BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,res...BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,resulting in intra-abdominal ab-scess if the gallstones were not retrieved.The diagnosis of intra-abdominal ab-scess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies,such as abdominal ultrasonography or computed tomo-graphy(CT).Here we present a case of abscess formation from unretrieved gall-stone following laparoscopic cholecystectomy,which mimics the imaging findings of metastatic gallbladder ade-nocarcinoma.CASE SUMMARY This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery.After adjuvant chemotherapy,the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered.Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.CONCLUSION Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery.For spilled gall bladder stones,surgeons may consider regular computerized tomography follow-up,and if necessary,laparoscopic examination can be used as a means of confirming the diagnostic and treatment.展开更多
Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers...Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively.However,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell types.Here,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro.Less than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular matrix.Delivery efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was analyzed.The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo.The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of nanocarrier.The overall efficiency into sinusoidal ECswas greatly lower than that into arteriole ECs.All nanocarriers were hard to be delivered into OBs(<1%).Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro.This study provided the methodology for niche-directed nanotherapeutics development.展开更多
Cytomegalovirus(CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons.The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lackin...Cytomegalovirus(CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons.The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine.Critically ill patients in ICU who had associated risk factors such as mechanical ventilation,severe sepsis, or blood transfusion are more prone to CMV activation,which in turn led to increased mortality and morbidity in tenns of increased ICU stay,longer duration of mechanical ventilation,and higher rates of nosocomial infections.However,severe CMV as initial presentation mimicking dengue infection is rare.We recently came across seven cases with positive CMV serology at ICU admission,which we discuss in the light of current literature.展开更多
To the Editor:IgG4-related sclerosing cholangitis(IgG4-SC)has re cently been recognized as a biliary manifestation of IgG4-related disease(IgG4-RD).Type 3 IgG4-SC pre sented biliary strictures in both the porta he...To the Editor:IgG4-related sclerosing cholangitis(IgG4-SC)has re cently been recognized as a biliary manifestation of IgG4-related disease(IgG4-RD).Type 3 IgG4-SC pre sented biliary strictures in both the porta hepatis and the distal common bile duct(CBD).;Its manifestation especially in the absence of autoimmune pancreatitis,is extremely rare and very similar to that of cholangiocarci noma(CC).展开更多
BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multisli...BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multislice-based texture acquired from CECT in the differentiation between pyogenic hepatic abscesses and malignant mimickers.METHODS: This retrospective study included 25 abscesses in 20 patients and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also enrolled 19 patients with hepatic single simple cyst. The images from CECT were analyzed using a Laplacian of Gaussian band-pass filter(5 filter levels with sigma weighting ranging from 1.0 to 2.5). We also quantified the uniformity, entropy, kurtosis and skewness of the multislice-based texture at different sigma weightings. Statistical significance for these parameters was tested with oneway ANOVA followed by Tukey honestly significant difference(HSD) test. Diagnostic performance was evaluated using the receiver operating characteristic(ROC) curve analysis.RESULTS: There were significant differences in entropy and uniformity at all sigma weightings(P〈0.001) among hepatic abscesses, malignant mimickers and simple cysts. The significant difference in kurtosis and skewness was shown at sigma 1.8 and 2.0 weightings(P=0.002-0.006). Tukey HSD testshowed that the abscesses had a significantly higher entropy and lower uniformity compared with malignant mimickers(P=0.000-0.004). Entropy(at a sigma 2.0 weighting) had the largest area under the ROC curve(0.888) in differentiating abscesses from malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when the cutoff value was set to 3.64.CONCLUSION: Multislice-based texture analysis may be useful for differentiating pyogenic hepatic abscesses from malignant mimickers.展开更多
