BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication ...BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Review...Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.展开更多
Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell...Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.展开更多
Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-...Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.展开更多
In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions e...In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein.The study has provided important evidence to improve maternal and child health in the Asian population.The methods,however,appear to have considerable limi-tations,wherein the time point of diagnosis of GDM,severity of GDM,selection bias,compliance to therapy,important maternal covariates,observable microvascular abnormalities and the confounding effect of added insulin have not been considered.We have provided suggestions to improve the external validity of the study,including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.展开更多
Glaucoma,a prevalent and debilitating eye disease,has long been associated with vision impairment and blindness.However,recent research has shed light on the often-underestimated psychological dimensions of this condi...Glaucoma,a prevalent and debilitating eye disease,has long been associated with vision impairment and blindness.However,recent research has shed light on the often-underestimated psychological dimensions of this condition.Anxiety and depression,two pervasive psychiatric comorbidities,have been increasingly recognized among glaucoma patients.This comprehensive review aims to explore the intricate relationship between psychiatry and ophthalmology,in the context of managing depression and anxiety in glaucoma patients.By meticulously examining peer-reviewed literature,we synthesize current knowledge on the prevalence,risk factors,and underlying mechanisms of anxiety and depression in glaucoma.The evidence reveals that glaucoma patients face an elevated risk of experiencing these mood disorders.Factors such as progressive vision loss,complex medication regimens,and the fear of further visual deterioration contribute to their vulnerability.Moreover,we delve into the bidirectional relationship between glaucoma and mood disorders,shedding light on the complex interplay between ocular and emotional health.Our review investigates the implications of anxiety and depression on glaucoma management,including their potential impact on treatment adherence,disease progression,and overall quality of life.We also explore the neurobiological pathways linking glaucoma and mood disorders,providing a foundation for future research and potential therapeutic interventions.In conclusion,recognizing the psychological burden carried by glaucoma patients is essential for holistic and patient-centered care.This review underscores the pressing need for integrated approaches that bring together ophthalmological and psychiatric expertise to optimize the well-being of individuals facing the challenges of glaucoma.By addressing anxiety and depression in glaucoma care,healthcare providers can enhance the overall quality of life for these patients,ultimately leading to improved outcomes and a brighter future for those affected by this condition.This review offers valuable insight for healthcare practitioners and researchers,providing a concise overview of key topics and research in the field of managing depression and anxiety in glaucoma patients.展开更多
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial con...A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.展开更多
The recently re-emerged mpox(monkeypox)virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide.Numerous studies have contributed to our understanding of its evolution...The recently re-emerged mpox(monkeypox)virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide.Numerous studies have contributed to our understanding of its evolution,pathophysiology,and clinical manifestations.The current outbreak of the mpox virus depicts its novel route of transmission as a new variant.However,the exact reason for its transition from an epidemic to a pandemic remains unclear.Furthermore,other poxviruses such as vaccinia virus,variola virus,and cowpox virus,also belong to the same genus,Orthopoxvirus.In the present review,our objective was to summarize the evidence on evolution,pathophysiology,and clinical manifestations of mpox virus and its related poxviruses.The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses.In addition,the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities.While they exhibit differences in virulence,studying these genetic relationships is crucial for understanding their biology,pathogenicity,and the development of effective vaccines and antiviral therapeutics to curb mpox disease.展开更多
