Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hund...Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research h...Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.展开更多
Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network lev...Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.展开更多
Introduction The phenome is a set of measurable traits,including the physical,chemical and biological traits of individuals and populations,that result from the complex interactions of genes,epigenetics,symbiotic micr...Introduction The phenome is a set of measurable traits,including the physical,chemical and biological traits of individuals and populations,that result from the complex interactions of genes,epigenetics,symbiotic microorganisms,diet and environmental exposures(Jin 2021).The aim of human phe-nomics is to precisely measure the human phenotypes and to comprehensively analyze the human phenome.In doing so,we can systemically deconstruct the relationship among perceived phenotypes,compile phenotypic network,expand multi-dimensional and cross-scale correlations between macro and micro phenotypes,and eventually clarify the correlations among these phenotypes.After the completion of the Human Genome Project,there is an urgent need for discovering the multi-level association among genes,envi-ronment and phenotypes to complement the other half of the required information for human health.Therefore,Fudan University has initiated the International Human Phenome Project in 2018,providing a new opportunity for biomedical research and leading the development of biomedicine.展开更多
The human microbiome plays a crucial role in human health.In the past decade,advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiom...The human microbiome plays a crucial role in human health.In the past decade,advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome.However,most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection,handling,and processing procedures,which impedes obtaining valid and timely microbial taxonomic and functional results.This protocol provides detailed operation methods of human microbial sample collection,DNA extraction,and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity,oral cavity,and skin,as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult par-ticipants.This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples.展开更多
Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomizatio...Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.展开更多
Introduction Why do we focus on human liver biliary organoids?The three-dimensional(3D)organoid approach is emerging as a powerful tool for basic study and biomedical applications due to its excellent recapitulation o...Introduction Why do we focus on human liver biliary organoids?The three-dimensional(3D)organoid approach is emerging as a powerful tool for basic study and biomedical applications due to its excellent recapitulation of the structure and functions of the primary tissues[1-3].Liver biliary organoids are derived from the biliary tree,which includes the intrahepatic bile duct(IHBD)and extrahepatic bile duct(EHBD).展开更多
Magnesium plays a critical role in the human's life activities and energy metabolism. This study aimed to evaluate the magnesium status of athletes via a systematic review of cross-sectional studies. A comprehensi...Magnesium plays a critical role in the human's life activities and energy metabolism. This study aimed to evaluate the magnesium status of athletes via a systematic review of cross-sectional studies. A comprehensive systematic search was conducted in PubMed, Web of Science, SPORTDiscus, Cochrane Library electronic databases, and other sources before April 5, 2021. Fourteen studies were included in the systematic review, involving 855 athletes and 521 control subjects. Serum magnesium concentration was significantly lower in athletes(mean difference(MD):-0.04 mmol/L;95% confidence interval(CI):-0.06 to-0.01;P = 0.02)in spite of significantly higher dietary magnesium intake(MD: 51.72 mg/day;95% CI: 14.62 to 88.83;P = 0.006). Meta-analysis showed that 24-h urinary magnesium excretion in athletes was significantly higher than that in the untrained population(MD: 0.76 mmol/day;95% CI: 0.11 to 1.41;P = 0.02). Despite higher total dietary magnesium intake, athletes generally have lower serum magnesium concentration and higher 24-h urinary magnesium excretion, demonstrating that the magnesium requirement of athletes is higher than the untrained population. It is necessary to carry out a dietary assessment and nutrition counseling to help athletes adopt proper diets to meet their nutritional needs in exercise.展开更多
Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignm...Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignments of NMR signals for some lowconcentration bile acids are still needed.This study combined 1D nuclear magnetic resonance(NMR)and 2D NMR techniques including 1He1H correlation spectroscopy(COSY),1He1H total correlation spectroscopy(TOCSY),1H J-resolved spectroscopy(J-Res),1He13C heteronuclear single quantum coherence spectroscopy(HSQC),and 1He13C heteronuclear multiple bond correlation spectroscopy(HMBC)to assign the 1H and 13C signals of six bile acids in aqueous solution at physiological pH(~7.4)and nine bile acids in methanol.These data are of importance to the NMR-based studies on lipid digestion,absorption,and metabolism.展开更多
Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctua...Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.展开更多
Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is ...Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.展开更多
Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human Reproduction and Embryology[ESHRE]Guideline Group on POI et al.,20...Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human Reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life quality.By contrast,POl is a representative heterogeneous disease with multiple etiologies.While more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.展开更多
Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI...Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.展开更多
Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnin...Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer,accounting for about 90%of liver cancer cases.It is currently the fifth most common cancer in the world and the third leading cause of cancer-relate...Hepatocellular carcinoma(HCC)is the most common primary liver cancer,accounting for about 90%of liver cancer cases.It is currently the fifth most common cancer in the world and the third leading cause of cancer-related mortality.Moreover,recurrence of HCC is common.Microvascular invasion(MVI)is a major factor associated with recurrence in postoperative HCC.It is difficult to evaluate MVI using traditional imaging modalities.Currently,MVI is assessed primarily through pathological and immunohistochemical analyses of postoperative tissue samples.Needle biopsy is the primary method used to confirm MVI diagnosis before surgery.As the puncture specimens represent just a small part of the tumor,and given the heterogeneity of HCC,biopsy samples may yield false-negative results.Radiomics,an emerging,powerful,and non-invasive tool based on various imaging modalities,such as computed tomography,magnetic resonance imaging,ultrasound,and positron emission tomography,can predict the HCC-MVI status preoperatively by delineating the tumor and/or the regions at a certain distance from the surface of the tumor to extract the image features.Although positive results have been reported for radiomics,its drawbacks have limited its clinical translation.This article reviews the application of radiomics,based on various imaging modalities,in preoperative evaluation of HCC-MVI and explores future research directions that facilitate its clinical translation.展开更多
The lignification triggered by biotic or abiotic stresses hardens fruits and vegetables and eventually influences their consumer appeal.Extensive prior efforts have been made to unveil the underlying mechanism of fles...The lignification triggered by biotic or abiotic stresses hardens fruits and vegetables and eventually influences their consumer appeal.Extensive prior efforts have been made to unveil the underlying mechanism of flesh lignification,primarily focused on its physicochemical and molecular biological properties.Nevertheless,most of these studies used destroyed and homogenized bulk tissues as analytes;as a result,potentially valuable spatial information was lost.In this study,the deposition of lignin in loquat flesh during lignification was visualized from the tissue level to the singlecell level by combining the advantages of stimulated Raman scattering(SRS)and spontaneous Raman microscopy using label-free in situ molecular imaging.SRS has the advantages of being fast and providing large-area chemical imaging to reveal the spatial heterogeneity of lignin and cell wall polysaccharide distribution in loquat flesh.After 2 days of storage at 0℃,increased lignins were observed by large-area SRS imaging.In addition,microscopic SRS images of the flesh cells indicated that the increased lignins were trapped in the cell corner(CC)and middle lamella(ML).Furthermore,the compositional and structural features of lignified cells(LCs),CC and ML of loquat flesh were investigated by spontaneous Raman microscopy,and the results showed that the LCs were a combination of lignin,cellulose,and hemicellulose,whereas CC and ML showed only deposited lignin and pectin without cross-linked cellulose and hemicellulose.This result further suggests that the lignins in the CC and ML regions of loquats were later synthesized alone during postharvest storage.This innovative combination of SRS and spontaneous Raman microscopy allows the label-free macroscale and fine chemical imaging of plant cell walls and will enhance our fundamental understanding of the structures and functions of the plant cell wall.展开更多