We present the case of a 74-year-old man with diabetes and hypertension who had to be rescued owing to a near-drowning syndrome at sea.When he was rescued,he complained of dyspnea and chest pain.An electrocardiogram(E...We present the case of a 74-year-old man with diabetes and hypertension who had to be rescued owing to a near-drowning syndrome at sea.When he was rescued,he complained of dyspnea and chest pain.An electrocardiogram(ECG)suggested acute coronary syndrome(ACS)affecting the left main coronary artery.Therefore,he was referred to our hospital for urgent coronary angiography.展开更多
BACKGROUND Disc herniation refers to the displacement of disc material beyond its anatomical space.Disc sequestration is defined as migration of the herniated disc fragment into the epidural space,completely separatin...BACKGROUND Disc herniation refers to the displacement of disc material beyond its anatomical space.Disc sequestration is defined as migration of the herniated disc fragment into the epidural space,completely separating it from the parent disc.The fragment can move in upward,inferior,and lateral directions,which often causes low back pain and discomfort,abnormal sensation,and movement of lower limbs.The free disc fragments detached from the parent disc often mimic spinal tumors.Tumor like lumbar disc herniation can cause clinical symptoms similar to spinal tumors,such as lumbar soreness,pain,numbness and weakness of lower limbs,radiation pain of lower limbs,etc.It is usually necessary to diagnose the disease according to the doctor’s clinical experience,and make preliminary diagnosis and differential diagnosis with the help of magnetic resonance imaging(MRI)and contrast-enhanced MRI.However,pathological examination is the gold standard that distinguishes tumoral from non-tumoral status.We report four cases of disc herniation mimicking a tumor,and all the pathological results were intervertebral disc tissue.CASE SUMMARY The first case was a 71-year-old man with low back pain accompanied by left lower extremity radiating pain for 1 year,with exacerbation over the last 2 wk.After admission,MRI revealed a circular T2-hypointense lesion in the spinal canal of the L4 vertebral segment,with enhancement on contrast-enhanced MRI suggesting neurilemmoma.The second case was a 74-year-old man with pain in both knees associated with movement limitation for 3 years,with exacerbation over the last 3 mo.MRI revealed an oval T2-hyperintense lesion in the spinal canal at the L4–5 level,with obvious peripheral enhancement on contrast-enhanced MRI.Thus,neurilemmoma was suspected.The third case was a 53-year-old man who presented with numbness and weakness of the lumbar spine and right lower extremity for 2 wk.MRI revealed a round T2-hyperintense lesion in the spinal canal at the L4–5 level,with obvious rim enhancement on contrast-enhanced MRI.Thus,a spinal tumor was suspected.The fourth case was a 75-year-old man with right lower extremity pain for 2 wk,with exacerbation over the last week.MRI revealed a round T1-isointense lesion in the spinal canal of the L3 vertebral segment and a T2-hyperintense signal from the lesion.There was no obvious enhancement on contrast-enhanced MRI,so a spinal tumor was suspected.All four patients underwent surgery and recovered to ASIA grade E on postoperative days 5,8,8,and 6,respectively.All patients had an uneventful postoperative course and fully recovered within 3 mo.CONCLUSION Disc herniation mimicking a tumor is a relatively rare clinical entity and can be easily misdiagnosed as a spinal tumor.Examinations and tests should be improved preoperatively.Patients should undergo comprehensive preoperative evaluations,and the lesions should be removed surgically and confirmed by pathological diagnosis.展开更多
Dear editor,We report a case of a 47-year-old female who presented with a toxic bupropion ingestion leading to cardiac arrest.She initially exhibited a loss of brainstem reflexes in conjunction with burst-suppression ...Dear editor,We report a case of a 47-year-old female who presented with a toxic bupropion ingestion leading to cardiac arrest.She initially exhibited a loss of brainstem reflexes in conjunction with burst-suppression pattern on EEG.Burst suppression is an EEG waveform pattern of alternating isoelectric suppressions and high voltage bursts.^([1])展开更多
Dear Sir, I am B. Spajic, the urologist from Clinical Department of Urology, Sestre Milosrdnice University Hospital, Zagreb, Croatia. Recently, we had a rare case of a cholesterol granuloma of the right epididymis at...Dear Sir, I am B. Spajic, the urologist from Clinical Department of Urology, Sestre Milosrdnice University Hospital, Zagreb, Croatia. Recently, we had a rare case of a cholesterol granuloma of the right epididymis at our department, showing clinical signs of acute scrotum. The case described here appears to be the second reporting cholesterol granuloma in the epididymis and the first one presenting with clinical signs of acute scrotum.展开更多
