Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an i...Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary ...Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary to give a chance to the patient. We herein describe a case of blunt abdominal trauma in a 29-year- old man whose pancreatic rupture was associated with hepatic artery, splenic vein and extrahepatic bile duct damage. Immediate surgery was performed after computer tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the operating room. Spleno-pancreatic resection was done with reconstruction of the hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal diversion. The early post-operative course was complicated by stenosis of the arterial reconstruction, which was treated by endovascular angioplasty followed by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics. Finally, the patient was discharged and was alive without clinical problems at the time when we wrote this case report. The present case underlines the clinical relevance of vascular and visceral injuries associated with pancreatic trauma and the problems arising in the diagnostic evaluation and the surgical strategy of complex multiple visceral and vascular lesions in blunt abdominal trauma.展开更多
AIM: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC. METHODS: We included 180 patient...AIM: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC. METHODS: We included 180 patients with PBC (cases) and 151 patients seen for HCV infection (controls). Medical records were reviewed and statistical analyses were performed as appropriate. RESULTS: When compared to controls, PBC patients were older, leaner and had higher serum levels of total cholesterol, high density lipoprotein and low density cholesterol. There were more females in the PBC group (91.7% vs 43%, P < 0.001). More control subjects had smoked than the PBC patients (63.6% vs 35%, P < 0.001). The prevalence of hypertension, diabetes, coronary artery disease and stroke was similar between the two groups. Seven percent of controls and 10% of cases developed any type of cardiovascular disease (P = 0.3). Only 36.7% were asymptomatic at diagnosis. Three cardiovascular events were documented among asymptomatic patients (4.5%) and fifteen among symptomatic patients (13.2%; P = 0.06). Among PBC patients with fatigue, 10 (13.5%) had a cardiovascular event compared to 7 (6.7%) among patients without fatigue (P = 0.1). CONCLUSION: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patients suffering with fatigue.展开更多
In order to study the mechanism of decreased blood pressure caused by an acute increase in biliary tract pressure, we observed house rabbit model of self-made caecus for changes in cardiovascular function when biliary...In order to study the mechanism of decreased blood pressure caused by an acute increase in biliary tract pressure, we observed house rabbit model of self-made caecus for changes in cardiovascular function when biliary tract pressure was increased.It was found that both the blood pressure and cardiac output evidently decreased (P<0.05) parallelly, and the systolic pressure decreased more markedly than diastolic pressure. At the same time there was fluctuation in heart rate and in central venous pressure; but there was no significant difference between them (P>0. 05), suggesting that in the absence of infective agents,the increased biliary tract pressure can bring about a decrease in cardiac output, which is an important factor contributing to an early blood pressure decrease in acute cholangitis of severe type (ACST).展开更多
This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obst...This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obstruction,the technical aspects of stenting,and the clinical outcomes.By comparison of endoscopic stenting with percutaneous biliary drainage,improvements and complications are focused on.Additionally,patient selection for stenting and future advancements in stent technology are important.Overall,endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice,especially those ineligibles for surgery.展开更多
Biliary system,which is responsible for transporting bile from the liver into the intestine,is commonly damaged by inflammation or tumors eventually causing liver failure or death.The implantation of biliary stents ca...Biliary system,which is responsible for transporting bile from the liver into the intestine,is commonly damaged by inflammation or tumors eventually causing liver failure or death.The implantation of biliary stents can effectively alleviate both benign and malignant biliary strictures,but the plastic and metal stents that are currently used cannot degrade and nearly has no beneficial biological effects,therefore their long-term service can result into inflammation,the formation of sludges and re-obstruction of bile duct.In recent years,magnesium(Mg)metal has been received increasing attention in the field of biomedical application due to its excellent biocompatibility,adequate mechanical properties,biodegradability and other advantages,such as anti-inflammatory and anti-tumor properties.The research on biliary stents made of magnesium metals(BSMM)has also made significant progress and a series of experiments in vitro and vivo has proved their possibility.However,there are still some problems holding back BSMM’s clinical use,including rapid corrosion rate and potential harmful reaction.In this review,we would summarize the current research of BSMM,evaluate their clinical benefits,find the choke points,and discuss the solving method.展开更多
BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who ex...BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who experienced proximal BDI during LC in 2017,leading to multiple episodes of cholangitis and subsequent hepaticojejunostomy in 2018.Despite these interventions,persistent biliary complications necessitated repeated hospital admissions and antibiotic treatment.Imaging studies revealed persistent stricture at the site of hepaticojejunostomy,prompting a series of percutaneous procedures,including balloon dilatation and biliary drainage.In August 2024,she underwent biodegradable biliary stenting,which significantly improved her condition.Subsequently,she remained clinically stable for 5 months without further episodes of cholangitis and had improved liver function tests.This case highlighted the complexities of managing postinjury biliary stricture,underscored the potential of biodegradable stents as an effective treatment option,and emphasized the need for a multidisciplinary approach in managing such complications.Long-term follow-up is essential for monitoring treatment effectiveness and preventing recurrence.CASE SUMMARY A 39-year-old female had a routine LC in 2017.The patient sustained a proximal BDI during the surgery.In the months that followed,recurrent bouts of cholangitis occurred.A hepaticojejunostomy biliary reconstruction was performed in 2018.However,hepatic cholangitis persisted.In 2021 and 2022,MRCP scans revealed biliary stasis,duct dilation,and a stricture at the hepaticojejunostomy site.A subsequent percutaneous transhepatic cholangiography(PTC)confirmed these findings and led to drain placement.The treatment included internal and external biliary drain placements,repeated balloon dilations of the stricture,percutaneous transhepatic cholangioscopy to extract intrahepatic lithiasis,and insertion of a biodegradable biliary stent.Since the first PTC intervention,there have been no hospital admissions for cholangitis.Liver function tests showed improvement,and for five months following the biodegradable stenting,the condition remained stable.Long-term surveillance with regular imaging and blood work has been emphasized.The final diagnosis is recurrent biliary stricture secondary to proximal BDI.Treatment,including hepaticojejunostomy,repeated PTC with balloon dilation,and biodegradable biliary stenting,has led to complete drainage of the biliary system.Ongoing follow-up remains crucial for monitoring the patient's progress and maintaining their health.CONCLUSION This case demonstrated how strictures and recurrent cholangitis complicate the management of BDI after LC.A customized and multidisciplinary approach to control chronic biliary disease was proven effective,as shown by the patient’s good outcome.This was achieved by integrating balloon dilatation sessions,biliary drainage,stone clearing,and biodegradable stent placement.Long-term follow-up and continued monitoring remain essential to ensure patient stability and prevent further complications.展开更多
Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,th...Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.展开更多
Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
BACKGROUND Needle-knife precut papillotomy(NKP)is typically performed freehand.However,it remains unclear whether pancreatic stent(PS)placement can improve the outcomes of NKP.AIM To explore whether PS placement impro...BACKGROUND Needle-knife precut papillotomy(NKP)is typically performed freehand.However,it remains unclear whether pancreatic stent(PS)placement can improve the outcomes of NKP.AIM To explore whether PS placement improves the success rate of NKP in patients with difficult biliary cannulation.METHODS This single-center retrospective study included 190 patients who underwent NKP between January 2017 and December 2021 after failed conventional biliary cannulation.In cases with incidental pancreatic duct cannulation during conventional biliary cannulation,the decision for pre-NKP PS placement was made at the endoscopist's discretion.The primary outcome was the difference in the NKP success rate between patients with and without PS placement;the secondary outcome was the adverse event rate.RESULTS Among the 190 participants,82 received pre-NKP PS(PS-NKP group)whereas 108 did not[freehand or freehand NKP(FH-NKP)group].Post-NKP selective biliary cannulation was successful in 167(87.9%)patients,and the PS-NKP had a significantly higher success rate than the FH-NKP group(93.9%vs 83.3%,P=0.027).The overall adverse event rates were 7.3%and 11.1%in the PS-NKP and FH-NKP groups,respectively(P=0.493).A periampullary diverticulum(PAD)and significant intraoperative bleeding during NKP were independently associated with NKP failure;however,a pre-NKP PS was the only predictor of NKP success.Among the 44 participants with PADs,the PS-NKP group had a non-significantly higher NKP success rate than the FH-NKP group(87.5%and 65%,respectively;P=0.076).CONCLUSION PS significantly improved the success rate of NKP in patients with difficult biliary cannulation.展开更多