The main challenge in bone ultrasound imaging is the large acoustic impedance contrast and sound velocity differences between the bone and surrounding soft tissue. It is difficult for conventional pulse-echo modalitie...The main challenge in bone ultrasound imaging is the large acoustic impedance contrast and sound velocity differences between the bone and surrounding soft tissue. It is difficult for conventional pulse-echo modalities to give accurate ultrasound images for irregular bone boundaries and microstructures using uniform sound velocity assumption rather than getting a prior knowledge of sound speed. To overcome these limitations, this paper proposed a frequency-domain fullwaveform inversion(FDFWI) algorithm for bone quantitative imaging utilizing ultrasonic computed tomography(USCT).The forward model was calculated in the frequency domain by solving the full-wave equation. The inverse problem was solved iteratively from low to high discrete frequency components via minimizing a cost function between the modeled and measured data. A quasi-Newton method called the limited-memory Broyden–Fletcher–Goldfarb–Shanno algorithm(L-BFGS) was utilized in the optimization process. Then, bone images were obtained based on the estimation of the velocity and density. The performance of the proposed method was verified by numerical examples, from tubular bone phantom to single distal fibula model, and finally with a distal tibia-fibula pair model. Compared with the high-resolution peripheral quantitative computed tomography(HR-p QCT), the proposed FDFWI can also clearly and accurately presented the wavelength scaled pores and trabeculae in bone images. The results proved that the FDFWI is capable of reconstructing high-resolution ultrasound bone images with sub-millimeter resolution. The parametric bone images may have the potential for the diagnosis of bone disease.展开更多
BACKGROUND Immunoglobin G4(IgG4)-related hypophysitis(IgG4-RH)is a rare form of IgG4-related disease(IgG4-RD),which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically ...BACKGROUND Immunoglobin G4(IgG4)-related hypophysitis(IgG4-RH)is a rare form of IgG4-related disease(IgG4-RD),which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically and by imaging.There are few reports of imaging findings of IgG4-RH.Therefore,we describe a case of IgG4-RH,which mimicked a pituitary macroadenoma,that was detected by computed tomography(CT)and magnetic resonance imaging(MRI),and review the previous literature in order to further the understanding of IgG4-RH.CASE SUMMARY A 47-year-old man presented with a history of blurred vision for more than 2 mo,without other symptoms.A preoperative unenhanced CT scan revealed a slightly hyperdense mass in the sellar region measuring 2.5 cm×2.3 cm×1.8 cm,with a CT value of 45 HU.T1-weighted imaging(T1WI)and T2-weighted imaging showed iso-hypointensity,and gadolinium contrast-enhanced T1WI showed obvious homogeneous enhancement.The MRI revealed involvement of the pituitary gland and stalk.Preoperative laboratory tests revealed abnormal pituitary hormone levels,including an increased prolactin level,and decreased levels of insulin-like growth factor,dehydroepiandrosterone,and testosterone.The lesion was surgically resected.Postoperative histopathological examination of a tissue sample and an elevated serum IgG4 level confirmed the diagnosis of IgG4-RH.The patient was treated with cortisone acetate postoperatively and made a good recovery without developing any neurological deficit.CONCLUSION An elevated serum IgG4 concentration is the main clue for diagnosis of IgG4-RD.Imaging combined with laboratory testing is useful for preoperative diagnosis of IgG4-RH.展开更多
基金financial supports from the National Key R&D Program of China(Grant Nos.:2022YFC3400700,2022YFA0806400,and 2020YFE0201600)Shanghai Municipal Science and Technology Major Project(Grant No.:2017SHZDZX01)the National Natural Science Foundation of China(Grant No.:31821002).
文摘Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077,81961128025,and 82121002)the Research Projects from the Science and Technology Commission of Shanghai Municipality(Grant Nos.21JC1401200,20JC1418900,and 21JC1410100)to QG,the China National Postdoctoral Program for Innovative Talents(Grant No.BX20240090)the China Postdoctoral Science Foundation(Grant No.2024M750551)to MZ.
文摘Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.
基金supported by the National Natural Science Foundation of China,Nos.81871836(to MZ),82172554(to XH),and 81802249(to XH),81902301(to JW)the National Key R&D Program of China,Nos.2018YFC2001600(to JX)and 2018YFC2001604(to JX)+3 种基金Shanghai Rising Star Program,No.19QA1409000(to MZ)Shanghai Municipal Commission of Health and Family Planning,No.2018YQ02(to MZ)Shanghai Youth Top Talent Development PlanShanghai“Rising Stars of Medical Talent”Youth Development Program,No.RY411.19.01.10(to XH)。
文摘Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.
基金supported by Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Shanghai Soft Science Research Project(21692101800,21692102400).
