Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most...Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.展开更多
BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and h...BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.展开更多
In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research sch...In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.展开更多
In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhance...In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.展开更多
The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main c...The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main cause of the current global warming trend. The main inference from this stance is that the increase in temperature must occur after the release of greenhouse gases originating from the anthropic activities. However, no scientific evidence has been provided for this basic notion. Earth paleoclimatic records document the antecedence of temperature over CO<sub>2</sub> levels. For the past 65 Ma, the temperature parameter has controlled the subsequent increase in CO<sub>2</sub>. This includes the three rapid aberrant shifts and extreme climate transients at 55 Ma, 34 Ma, and 23 Ma REF _Ref159913672 \r \h \* MERGEFORMAT [1]. The simple fact of their existence points to the potential for highly nonlinear responses in climate forcing. Whatever these shifts and transients are, CO<sub>2</sub> remains a second order parameter in their evolution through time. Confronted with the past, a suitable response must therefore be given to the unresolved question of whether the CO<sub>2</sub> trends precede the temperature trends in the current period, or not. The assertion that the current global warming is anthropogenic in origin implicitly presupposes a change of paradigm, with the consequence (the increase in CO<sub>2</sub> levels) that occurred in Earth’s past being positioned as the cause of the warming for its present day climatic evolution. The compulsory assumption regarding the antecedence of CO<sub>2</sub> levels over the temperature trends is associated with the haziness of the methodological framework—i.e. the paradigm—and tightens the research fields on the likely origins of global warming. The possible involvement of an “aberrant” natural event, hidden behind the massive release of greenhouse gases, has not been considered by the MSC.展开更多
This study proposes a novel strategy for the design of a new family of metastable Zr alloys.These al-loys offer improved mechanical properties for implants,particularly in applications where conventional stainless ste...This study proposes a novel strategy for the design of a new family of metastable Zr alloys.These al-loys offer improved mechanical properties for implants,particularly in applications where conventional stainless steels and Co-Cr alloys are currently used but lack suitability.The design approach is based on the controlled twinning-induced plasticity(TWIP)effect,significantly enhancing the ductility and strain-hardenability of the Zr alloys.In order to draw a“blueprint”for the compositional design of biomedical T WIP(Bio-T WIP)Zr alloys-using only non-toxic elements,the study combines D-electron phase stability calculations(specifically bond order(Bo)and mean d-orbital energy(Md))with a systematic experimental screening of active deformation mechanisms within the Zr-Nb-Sn alloy system.This research aids in ac-curately identifying the TWIP line,which signifies the mechanism shift between TWIP and classic slip as the primary deformation mechanism.To demonstrate the efficacy of the TWIP mechanism in enhancing mechanical properties,Zr-12Nb-2Sn,Zr-13Nb-1Sn,and Zr-14Nb-3Sn alloys are selected.Results indicate that the TWIP mechanism leads to a significant improvement of strain-hardening rate and a uniform elongation of∼20%in Zr-12Nb-2Sn,which displays both{332}<113>mechanical twinning and disloca-tion slip as the primary deformation mechanisms.Conversely,Zr-14Nb-3Sn exhibits the typical mechan-ical properties found in stable body-centered cubic(BCC)alloys,characterized by the sole occurrence of dislocation slip.Cell viability tests confirm the superior biocompatibility of Zr-Nb-based alloys with deformation twins on the surface,in line with existing literature.Based on the whole set of results,a comprehensive design diagram is proposed.展开更多
BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharma...BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharmacological factors are rare.This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition,leading to interstitial nephritis.The aim is to outline the case and its management,emphasizing the significance of recognizing uncommon causes of interstitial nephritis.CASE SUMMARY A 71-year-old female presented with stroke-like symptoms,including weakness,speech difficulties,and cognitive impairment.Chronic hypertension had been managed with hydrochlorothiazide(HCTZ)for over two decades.Upon admis-sion,severe hypokalemia and AKI were noted,prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis.Further investigations,including kidney biopsy,confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause.Despite treatment,initial renal function showed minimal improvement.However,with prednisolone therapy and supportive measures,her condition gradually improved,high-lighting the importance of comprehensive management.CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis.The occurrence of interstitial nephritis due to oxalate crystal deposition,especially without typical risk factors,emphasizes the need for vigilance in clinical practice.展开更多
BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trend...BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.展开更多
We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft ...We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
基金supported in part by DOD Idea Development Award(HT9425-23-1-0295)NIH grants(R01 CA265897 and R21 CA280467)by the Department of Urology,University of Pittsburgh School of Medicine,Pittsburgh,PA,USA。
文摘Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
文摘BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.
