Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts o...Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.展开更多
The development of catalytic multicomponent reactions for constructing complex organic scaffolds from readily accessible commodity chemicals is a key pursuit in contemporary synthetic chemistry.Current methods for syn...The development of catalytic multicomponent reactions for constructing complex organic scaffolds from readily accessible commodity chemicals is a key pursuit in contemporary synthetic chemistry.Current methods for synthesizing thioesters primarily rely on the acylation of thiols,which produces substantial waste and requires malodorous,unstable sulfur sources.In this work,we introduce a photocatalyzed hydrogen transfer strategy that enables a three-component synthesis of thioesters using abundant primary alcohols,easily available alkenes and elemental sulfur under mild conditions.This protocol demonstrates broad applicability and high chemo-and regioselectivity for both primary alcohols and alkenes,highlighting the advantage and potential of photo-mediated hydrogen transfer in facilitating multicomponent reactions using primary alcohol and elemental sulfur feedstocks.展开更多
BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different ...BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.展开更多
Objective:To identify the root causes of typical adverse drug events through the lens of patient experiences proposing novel strategies to mitigate preventable harm.Methods:A qualitative case study leveraging in-depth...Objective:To identify the root causes of typical adverse drug events through the lens of patient experiences proposing novel strategies to mitigate preventable harm.Methods:A qualitative case study leveraging in-depth interviews with patients and families,anchored by Interactive Patient Par ticipation Theory,to analyze 4 high-severity adverse drug events(ADE)cases.Cases were purposively sampled from 8 communities in China's National Adverse Event Monitor Center(2018-2023).Semi-structured interviews explored patient perspectives,with data analyzed via thematic coding and triangulation against clinical records.Results:Five interconnected themes emerged:(1)erosion of trust,(2)communication breakdowns,(3)information asymmetry,(4)environmental inadequacies,and(5)technological alienation.Notably,75% of participants had≤high school education,and 50% used≥7 medications daily,compounding ADE risks.Conclusions:We considered elements mentioned by theory,exploring trust,communication,information,and suppor t as the root causes.In addition,we added“adaptability to new technology”as an impor tant and necessary component.It is impor tant and necessary to analyze typical adverse drug events from the perspectives of patients.展开更多
Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord ...Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.展开更多
For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-base...For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).展开更多
AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longit...AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.展开更多
Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simula...Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simulations to explore the CSRO effect on the generation and evolution behaviors of irradiation defects.The results demonstrate that CSRO can suppress the formation of Frenkel pairs in TiVTaNb HEAs,with the suppression effect becoming more pronounced as the degree of CSRO increases.CSRO can change the types of interstitial defects generated during cascade collisions.Specifically,as the degree of CSRO increases,the proportion of Ti-related interstitials shows a marked enhancement,primarily evidenced by a significant rise in Ti–Ti dumbbells accompanied by a corresponding decrease in Ti–V dumbbells.CSRO exhibits negligible influence on defect clustering and the nucleation and evolution of dislocation loops.Regardless of CSRO conditions,TiVTaNb HEAs preserve exceptional radiation tolerance throughout the cascade damage process,suggesting that the intrinsic properties of this multi-principal element system dominate its radiation response.These findings provide fundamental insights into the CSRO effect on defect formation and evolution behaviors in HEAs,which may provide new design strategies for high-entropy alloys.展开更多
Facing the economic challenges of significant frequency regulation wear and tear on thermal power units and short energy storage lifespan in thermal-energy storage combined systems participating in grid primary freque...Facing the economic challenges of significant frequency regulation wear and tear on thermal power units and short energy storage lifespan in thermal-energy storage combined systems participating in grid primary frequency regulation(PFR),this paper proposes a novel hybrid energy storage system(HESS)control strategy based on Newton-Raphson optimization algorithm(NRBO)-VMD and a fuzzy neural network(FNN)for PFR.In the primary power allocation stage,the high inertia and slow response of thermal power units prevent them from promptly responding to the high-frequency components of PFR signals,leading to increased mechanical