文摘Introduction The phenome is a set of measurable traits,including the physical,chemical and biological traits of individuals and populations,that result from the complex interactions of genes,epigenetics,symbiotic microorganisms,diet and environmental exposures(Jin 2021).The aim of human phe-nomics is to precisely measure the human phenotypes and to comprehensively analyze the human phenome.In doing so,we can systemically deconstruct the relationship among perceived phenotypes,compile phenotypic network,expand multi-dimensional and cross-scale correlations between macro and micro phenotypes,and eventually clarify the correlations among these phenotypes.After the completion of the Human Genome Project,there is an urgent need for discovering the multi-level association among genes,envi-ronment and phenotypes to complement the other half of the required information for human health.Therefore,Fudan University has initiated the International Human Phenome Project in 2018,providing a new opportunity for biomedical research and leading the development of biomedicine.
基金supported by the National Key Research and Development Program of China(2021YFA1301000)the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘The human microbiome plays a crucial role in human health.In the past decade,advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome.However,most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection,handling,and processing procedures,which impedes obtaining valid and timely microbial taxonomic and functional results.This protocol provides detailed operation methods of human microbial sample collection,DNA extraction,and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity,oral cavity,and skin,as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult par-ticipants.This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples.
基金supported by grants from the Natural Science Foundation of China(No.82102199)the General Program of Shanghai Municipal Commission of Health and Family Planning(No.202040479).
文摘Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.
基金supported by grants from the National Key Research and Development Program of China(2018YFA0109400)the National Natural Science Foundation of China(32022022)the Shanghai Pilot Program for Basic Research—Fudan University 21TQ1400100(21TQ003)。
文摘Introduction Why do we focus on human liver biliary organoids?The three-dimensional(3D)organoid approach is emerging as a powerful tool for basic study and biomedical applications due to its excellent recapitulation of the structure and functions of the primary tissues[1-3].Liver biliary organoids are derived from the biliary tree,which includes the intrahepatic bile duct(IHBD)and extrahepatic bile duct(EHBD).
基金supported by the National Key R&D Program of China (2020YFA0803800)the National Natural Science Foundation of China (31971097)。
文摘Magnesium plays a critical role in the human's life activities and energy metabolism. This study aimed to evaluate the magnesium status of athletes via a systematic review of cross-sectional studies. A comprehensive systematic search was conducted in PubMed, Web of Science, SPORTDiscus, Cochrane Library electronic databases, and other sources before April 5, 2021. Fourteen studies were included in the systematic review, involving 855 athletes and 521 control subjects. Serum magnesium concentration was significantly lower in athletes(mean difference(MD):-0.04 mmol/L;95% confidence interval(CI):-0.06 to-0.01;P = 0.02)in spite of significantly higher dietary magnesium intake(MD: 51.72 mg/day;95% CI: 14.62 to 88.83;P = 0.006). Meta-analysis showed that 24-h urinary magnesium excretion in athletes was significantly higher than that in the untrained population(MD: 0.76 mmol/day;95% CI: 0.11 to 1.41;P = 0.02). Despite higher total dietary magnesium intake, athletes generally have lower serum magnesium concentration and higher 24-h urinary magnesium excretion, demonstrating that the magnesium requirement of athletes is higher than the untrained population. It is necessary to carry out a dietary assessment and nutrition counseling to help athletes adopt proper diets to meet their nutritional needs in exercise.
文摘Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignments of NMR signals for some lowconcentration bile acids are still needed.This study combined 1D nuclear magnetic resonance(NMR)and 2D NMR techniques including 1He1H correlation spectroscopy(COSY),1He1H total correlation spectroscopy(TOCSY),1H J-resolved spectroscopy(J-Res),1He13C heteronuclear single quantum coherence spectroscopy(HSQC),and 1He13C heteronuclear multiple bond correlation spectroscopy(HMBC)to assign the 1H and 13C signals of six bile acids in aqueous solution at physiological pH(~7.4)and nine bile acids in methanol.These data are of importance to the NMR-based studies on lipid digestion,absorption,and metabolism.
基金supported by the National Key R&D Program of China,Nos.2020YFC2004202(to DSX),2018 YFC2001600(to XYH)the National Natural Science Foundation of China,Nos.81974358(to DSX),81802249(to XYH)and 82172554(to XYH)。
文摘Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.
基金This work was financially supported by the National Natural Science Foundation of China(92249302,32370592)the National Key Research and Development Program of China(2023YFC3603300,2021YFA0909300).
文摘Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.