文摘In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.
文摘In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.
文摘The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main cause of the current global warming trend. The main inference from this stance is that the increase in temperature must occur after the release of greenhouse gases originating from the anthropic activities. However, no scientific evidence has been provided for this basic notion. Earth paleoclimatic records document the antecedence of temperature over CO<sub>2</sub> levels. For the past 65 Ma, the temperature parameter has controlled the subsequent increase in CO<sub>2</sub>. This includes the three rapid aberrant shifts and extreme climate transients at 55 Ma, 34 Ma, and 23 Ma REF _Ref159913672 \r \h \* MERGEFORMAT [1]. The simple fact of their existence points to the potential for highly nonlinear responses in climate forcing. Whatever these shifts and transients are, CO<sub>2</sub> remains a second order parameter in their evolution through time. Confronted with the past, a suitable response must therefore be given to the unresolved question of whether the CO<sub>2</sub> trends precede the temperature trends in the current period, or not. The assertion that the current global warming is anthropogenic in origin implicitly presupposes a change of paradigm, with the consequence (the increase in CO<sub>2</sub> levels) that occurred in Earth’s past being positioned as the cause of the warming for its present day climatic evolution. The compulsory assumption regarding the antecedence of CO<sub>2</sub> levels over the temperature trends is associated with the haziness of the methodological framework—i.e. the paradigm—and tightens the research fields on the likely origins of global warming. The possible involvement of an “aberrant” natural event, hidden behind the massive release of greenhouse gases, has not been considered by the MSC.
基金the support of the French Agence Nationale de la Recherche(ANR),under grant ANR-21-CE08-0022(project ISANAMI)Junhui TANG is sponsored by the China Scholarship Council.
文摘This study proposes a novel strategy for the design of a new family of metastable Zr alloys.These al-loys offer improved mechanical properties for implants,particularly in applications where conventional stainless steels and Co-Cr alloys are currently used but lack suitability.The design approach is based on the controlled twinning-induced plasticity(TWIP)effect,significantly enhancing the ductility and strain-hardenability of the Zr alloys.In order to draw a“blueprint”for the compositional design of biomedical T WIP(Bio-T WIP)Zr alloys-using only non-toxic elements,the study combines D-electron phase stability calculations(specifically bond order(Bo)and mean d-orbital energy(Md))with a systematic experimental screening of active deformation mechanisms within the Zr-Nb-Sn alloy system.This research aids in ac-curately identifying the TWIP line,which signifies the mechanism shift between TWIP and classic slip as the primary deformation mechanism.To demonstrate the efficacy of the TWIP mechanism in enhancing mechanical properties,Zr-12Nb-2Sn,Zr-13Nb-1Sn,and Zr-14Nb-3Sn alloys are selected.Results indicate that the TWIP mechanism leads to a significant improvement of strain-hardening rate and a uniform elongation of∼20%in Zr-12Nb-2Sn,which displays both{332}<113>mechanical twinning and disloca-tion slip as the primary deformation mechanisms.Conversely,Zr-14Nb-3Sn exhibits the typical mechan-ical properties found in stable body-centered cubic(BCC)alloys,characterized by the sole occurrence of dislocation slip.Cell viability tests confirm the superior biocompatibility of Zr-Nb-based alloys with deformation twins on the surface,in line with existing literature.Based on the whole set of results,a comprehensive design diagram is proposed.
文摘BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharmacological factors are rare.This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition,leading to interstitial nephritis.The aim is to outline the case and its management,emphasizing the significance of recognizing uncommon causes of interstitial nephritis.CASE SUMMARY A 71-year-old female presented with stroke-like symptoms,including weakness,speech difficulties,and cognitive impairment.Chronic hypertension had been managed with hydrochlorothiazide(HCTZ)for over two decades.Upon admis-sion,severe hypokalemia and AKI were noted,prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis.Further investigations,including kidney biopsy,confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause.Despite treatment,initial renal function showed minimal improvement.However,with prednisolone therapy and supportive measures,her condition gradually improved,high-lighting the importance of comprehensive management.CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis.The occurrence of interstitial nephritis due to oxalate crystal deposition,especially without typical risk factors,emphasizes the need for vigilance in clinical practice.
文摘BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.
文摘We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