stress.To address the distinct response characteristics of thermal units and HESS,an NRBO-VMD based decomposition method for PFR signals is proposed,enabling a flexible system response to grid frequency deviations.Within the HESS,an adaptive coordinated control strategy and a State of Charge(SOC)self-recovery strategy are introduced.These strategies autonomously adjust the virtual inertia and droop coefficients based on the depth of frequency regulation and the real-time SOC.Furthermore,a FNN is constructed to perform secondary refinement of the internal power distribution within the HESS.Finally,simulations under various operational conditions demonstrate that the proposed strategy effectively mitigates frequent power adjustments of the thermal unit during PFR,adaptively achieves optimal power decomposition and distribution,maintains the flywheel energy storage’s SOC within an optimal range,and ensures the long-term stable operation of the HESS.展开更多
AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF...AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.展开更多
Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
In recent years,the prevalence of diabetes in China has increased significantly,and approximately 11.9%of Chinese adults had diabetes in 2020.Moreover,there are several rigorous challenges in diabetes prevention and g...In recent years,the prevalence of diabetes in China has increased significantly,and approximately 11.9%of Chinese adults had diabetes in 2020.Moreover,there are several rigorous challenges in diabetes prevention and glycaemic control,especially at the primary medical care level.In order to guide primary healthcare providers in providing comprehensive and continuous care to affected patients,the Office for Primary Diabetes Care of the National Basic Public Health Service Program and the Chinese Diabetes Society issued national guidelines for the prevention and control of diabetes at the primary care level in 2025.The management objects were adults with type 2 diabetes aged≥18 years.The main contents include basic requirements for management,health management process,diagnosis,screening,evaluation,treatment,recognition and management of acute complications,traditional Chinese medicine,referral and health management and education.展开更多
Li/MnO_(2) primary batteries are widely used in industry for their high specific capacity and safety.However,a deep comprehension of the Li^(+)insertion mechanism and the high self-discharge rate of the batteries is s...Li/MnO_(2) primary batteries are widely used in industry for their high specific capacity and safety.However,a deep comprehension of the Li^(+)insertion mechanism and the high self-discharge rate of the batteries is still needed.Here,the storage mechanism of Li^(+)in the tunnel structure of MnO_(2) as well as the dissolution and migration of Mn-ions were investigated based on multi-scale approaches.The Li/Mn ratio(at%)is determined at about 0.82 when the discharge voltage decreases to 2 V.The limited Li-ions transport rate in the bulk MnO_(2) restrains the reduction reaction,resulting in a low practical specific capacity.Moreover,utilizing spherical aberration-corrected transmission electron microscopy(TEM)coupled with electron energy loss spectroscopy(EELS),the presence of a mixed valence state layer of Mn^(2+)/Mn^(3+)/Mn^(4+)on the surface of the original 20 nm MnO_(2) particles was identified,which could contribute to the initial dissolution of Mn-ions.The battery separator exhibited channels for Mn-ions migration and diffusion and aggregated Mn particles.We put forward the discharge and degradation route in the ways of Mn-ions trajectories,and our findings provide a deep understanding of the high self-discharge rates and the capacity decay of Li-Mn primary batteries.展开更多
Parental educational anxiety has become a social symptom in China,and rural primary school students’mothers exhibit unique educational anxieties due to their special living environment.Based on interviews with 10 rur...Parental educational anxiety has become a social symptom in China,and rural primary school students’mothers exhibit unique educational anxieties due to their special living environment.Based on interviews with 10 rural primary school students’mothers,five typical educational anxiety experiences were selected for analysis,and themes such as rural life burden,children’s learning habits,mothers’educational expectations,mothers’educational methods,mothers’emotional state,deviation between reality and expectations,homework guidance ability,mothers’educational level,and attitudes towards children’s future development were refined.The root causes of educational anxiety among rural primary school students’mothers include the deviation between children’s actual performance and mothers’educational expectations,the sense of disparity under social comparison,physical and mental exhaustion caused by role overload,anxiety triggered by excessive economic burden,and a sense of powerlessness towards children’s educational outcomes.To alleviate the educational anxiety of rural primary school students’mothers,mothers should actively adjust themselves,fathers should actively participate in their children’s education,society should create a healthy atmosphere,and schools should strengthen family education guidance.展开更多