Objective:The complexity of urethral strictures can predict outcomes following urethroplasty.The previously described urethral stricture score(U score)considered only stricture-related factors to grade the complexity ...Objective:The complexity of urethral strictures can predict outcomes following urethroplasty.The previously described urethral stricture score(U score)considered only stricture-related factors to grade the complexity of urethral strictures and to predict recurrence post urethroplasty,but not considered patient-related factors for the same.We aimed to study the correlation of both of these factors to the outcomes of oral mucosal graft urethroplasty.Methods:We retrospectively reviewed data of 101 patients who underwent oral mucosal graft urethroplasty in our institute with a minimum follow-up of 6 months.Baseline patient characteristics and stricture-related parameters were noted.The U score was calculated for all patients which consisted of the length,location,number,and etiology of stricture.Univariate and multivariate Cox proportional hazard regression models were used to determine significant risk factors of recurrence.Results:The mean follow-up of patients was 15 months.Recurrence was seen in 28 patients and the mean time for detection of recurrence was 8 months of follow-up.The Charlson Comorbidity Index,history of previous intervention,length of strictures,location of strictures,number of strictures,history of smoking,and etiology were independent predictors of recurrence following urethroplasty.Based on these parameters,we formulated the modified U score(MU score).The scores ranged from 0 to 6 and a score of>2 was found to be predictive of recurrence.On comparing receiver operating characteristic curves for both scores by the DeLong test,the MU score had larger area under the curve than the U score.Conclusion:The MU scoring system is the first of its kind attempt taking into consideration both patient-and stricture-related factors to predict recurrence following oral mucosal graft urethroplasty.展开更多
BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.MET...BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.展开更多
This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recen...This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recent review.While the review provides significant insights,it relies heavily on cross-sectional and observational studies,which limits the ability to draw causal inferences.The heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the findings.This letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing literature.The implications of these issues are discussed in the context of both CD and UC,and future research directions are proposed to address these shortcomings.展开更多
BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian cancer.Herein,we report the case of a woman with retroperitoneal HGSC of unknown origin...BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian cancer.Herein,we report the case of a woman with retroperitoneal HGSC of unknown origin and describe how she was diagnosed and treated.CASE SUMMARY A 71-year-old female presented with the tumor marker CA125 elevated to 1041.9 U/mL upon a regular health examination.Computed tomography revealed retroperitoneal lymph node enlargement.Subsequently,positron emission tomography scanning revealed lesions with increased F-18 fluorodeoxyglucose uptake at the nodes.As a result,she underwent laparoscopic lymph node resection,and pathology revealed metastatic adenocarcinoma with CK7(+),PAX8(+),WT1(+),PR(-),and p53 mutational loss of expression,indicating that the origin may be from the adnexa.The patient was admitted to our ward and underwent laparoscopic staging;however,the pathological results were negative.Under the suspicion of retroperitoneal HGSC of unknown origin,chemotherapy and targeted therapy were initiated.Tumor marker levels decreased after treatment.CONCLUSION We present a case of HGSC of unknown origin managed using retroperitoneal lymphadenectomy,staging surgery,chemotherapy,and targeted therapy.展开更多
The recently published mini-review article by Miotti et al is an effort to clarify various aspects regarding the choice between fat grafts and fillers in facial aesthetic surgery.One of the complications associated wi...The recently published mini-review article by Miotti et al is an effort to clarify various aspects regarding the choice between fat grafts and fillers in facial aesthetic surgery.One of the complications associated with the administration of fillers is the possibility of vascular injury and spread of the dermal filler into the orbit,causing unexpected effects at a site distant from that of the initial injection,including ophthalmoplegia,ptosis and even visual compromise.Acute vision loss following filler injection is a devastating complication,occurring in up to 0.0008%of cases.The greatest risk of this complication occurs with nasal augmentation,followed by glabellar wrinkle treatment.While injected autologous fat predominantly occludes the proximal portion of the ophthalmic artery,hyaluronic acid fillers obstruct the ophthalmic artery comparatively distally.Treatment interventions include thrombolysis,hyperbaric oxygen therapy,oral aspirin,cobamamide and acetazolamide and administration of corticosteroids.However,most studies show a poor prognosis in the form of partial or no recovery of vision.Hence,prevention is of paramount importance.A high index of suspicion is also warranted on the part of both those administering as well as receiving injections of facial fillers to prevent potentially vision-threatening complications of this seemingly innocuous procedure.展开更多
The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic st...The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.展开更多