BACKGROUND Laparoscopic hepatectomy(LH)has been applied in the treatment of hepatolithiasisa in patients with a history of biliary surgery and has already achieved good clinical outcomes.However,reoperative LH(rLH)inc...BACKGROUND Laparoscopic hepatectomy(LH)has been applied in the treatment of hepatolithiasisa in patients with a history of biliary surgery and has already achieved good clinical outcomes.However,reoperative LH(rLH)includes multiple procedures,and the no studies have examined the clinical value of individual laparoscopic procedures.AIM To evaluate the safety and feasibility of each rLH procedure for hepatolithiasisa in patients with a history of biliary surgery.METHODS Patients with previous biliary surgery who underwent reoperative hepatectomy for hepatolithiasis were studied.Liver resection procedures were divided into three categories:(1)Laparoscopic/open left lateral sectionectomy[reoperative laparoscopic left lateral sectionectomy(rLLLS)/reoperative open left lateral sectionectomy(rOLLS)];(2)Laparoscopic/open left hemihepatectomy[reoperative laparoscopic left hemihepatectomy(rLLH)/reoperative open left hemihepatectomy(rOLH)];and(3)Laparoscopic/open complex hepatectomy[reoperative laparoscopic complex hepatectomy(rLCH)/reoperative open complex hepate ctomy(rOCH)].The clinical outcomes were compared between the rLLLS,rLLH,and rLCH groups,and subgroup analyses were performed for the rLLLS/rOLLS,rLLH/rOLH,and rLCH/rOCH subgroups.RESULTS A total of 185 patients were studied,including 101 rLH patients(40 rLLLS,50 rLLH,and 11 rLCH)and 84 reoperative open hepatectomy(40 rOLLS,33 rOLH,and 11 rOCH).Among the three types of rLH procedure,rLLLS required the shortest operation time(240.0 minutes vs 325.0 minutes vs 350.0 minutes,P=0.001)and the lowest blood transfusion rate(10.0%vs 22.0%vs 54.5%,P=0.005),followed by rLLH.The rLCH had the highest conversion rate(P<0.05)and postoperative intensive care unit stay rate(P=0.001).Most clinical outcomes in rLLLS and rLLH were superior or similar to those in the corresponding open surgery,while there were no differences in all outcomes between the rLCH and rOCH subgroups.CONCLUSION The rLH is safe for hepatolithiasis patients with a history of biliary surgery.The rLLLS and rLLH can be recommended for these patients,whereas rLCH should be applied with caution.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic ...BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial...Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.展开更多
BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are e...BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
基金supported by the Natural Science Foundation of Beijing,No.7232279(to XW)the National Natural Science Foundation of China,No.U21A20400(to QW)Key Project of Beijing University of Chinese Medicine,Nos.2022-JYB-JBZR-004(to XW),2024-JYB-JBZD-043(to CL).
文摘Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
基金Supported by Sigrid Juselius Foundationthe Finnish Pediatric Research Foundation
文摘AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
文摘Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary to give a chance to the patient. We herein describe a case of blunt abdominal trauma in a 29-year- old man whose pancreatic rupture was associated with hepatic artery, splenic vein and extrahepatic bile duct damage. Immediate surgery was performed after computer tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the operating room. Spleno-pancreatic resection was done with reconstruction of the hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal diversion. The early post-operative course was complicated by stenosis of the arterial reconstruction, which was treated by endovascular angioplasty followed by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics. Finally, the patient was discharged and was alive without clinical problems at the time when we wrote this case report. The present case underlines the clinical relevance of vascular and visceral injuries associated with pancreatic trauma and the problems arising in the diagnostic evaluation and the surgical strategy of complex multiple visceral and vascular lesions in blunt abdominal trauma.
文摘AIM: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC. METHODS: We included 180 patients with PBC (cases) and 151 patients seen for HCV infection (controls). Medical records were reviewed and statistical analyses were performed as appropriate. RESULTS: When compared to controls, PBC patients were older, leaner and had higher serum levels of total cholesterol, high density lipoprotein and low density cholesterol. There were more females in the PBC group (91.7% vs 43%, P < 0.001). More control subjects had smoked than the PBC patients (63.6% vs 35%, P < 0.001). The prevalence of hypertension, diabetes, coronary artery disease and stroke was similar between the two groups. Seven percent of controls and 10% of cases developed any type of cardiovascular disease (P = 0.3). Only 36.7% were asymptomatic at diagnosis. Three cardiovascular events were documented among asymptomatic patients (4.5%) and fifteen among symptomatic patients (13.2%; P = 0.06). Among PBC patients with fatigue, 10 (13.5%) had a cardiovascular event compared to 7 (6.7%) among patients without fatigue (P = 0.1). CONCLUSION: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patients suffering with fatigue.
