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
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
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
BACKGROUND Colorectal cancer(CRC)ranks high among the most common types of malignant tumors.The primary cause of cancer-related mortality is metastasis,with lung metastases accounting for 32.9%of all cases of metastat...BACKGROUND Colorectal cancer(CRC)ranks high among the most common types of malignant tumors.The primary cause of cancer-related mortality is metastasis,with lung metastases accounting for 32.9%of all cases of metastatic CRC(MCRC).However,cases of MCRC in the lungs,which present concurrently with primary peripheral lung adenocarcinoma,are exceptionally rare.CASE SUMMARY This report describes the case of a 52-year-old female patient who,following a colonoscopy,was diagnosed with moderately differentiated adenocarcinoma based on rectal mucosal biopsy findings.A preoperative chest computed tomography scan revealed a ground-glass nodule in the right lung and a small nodule(approximately 0.6 cm in diameter)in the extramural basal segment of the left lower lobe,which suggested multiple lung metastases from rectal cancer.Subsequent treatment and follow-up led to a diagnosis of rectal cancer with left lung metastasis and peripheral adenocarcinoma of the lower lobe of the right lung.CONCLUSION This case report describes the therapeutic journey of a patient with lung metastasis from rectal cancer in addition to primary peripheral adenocarcinoma,thus underscoring the critical roles of multidisciplinary collaboration,personalized treatment strategies,and comprehensive patient rehabilitation guidance.展开更多
The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum S...The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum State,Sudan.It also aims to examine whether test’s factor structure in this sample replicated that of the original WPPSI-III.The study sample consisted of 384 kindergarten and primary school children in Khartoum State(females=50%mean age=4.14,SD=1.37),selected using stratified random sampling across its seven localities:Khartoum,Jebel Awliya,Khartoum Bahri,East Nile,Omdurman,Ombada,Karari.For concurrent validation,the children additionally completed the Goodenough Draw-a-Man Test,and the Colored Progressive Matrices.WPPSI-III scores demonstrated high internal consistency across the subtest items.Confirmatory factor analysis indicators for total,verbal,and performance intelligence were all excellent.The scale also showed weak to strong score stability ranging from 0.25(weak)to 0.88(strong)based on the Spearman-Brown equation,0.25 to 0.75 based on the Guttman split-half method.The Cronbach’s alpha coefficient scores ranged from 0.54 to 0.93.The WPPSI-III and Goodenough Draw-a-Man Test scores concurrent validity scores were poor(0.05)to modest(0.31),and while those with the Colored Progressive Matrices test were poor(r=0.04–0.18).Thesefindings provide evidence to suggest that the WPPSI-III is appropriate for research use with kindergarten and lower primary school students in Khartoum State,Sudan.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
Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over...Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over 20%in the elderly(Yamada et al.,2013),yet the underlying mechanisms of brain calcification remain poorly understood.Specifically,calcification in the basal ganglia is detected in approximately 5.5%-20%of CT scans in patients over 50 years old(Auffray-Calvier et al.,2020).展开更多
Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged wo...Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.展开更多
Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal gan...Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal ganglia,thalamus,and brainstem.Among these connections,the corticostriatal system plays a significant role in functions including action selection,motor control,sequence learning,and habit formation[2].展开更多
Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing ...Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.展开更多
In this manuscript,we provide critical commentary on the systematic review by Augustin et al,which investigated acute pancreatitis induced by primary hyperparathyroidism during pregnancy.Although this is an infrequent...In this manuscript,we provide critical commentary on the systematic review by Augustin et al,which investigated acute pancreatitis induced by primary hyperparathyroidism during pregnancy.Although this is an infrequent complication,it poses severe risks to both maternal and fetal health.Due to its infrequent occurrence in clinical practice,this review is based on an analysis of individual case reports over the past 55 years.While this is not the first study to utilize this sampling method for primary hyperparathyroidism-induced acute pancreatitis,it is unique in that it has a sufficiently large sample size with statistically significant results.Our discussion focuses on the diagnostic challenges associated with this condition,which are grounded in the mechanisms of parathyroid hormone secretion and variations in serum calcium levels.We also address the limitations of the current review and suggest potential strategies to increase diagnostic accuracy and improve health outcomes for both mothers and fetuses during pregnancy.展开更多