Prostate cancer is the second most common cancer in men worldwide and the commonest cause of mortality in men. It is the commonest diagnosed cancer in African men. The earliest and common sites of metastasis are the a...Prostate cancer is the second most common cancer in men worldwide and the commonest cause of mortality in men. It is the commonest diagnosed cancer in African men. The earliest and common sites of metastasis are the axial skeleton and regional lymph nodes. Initial presentation of the metastatic disease with cervical or supraclavicular lymphadenopathy is rarely reported. We report 3 cases of metastatic cancer of the prostate presenting initially to physicians with huge cervical and supraclavicular lymph nodes enlargement which on biopsy revealed metastatic adenocarcinoma. On further evaluation, there were non-bothersome storage symptoms, elevated prostate specific antigen and abnormal digital rectal examination. Transrectal ultrasound (TRUS)-guided biopsy of hypoechoic nodules revealed high-grade adenocarcinoma of the prostate on histopathological examination. The cervical and supraclavicular lymphadenopathy resolved after commencement of androgen deprivation therapy. We advocate for prostate cancer screening in African men above 50 years of age presenting with cervical or supraclavicular lymphadenopthy to primary care physicians even in the absence of lower urinary tract symptoms.展开更多
Rat-bite is uncommon worldwide, excluding developing countries. The history of a bite is usually missed if not meticulously asked for in history, proper exposure and examination. Today we report a case of culture-nega...Rat-bite is uncommon worldwide, excluding developing countries. The history of a bite is usually missed if not meticulously asked for in history, proper exposure and examination. Today we report a case of culture-negative rat-bite fever with poly septic arthritis resembling a rheumatoid arthritis-like picture in a 64-year-old gentleman. The presentation at first imitated an arthritis-like picture which was polyarthritis affecting the right ankle, right knee, right wrist, right proximal interphalangeal, left metacarpophalangeal and proximal interphalangeal joints.展开更多
Mycosis fungoides, the most common primary cutaneous lymphoma, may present with a broad spectrum of clinical features. As both clinical and dermatopathological findings in mycosis fungoides occasionally closely imitat...Mycosis fungoides, the most common primary cutaneous lymphoma, may present with a broad spectrum of clinical features. As both clinical and dermatopathological findings in mycosis fungoides occasionally closely imitateother dermatoses, correct diagnosis may be a challenge both for clinicians as well as dermatopathologists. As a consequence, diagnosis of cutaneous lymphoma may be initially missed and, therefore, prompt and adequate therapeutic measures delayed. Hence, the purpose of our article was to give an overview of hitherto published "mimickers" of mycosis fungoides with a review of its diverse clinical features to alert the clinicians about the wide spectrum of this dissimulating disease. By integrating our own encountered atypical cases of mycosis fungoides we provide a comprehensive illustrated histological and moleculargenetic workup thereof and thereby critically revise the different available diagnostic tools of daily routine. Finally, we derive a practical algorithm to obtain the correct diagnosis even in such ambiguous cases of mycosis fungoides.展开更多
Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conj...Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells(ECs),which represent the main technical difficulties for vaccine development,reside in the harsh,acidic human vaginal environment.Different from frequently employed viral vectors,two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses.Differing design concepts include the charge-reversal property(DRLS)to mimic a virus that uses any cells as factories,as well as the addition of a hyaluronic acid coating(HA/RLS)to directly target dendritic cells(DCs).With a suitable size and electrostatic neutrality,these two nanoparticles penetrate a mucus hydrogel with similar diffusivity.The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo.Therefore it induced more robust mucosal,cellular,and humoral immune responses.Moreover,the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA(naked),indicating timely protection against pathogens at the mucus layer.These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.展开更多
Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while ...Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.展开更多
Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,...Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,GO has been employed for photosensitized generation of reactive oxygen species(ROS).Herein,we demonstrate that GO sheets could cleave DNA as anuclease mimicking nanozyme in the presence of UV or blue light.For various DNA sequences and lengths,well-defined product bands were observed along with photobleaching of the fluorophore label on the DNA.Different from previously reported GO cleavage of DNA,our method did not require metal ions such as Cu^2+.Fluorescence spectroscopy suggested a high adsorption affinity between GO and DNA.For comparison,although zero-dimensional fluorescent carbon dots(C-dots)had higher photosensitivity ir terms of producing ROS,their cleavage activity was much lower and only smeared cleavage products were observed,indicatingthat the ROS acted on the DNA in solution.Based on the results,GO behaved like a classic heterogeneous catalyst following substrate adsorption,reaction,and product desorption steps.This simple strategy may help in the design of new nanozymes by introducing light.展开更多
Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical...Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component.Herein,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking surface.The stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA coating.Using a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry.Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 month.As a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.展开更多
H_(2)O_(2) and glutathione(GSH)are critical redox molecules in the organism.Abnormal levels of cellular H_(2)O_(2) and GSH are closely related to some diseases.Thus,it is imperative to detect H_(2)O_(2) and GSH effi-c...H_(2)O_(2) and glutathione(GSH)are critical redox molecules in the organism.Abnormal levels of cellular H_(2)O_(2) and GSH are closely related to some diseases.Thus,it is imperative to detect H_(2)O_(2) and GSH effi-ciently.In this work,FeeNeC single atom nanozymes(SANs)with both peroxidase and oxidasemimicking activities were successfully prepared with the help of formamide condensation by one-step hydrothermal method.The FeeNeC SANs show excellent peroxidase-like activity,which possess a higher affinity for H_(2)O_(2) and 3,30,5,50-tetramethylbenzidine(TMB)than horseradish peroxidase(HRP).Then,based on the chromogenic reaction of TMB,a colorimetric biosensor to detect H_(2)O_(2) and GSH was developed.This biosensor has the linear ranges of 10-600 mmol/L for H_(2)O_(2) with a low detection limit of 4.360 mmol/L and 100-400 mmol/L for GSH with a low detection limit of 78.33 mmol/L.Besides,this colorimetric biosensor exhibited a good recovery of H_(2)O_(2) and GSH in diluted human serum.Finally,the FeeNeC SANs were encapsulated into agar gel to self-quantitatively detect GSH by naked eyes.This work provides a non-pyrolytic way to prepare SANs,which broadens the synthetic method of SANs and may promote the development of SANs for biosensor application.展开更多
1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic o...1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h...展开更多
Four chiral μ phenolato dinuclear (VO) 2, Cr 2, Mn 2, and Fe 2 complexes with a phenolic ligand bearing two L phenylanalines as complexing arms have been synthesized and characterized. Asymmetric epoxidations of styr...Four chiral μ phenolato dinuclear (VO) 2, Cr 2, Mn 2, and Fe 2 complexes with a phenolic ligand bearing two L phenylanalines as complexing arms have been synthesized and characterized. Asymmetric epoxidations of styrene with these complexes as chiral models of methane monooxygenase (MMO) and iodosylbenzene as an oxygen atom donor have been studied. The results reveal that the Mn 2 complex catalyzes asymmetric epoxidation of styrene with the formation of R (+) styrene oxide in 42.8% e.e. Contrarily, the (VO) 2 analogue complex gives S (-) styrene oxide in 19.2% e.e. EPR investigations suggest that the catalyzed epoxidations with the Mn 2, Cr 2 and Fe 2 complexes proceed via high valent oxometal intermediates; while in the case of the (VO) 2 complex as catalyst, the epoxidation proceeds by a pathway that involves a complex of metal iodine ligand. The catalytic activities of the complexes decrease in a sequence of Mn 2>Cr 2>(VO) 2>Fe 2.展开更多
文摘BACKGROUND Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status.The gallstones may sometime be spilled into the peritoneal cavity,resulting in intra-abdominal ab-scess if the gallstones were not retrieved.The diagnosis of intra-abdominal ab-scess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies,such as abdominal ultrasonography or computed tomo-graphy(CT).Here we present a case of abscess formation from unretrieved gall-stone following laparoscopic cholecystectomy,which mimics the imaging findings of metastatic gallbladder ade-nocarcinoma.CASE SUMMARY This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery.After adjuvant chemotherapy,the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered.Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.CONCLUSION Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery.For spilled gall bladder stones,surgeons may consider regular computerized tomography follow-up,and if necessary,laparoscopic examination can be used as a means of confirming the diagnostic and treatment.