基金supported by the National Natural Science Foundation of China(32270658 and 32288101)the National Key Research and Development Program of China(2022YFC2703800)the Natural Science Foundation of Shanghai(20ZR1407000).
文摘Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human Reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life quality.By contrast,POl is a representative heterogeneous disease with multiple etiologies.While more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.
基金supported by the National Natural Science Foundation of China(32288101)the National Key Research and Development Program of China(2021YFC2701400)Shenkang Clinical Technology Innovation Project(SHDC22021219)。
文摘Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
基金grants from the National Key Research and Development Program of China (2023YFE0109700)the National Natural Science Foundation of China (82125032, 81930095, 32071023, 82272079, and 32200967)+4 种基金the Science and Technology Commission of Shanghai Municipality (23Y21900500, 2018SHZDZX01, 22XD1420700, 23XD142300, and 23YF1425700)the Shanghai Municipal Commission of Health and Family Planning (GWV-11.1-34, 2020CXJQ01, 2018YJRC03, and 2022XD046)the Innovative research team of high-level local universities in Shanghai (SHSMU-ZDCX20211100)the Guangdong Key Project (2018B030335001)University of Sydney - Fudan University BISA Flagship Research Program. Y.Y. and T.Z. were awarded the fellowship of China Postdoctoral Science Foundation (2021M700851, 2023T160117, and 2022M712125).
文摘Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.
基金Supported by the Shanghai Municipal Commission of Science and Technology, No. 19411951200Clinical Research Plan of SHDC, No. SHDC2020CR3020Athe Research Startup Fund of Huashan Hospital Fudan University, No.2021QD035
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer,accounting for about 90%of liver cancer cases.It is currently the fifth most common cancer in the world and the third leading cause of cancer-related mortality.Moreover,recurrence of HCC is common.Microvascular invasion(MVI)is a major factor associated with recurrence in postoperative HCC.It is difficult to evaluate MVI using traditional imaging modalities.Currently,MVI is assessed primarily through pathological and immunohistochemical analyses of postoperative tissue samples.Needle biopsy is the primary method used to confirm MVI diagnosis before surgery.As the puncture specimens represent just a small part of the tumor,and given the heterogeneity of HCC,biopsy samples may yield false-negative results.Radiomics,an emerging,powerful,and non-invasive tool based on various imaging modalities,such as computed tomography,magnetic resonance imaging,ultrasound,and positron emission tomography,can predict the HCC-MVI status preoperatively by delineating the tumor and/or the regions at a certain distance from the surface of the tumor to extract the image features.Although positive results have been reported for radiomics,its drawbacks have limited its clinical translation.This article reviews the application of radiomics,based on various imaging modalities,in preoperative evaluation of HCC-MVI and explores future research directions that facilitate its clinical translation.
基金supported by the National Key R&D Program of China(2016YFD0400106)National Natural Science Foundation of China(31630067,31671902,31401541,81671725)+1 种基金Talent Project of Zhejiang Association for Science and Technology(2018YCGC006)the 111 Project(B17039).