S100 proteins govern cellular proliferation,differentiation,apoptosis,calcium homeostasis,energy metabolism,and inflammation.This heterodimeric calcium-binding protein,consisting of the S100A8 and S100A9 subunits,modu...S100 proteins govern cellular proliferation,differentiation,apoptosis,calcium homeostasis,energy metabolism,and inflammation.This heterodimeric calcium-binding protein,consisting of the S100A8 and S100A9 subunits,modulates myeloid cell development.展开更多
BACKGROUND Glaucoma,a condition frequently linked to severe depression,anxiety,and sleep disturbances,affects treatment adherence while potentially compromising effectiveness.AIM To explore illness uncertainty(IU),anx...BACKGROUND Glaucoma,a condition frequently linked to severe depression,anxiety,and sleep disturbances,affects treatment adherence while potentially compromising effectiveness.AIM To explore illness uncertainty(IU),anxiety,and depressive symptoms in primary glaucoma and to discuss underlying triggers.METHODS We recruited 120 primary glaucoma cases between January 2022 and November 2023.The Mishel Uncertainty in Illness Scale(MUIS)and the Hospital Anxiety and Depression Scale(HADS)[include HADS-anxiety subscale(HADS-A)and HADS-depression subscale(HADS-D)]subscales,were used to assess IU and emotional distress(anxiety/depression),respectively.The MUIS-HADS subscale interrelationships were determined by Pearson correlation.IU-associated determinants were identified using univariate and binary logistic regression analyses.RESULTS The cohort showed a mean MUIS score of 79.73±8.97,corresponding to a moderately high IU level.The HADS-A and HADS-D scores averaged 6.57±3.89 and 7.08±5.05 points,respectively,with 15.00%of participants showing anxiety symptoms and 24.17%exhibiting depressive signs.Significant positive connections were observed between MUIS and both HADS-A(r=0.359,P<0.001)and HADSD(r=0.426,P<0.001).Univariate analysis revealed that disease duration,insomnia,monthly household income per capita,and the presence of comorbid chronic conditions were significantly associated with anxiety or depression.Multivariate analysis identified insomnia as a risk factor and higher monthly household income as a protective factor.CONCLUSION Patients with primary glaucoma experience moderate IU levels,generally low anxiety,and mild depression.Specifically,the anxiety and depression risks were 15.00%and 24.17%,respectively.A significant positive correlation existed between IU and anxiety/depression in these patients.Additionally,insomnia or lower monthly household income elevated anxiety/depression risks,enabling reliable anxiety/depression risk categorization among patients.展开更多
BACKGROUND Dilated cardiomyopathy(DCM)is a common cause of systolic heart failure,and is the most prevalent type of non-ischemic cardiomyopathy.Primary hyperparathyroidism(PHPT)is characterized by hypercalcemia and ex...BACKGROUND Dilated cardiomyopathy(DCM)is a common cause of systolic heart failure,and is the most prevalent type of non-ischemic cardiomyopathy.Primary hyperparathyroidism(PHPT)is characterized by hypercalcemia and excessive secretion of parathyroid hormone(PTH).Generally,PHPT is asymptomatic and is incidentally identified during routine laboratory assessments.CASE SUMMARY This case report details a 52-year-old man diagnosed with DCM and refractory hypercalcemia,who presented with clinical manifestations including dyspnea,recurrent anorexia,and abdominal distention.Laboratory investigations indicated an elevated serum PTH level,and the sestamibi scan suggested the presence of a parathyroid adenoma.Hence,the patient underwent a parathyroidectomy,which pathologically confirmed the diagnosis of a parathyroid adenoma.Postoperatively,the patient's hypercalcemia was corrected,the dimensions of the cardiac chambers were reduced,and there was a marked improvement in cardiac function.CONCLUSION Our findings emphasize the importance of PTH assessment in patients with DCM and concurrent hypercalcemia.展开更多
Acute pancreatitis recurrence should always alert clinicians to primary hyperparathyroidism,especially in younger patients and those with a hereditary condition.When parathyroid abnormalities are adequately recognized...Acute pancreatitis recurrence should always alert clinicians to primary hyperparathyroidism,especially in younger patients and those with a hereditary condition.When parathyroid abnormalities are adequately recognized and addressed,more recurrent attacks of acute pancreatitis are unlikely to occur.展开更多
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.