基金support from the National Natural Science Foundation of China(81703713,82174095,82274364)Natural Science Foundation of Zhejiang Province grants(LZ23H290001,LZ22H290001)internal support from Zhejiang Chinese Medical University(2022GJYY011).
文摘Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively.However,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell types.Here,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro.Less than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular matrix.Delivery efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was analyzed.The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo.The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of nanocarrier.The overall efficiency into sinusoidal ECswas greatly lower than that into arteriole ECs.All nanocarriers were hard to be delivered into OBs(<1%).Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro.This study provided the methodology for niche-directed nanotherapeutics development.
文摘Cytomegalovirus(CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons.The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine.Critically ill patients in ICU who had associated risk factors such as mechanical ventilation,severe sepsis, or blood transfusion are more prone to CMV activation,which in turn led to increased mortality and morbidity in tenns of increased ICU stay,longer duration of mechanical ventilation,and higher rates of nosocomial infections.However,severe CMV as initial presentation mimicking dengue infection is rare.We recently came across seven cases with positive CMV serology at ICU admission,which we discuss in the light of current literature.
基金supported by a grant from the National Natural Science Foundation of China(81270544)
文摘To the Editor:IgG4-related sclerosing cholangitis(IgG4-SC)has re cently been recognized as a biliary manifestation of IgG4-related disease(IgG4-RD).Type 3 IgG4-SC pre sented biliary strictures in both the porta hepatis and the distal common bile duct(CBD).;Its manifestation especially in the absence of autoimmune pancreatitis,is extremely rare and very similar to that of cholangiocarci noma(CC).
基金supported by grants from Medical Engineering Cross Research Foundation of Shanghai Jiaotong University(YG2013MS37 and YG2012MS16)the National Natural Science Foundation of China(81201172,81371660 and 81371622)
文摘BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography(CECT). The present study was to explore the usefulness of the analysis of multislice-based texture acquired from CECT in the differentiation between pyogenic hepatic abscesses and malignant mimickers.METHODS: This retrospective study included 25 abscesses in 20 patients and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also enrolled 19 patients with hepatic single simple cyst. The images from CECT were analyzed using a Laplacian of Gaussian band-pass filter(5 filter levels with sigma weighting ranging from 1.0 to 2.5). We also quantified the uniformity, entropy, kurtosis and skewness of the multislice-based texture at different sigma weightings. Statistical significance for these parameters was tested with oneway ANOVA followed by Tukey honestly significant difference(HSD) test. Diagnostic performance was evaluated using the receiver operating characteristic(ROC) curve analysis.RESULTS: There were significant differences in entropy and uniformity at all sigma weightings(P〈0.001) among hepatic abscesses, malignant mimickers and simple cysts. The significant difference in kurtosis and skewness was shown at sigma 1.8 and 2.0 weightings(P=0.002-0.006). Tukey HSD testshowed that the abscesses had a significantly higher entropy and lower uniformity compared with malignant mimickers(P=0.000-0.004). Entropy(at a sigma 2.0 weighting) had the largest area under the ROC curve(0.888) in differentiating abscesses from malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when the cutoff value was set to 3.64.CONCLUSION: Multislice-based texture analysis may be useful for differentiating pyogenic hepatic abscesses from malignant mimickers.