The study by Zhao et al identifies the factors leading to the failure of unicompartmental knee arthroplasty(UKA)in their patients.These factors include substandard suturing of the wound,the presence of osteophytes and...The study by Zhao et al identifies the factors leading to the failure of unicompartmental knee arthroplasty(UKA)in their patients.These factors include substandard suturing of the wound,the presence of osteophytes and intra-articular loose bodies causing impingement,premature loosening of the tibial component,choosing unsuitable patients for the procedure,dislocation of the movable insert,and damage to the anterior cruciate ligament and medial collateral ligament.The findings suggest that employing the correct surgical techniques and indications is essential for successful outcomes in the UKA.展开更多
Laparoscopy within the urology field has undergone a noteworthy surge in popularity over the past decade,with particular importance given to renal surgeries such as simple nephrectomy,radical nephrectomy,donor nephrec...Laparoscopy within the urology field has undergone a noteworthy surge in popularity over the past decade,with particular importance given to renal surgeries such as simple nephrectomy,radical nephrectomy,donor nephrectomy,nephroureterectomy,and partial nephrectomy.1 This shift toward laparoscopic procedures among urologists can be attributed to the many benefits of these procedures,including reduced postoperative pain,shorter hospital stays,and faster recovery times.2 However,as with any evolving surgical technique,laparoscopic procedures in renal surgery bring forth their own set of distinctive challenges and complications.展开更多
Higher education plays an important role in all aspects of sustainability.Infusing climate change and sustainability into the curriculum is important to prepare future health-care professionals for climate change and ...Higher education plays an important role in all aspects of sustainability.Infusing climate change and sustainability into the curriculum is important to prepare future health-care professionals for climate change and sustainability actions to build resilient health systems.In this study,we evaluated the preparedness,knowledge,and perception regarding climate change and its impact on human health among Indian nursing students.A quantitative descriptive survey was conducted among 644 undergraduate nursing students studying in three institutes in the southern,northern,and western parts of India.We used a structured online questionnaire with established validity and reliability to collect data.The data were analyzed using Statistical Package for the Social Sciences version 26 software.The results showed that more than half of the students reported experiencing excessive increase(362;56.2%)and decrease(374;58.1%)in temperature in recent years.Though more than three quarters of the students(494;76.7%)accepted the general truth that climate change is mainly caused by human activities,only less than half of the students(309;48.0%)perceived the impact of climate change to be high.Three quarters of the students(483;75.0%)had a high level of knowledge regarding climate change.The students who had a high level of knowledge about climate change exerted a high perceived impact of climate change(χ^(2)=75.47;P<0.01).More than half of the students(50.9%)felt that they needed information about climate change to be included in the nursing curriculum,and only one sixth of the students(16.1%)were highly confident about engaging in climate change-related conversation with patients.Most of the students who participated in the study had basic knowledge about climate change and its impact on human health.However,there is an observed gap between knowledge and their preparedness and confidence to engage in climate change actions.Hence,we propose to strengthen the nursing curriculum by integrating various curricular and co-curricular activities related to climate change,so that future nurses are empowered to become climate change advocates.展开更多
Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases o...Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.展开更多
Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosph...Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.展开更多
文摘BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金supported partly by the National Natural Science Foundation of China,Nos.32161143021 and 81271410the Natural Science Foundation of Henan Province of China,No.182300410313(all to JW)。
文摘Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.
基金supported by the National Natural Science Foundation of China,Nos.81974207(to JH),82001383(to DW)the Special Clinical Research Project of Health Profession of Shanghai Municipal Health Commission,No.20204Y0076(to DW)。
文摘Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.
基金supported by the Robert Campeau Family Foundation/Dr.C.H.Tator Chair in Brain and Spinal Cord Research(to MGF)。
文摘Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.
文摘In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein.The study has provided important evidence to improve maternal and child health in the Asian population.The methods,however,appear to have considerable limi-tations,wherein the time point of diagnosis of GDM,severity of GDM,selection bias,compliance to therapy,important maternal covariates,observable microvascular abnormalities and the confounding effect of added insulin have not been considered.We have provided suggestions to improve the external validity of the study,including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.