AIM:To investigate decisional conflict among patients diagnosed with primary angle-closure suspect(PACS)or primary angle-closure(PAC)who are considering laser peripheral iridotomy(LPI)treatment.METHODS:A total of 111 ...AIM:To investigate decisional conflict among patients diagnosed with primary angle-closure suspect(PACS)or primary angle-closure(PAC)who are considering laser peripheral iridotomy(LPI)treatment.METHODS:A total of 111 individuals diagnosed with PACS or PAC were selected through convenient sampling from March 2023 to December 2023.These participants then completed a general information questionnaire and the Decision Conflict Scale.Data analysis was performed using multiple linear regression to reveal factors influencing decisional conflict.RESULTS:The mean Decisional Conflict Score among patients with PACS or PAC was 48.58±10.01,with 99.1%of these individuals reporting experiencing decisional conflict.Multiple linear regression analysis revealed that females(P=0.002)and patients with a shorter duration of the disease(P=0.006)had higher levels of decisional conflict.Additionally,patients diagnosed during medical visits(P=0.049),those who refused LPI treatment(P=0.032),and individuals facing significant economic burdens related to medical expenses(P=0.005)exhibited higher levels of decisional conflict.Furthermore,patients who preferred to make medical decisions independently(P=0.023)and those who favored involving family members in decisionmaking(P=0.005)experienced increased levels of decisional conflict.CONCLUSION:Patients with PACS or PAC who undergo LPI treatment often encounter significant decisional conflict.Healthcare professionals should thoroughly assess a range of factors that influence this conflict,including gender,duration of disease,method of diagnosis acquisition,LPI treatment,economic burden of medical expenses,and patient preferences regarding medical decision-making.By considering these variables,tailored decision support can be developed to address individual patient needs,ultimately reducing decisional conflict and optimizing the quality of decisions made regarding treatment options.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stage...Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.展开更多
Silicon-based anodes,utilizing nanosized silicon materials,hold great promise for the next-generation of lithium-ion batteries due to their high capacity and stable expansion.This study aims to address challenges in t...Silicon-based anodes,utilizing nanosized silicon materials,hold great promise for the next-generation of lithium-ion batteries due to their high capacity and stable expansion.This study aims to address challenges in traditional slurry-coated anodes,such as agglomeration and low adhesive strength,through the application of laser powder bed fusion(LPBF).The process involves fabricating an Al-Si-Cu alloy layer on a Cu foil current collector,followed by dealloying to create a porous Si-Cu anode.Simulated and experimental results demonstrate successful alloy layer formation through optimized laser spot(55μm)and powder sizes(1-5μm).Controlled cooling produces primary Si particles ranging from 150 nm to 1μm.The resulting microstructure enhances electrochemical performance,particularly by tailoring the size of primary Si.The resultant porous Si-Cu anode,featuring uniformly distributed primary Si(200 nm)metallurgically bonded with Cu networks,exhibits an initial coulombic efficiency of 83% and a remarkable capacity retention of 80% after 300 cycles at 2 C.In-situ and ex-situ observations confirm the crucial role of anode architecture in performance enhancement.This study elucidates the influence of the LPBF microstructure on anode performance and broadens the potential application of laser powder bed fusion in battery manufacturing.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic ...BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities...Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.展开更多
文摘Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.
基金National Natural Science Foundation of China (Nos.22071185 and 22271224)the Fundamental Research Funds for the Central Universities (No.2042019kf0008)Wuhan University startup funding for financial support。
文摘The development of catalytic multicomponent reactions for constructing complex organic scaffolds from readily accessible commodity chemicals is a key pursuit in contemporary synthetic chemistry.Current methods for synthesizing thioesters primarily rely on the acylation of thiols,which produces substantial waste and requires malodorous,unstable sulfur sources.In this work,we introduce a photocatalyzed hydrogen transfer strategy that enables a three-component synthesis of thioesters using abundant primary alcohols,easily available alkenes and elemental sulfur under mild conditions.This protocol demonstrates broad applicability and high chemo-and regioselectivity for both primary alcohols and alkenes,highlighting the advantage and potential of photo-mediated hydrogen transfer in facilitating multicomponent reactions using primary alcohol and elemental sulfur feedstocks.