文摘We present the case of a 74-year-old man with diabetes and hypertension who had to be rescued owing to a near-drowning syndrome at sea.When he was rescued,he complained of dyspnea and chest pain.An electrocardiogram(ECG)suggested acute coronary syndrome(ACS)affecting the left main coronary artery.Therefore,he was referred to our hospital for urgent coronary angiography.
基金Supported by Chinese People’s Liberation Army Medical Technology Youth Training Program,No. 20QNPY071
文摘BACKGROUND Disc herniation refers to the displacement of disc material beyond its anatomical space.Disc sequestration is defined as migration of the herniated disc fragment into the epidural space,completely separating it from the parent disc.The fragment can move in upward,inferior,and lateral directions,which often causes low back pain and discomfort,abnormal sensation,and movement of lower limbs.The free disc fragments detached from the parent disc often mimic spinal tumors.Tumor like lumbar disc herniation can cause clinical symptoms similar to spinal tumors,such as lumbar soreness,pain,numbness and weakness of lower limbs,radiation pain of lower limbs,etc.It is usually necessary to diagnose the disease according to the doctor’s clinical experience,and make preliminary diagnosis and differential diagnosis with the help of magnetic resonance imaging(MRI)and contrast-enhanced MRI.However,pathological examination is the gold standard that distinguishes tumoral from non-tumoral status.We report four cases of disc herniation mimicking a tumor,and all the pathological results were intervertebral disc tissue.CASE SUMMARY The first case was a 71-year-old man with low back pain accompanied by left lower extremity radiating pain for 1 year,with exacerbation over the last 2 wk.After admission,MRI revealed a circular T2-hypointense lesion in the spinal canal of the L4 vertebral segment,with enhancement on contrast-enhanced MRI suggesting neurilemmoma.The second case was a 74-year-old man with pain in both knees associated with movement limitation for 3 years,with exacerbation over the last 3 mo.MRI revealed an oval T2-hyperintense lesion in the spinal canal at the L4–5 level,with obvious peripheral enhancement on contrast-enhanced MRI.Thus,neurilemmoma was suspected.The third case was a 53-year-old man who presented with numbness and weakness of the lumbar spine and right lower extremity for 2 wk.MRI revealed a round T2-hyperintense lesion in the spinal canal at the L4–5 level,with obvious rim enhancement on contrast-enhanced MRI.Thus,a spinal tumor was suspected.The fourth case was a 75-year-old man with right lower extremity pain for 2 wk,with exacerbation over the last week.MRI revealed a round T1-isointense lesion in the spinal canal of the L3 vertebral segment and a T2-hyperintense signal from the lesion.There was no obvious enhancement on contrast-enhanced MRI,so a spinal tumor was suspected.All four patients underwent surgery and recovered to ASIA grade E on postoperative days 5,8,8,and 6,respectively.All patients had an uneventful postoperative course and fully recovered within 3 mo.CONCLUSION Disc herniation mimicking a tumor is a relatively rare clinical entity and can be easily misdiagnosed as a spinal tumor.Examinations and tests should be improved preoperatively.Patients should undergo comprehensive preoperative evaluations,and the lesions should be removed surgically and confirmed by pathological diagnosis.
文摘Dear editor,We report a case of a 47-year-old female who presented with a toxic bupropion ingestion leading to cardiac arrest.She initially exhibited a loss of brainstem reflexes in conjunction with burst-suppression pattern on EEG.Burst suppression is an EEG waveform pattern of alternating isoelectric suppressions and high voltage bursts.^([1])
文摘Dear Sir, I am B. Spajic, the urologist from Clinical Department of Urology, Sestre Milosrdnice University Hospital, Zagreb, Croatia. Recently, we had a rare case of a cholesterol granuloma of the right epididymis at our department, showing clinical signs of acute scrotum. The case described here appears to be the second reporting cholesterol granuloma in the epididymis and the first one presenting with clinical signs of acute scrotum.