文摘BACKGROUND Colorectal cancer(CRC)ranks high among the most common types of malignant tumors.The primary cause of cancer-related mortality is metastasis,with lung metastases accounting for 32.9%of all cases of metastatic CRC(MCRC).However,cases of MCRC in the lungs,which present concurrently with primary peripheral lung adenocarcinoma,are exceptionally rare.CASE SUMMARY This report describes the case of a 52-year-old female patient who,following a colonoscopy,was diagnosed with moderately differentiated adenocarcinoma based on rectal mucosal biopsy findings.A preoperative chest computed tomography scan revealed a ground-glass nodule in the right lung and a small nodule(approximately 0.6 cm in diameter)in the extramural basal segment of the left lower lobe,which suggested multiple lung metastases from rectal cancer.Subsequent treatment and follow-up led to a diagnosis of rectal cancer with left lung metastasis and peripheral adenocarcinoma of the lower lobe of the right lung.CONCLUSION This case report describes the therapeutic journey of a patient with lung metastasis from rectal cancer in addition to primary peripheral adenocarcinoma,thus underscoring the critical roles of multidisciplinary collaboration,personalized treatment strategies,and comprehensive patient rehabilitation guidance.
基金The authors extend their appreciation to the Ongoing Research Funding Program,number(ORF2025R705),King Saud University,Riyadh,Saudi Arabia,for funding this work.
文摘The study aims to determine the validity and reliability of the Wechsler Preschool and Primary Scale of Intelligence–Third Edition(WPPSI-III)scores in a sample of kindergarten and lower primary pupils from Khartoum State,Sudan.It also aims to examine whether test’s factor structure in this sample replicated that of the original WPPSI-III.The study sample consisted of 384 kindergarten and primary school children in Khartoum State(females=50%mean age=4.14,SD=1.37),selected using stratified random sampling across its seven localities:Khartoum,Jebel Awliya,Khartoum Bahri,East Nile,Omdurman,Ombada,Karari.For concurrent validation,the children additionally completed the Goodenough Draw-a-Man Test,and the Colored Progressive Matrices.WPPSI-III scores demonstrated high internal consistency across the subtest items.Confirmatory factor analysis indicators for total,verbal,and performance intelligence were all excellent.The scale also showed weak to strong score stability ranging from 0.25(weak)to 0.88(strong)based on the Spearman-Brown equation,0.25 to 0.75 based on the Guttman split-half method.The Cronbach’s alpha coefficient scores ranged from 0.54 to 0.93.The WPPSI-III and Goodenough Draw-a-Man Test scores concurrent validity scores were poor(0.05)to modest(0.31),and while those with the Colored Progressive Matrices test were poor(r=0.04–0.18).Thesefindings provide evidence to suggest that the WPPSI-III is appropriate for research use with kindergarten and lower primary school students in Khartoum State,Sudan.
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 the Natural Science Foundation of China(32270663 and 31230045 to J.Y.L.)China Postdoctoral Science Foundation(2024M762007 and GZB20240453 to J.L.)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05 to J.Y.L.).
文摘Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over 20%in the elderly(Yamada et al.,2013),yet the underlying mechanisms of brain calcification remain poorly understood.Specifically,calcification in the basal ganglia is detected in approximately 5.5%-20%of CT scans in patients over 50 years old(Auffray-Calvier et al.,2020).
文摘Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.
基金supported by the National Key R&D Program of China(2020YFE0205900 and 2022YEF0203200)the STI 2030-Major Project(2021ZD0200104 and 2022ZD0205203)+2 种基金the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027,and JCYJ20210324102006018)the Youth Innovation Promotion Association CAS(2022367)the Shenzhen Technological Research Center for Primate Translational Medicine grant(XMHT20220104005).
文摘Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal ganglia,thalamus,and brainstem.Among these connections,the corticostriatal system plays a significant role in functions including action selection,motor control,sequence learning,and habit formation[2].
文摘Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.