文摘Glaucoma,a prevalent and debilitating eye disease,has long been associated with vision impairment and blindness.However,recent research has shed light on the often-underestimated psychological dimensions of this condition.Anxiety and depression,two pervasive psychiatric comorbidities,have been increasingly recognized among glaucoma patients.This comprehensive review aims to explore the intricate relationship between psychiatry and ophthalmology,in the context of managing depression and anxiety in glaucoma patients.By meticulously examining peer-reviewed literature,we synthesize current knowledge on the prevalence,risk factors,and underlying mechanisms of anxiety and depression in glaucoma.The evidence reveals that glaucoma patients face an elevated risk of experiencing these mood disorders.Factors such as progressive vision loss,complex medication regimens,and the fear of further visual deterioration contribute to their vulnerability.Moreover,we delve into the bidirectional relationship between glaucoma and mood disorders,shedding light on the complex interplay between ocular and emotional health.Our review investigates the implications of anxiety and depression on glaucoma management,including their potential impact on treatment adherence,disease progression,and overall quality of life.We also explore the neurobiological pathways linking glaucoma and mood disorders,providing a foundation for future research and potential therapeutic interventions.In conclusion,recognizing the psychological burden carried by glaucoma patients is essential for holistic and patient-centered care.This review underscores the pressing need for integrated approaches that bring together ophthalmological and psychiatric expertise to optimize the well-being of individuals facing the challenges of glaucoma.By addressing anxiety and depression in glaucoma care,healthcare providers can enhance the overall quality of life for these patients,ultimately leading to improved outcomes and a brighter future for those affected by this condition.This review offers valuable insight for healthcare practitioners and researchers,providing a concise overview of key topics and research in the field of managing depression and anxiety in glaucoma patients.
文摘A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
文摘The recently re-emerged mpox(monkeypox)virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide.Numerous studies have contributed to our understanding of its evolution,pathophysiology,and clinical manifestations.The current outbreak of the mpox virus depicts its novel route of transmission as a new variant.However,the exact reason for its transition from an epidemic to a pandemic remains unclear.Furthermore,other poxviruses such as vaccinia virus,variola virus,and cowpox virus,also belong to the same genus,Orthopoxvirus.In the present review,our objective was to summarize the evidence on evolution,pathophysiology,and clinical manifestations of mpox virus and its related poxviruses.The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses.In addition,the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities.While they exhibit differences in virulence,studying these genetic relationships is crucial for understanding their biology,pathogenicity,and the development of effective vaccines and antiviral therapeutics to curb mpox disease.
文摘Objective:The complexity of urethral strictures can predict outcomes following urethroplasty.The previously described urethral stricture score(U score)considered only stricture-related factors to grade the complexity of urethral strictures and to predict recurrence post urethroplasty,but not considered patient-related factors for the same.We aimed to study the correlation of both of these factors to the outcomes of oral mucosal graft urethroplasty.Methods:We retrospectively reviewed data of 101 patients who underwent oral mucosal graft urethroplasty in our institute with a minimum follow-up of 6 months.Baseline patient characteristics and stricture-related parameters were noted.The U score was calculated for all patients which consisted of the length,location,number,and etiology of stricture.Univariate and multivariate Cox proportional hazard regression models were used to determine significant risk factors of recurrence.Results:The mean follow-up of patients was 15 months.Recurrence was seen in 28 patients and the mean time for detection of recurrence was 8 months of follow-up.The Charlson Comorbidity Index,history of previous intervention,length of strictures,location of strictures,number of strictures,history of smoking,and etiology were independent predictors of recurrence following urethroplasty.Based on these parameters,we formulated the modified U score(MU score).The scores ranged from 0 to 6 and a score of>2 was found to be predictive of recurrence.On comparing receiver operating characteristic curves for both scores by the DeLong test,the MU score had larger area under the curve than the U score.Conclusion:The MU scoring system is the first of its kind attempt taking into consideration both patient-and stricture-related factors to predict recurrence following oral mucosal graft urethroplasty.
基金This study was reviewed and approved by the Ethics Committee of the All India Institute of Medical Sciences,New Delhi(Approval No.IEC/NP-458/12.12.2014,RP 22-2015).
文摘BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.
文摘This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recent review.While the review provides significant insights,it relies heavily on cross-sectional and observational studies,which limits the ability to draw causal inferences.The heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the findings.This letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing literature.The implications of these issues are discussed in the context of both CD and UC,and future research directions are proposed to address these shortcomings.
文摘BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian cancer.Herein,we report the case of a woman with retroperitoneal HGSC of unknown origin and describe how she was diagnosed and treated.CASE SUMMARY A 71-year-old female presented with the tumor marker CA125 elevated to 1041.9 U/mL upon a regular health examination.Computed tomography revealed retroperitoneal lymph node enlargement.Subsequently,positron emission tomography scanning revealed lesions with increased F-18 fluorodeoxyglucose uptake at the nodes.As a result,she underwent laparoscopic lymph node resection,and pathology revealed metastatic adenocarcinoma with CK7(+),PAX8(+),WT1(+),PR(-),and p53 mutational loss of expression,indicating that the origin may be from the adnexa.The patient was admitted to our ward and underwent laparoscopic staging;however,the pathological results were negative.Under the suspicion of retroperitoneal HGSC of unknown origin,chemotherapy and targeted therapy were initiated.Tumor marker levels decreased after treatment.CONCLUSION We present a case of HGSC of unknown origin managed using retroperitoneal lymphadenectomy,staging surgery,chemotherapy,and targeted therapy.
