences(SMDs)and 95%confidence intervals(CIs).Subgroup analyses were performed to look at the effects of different doses,intervention periods,and geographic areas.Additionally,publication bias was assessed using Egger’s test.RESULTS:Ten studies including 1035 participants with myopia were analyzed.Supplementation with lutein and zeaxanthin resulted in a significant reduction in axial length elongation among adolescents in the intervention group(SMD=-0.40,P=0.001),an increase in macular pigment optical density(SMD=0.50,P=0.010),and an enhancement in visual sensitivity(SMD=0.53,P=0.008).Subgroup analyses revealed that participants receiving high doses and those undergoing intervention for more than 12mo exhibited significantly improved outcomes compared to those in the low-dose and short-term groups(high-dose vs low-dose:SMD=-0.41 vs-0.22,P=0.003;>12mo vs 6-12mo:SMD=-0.43 vs-0.23,P=0.004,respectively).Furthermore,Egger’s test indicated no significant publication bias(P=0.094).CONCLUSION:Combined lutein and zeaxanthin supplementation has a significant effect on myopia prevention in adolescents,with more pronounced benefits observed in high-dose and long-term interventions.The findings provide scientific evidence for its use as an adjunctive approach in myopia control.
文摘BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.
基金supported by The Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2023-00244901)(to RB)。
文摘Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.
文摘With the intensification of population aging,knee and hip joint replacement surgeries have become core methods for treating end-stage joint diseases,with over a million cases performed globally each year.Postoperative rehabilitation nursing,as a crucial aspect of enhancing surgical outcomes,reducing complications,and facilitating patients’return to normal life,has its scientific and effective protocols directly influencing patient prognosis.This article systematically reviews the core research findings on rehabilitation nursing after joint replacement surgery based on the concept of evidence-based medicine,aiming to provide references for the formulation of standardized and personalized rehabilitation nursing plans in clinical settings.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
文摘Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.
