Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key mol...Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.展开更多
Understanding the acoustic characteristics of hydrates in various sediments is crucial for hydrate resource detection and safe and efficient exploitation,as hydrate occurrence patterns vary greatly in different sedime...Understanding the acoustic characteristics of hydrates in various sediments is crucial for hydrate resource detection and safe and efficient exploitation,as hydrate occurrence patterns vary greatly in different sediments.In this work,sediments with different bentonite contents,water saturations,and types were prepared to investigate the characteristics of P-wave velocity(reflecting the magnitude of hydrate saturation in the sediment)and amplitude(reflecting the degree of hydrate-sediment cementation)during hydrate formation and depressurization.During hydrate formation,the P-wave velocity and amplitude have similar trends.As clay content increases,the P-wave velocity increase rates quickened.On the other hand,the increased rate of P-wave velocity slows down with the increase of water saturation in the clay-bearing sediments.Comparing various types of sediment shows that the water absorption and swelling of bentonite reduce the pore space,speeding up the cementation of the hydrate with the sediment and increasing P-wave velocity at a faster rate.Correspondence between P-wave velocity and hydrate saturation is strongly related to sediment type,clay content,and water saturation.The rapidly decreasing amplitude in the early stage of hydrate depressurization indicates that hydrate in clay-bearing sediments is weakly cemented to the sediments,which is prone to stratigraphic instability.The findings of this study offer guidance for hydrate resource assessments in clay-bearing sediments as well as geologic risk estimations during hydrate mining.展开更多
Dear Editor,Timely and effective hemostasis is of great significance for reducing body damage and mortality of patients [1]. Alginate is generally considered to be an excellent hemostatic polymer-based biomaterial and...Dear Editor,Timely and effective hemostasis is of great significance for reducing body damage and mortality of patients [1]. Alginate is generally considered to be an excellent hemostatic polymer-based biomaterial and has been approved by the Food and Drug Administration as Generally Recognized as Safe [2]. However, the violent crosslinking reaction and unstable structure at the wound site limit its clinical applications. Hence, we report a biocompatible and injectable composite hydrogel methacrylate alginate (Alg-AEMA)-based Eosin Y/N-phenylglycine (NPG)-initiated composite hydrogel (AEC) composed of photocrosslinkable alginate, viscosity modifiers and novel white light photoinitiator, namely Eosin Y/NPG system, for instant hemorrhage control.展开更多
●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:T...●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.展开更多
The kagome system has attracted great interest in condensed matter physics due to its unique structure that canhost various exotic states such as superconductivity(SC),charge density waves(CDWs)and nontrivial topologi...The kagome system has attracted great interest in condensed matter physics due to its unique structure that canhost various exotic states such as superconductivity(SC),charge density waves(CDWs)and nontrivial topological states.The topological semimetal RbTi_(3)Bi_(5)consisting of a Ti kagome layer shares a similar crystal structure to the topologicalcorrelated materials AV_(3)Sb_(5)(A=K,Rb,Cs)but without the absence of CDW and SC.Systematic de Haas-van Alphenoscillation measurements are performed on single crystals of RbTi_(3)Bi_(5)to pursue nontrivial topological physics and exoticstates.Combining this with theoretical calculations,the detailed Fermi surface topology and band structure are investigated.A two-dimensional Fermi pocket b is revealed with a light effective mass,consistent with the semimetal predictions.TheLandau fan diagram of RbTi_(3)Bi_(5)reveals a zero Berry phase for the b oscillation in contrast to that of CsTi_(3)Bi_(5).Theseresults suggest that kagome RbTi_(3)Bi_(5)is a good candidate for exploring nontrivial topological exotic states and topologicalcorrelated physics.展开更多