文摘In order to study the mechanism of decreased blood pressure caused by an acute increase in biliary tract pressure, we observed house rabbit model of self-made caecus for changes in cardiovascular function when biliary tract pressure was increased.It was found that both the blood pressure and cardiac output evidently decreased (P<0.05) parallelly, and the systolic pressure decreased more markedly than diastolic pressure. At the same time there was fluctuation in heart rate and in central venous pressure; but there was no significant difference between them (P>0. 05), suggesting that in the absence of infective agents,the increased biliary tract pressure can bring about a decrease in cardiac output, which is an important factor contributing to an early blood pressure decrease in acute cholangitis of severe type (ACST).
文摘This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obstruction,the technical aspects of stenting,and the clinical outcomes.By comparison of endoscopic stenting with percutaneous biliary drainage,improvements and complications are focused on.Additionally,patient selection for stenting and future advancements in stent technology are important.Overall,endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice,especially those ineligibles for surgery.
基金supported by Natural Science Foundation of Hunan Province(2021JJ31081,2024JJ5619)the Science Fund of State Key Laboratory of Advanced Design and Manufacturing Technology for Vehicle(No 32215004).
文摘Biliary system,which is responsible for transporting bile from the liver into the intestine,is commonly damaged by inflammation or tumors eventually causing liver failure or death.The implantation of biliary stents can effectively alleviate both benign and malignant biliary strictures,but the plastic and metal stents that are currently used cannot degrade and nearly has no beneficial biological effects,therefore their long-term service can result into inflammation,the formation of sludges and re-obstruction of bile duct.In recent years,magnesium(Mg)metal has been received increasing attention in the field of biomedical application due to its excellent biocompatibility,adequate mechanical properties,biodegradability and other advantages,such as anti-inflammatory and anti-tumor properties.The research on biliary stents made of magnesium metals(BSMM)has also made significant progress and a series of experiments in vitro and vivo has proved their possibility.However,there are still some problems holding back BSMM’s clinical use,including rapid corrosion rate and potential harmful reaction.In this review,we would summarize the current research of BSMM,evaluate their clinical benefits,find the choke points,and discuss the solving method.
文摘BACKGROUND Proximal bile duct injury(BDI),which often occurs after laparoscopic cholecystectomy(LC),can lead to complex biliary stricture and recurrent cholangitis.This case report presented a 39-year-old woman who experienced proximal BDI during LC in 2017,leading to multiple episodes of cholangitis and subsequent hepaticojejunostomy in 2018.Despite these interventions,persistent biliary complications necessitated repeated hospital admissions and antibiotic treatment.Imaging studies revealed persistent stricture at the site of hepaticojejunostomy,prompting a series of percutaneous procedures,including balloon dilatation and biliary drainage.In August 2024,she underwent biodegradable biliary stenting,which significantly improved her condition.Subsequently,she remained clinically stable for 5 months without further episodes of cholangitis and had improved liver function tests.This case highlighted the complexities of managing postinjury biliary stricture,underscored the potential of biodegradable stents as an effective treatment option,and emphasized the need for a multidisciplinary approach in managing such complications.Long-term follow-up is essential for monitoring treatment effectiveness and preventing recurrence.CASE SUMMARY A 39-year-old female had a routine LC in 2017.The patient sustained a proximal BDI during the surgery.In the months that followed,recurrent bouts of cholangitis occurred.A hepaticojejunostomy biliary reconstruction was performed in 2018.However,hepatic cholangitis persisted.In 2021 and 2022,MRCP scans revealed biliary stasis,duct dilation,and a stricture at the hepaticojejunostomy site.A subsequent percutaneous transhepatic cholangiography(PTC)confirmed these findings and led to drain placement.The treatment included internal and external biliary drain placements,repeated balloon dilations of the stricture,percutaneous transhepatic cholangioscopy to extract intrahepatic lithiasis,and insertion of a biodegradable biliary stent.Since the first PTC intervention,there have been no hospital admissions for cholangitis.Liver function tests showed improvement,and for five months following the biodegradable stenting,the condition remained stable.Long-term surveillance with regular imaging and blood work has been emphasized.The final diagnosis is recurrent biliary stricture secondary to proximal BDI.Treatment,including hepaticojejunostomy,repeated PTC with balloon dilation,and biodegradable biliary stenting,has led to complete drainage of the biliary system.Ongoing follow-up remains crucial for monitoring the patient's progress and maintaining their health.CONCLUSION This case demonstrated how strictures and recurrent cholangitis complicate the management of BDI after LC.A customized and multidisciplinary approach to control chronic biliary disease was proven effective,as shown by the patient’s good outcome.This was achieved by integrating balloon dilatation sessions,biliary drainage,stone clearing,and biodegradable stent placement.Long-term follow-up and continued monitoring remain essential to ensure patient stability and prevent further complications.