基金Supported by the National Natural Science Foundation of China,No.82402789Beijing Jishuitan Hospital Youcai Plan,No.KYYC202402+1 种基金Beijing Jishuitan Research Funding,No.HL202402and Beijing Natural Science Foundation,No.L232062,No.L222063.
文摘BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.
基金supported by the Science and Technology Fund Project of Guizhou Health Commission(gzwkj2025-163)。
文摘Objective:To identify the root causes of typical adverse drug events through the lens of patient experiences proposing novel strategies to mitigate preventable harm.Methods:A qualitative case study leveraging in-depth interviews with patients and families,anchored by Interactive Patient Par ticipation Theory,to analyze 4 high-severity adverse drug events(ADE)cases.Cases were purposively sampled from 8 communities in China's National Adverse Event Monitor Center(2018-2023).Semi-structured interviews explored patient perspectives,with data analyzed via thematic coding and triangulation against clinical records.Results:Five interconnected themes emerged:(1)erosion of trust,(2)communication breakdowns,(3)information asymmetry,(4)environmental inadequacies,and(5)technological alienation.Notably,75% of participants had≤high school education,and 50% used≥7 medications daily,compounding ADE risks.Conclusions:We considered elements mentioned by theory,exploring trust,communication,information,and suppor t as the root causes.In addition,we added“adaptability to new technology”as an impor tant and necessary component.It is impor tant and necessary to analyze typical adverse drug events from the perspectives of patients.
基金supported by a grant from Ministry of Science and Technology China,No.2022ZD0204704(to WW)the National Natural Science Foundation of China,No.82301572(to XZ)the China Postdoctoral Science Foundation,No.2023M731202(to XZ)。
文摘Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
基金supported by the National Natural Science Foundation of China(Grant Nos.32270688,31801117,and 82430107 to X.L.,and 32500589 to H.S.)the China Postdoctoral Science Foundation(Grant Nos.BX20240253 and 2024M762384 to H.S.)+1 种基金the Natural Science Foundation of Tianjin(Grant No.24JCQNJC01280 to H.S.)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-3-003A).
文摘For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).
文摘AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.
基金Project supported by the Youth Program of the National Natural Science Foundation of China(Grant No.12405324)the CNNC Science Fund for Talented Young Scholars(Grant No.24940)the CNNC Basic Science Fund(Grant No.24851)。
文摘Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simulations to explore the CSRO effect on the generation and evolution behaviors of irradiation defects.The results demonstrate that CSRO can suppress the formation of Frenkel pairs in TiVTaNb HEAs,with the suppression effect becoming more pronounced as the degree of CSRO increases.CSRO can change the types of interstitial defects generated during cascade collisions.Specifically,as the degree of CSRO increases,the proportion of Ti-related interstitials shows a marked enhancement,primarily evidenced by a significant rise in Ti–Ti dumbbells accompanied by a corresponding decrease in Ti–V dumbbells.CSRO exhibits negligible influence on defect clustering and the nucleation and evolution of dislocation loops.Regardless of CSRO conditions,TiVTaNb HEAs preserve exceptional radiation tolerance throughout the cascade damage process,suggesting that the intrinsic properties of this multi-principal element system dominate its radiation response.These findings provide fundamental insights into the CSRO effect on defect formation and evolution behaviors in HEAs,which may provide new design strategies for high-entropy alloys.
基金supported by the Lanzhou Science and Technology Plan Project(XM1753694781389).