Objective:To analyze the clinical effect of a simple egg membrane patch bridging method in repairing tympanic membrane perforation.Methods:A total of 93 tympanic membrane perforation patients admitted to the hospital ...Objective:To analyze the clinical effect of a simple egg membrane patch bridging method in repairing tympanic membrane perforation.Methods:A total of 93 tympanic membrane perforation patients admitted to the hospital between September 2022 and October 2023 were selected and divided into two groups according to the random number table method.The control group implemented the conventional treatment(n=46 cases),and the patch group adopted the simple egg membrane patch bridging method(n=47 cases).The healing rate of the tympanic membrane,the air-bone gap,the air conduction hearing threshold,the dry ear rate,and the incidence of complications in both groups were compared before and after treatment.Results:The healing rate of the tympanic membrane in the patch group was significantly higher than that of the control group(95.75%vs.76.09%),with P<0.05;there was no difference in the air-bone gap and air conduction hearing threshold levels between the two groups before treatment(P>0.05),and the hearing indexes of the patch group were significantly lower than those of the control group 3 months after treatment(P<0.05);the dry ear rate in the patch group was significantly higher than that of the control group after treatment(85.11%vs.67.39%),and the total incidence of complications was also significantly lower than that of the control group(6.38%vs.21.74%),with P<0.05.Conclusion:The simple egg membrane patch bridging method is effective in repairing tympanic membrane perforation,which can effectively improve patients’hearing levels and reduce the occurrence of post-treatment complications.Thus,it is worth popularizing and applying in the clinic.展开更多
Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management...Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.展开更多
Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resist...Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.展开更多
Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunot...Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.展开更多
Oxidative dehydrogenation of propane with carbon dioxide(CO_(2)-ODP)characterizes the tandem dehydrogenation of propane to propylene with the reduction of the greenhouse gas of CO_(2)to valuable CO.However,the existin...Oxidative dehydrogenation of propane with carbon dioxide(CO_(2)-ODP)characterizes the tandem dehydrogenation of propane to propylene with the reduction of the greenhouse gas of CO_(2)to valuable CO.However,the existing catalyst is limited due to the poor activity and stability,which hinders its industrialization.Herein,we design the finned Zn-MFI zeolite encapsulated noble metal nanoparticles(NPs)as bifunctional catalysts(NPs@Zn-MFI)for CO_(2)-ODP.Characterization results reveal that the Zn2+species are coordinated with the MFI zeolite matrix as isolated cations and the NPs of Pt,Rh,or Rh Pt are highly dispersed in the zeolite crystals.The isolated Zn2+cations are very effective for activating the propane and the small NPs are favorable for activating the CO_(2),which synergistically promote the selective transformation of propane and CO_(2)to propylene and CO.As a result,the optimal 0.25%Rh0.50%Pt@Zn-MFI catalyst shows the best propylene yield,satisfactory CO_(2)conversion,and long-term stability.Moreover,considering the tunable synergetic effects between the isolated cations and NPs,the developed approach offers a general guideline to design more efficient CO_(2)-ODP catalysts,which is validated by the improved performance of the bifunctional catalysts via simply substituting Sn4+cations for Zn2+cations in the MFI zeolite matrix.展开更多
We report the synthesis and characterization of a Si-based ternary semiconductor Mg_(3)Si_(2)Te_(6),which exhibits a quasitwo-dimensional structure,where the trigonal Mg_(3)Si_(2)Te_(6)layers are separated by Mg ions....We report the synthesis and characterization of a Si-based ternary semiconductor Mg_(3)Si_(2)Te_(6),which exhibits a quasitwo-dimensional structure,where the trigonal Mg_(3)Si_(2)Te_(6)layers are separated by Mg ions.Ultraviolet-visible absorption spectroscopy and density functional theory calculations were performed to investigate the electronic structure.The experimentally determined direct band gap is 1.39 eV,consistent with the value of the density function theory calculations.Our results reveal that Mg_(3)Si_(2)Te_(6)is a direct gap semiconductor,which is a potential candidate for near-infrared optoelectronic devices.展开更多