文摘Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
文摘BACKGROUND Needle-knife precut papillotomy(NKP)is typically performed freehand.However,it remains unclear whether pancreatic stent(PS)placement can improve the outcomes of NKP.AIM To explore whether PS placement improves the success rate of NKP in patients with difficult biliary cannulation.METHODS This single-center retrospective study included 190 patients who underwent NKP between January 2017 and December 2021 after failed conventional biliary cannulation.In cases with incidental pancreatic duct cannulation during conventional biliary cannulation,the decision for pre-NKP PS placement was made at the endoscopist's discretion.The primary outcome was the difference in the NKP success rate between patients with and without PS placement;the secondary outcome was the adverse event rate.RESULTS Among the 190 participants,82 received pre-NKP PS(PS-NKP group)whereas 108 did not[freehand or freehand NKP(FH-NKP)group].Post-NKP selective biliary cannulation was successful in 167(87.9%)patients,and the PS-NKP had a significantly higher success rate than the FH-NKP group(93.9%vs 83.3%,P=0.027).The overall adverse event rates were 7.3%and 11.1%in the PS-NKP and FH-NKP groups,respectively(P=0.493).A periampullary diverticulum(PAD)and significant intraoperative bleeding during NKP were independently associated with NKP failure;however,a pre-NKP PS was the only predictor of NKP success.Among the 44 participants with PADs,the PS-NKP group had a non-significantly higher NKP success rate than the FH-NKP group(87.5%and 65%,respectively;P=0.076).CONCLUSION PS significantly improved the success rate of NKP in patients with difficult biliary cannulation.
基金Supported by The Key Research and Development Program of Anhui Province of China,No.1804h08020273The Key Research Project of Health Commission of Anhui Province of China,No.AHWJ2022a016.
文摘BACKGROUND Laparoscopic hepatectomy(LH)has been applied in the treatment of hepatolithiasisa in patients with a history of biliary surgery and has already achieved good clinical outcomes.However,reoperative LH(rLH)includes multiple procedures,and the no studies have examined the clinical value of individual laparoscopic procedures.AIM To evaluate the safety and feasibility of each rLH procedure for hepatolithiasisa in patients with a history of biliary surgery.METHODS Patients with previous biliary surgery who underwent reoperative hepatectomy for hepatolithiasis were studied.Liver resection procedures were divided into three categories:(1)Laparoscopic/open left lateral sectionectomy[reoperative laparoscopic left lateral sectionectomy(rLLLS)/reoperative open left lateral sectionectomy(rOLLS)];(2)Laparoscopic/open left hemihepatectomy[reoperative laparoscopic left hemihepatectomy(rLLH)/reoperative open left hemihepatectomy(rOLH)];and(3)Laparoscopic/open complex hepatectomy[reoperative laparoscopic complex hepatectomy(rLCH)/reoperative open complex hepate ctomy(rOCH)].The clinical outcomes were compared between the rLLLS,rLLH,and rLCH groups,and subgroup analyses were performed for the rLLLS/rOLLS,rLLH/rOLH,and rLCH/rOCH subgroups.RESULTS A total of 185 patients were studied,including 101 rLH patients(40 rLLLS,50 rLLH,and 11 rLCH)and 84 reoperative open hepatectomy(40 rOLLS,33 rOLH,and 11 rOCH).Among the three types of rLH procedure,rLLLS required the shortest operation time(240.0 minutes vs 325.0 minutes vs 350.0 minutes,P=0.001)and the lowest blood transfusion rate(10.0%vs 22.0%vs 54.5%,P=0.005),followed by rLLH.The rLCH had the highest conversion rate(P<0.05)and postoperative intensive care unit stay rate(P=0.001).Most clinical outcomes in rLLLS and rLLH were superior or similar to those in the corresponding open surgery,while there were no differences in all outcomes between the rLCH and rOCH subgroups.CONCLUSION The rLH is safe for hepatolithiasis patients with a history of biliary surgery.The rLLLS and rLLH can be recommended for these patients,whereas rLCH should be applied with caution.
基金Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund,No.H2021206239.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
基金supported by the MISP program at Merck Sharp&Dohme Corp.,USAa grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(Grant Number:HR20C0025).
文摘Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.
文摘BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.