文摘In this manuscript,we provide critical commentary on the systematic review by Augustin et al,which investigated acute pancreatitis induced by primary hyperparathyroidism during pregnancy.Although this is an infrequent complication,it poses severe risks to both maternal and fetal health.Due to its infrequent occurrence in clinical practice,this review is based on an analysis of individual case reports over the past 55 years.While this is not the first study to utilize this sampling method for primary hyperparathyroidism-induced acute pancreatitis,it is unique in that it has a sufficiently large sample size with statistically significant results.Our discussion focuses on the diagnostic challenges associated with this condition,which are grounded in the mechanisms of parathyroid hormone secretion and variations in serum calcium levels.We also address the limitations of the current review and suggest potential strategies to increase diagnostic accuracy and improve health outcomes for both mothers and fetuses during pregnancy.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82170160 and 32000604)the Provincial Natural Science Foundation of Hunan(Grant Nos.2021JJ30163 and 2022JJ20021)+3 种基金the Changsha Municipal Natural Science Foundation(Grant No.kq2007053)the Global Research Award from American Society of Hematology to Y.Mpartially supported by the National Natural Science Foundation of China(Grant No.82470145)Mount Taishan Scholar Young Expert of Shandong Province(Grant No.tsqn202103167)to S.X。
文摘S100 proteins govern cellular proliferation,differentiation,apoptosis,calcium homeostasis,energy metabolism,and inflammation.This heterodimeric calcium-binding protein,consisting of the S100A8 and S100A9 subunits,modulates myeloid cell development.
文摘BACKGROUND Glaucoma,a condition frequently linked to severe depression,anxiety,and sleep disturbances,affects treatment adherence while potentially compromising effectiveness.AIM To explore illness uncertainty(IU),anxiety,and depressive symptoms in primary glaucoma and to discuss underlying triggers.METHODS We recruited 120 primary glaucoma cases between January 2022 and November 2023.The Mishel Uncertainty in Illness Scale(MUIS)and the Hospital Anxiety and Depression Scale(HADS)[include HADS-anxiety subscale(HADS-A)and HADS-depression subscale(HADS-D)]subscales,were used to assess IU and emotional distress(anxiety/depression),respectively.The MUIS-HADS subscale interrelationships were determined by Pearson correlation.IU-associated determinants were identified using univariate and binary logistic regression analyses.RESULTS The cohort showed a mean MUIS score of 79.73±8.97,corresponding to a moderately high IU level.The HADS-A and HADS-D scores averaged 6.57±3.89 and 7.08±5.05 points,respectively,with 15.00%of participants showing anxiety symptoms and 24.17%exhibiting depressive signs.Significant positive connections were observed between MUIS and both HADS-A(r=0.359,P<0.001)and HADSD(r=0.426,P<0.001).Univariate analysis revealed that disease duration,insomnia,monthly household income per capita,and the presence of comorbid chronic conditions were significantly associated with anxiety or depression.Multivariate analysis identified insomnia as a risk factor and higher monthly household income as a protective factor.CONCLUSION Patients with primary glaucoma experience moderate IU levels,generally low anxiety,and mild depression.Specifically,the anxiety and depression risks were 15.00%and 24.17%,respectively.A significant positive correlation existed between IU and anxiety/depression in these patients.Additionally,insomnia or lower monthly household income elevated anxiety/depression risks,enabling reliable anxiety/depression risk categorization among patients.
基金Supported by Sichuan Province Science and Technology Program,No.2024YFHZ0214 and No.2023YFS0299Chengdu Science and Technology Program,No.2024-YF05-01820-SN.
文摘BACKGROUND Dilated cardiomyopathy(DCM)is a common cause of systolic heart failure,and is the most prevalent type of non-ischemic cardiomyopathy.Primary hyperparathyroidism(PHPT)is characterized by hypercalcemia and excessive secretion of parathyroid hormone(PTH).Generally,PHPT is asymptomatic and is incidentally identified during routine laboratory assessments.CASE SUMMARY This case report details a 52-year-old man diagnosed with DCM and refractory hypercalcemia,who presented with clinical manifestations including dyspnea,recurrent anorexia,and abdominal distention.Laboratory investigations indicated an elevated serum PTH level,and the sestamibi scan suggested the presence of a parathyroid adenoma.Hence,the patient underwent a parathyroidectomy,which pathologically confirmed the diagnosis of a parathyroid adenoma.Postoperatively,the patient's hypercalcemia was corrected,the dimensions of the cardiac chambers were reduced,and there was a marked improvement in cardiac function.CONCLUSION Our findings emphasize the importance of PTH assessment in patients with DCM and concurrent hypercalcemia.
文摘Acute pancreatitis recurrence should always alert clinicians to primary hyperparathyroidism,especially in younger patients and those with a hereditary condition.When parathyroid abnormalities are adequately recognized and addressed,more recurrent attacks of acute pancreatitis are unlikely to occur.