Objective:To explore the characteristics of plasma metabolites,feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern(AIS-PHP)....Objective:To explore the characteristics of plasma metabolites,feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern(AIS-PHP).Methods:The metabolic and microbiome profiles of 20 AIS-PHP patients and 20 healthy controls(HCs)were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based metabolomics and 16s rDNA sequencing,respectively.The covariation between LC-MS/MS-based metabolite data and 16s rDNA sequence data was presented.Results:Distinct alterations in the plasma metabolic phenotype of AIS-PHP patients were found,in which 16 metabolites differed significantly between the AIS-PHP patients and the HCs.These metabolites represented 17 different metabolic pathways,including amino acid metabolism,lipid metabolism,and nucleotide metabolism.Additionally,significant alterations of gut microbiota composition and taxon were revealed at the phylum level between the AIS-PHP patients and the HCs.In AIS-PHP,Bacteroidetes,Firmicutes,and Proteobacteria dominated.Moreover,some microbes that differed between the 2 groups manifested a sole association with certain metabolites,such as the connection between Bacteroides and inosine and between Lachnospiraceae_unclassified and hypoxanthine.Conclusion:The present study preliminarily investigated the metabolomic and gut microbiome characteristics of AIS-PHP patient indicators.The link between metabolic and microbial dysbiosis in AIS-PHP sheds new light on the function of gut microbiota and associated metabolomics in the pathogenesis of the disease.展开更多
Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethra...Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.展开更多
Background:Many healthcare workers were infected by coronavirus disease 2019(COVID-19)early in the epidemic posing a big challenge for epidemic control.Hence,this study aims to explore perceived infection routes,influ...Background:Many healthcare workers were infected by coronavirus disease 2019(COVID-19)early in the epidemic posing a big challenge for epidemic control.Hence,this study aims to explore perceived infection routes,influencing factors,psychosocial changes,and management procedures for COVID-19 infected healthcare workers.Methods:This is a cross-sectional,single hospital-based study.We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29,2020.All participants completed a validated questionnaire.Electronic consent was obtained from all participants.Perceived causes of infection,infection prevention,control knowledge and behaviour,psychological changes,symptoms and treatment were measured.Results:Finally,103 professional staff with COVID-19 finished the questionnaire and was included(response rate:98.1%).Of them,87 cases(84.5%)thought they were infected in working environment in hospital,one(1.0%)thought their infection was due to the laboratory environment,and 5(4.9%)thought they were infected in daily life or community environment.Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively.Forty-three(41.8%)thought their infection was related to protective equipment,utilization of common equipment(masks and gloves).The top three first symptoms displayed before diagnosis were fever(41.8%),lethargy(33.0%)and muscle aches(30.1%).After diagnosis,88.3%staff experienced psychological stress or emotional changes during their isolation period,only 11.7%had almost no emotional changes.Arbidol(Umifenovir;an anti-influza drug;69.2%)was the drug most commonly used to target infection in mild and moderate symptoms.Conclusion:The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases.Positive psychological intervention is necessary.展开更多
Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most pr...Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis, qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.展开更多
基金supported by the Science and Technology Department of Hubei Province Key Project(YYXKNL2022001)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT320-004)+2 种基金the Hubei Provincial Natural Science Foundation(2021CFB453)the Science,Technology and Innovation Seed Fund of Zhongnan Hospital of Wuhan University(CXPY2020031)the Climbing Program for Medical Talents of Zhongnan Hospital of Wuhan University(PDJH202206,PDJH202208)。
文摘Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.