文摘Prostate cancer is the second most common cancer in men worldwide and the commonest cause of mortality in men. It is the commonest diagnosed cancer in African men. The earliest and common sites of metastasis are the axial skeleton and regional lymph nodes. Initial presentation of the metastatic disease with cervical or supraclavicular lymphadenopathy is rarely reported. We report 3 cases of metastatic cancer of the prostate presenting initially to physicians with huge cervical and supraclavicular lymph nodes enlargement which on biopsy revealed metastatic adenocarcinoma. On further evaluation, there were non-bothersome storage symptoms, elevated prostate specific antigen and abnormal digital rectal examination. Transrectal ultrasound (TRUS)-guided biopsy of hypoechoic nodules revealed high-grade adenocarcinoma of the prostate on histopathological examination. The cervical and supraclavicular lymphadenopathy resolved after commencement of androgen deprivation therapy. We advocate for prostate cancer screening in African men above 50 years of age presenting with cervical or supraclavicular lymphadenopthy to primary care physicians even in the absence of lower urinary tract symptoms.
文摘Rat-bite is uncommon worldwide, excluding developing countries. The history of a bite is usually missed if not meticulously asked for in history, proper exposure and examination. Today we report a case of culture-negative rat-bite fever with poly septic arthritis resembling a rheumatoid arthritis-like picture in a 64-year-old gentleman. The presentation at first imitated an arthritis-like picture which was polyarthritis affecting the right ankle, right knee, right wrist, right proximal interphalangeal, left metacarpophalangeal and proximal interphalangeal joints.
文摘Mycosis fungoides, the most common primary cutaneous lymphoma, may present with a broad spectrum of clinical features. As both clinical and dermatopathological findings in mycosis fungoides occasionally closely imitateother dermatoses, correct diagnosis may be a challenge both for clinicians as well as dermatopathologists. As a consequence, diagnosis of cutaneous lymphoma may be initially missed and, therefore, prompt and adequate therapeutic measures delayed. Hence, the purpose of our article was to give an overview of hitherto published "mimickers" of mycosis fungoides with a review of its diverse clinical features to alert the clinicians about the wide spectrum of this dissimulating disease. By integrating our own encountered atypical cases of mycosis fungoides we provide a comprehensive illustrated histological and moleculargenetic workup thereof and thereby critically revise the different available diagnostic tools of daily routine. Finally, we derive a practical algorithm to obtain the correct diagnosis even in such ambiguous cases of mycosis fungoides.
基金financially supported by National Natural Science Foundation of China (NSFC,Nos.81873921 and 51903174)Sino-German Cooperation Group Project (GZ1512)+2 种基金Chengdu Science and Technology Program (2020-GH02-00007-HZ,China)Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundationthe Fundamental Research Funds for Central Universities (2021SCU12070,China)
文摘Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells(ECs),which represent the main technical difficulties for vaccine development,reside in the harsh,acidic human vaginal environment.Different from frequently employed viral vectors,two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses.Differing design concepts include the charge-reversal property(DRLS)to mimic a virus that uses any cells as factories,as well as the addition of a hyaluronic acid coating(HA/RLS)to directly target dendritic cells(DCs).With a suitable size and electrostatic neutrality,these two nanoparticles penetrate a mucus hydrogel with similar diffusivity.The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo.Therefore it induced more robust mucosal,cellular,and humoral immune responses.Moreover,the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA(naked),indicating timely protection against pathogens at the mucus layer.These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.
基金the National Natural Science Foundation of China(32222041,82102619,81925027,21875092)the Natural Science Foundation of Jiangsu Province(BK20220059)the National Key Research and Development Program of China(2019YFA0112000)。
文摘Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.