文摘The lignification triggered by biotic or abiotic stresses hardens fruits and vegetables and eventually influences their consumer appeal.Extensive prior efforts have been made to unveil the underlying mechanism of flesh lignification,primarily focused on its physicochemical and molecular biological properties.Nevertheless,most of these studies used destroyed and homogenized bulk tissues as analytes;as a result,potentially valuable spatial information was lost.In this study,the deposition of lignin in loquat flesh during lignification was visualized from the tissue level to the singlecell level by combining the advantages of stimulated Raman scattering(SRS)and spontaneous Raman microscopy using label-free in situ molecular imaging.SRS has the advantages of being fast and providing large-area chemical imaging to reveal the spatial heterogeneity of lignin and cell wall polysaccharide distribution in loquat flesh.After 2 days of storage at 0℃,increased lignins were observed by large-area SRS imaging.In addition,microscopic SRS images of the flesh cells indicated that the increased lignins were trapped in the cell corner(CC)and middle lamella(ML).Furthermore,the compositional and structural features of lignified cells(LCs),CC and ML of loquat flesh were investigated by spontaneous Raman microscopy,and the results showed that the LCs were a combination of lignin,cellulose,and hemicellulose,whereas CC and ML showed only deposited lignin and pectin without cross-linked cellulose and hemicellulose.This result further suggests that the lignins in the CC and ML regions of loquats were later synthesized alone during postharvest storage.This innovative combination of SRS and spontaneous Raman microscopy allows the label-free macroscale and fine chemical imaging of plant cell walls and will enhance our fundamental understanding of the structures and functions of the plant cell wall.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11827808,11874289,and 11804056)the National Science Fund for Distinguished Young Scholars of China(Grant No.11525416)+3 种基金Shanghai Municipal Science and Technology Major Project,China(Grant No.2017SHZDZX01)Shanghai Talent Development Fund(Grant No.2018112)State Key Laboratory of ASIC and System Project(Grant No.2018MS004)China Postdoctoral Science Foundation(Grant No.2019M661334)。
文摘The main challenge in bone ultrasound imaging is the large acoustic impedance contrast and sound velocity differences between the bone and surrounding soft tissue. It is difficult for conventional pulse-echo modalities to give accurate ultrasound images for irregular bone boundaries and microstructures using uniform sound velocity assumption rather than getting a prior knowledge of sound speed. To overcome these limitations, this paper proposed a frequency-domain fullwaveform inversion(FDFWI) algorithm for bone quantitative imaging utilizing ultrasonic computed tomography(USCT).The forward model was calculated in the frequency domain by solving the full-wave equation. The inverse problem was solved iteratively from low to high discrete frequency components via minimizing a cost function between the modeled and measured data. A quasi-Newton method called the limited-memory Broyden–Fletcher–Goldfarb–Shanno algorithm(L-BFGS) was utilized in the optimization process. Then, bone images were obtained based on the estimation of the velocity and density. The performance of the proposed method was verified by numerical examples, from tubular bone phantom to single distal fibula model, and finally with a distal tibia-fibula pair model. Compared with the high-resolution peripheral quantitative computed tomography(HR-p QCT), the proposed FDFWI can also clearly and accurately presented the wavelength scaled pores and trabeculae in bone images. The results proved that the FDFWI is capable of reconstructing high-resolution ultrasound bone images with sub-millimeter resolution. The parametric bone images may have the potential for the diagnosis of bone disease.
基金Supported by National Key R&D Program of China,No.2019YFC0120602Clinical Research Plan of SHDC,No.SHDC2020CR3020A+2 种基金Research Startup Fund of Huashan Hospital,Fudan University,No.2021QD035Shanghai Municipal Commission of Science and Technology,No.22S31905300Greater Bay Area Institute of Precision Medicine(Guangzhou),No.KCH2310094。
文摘BACKGROUND Immunoglobin G4(IgG4)-related hypophysitis(IgG4-RH)is a rare form of IgG4-related disease(IgG4-RD),which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically and by imaging.There are few reports of imaging findings of IgG4-RH.Therefore,we describe a case of IgG4-RH,which mimicked a pituitary macroadenoma,that was detected by computed tomography(CT)and magnetic resonance imaging(MRI),and review the previous literature in order to further the understanding of IgG4-RH.CASE SUMMARY A 47-year-old man presented with a history of blurred vision for more than 2 mo,without other symptoms.A preoperative unenhanced CT scan revealed a slightly hyperdense mass in the sellar region measuring 2.5 cm×2.3 cm×1.8 cm,with a CT value of 45 HU.T1-weighted imaging(T1WI)and T2-weighted imaging showed iso-hypointensity,and gadolinium contrast-enhanced T1WI showed obvious homogeneous enhancement.The MRI revealed involvement of the pituitary gland and stalk.Preoperative laboratory tests revealed abnormal pituitary hormone levels,including an increased prolactin level,and decreased levels of insulin-like growth factor,dehydroepiandrosterone,and testosterone.The lesion was surgically resected.Postoperative histopathological examination of a tissue sample and an elevated serum IgG4 level confirmed the diagnosis of IgG4-RH.The patient was treated with cortisone acetate postoperatively and made a good recovery without developing any neurological deficit.CONCLUSION An elevated serum IgG4 concentration is the main clue for diagnosis of IgG4-RD.Imaging combined with laboratory testing is useful for preoperative diagnosis of IgG4-RH.