基金financially supported by the National Key Research and Development Program of China (No.2021YFC2800902)the Basic Research Program of Qinghai Province (2023-ZJ-703)the National Natural Science Foundation of China (Nos.22178379,22127812)。
文摘Understanding the acoustic characteristics of hydrates in various sediments is crucial for hydrate resource detection and safe and efficient exploitation,as hydrate occurrence patterns vary greatly in different sediments.In this work,sediments with different bentonite contents,water saturations,and types were prepared to investigate the characteristics of P-wave velocity(reflecting the magnitude of hydrate saturation in the sediment)and amplitude(reflecting the degree of hydrate-sediment cementation)during hydrate formation and depressurization.During hydrate formation,the P-wave velocity and amplitude have similar trends.As clay content increases,the P-wave velocity increase rates quickened.On the other hand,the increased rate of P-wave velocity slows down with the increase of water saturation in the clay-bearing sediments.Comparing various types of sediment shows that the water absorption and swelling of bentonite reduce the pore space,speeding up the cementation of the hydrate with the sediment and increasing P-wave velocity at a faster rate.Correspondence between P-wave velocity and hydrate saturation is strongly related to sediment type,clay content,and water saturation.The rapidly decreasing amplitude in the early stage of hydrate depressurization indicates that hydrate in clay-bearing sediments is weakly cemented to the sediments,which is prone to stratigraphic instability.The findings of this study offer guidance for hydrate resource assessments in clay-bearing sediments as well as geologic risk estimations during hydrate mining.
基金National Key Research and Development Program(2022YFA1104604,2017YFC1103303)Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)+2 种基金National Nature Science Foundation of China(32000969,82002056,92268206)Military Medical Research Projects(145AKJ260015000X,2022-JCJQ-ZD-096-00)Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Dear Editor,Timely and effective hemostasis is of great significance for reducing body damage and mortality of patients [1]. Alginate is generally considered to be an excellent hemostatic polymer-based biomaterial and has been approved by the Food and Drug Administration as Generally Recognized as Safe [2]. However, the violent crosslinking reaction and unstable structure at the wound site limit its clinical applications. Hence, we report a biocompatible and injectable composite hydrogel methacrylate alginate (Alg-AEMA)-based Eosin Y/N-phenylglycine (NPG)-initiated composite hydrogel (AEC) composed of photocrosslinkable alginate, viscosity modifiers and novel white light photoinitiator, namely Eosin Y/NPG system, for instant hemorrhage control.
文摘●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.
基金supported by the National Key Research and Development Program of China(Grant No.2023YFA1406500)the National Natural Science Foundation of China(Grant Nos.12174454,U2130101,and 92165204)+2 种基金the Guangdong Basic and Applied Basic Research Funds(Grant Nos.2024B1515020040 and 2022A1515010035)Guangzhou Basic and Applied Basic Research Funds(Grant No.2024A04J6417)Guangdong Provincial Key Laboratory of Magnetoelectric Physics and Devices(Grant No.2022B1212010008).
文摘The kagome system has attracted great interest in condensed matter physics due to its unique structure that canhost various exotic states such as superconductivity(SC),charge density waves(CDWs)and nontrivial topological states.The topological semimetal RbTi_(3)Bi_(5)consisting of a Ti kagome layer shares a similar crystal structure to the topologicalcorrelated materials AV_(3)Sb_(5)(A=K,Rb,Cs)but without the absence of CDW and SC.Systematic de Haas-van Alphenoscillation measurements are performed on single crystals of RbTi_(3)Bi_(5)to pursue nontrivial topological physics and exoticstates.Combining this with theoretical calculations,the detailed Fermi surface topology and band structure are investigated.A two-dimensional Fermi pocket b is revealed with a light effective mass,consistent with the semimetal predictions.TheLandau fan diagram of RbTi_(3)Bi_(5)reveals a zero Berry phase for the b oscillation in contrast to that of CsTi_(3)Bi_(5).Theseresults suggest that kagome RbTi_(3)Bi_(5)is a good candidate for exploring nontrivial topological exotic states and topologicalcorrelated physics.