文摘The recently published mini-review article by Miotti et al is an effort to clarify various aspects regarding the choice between fat grafts and fillers in facial aesthetic surgery.One of the complications associated with the administration of fillers is the possibility of vascular injury and spread of the dermal filler into the orbit,causing unexpected effects at a site distant from that of the initial injection,including ophthalmoplegia,ptosis and even visual compromise.Acute vision loss following filler injection is a devastating complication,occurring in up to 0.0008%of cases.The greatest risk of this complication occurs with nasal augmentation,followed by glabellar wrinkle treatment.While injected autologous fat predominantly occludes the proximal portion of the ophthalmic artery,hyaluronic acid fillers obstruct the ophthalmic artery comparatively distally.Treatment interventions include thrombolysis,hyperbaric oxygen therapy,oral aspirin,cobamamide and acetazolamide and administration of corticosteroids.However,most studies show a poor prognosis in the form of partial or no recovery of vision.Hence,prevention is of paramount importance.A high index of suspicion is also warranted on the part of both those administering as well as receiving injections of facial fillers to prevent potentially vision-threatening complications of this seemingly innocuous procedure.
文摘The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.
文摘The study by Zhao et al identifies the factors leading to the failure of unicompartmental knee arthroplasty(UKA)in their patients.These factors include substandard suturing of the wound,the presence of osteophytes and intra-articular loose bodies causing impingement,premature loosening of the tibial component,choosing unsuitable patients for the procedure,dislocation of the movable insert,and damage to the anterior cruciate ligament and medial collateral ligament.The findings suggest that employing the correct surgical techniques and indications is essential for successful outcomes in the UKA.
文摘Laparoscopy within the urology field has undergone a noteworthy surge in popularity over the past decade,with particular importance given to renal surgeries such as simple nephrectomy,radical nephrectomy,donor nephrectomy,nephroureterectomy,and partial nephrectomy.1 This shift toward laparoscopic procedures among urologists can be attributed to the many benefits of these procedures,including reduced postoperative pain,shorter hospital stays,and faster recovery times.2 However,as with any evolving surgical technique,laparoscopic procedures in renal surgery bring forth their own set of distinctive challenges and complications.
文摘Higher education plays an important role in all aspects of sustainability.Infusing climate change and sustainability into the curriculum is important to prepare future health-care professionals for climate change and sustainability actions to build resilient health systems.In this study,we evaluated the preparedness,knowledge,and perception regarding climate change and its impact on human health among Indian nursing students.A quantitative descriptive survey was conducted among 644 undergraduate nursing students studying in three institutes in the southern,northern,and western parts of India.We used a structured online questionnaire with established validity and reliability to collect data.The data were analyzed using Statistical Package for the Social Sciences version 26 software.The results showed that more than half of the students reported experiencing excessive increase(362;56.2%)and decrease(374;58.1%)in temperature in recent years.Though more than three quarters of the students(494;76.7%)accepted the general truth that climate change is mainly caused by human activities,only less than half of the students(309;48.0%)perceived the impact of climate change to be high.Three quarters of the students(483;75.0%)had a high level of knowledge regarding climate change.The students who had a high level of knowledge about climate change exerted a high perceived impact of climate change(χ^(2)=75.47;P<0.01).More than half of the students(50.9%)felt that they needed information about climate change to be included in the nursing curriculum,and only one sixth of the students(16.1%)were highly confident about engaging in climate change-related conversation with patients.Most of the students who participated in the study had basic knowledge about climate change and its impact on human health.However,there is an observed gap between knowledge and their preparedness and confidence to engage in climate change actions.Hence,we propose to strengthen the nursing curriculum by integrating various curricular and co-curricular activities related to climate change,so that future nurses are empowered to become climate change advocates.
文摘Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.
基金The National Science and Technology Council of Taiwan funded this study.
文摘Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.