文摘Facing the economic challenges of significant frequency regulation wear and tear on thermal power units and short energy storage lifespan in thermal-energy storage combined systems participating in grid primary frequency regulation(PFR),this paper proposes a novel hybrid energy storage system(HESS)control strategy based on Newton-Raphson optimization algorithm(NRBO)-VMD and a fuzzy neural network(FNN)for PFR.In the primary power allocation stage,the high inertia and slow response of thermal power units prevent them from promptly responding to the high-frequency components of PFR signals,leading to increased mechanical stress.To address the distinct response characteristics of thermal units and HESS,an NRBO-VMD based decomposition method for PFR signals is proposed,enabling a flexible system response to grid frequency deviations.Within the HESS,an adaptive coordinated control strategy and a State of Charge(SOC)self-recovery strategy are introduced.These strategies autonomously adjust the virtual inertia and droop coefficients based on the depth of frequency regulation and the real-time SOC.Furthermore,a FNN is constructed to perform secondary refinement of the internal power distribution within the HESS.Finally,simulations under various operational conditions demonstrate that the proposed strategy effectively mitigates frequent power adjustments of the thermal unit during PFR,adaptively achieves optimal power decomposition and distribution,maintains the flywheel energy storage’s SOC within an optimal range,and ensures the long-term stable operation of the HESS.
基金Supported by National Natural Science Foundation of China(No.82260203).
文摘AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
基金funded by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0523300)the National Key Clinical Specialty Capacity Building for Endocrine and Metabolic Diseases(Z155080000004)+1 种基金the Shanghai Key Laboratory of Diabetes Mellitus(20DZ2270300)the Sanming Project of Medicine in Shenzhen(SZSM202311019).
文摘In recent years,the prevalence of diabetes in China has increased significantly,and approximately 11.9%of Chinese adults had diabetes in 2020.Moreover,there are several rigorous challenges in diabetes prevention and glycaemic control,especially at the primary medical care level.In order to guide primary healthcare providers in providing comprehensive and continuous care to affected patients,the Office for Primary Diabetes Care of the National Basic Public Health Service Program and the Chinese Diabetes Society issued national guidelines for the prevention and control of diabetes at the primary care level in 2025.The management objects were adults with type 2 diabetes aged≥18 years.The main contents include basic requirements for management,health management process,diagnosis,screening,evaluation,treatment,recognition and management of acute complications,traditional Chinese medicine,referral and health management and education.
基金supported by the National Natural Science Foundation of China(Nos.U2030206,12104022,52271014 and 22075003)the Presidential Foundation of CAEP(No.YZJJZL2023173)Sichuan Science and Technology Program(No.2021YFH0092).
文摘Li/MnO_(2) primary batteries are widely used in industry for their high specific capacity and safety.However,a deep comprehension of the Li^(+)insertion mechanism and the high self-discharge rate of the batteries is still needed.Here,the storage mechanism of Li^(+)in the tunnel structure of MnO_(2) as well as the dissolution and migration of Mn-ions were investigated based on multi-scale approaches.The Li/Mn ratio(at%)is determined at about 0.82 when the discharge voltage decreases to 2 V.The limited Li-ions transport rate in the bulk MnO_(2) restrains the reduction reaction,resulting in a low practical specific capacity.Moreover,utilizing spherical aberration-corrected transmission electron microscopy(TEM)coupled with electron energy loss spectroscopy(EELS),the presence of a mixed valence state layer of Mn^(2+)/Mn^(3+)/Mn^(4+)on the surface of the original 20 nm MnO_(2) particles was identified,which could contribute to the initial dissolution of Mn-ions.The battery separator exhibited channels for Mn-ions migration and diffusion and aggregated Mn particles.We put forward the discharge and degradation route in the ways of Mn-ions trajectories,and our findings provide a deep understanding of the high self-discharge rates and the capacity decay of Li-Mn primary batteries.