基金Funding for this work was from the Natural Sciences and Engineering Research Council of Canada(NSERC)the National Natural Science Foundation of China(No.U19A2005).
文摘Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,GO has been employed for photosensitized generation of reactive oxygen species(ROS).Herein,we demonstrate that GO sheets could cleave DNA as anuclease mimicking nanozyme in the presence of UV or blue light.For various DNA sequences and lengths,well-defined product bands were observed along with photobleaching of the fluorophore label on the DNA.Different from previously reported GO cleavage of DNA,our method did not require metal ions such as Cu^2+.Fluorescence spectroscopy suggested a high adsorption affinity between GO and DNA.For comparison,although zero-dimensional fluorescent carbon dots(C-dots)had higher photosensitivity ir terms of producing ROS,their cleavage activity was much lower and only smeared cleavage products were observed,indicatingthat the ROS acted on the DNA in solution.Based on the results,GO behaved like a classic heterogeneous catalyst following substrate adsorption,reaction,and product desorption steps.This simple strategy may help in the design of new nanozymes by introducing light.
基金This work was supported by the National Natural Science Foundation of China(Project 82072072)International Cooperation Project by Science and Technology Department of Sichuan Province(2021YFH0056,2019YFH0103)the Fundamental Research Funds for the Central Universities(2682020ZT82,2682020ZT76).
文摘Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component.Herein,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking surface.The stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA coating.Using a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry.Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 month.As a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.
基金financially supported by the National Natural Science Foundation of China(52001321),Science and Technology Commission of Shanghai Municipality(19JC1415500 and 20ZR1465000).
文摘H_(2)O_(2) and glutathione(GSH)are critical redox molecules in the organism.Abnormal levels of cellular H_(2)O_(2) and GSH are closely related to some diseases.Thus,it is imperative to detect H_(2)O_(2) and GSH effi-ciently.In this work,FeeNeC single atom nanozymes(SANs)with both peroxidase and oxidasemimicking activities were successfully prepared with the help of formamide condensation by one-step hydrothermal method.The FeeNeC SANs show excellent peroxidase-like activity,which possess a higher affinity for H_(2)O_(2) and 3,30,5,50-tetramethylbenzidine(TMB)than horseradish peroxidase(HRP).Then,based on the chromogenic reaction of TMB,a colorimetric biosensor to detect H_(2)O_(2) and GSH was developed.This biosensor has the linear ranges of 10-600 mmol/L for H_(2)O_(2) with a low detection limit of 4.360 mmol/L and 100-400 mmol/L for GSH with a low detection limit of 78.33 mmol/L.Besides,this colorimetric biosensor exhibited a good recovery of H_(2)O_(2) and GSH in diluted human serum.Finally,the FeeNeC SANs were encapsulated into agar gel to self-quantitatively detect GSH by naked eyes.This work provides a non-pyrolytic way to prepare SANs,which broadens the synthetic method of SANs and may promote the development of SANs for biosensor application.
文摘1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h...
文摘Four chiral μ phenolato dinuclear (VO) 2, Cr 2, Mn 2, and Fe 2 complexes with a phenolic ligand bearing two L phenylanalines as complexing arms have been synthesized and characterized. Asymmetric epoxidations of styrene with these complexes as chiral models of methane monooxygenase (MMO) and iodosylbenzene as an oxygen atom donor have been studied. The results reveal that the Mn 2 complex catalyzes asymmetric epoxidation of styrene with the formation of R (+) styrene oxide in 42.8% e.e. Contrarily, the (VO) 2 analogue complex gives S (-) styrene oxide in 19.2% e.e. EPR investigations suggest that the catalyzed epoxidations with the Mn 2, Cr 2 and Fe 2 complexes proceed via high valent oxometal intermediates; while in the case of the (VO) 2 complex as catalyst, the epoxidation proceeds by a pathway that involves a complex of metal iodine ligand. The catalytic activities of the complexes decrease in a sequence of Mn 2>Cr 2>(VO) 2>Fe 2.