文摘Objective:To analyze the clinical effect of a simple egg membrane patch bridging method in repairing tympanic membrane perforation.Methods:A total of 93 tympanic membrane perforation patients admitted to the hospital between September 2022 and October 2023 were selected and divided into two groups according to the random number table method.The control group implemented the conventional treatment(n=46 cases),and the patch group adopted the simple egg membrane patch bridging method(n=47 cases).The healing rate of the tympanic membrane,the air-bone gap,the air conduction hearing threshold,the dry ear rate,and the incidence of complications in both groups were compared before and after treatment.Results:The healing rate of the tympanic membrane in the patch group was significantly higher than that of the control group(95.75%vs.76.09%),with P<0.05;there was no difference in the air-bone gap and air conduction hearing threshold levels between the two groups before treatment(P>0.05),and the hearing indexes of the patch group were significantly lower than those of the control group 3 months after treatment(P<0.05);the dry ear rate in the patch group was significantly higher than that of the control group after treatment(85.11%vs.67.39%),and the total incidence of complications was also significantly lower than that of the control group(6.38%vs.21.74%),with P<0.05.Conclusion:The simple egg membrane patch bridging method is effective in repairing tympanic membrane perforation,which can effectively improve patients’hearing levels and reduce the occurrence of post-treatment complications.Thus,it is worth popularizing and applying in the clinic.
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.
基金supported by the National Natural Science Foundation of China (31970696, 81502975, 82188102, and 81830089)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar (LR22H160010)+2 种基金National Key Research and Development Program of China (2019YFC1316000)Zhejiang Provincial Key Research and Development Program (2019C03019)Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program (Young Talent Program)(2022R40122)
文摘Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
基金supported by the National Natural Science Foundation of China(31970696,81502975,81830089,U20A20378,82188102)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR22H160010)+2 种基金the National Key Research and Development Program(2019YFC1316000)the Zhejiang Provincial Key Research and Development Program(2019C03019)the Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program(Young Talent Program)(2022R40122)。
文摘Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
基金supported by the National Natural Science Foundation of China(21902097,21636006 and 21761132025)the China Postdoctoral Science Foundation(2019M653861XB)+1 种基金the Natural Science Foundation of Shaanxi Province(2020JQ-409)the Fundamental Research Funds for the Central Universities(GK201901001 and GK202003035)。
文摘Oxidative dehydrogenation of propane with carbon dioxide(CO_(2)-ODP)characterizes the tandem dehydrogenation of propane to propylene with the reduction of the greenhouse gas of CO_(2)to valuable CO.However,the existing catalyst is limited due to the poor activity and stability,which hinders its industrialization.Herein,we design the finned Zn-MFI zeolite encapsulated noble metal nanoparticles(NPs)as bifunctional catalysts(NPs@Zn-MFI)for CO_(2)-ODP.Characterization results reveal that the Zn2+species are coordinated with the MFI zeolite matrix as isolated cations and the NPs of Pt,Rh,or Rh Pt are highly dispersed in the zeolite crystals.The isolated Zn2+cations are very effective for activating the propane and the small NPs are favorable for activating the CO_(2),which synergistically promote the selective transformation of propane and CO_(2)to propylene and CO.As a result,the optimal 0.25%Rh0.50%Pt@Zn-MFI catalyst shows the best propylene yield,satisfactory CO_(2)conversion,and long-term stability.Moreover,considering the tunable synergetic effects between the isolated cations and NPs,the developed approach offers a general guideline to design more efficient CO_(2)-ODP catalysts,which is validated by the improved performance of the bifunctional catalysts via simply substituting Sn4+cations for Zn2+cations in the MFI zeolite matrix.
基金the National Natural Science Foundation of China(Grant Nos.12174454,11904414,11904416,and 12104427)the Guangdong Basic and Applied Basic Research Foundation,China(Grant No.2021B1515120015)+1 种基金the Guangzhou Basic and Applied Basic Research Foundation(Grant No.202201011123)the National Key Research and Development Program of China(Grant No.2019YFA0705702).
文摘We report the synthesis and characterization of a Si-based ternary semiconductor Mg_(3)Si_(2)Te_(6),which exhibits a quasitwo-dimensional structure,where the trigonal Mg_(3)Si_(2)Te_(6)layers are separated by Mg ions.Ultraviolet-visible absorption spectroscopy and density functional theory calculations were performed to investigate the electronic structure.The experimentally determined direct band gap is 1.39 eV,consistent with the value of the density function theory calculations.Our results reveal that Mg_(3)Si_(2)Te_(6)is a direct gap semiconductor,which is a potential candidate for near-infrared optoelectronic devices.