基金Hunan Provincial Social Science Foundation“A Phenomenological Study on the Educational Life Experiences of Rural Young Teachers”(20YBA017)。
文摘Parental educational anxiety has become a social symptom in China,and rural primary school students’mothers exhibit unique educational anxieties due to their special living environment.Based on interviews with 10 rural primary school students’mothers,five typical educational anxiety experiences were selected for analysis,and themes such as rural life burden,children’s learning habits,mothers’educational expectations,mothers’educational methods,mothers’emotional state,deviation between reality and expectations,homework guidance ability,mothers’educational level,and attitudes towards children’s future development were refined.The root causes of educational anxiety among rural primary school students’mothers include the deviation between children’s actual performance and mothers’educational expectations,the sense of disparity under social comparison,physical and mental exhaustion caused by role overload,anxiety triggered by excessive economic burden,and a sense of powerlessness towards children’s educational outcomes.To alleviate the educational anxiety of rural primary school students’mothers,mothers should actively adjust themselves,fathers should actively participate in their children’s education,society should create a healthy atmosphere,and schools should strengthen family education guidance.
基金Supported by Basic Scientific Research Projects of Wenzhou(No.Y20220155).
文摘AIM:To investigate decisional conflict among patients diagnosed with primary angle-closure suspect(PACS)or primary angle-closure(PAC)who are considering laser peripheral iridotomy(LPI)treatment.METHODS:A total of 111 individuals diagnosed with PACS or PAC were selected through convenient sampling from March 2023 to December 2023.These participants then completed a general information questionnaire and the Decision Conflict Scale.Data analysis was performed using multiple linear regression to reveal factors influencing decisional conflict.RESULTS:The mean Decisional Conflict Score among patients with PACS or PAC was 48.58±10.01,with 99.1%of these individuals reporting experiencing decisional conflict.Multiple linear regression analysis revealed that females(P=0.002)and patients with a shorter duration of the disease(P=0.006)had higher levels of decisional conflict.Additionally,patients diagnosed during medical visits(P=0.049),those who refused LPI treatment(P=0.032),and individuals facing significant economic burdens related to medical expenses(P=0.005)exhibited higher levels of decisional conflict.Furthermore,patients who preferred to make medical decisions independently(P=0.023)and those who favored involving family members in decisionmaking(P=0.005)experienced increased levels of decisional conflict.CONCLUSION:Patients with PACS or PAC who undergo LPI treatment often encounter significant decisional conflict.Healthcare professionals should thoroughly assess a range of factors that influence this conflict,including gender,duration of disease,method of diagnosis acquisition,LPI treatment,economic burden of medical expenses,and patient preferences regarding medical decision-making.By considering these variables,tailored decision support can be developed to address individual patient needs,ultimately reducing decisional conflict and optimizing the quality of decisions made regarding treatment options.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.
基金financially supported by the National Key Research and Development Program of China(2022YFB4602700)the National Natural Science Foundation of China(No.51975018)the Beijing Natural Science Foundation(No.2244085).
文摘Silicon-based anodes,utilizing nanosized silicon materials,hold great promise for the next-generation of lithium-ion batteries due to their high capacity and stable expansion.This study aims to address challenges in traditional slurry-coated anodes,such as agglomeration and low adhesive strength,through the application of laser powder bed fusion(LPBF).The process involves fabricating an Al-Si-Cu alloy layer on a Cu foil current collector,followed by dealloying to create a porous Si-Cu anode.Simulated and experimental results demonstrate successful alloy layer formation through optimized laser spot(55μm)and powder sizes(1-5μm).Controlled cooling produces primary Si particles ranging from 150 nm to 1μm.The resulting microstructure enhances electrochemical performance,particularly by tailoring the size of primary Si.The resultant porous Si-Cu anode,featuring uniformly distributed primary Si(200 nm)metallurgically bonded with Cu networks,exhibits an initial coulombic efficiency of 83% and a remarkable capacity retention of 80% after 300 cycles at 2 C.In-situ and ex-situ observations confirm the crucial role of anode architecture in performance enhancement.This study elucidates the influence of the LPBF microstructure on anode performance and broadens the potential application of laser powder bed fusion in battery manufacturing.
基金Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund,No.H2021206239.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
基金supported by the China Postdoctoral Science Foundation Grant(2023M734294)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202215)the National Natural Science Foundation of China(No.82001618).
文摘Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