基金funded by Chang Jingling Professor Scholars Programthe Special funds for basic scientific research in Central Universities of China(2019-JYB-TD-003)+2 种基金the National Natural Science Foundation of China(81973790)Huang Xing Scholars Program Central University Basic Scientific Research Operating Expenses Special Project(2022-JYB-XJSJJ-093)funded in part by the Austrian Agency for International Cooperation in Education and Research(OEAD)and the Federal Minister of Education,Science,and Research under the Scientific and Technological Cooperation with China Project(CN 06/2020)。
文摘Objective:To explore the characteristics of plasma metabolites,feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern(AIS-PHP).Methods:The metabolic and microbiome profiles of 20 AIS-PHP patients and 20 healthy controls(HCs)were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based metabolomics and 16s rDNA sequencing,respectively.The covariation between LC-MS/MS-based metabolite data and 16s rDNA sequence data was presented.Results:Distinct alterations in the plasma metabolic phenotype of AIS-PHP patients were found,in which 16 metabolites differed significantly between the AIS-PHP patients and the HCs.These metabolites represented 17 different metabolic pathways,including amino acid metabolism,lipid metabolism,and nucleotide metabolism.Additionally,significant alterations of gut microbiota composition and taxon were revealed at the phylum level between the AIS-PHP patients and the HCs.In AIS-PHP,Bacteroidetes,Firmicutes,and Proteobacteria dominated.Moreover,some microbes that differed between the 2 groups manifested a sole association with certain metabolites,such as the connection between Bacteroides and inosine and between Lachnospiraceae_unclassified and hypoxanthine.Conclusion:The present study preliminarily investigated the metabolomic and gut microbiome characteristics of AIS-PHP patient indicators.The link between metabolic and microbial dysbiosis in AIS-PHP sheds new light on the function of gut microbiota and associated metabolomics in the pathogenesis of the disease.
基金the National Key Research and Development Plan of China(Technology helps Economy 20202016YFC0106300)+1 种基金the National Natural Science Foundation of China(82174230)Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52).
文摘Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.
基金supported by the Emergency Science and Technology Project in Hubei Province(2020FCA008)
文摘Background:Many healthcare workers were infected by coronavirus disease 2019(COVID-19)early in the epidemic posing a big challenge for epidemic control.Hence,this study aims to explore perceived infection routes,influencing factors,psychosocial changes,and management procedures for COVID-19 infected healthcare workers.Methods:This is a cross-sectional,single hospital-based study.We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29,2020.All participants completed a validated questionnaire.Electronic consent was obtained from all participants.Perceived causes of infection,infection prevention,control knowledge and behaviour,psychological changes,symptoms and treatment were measured.Results:Finally,103 professional staff with COVID-19 finished the questionnaire and was included(response rate:98.1%).Of them,87 cases(84.5%)thought they were infected in working environment in hospital,one(1.0%)thought their infection was due to the laboratory environment,and 5(4.9%)thought they were infected in daily life or community environment.Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively.Forty-three(41.8%)thought their infection was related to protective equipment,utilization of common equipment(masks and gloves).The top three first symptoms displayed before diagnosis were fever(41.8%),lethargy(33.0%)and muscle aches(30.1%).After diagnosis,88.3%staff experienced psychological stress or emotional changes during their isolation period,only 11.7%had almost no emotional changes.Arbidol(Umifenovir;an anti-influza drug;69.2%)was the drug most commonly used to target infection in mild and moderate symptoms.Conclusion:The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases.Positive psychological intervention is necessary.
基金This project was supported by grants from the National Natural Science Foundation of China (No. 81470818, No. 81472735 and No. 81472033).
文摘Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis, qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.