Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,wh...Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,which are incapable of repairing the pulpdentin complex defects.Although biomaterial-based strategies show remarkable progress in antibacterial,anti-inflammatory,and pulp regeneration,the important modulatory effects of nerves within pulp cavity have been greatly overlooked,making it challenging to achieve functional pulp-dentin complex regeneration.In this study,we propose an injectable bioceramicscontaining composite hydrogel in combination of Li-Ca-Si(LCS)bioceramics and gelatin methacrylate matrix with photocrosslinking properties.Due to the sustained release of bioactive Li,Ca and Si ions from LCS,the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells,odontogenic differentiation of dental pulp stem cells,and neurogenesis-odontogenesis couples in vitro.In addition,the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair.More importantly,LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers,leading to the re-innervation of pulp tissues.Taken together,the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair,offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.展开更多
Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DP...Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
BACKGROUND： Studies have shown that abnormal innervation is an important factor impacting occurrence and development of pathological pain in endometriosis. OBJECTIVE： To observe uterine innervation of adenomyosis mi...BACKGROUND： Studies have shown that abnormal innervation is an important factor impacting occurrence and development of pathological pain in endometriosis. OBJECTIVE： To observe uterine innervation of adenomyosis mice and to analyze the cause of innervation changes due to nerve growth factor （NGF） expression, inflammation, and vascularization. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Research Institute of Obstetrics and Gynecology Hospital, and Central Laboratory of Zhongshan Hospital, Fudan University from March to December 2008. MATERIALS： Tamoxifen was provided by Fudan Forward, China. Rabbit anti-mouse NGF was purchased from Santa Cruz Corporation, USA; rabbit anti-protein gene product 9.5 （PGP9.5） and rabbit anti-substance P （SP） were purchased from Chemicon, USA. METHODS： A total of 40 newborn ICR mice were randomly assigned to adenomyosis model and control groups, with 20 animals in each group. Mice in the adenomyosis model group were orally administrated 2.7 μmol/kg tamoxifen on days 2-5 after birth, while the controls were not treated. MAIN OUTCOME MEASURES： Both uteri from all mice were harvested at days 135-145 after birth Expressions of polyclonal PGP9.5 and SP were immunohistochemically detected to demonstrate pan- and sensory nerve fibers. Microvessel density was quantified in the endometrium and myometrium using immunochemical staining for polyclonal rabbit anti-CD31, which stained vessels. Gene expression for NGF, high-affinity tyrosine kinase receptor （trkA）, p75 neuretrophin receptor （p75NTR）, bradykinin receptor-1 （BKR-1）, and 2 （BKR-2）, as well as substance P receptor （neurokininl receptor, NK1-R）, were detected by reverse transcription-polymerase chain reaction. NGF-13 protein expression was detected by Western blot analysis. RESULTS： More nerve fibers were stained with PGP9.5 in the endometrium and myometrium, and with SP in the endometrium, in adenomyosis mice compared with controls （P 〈 0.01 and P 〈 0.05）. Microvessel density in the myometrium of adenomyosis mice was significantly greater than the controls （P 〈 0.01）. In the uterus of adenomyosis mice, mRNA expression of NGF and its two receptors （trkA and p75 NTR）, BKR-1, and NK1-R, as well as protein expression of NGF-β, were greater than the control mice （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Uterine innervation in the adenomyosis mice was increased compared with the controls. Moreover, NGF expression, inflammation, and vascularization, which have been shown to be impact factors of innervation, were abnormal in the uteri of adenomyosis mice.展开更多
AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS： The liver, gallbladder and surrounding structures were imm...AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS： The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers （n = 10）. Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus （S. murinus） was examined employing whole mount immunohistochemistry.RESULTS： Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.CONCLUSION： The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.展开更多
AIM: To characterize changes in the cornea nerve and pain responses in fungal keratitis(FK).METHODS: A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were ...AIM: To characterize changes in the cornea nerve and pain responses in fungal keratitis(FK).METHODS: A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57 BL/6 mice were infected with Aspergillus fumigatus. Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7 d post infection(p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin(β-EP) and μ receptor protein expression was detected through Western blotting.RESULTS: Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1 d p.i., reaching a minimum at 5 d p.i. Clinical scores rose at 1 d p.i., peaked at 3 d p.i., and decreased at 5 d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and μ receptor protein expression increased after infection.CONCLUSION: Corneal nerve density is lower in FK patients and Aspergillus fumigatus-infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and μ receptor proteins are both upregulated in infected mouse corneas.展开更多
Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the ne...Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.展开更多
Liver innervation comprises sympathetic,parasympathetic and peptidergic nerve fibers,organized as either afferent or efferent nerves with different origins and roles.Their anatomy and physiology have been studied in t...Liver innervation comprises sympathetic,parasympathetic and peptidergic nerve fibers,organized as either afferent or efferent nerves with different origins and roles.Their anatomy and physiology have been studied in the past 30 years,with different results published over time.Hepatocytes are the main cell population of the liver,making up almost 80%of the total liver volume.The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways.In this short review,we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population,how it influences their metabolism and functions,and how different receptors and transmitters are involved in this complex process.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive lethal malignancy,characterized by late diagnosis,aggressive growth,and therapy resistance,leading to a poor overall prognosis.Emerging evidence shows that ...Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive lethal malignancy,characterized by late diagnosis,aggressive growth,and therapy resistance,leading to a poor overall prognosis.Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape.The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets.In this review,we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC,summarize the potential signaling pathways modulating the neuronal-cancer interaction,and discuss the current and future therapeutic possibilities for this condition.展开更多
Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the in- jured side occ...Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the in- jured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber＇s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.展开更多
AIM： To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS： The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a...AIM： To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS： The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount imm unohistochemistry. RESULTS： The innervation of the pyloric region in humans involved three routes： One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION： There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy （PPPD）. However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries （the right gastroepiploic and gastroduodenal arteries）, and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.展开更多
White adipose tissue(WAT) stores energy and also plays an important endocrine role in producing adipokines for communication with the peripheral and central nervous system. WAT consists of the major lipogenic unilocul...White adipose tissue(WAT) stores energy and also plays an important endocrine role in producing adipokines for communication with the peripheral and central nervous system. WAT consists of the major lipogenic unilocular adipocytes and the minor populations of beige and brite multilocular adipocytes. These multilocular adipocytes express thermogenic genes and have phenotypic similarity with thermogenic brown adipose tissue. According to a current paradigm, multilocular adipocytes have a thermogenic function in WAT. In this mini review, we discuss data revealing heterogeneity among multilocular cell subsets in WAT and their functions beyond thermogenesis. We propose a hypothetical neuroendocrine role for multilocular adipocytes subsets in the formation of adaptive sensory-sympathetic circuits between the central nervous system and adipose tissue, which activate lipolysis and thermogenesis in WAT in high energy demand situations.展开更多
In the present study, the oculomotor nerves were sectioned at the proximal （subtentorial） and distal （superior orbital fissure） ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that ...In the present study, the oculomotor nerves were sectioned at the proximal （subtentorial） and distal （superior orbital fissure） ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that the regenerating nerve fibers following oculomotor nerve injury in the superior orbital fissure had a high level of specificity for innervating extraocular muscles. The level of functional recovery of extraocular muscles in rats in the superior orbital fissure injury group was remarkably superior over that in rats undergoing oculomotor nerve injuries at the proximal end （subtentorium）. Horseradish peroxidase retrograde tracing through the right superior rectus muscle showed that the distribution of neurons in the nucleus of the oculomotor nerve was directly associated with the injury site, and that crude fibers were badly damaged. The closer the site of injury of the oculomotor nerve was to the extraocular muscle, the better the recovery of neurological function was. The mechanism may be associated with the aberrant number of regenerated nerve fibers passing through the injury site.展开更多
The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes.The experimental rabbits were killed after 6,8,10, 12weeks.Corneal innervation was studied by histochemical techniques and tra...The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes.The experimental rabbits were killed after 6,8,10, 12weeks.Corneal innervation was studied by histochemical techniques and transimission electron microscopy.The results revealed that in diabetic rabbits,from 6 weeks,the density of nerve-nets was markedly sparser,the fibers were thinner and the activity of nerves was lower than those of the control group.Ultrastructural changes showed swelling of axons,irregular distribution of fibril and degeneration of mitochondria of varying degree.With the progress of disease the above changes were becoming more marked gradually.It may be assumed that these changes are related to hyperglycemia.展开更多
Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the ant...Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.展开更多
Background: Altered myocardial sympathetic innervation activity (AMSI) is known to be present in systolic heart failure patients (SHF) and recently SPECT imaging using I-123 mIBG heart to mediastinum (H/M) ratio <1...Background: Altered myocardial sympathetic innervation activity (AMSI) is known to be present in systolic heart failure patients (SHF) and recently SPECT imaging using I-123 mIBG heart to mediastinum (H/M) ratio <1.6 has been shown to predict MACE in the ADMIRE-HF trial. Left ventricular mechanical dyssynchrony (LVMD) is known to be present in a substantial number of SHF patients and has been studied mainly to guide CRT therapy. Recently gated SPECT has shown promise to provide an accurate assessment of LVMD. It remains unclear how the combination of AMSI and LVMD collectively affect clinical outcomes and other cardiovascular parameters. Objectives: The objectives are to examine the clinical characteristics and incremental prognostic value for MACE of LVMD determined by SPECT in SHF patients with or without abnormal cardiac MIBG uptake (H/M ratio < 1.6). Methods: Out of 30 SHF patients who participated from our institution in the ADMIRE-HF trial studying MIBG based AMSI, we included 22 patients with abnormal MIBG H/M ratio of <1.6. We performed gated SPECT LVMD analysis on these patients using the Emory Cardiac Toolbox. The 2 SPECT variables for LVMD assessed were histogram bandwidth and phase standard deviation both of which assess the extent of dispersion of LV activation during contraction as a marker of LVMD. Patients were followed up for a mean period of 6 years. The primary end point was mortality from any cause and secondary end point was heart failure admission or myocardial infarction or ICD shock. Results: 2 Groups were defined: Group A: n = 17 with H/M MIBG ratio < 1.6 and +LVMD and Group B, n = 5 H/M MIBG ratio −LVMD. Baseline characteristics, cardiac risk factors and medications were comparable between both groups. LVEF was lower and RBBB was less common in Group A. There was no statistical difference in achievement of primary or secondary end points in the two groups including death heart failure readmissions, ICD shocks or MI. Conclusions: In our pilot study, we did not find definitive value of adding SPECT based LVMD to abnormal cardiac MIBG imaging in SHF patients with regards to predicting outcomes. Although our sample size is too small to make any definitive conclusions, it is possible that LVMD works independently through different pathways in the progression of SHF and hence may not necessarily add incremental value to AMSI determination using MIBG.展开更多
Background:Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation.Although dual innervation approaches using two neurotizers have shown promise,there is a lack of evidence-bas...Background:Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation.Although dual innervation approaches using two neurotizers have shown promise,there is a lack of evidence-based comparison in the literature.Furthermore,no animal model of dual reinnervation has yet been published.This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats.Methods:Fifteen Wistar rats were divided into four experimental groups and one control group.The sural nerve was exposed and used as a cross-face nerve graft(CFNG),which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead.The CFNG,the masseteric nerve(MN),and the recipient nerve were coapted in one or two stages.The length and width of the utilized structures were measured under an operating microscope.Return of whisker motion was visually confirmed.Results:Nine out of the eleven rats that underwent surgery survived the procedure.Whisker motion was observed in all experimental animals,indicating successful reinnervation.The mean duration of the surgical procedures did not differ significantly between the experimental groups,ensuring similar conditions for all groups.Conclusions:Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible,with a high success rate,and shows good prospects for future experiments.展开更多
Objective:This study aimed to describe the updated disease burden and temporal trends of stomach cancer(SC)and colorectal cancer(CRC),and to explore potential influence factors of the two cancers in the Western Pacifi...Objective:This study aimed to describe the updated disease burden and temporal trends of stomach cancer(SC)and colorectal cancer(CRC),and to explore potential influence factors of the two cancers in the Western Pacific region(WPR).Methods:Estimates of incidence,deaths,and disability-adjusted life years(DALYs)for SC and CRC were obtained from the Global Burden of Disease Study 2021.Trends in age-standardized incidence rates(ASIR),agestandardized mortality rates(ASMR),and age-standardized DALY rates(ASDR)were assessed.A decomposition analysis was conducted to quantify the role of three factors(i.e.,population aging,population growth,and epidemiological change)driving DALY changes between 2000 and 2021.Pearson correlation analysis was used to examine the association between cancer burden and Socio-demographic Index(SDI)at the national level in 2021.Results:In 2021,the WPR accounted for 61.77%of global incident SC cases and 43.07%of global incident CRC cases.From 2000 to 2021,the ASIR,ASMR,and ASDR of SC and the ASMR and ASDR of CRC decreased,whereas the ASIR of CRC increased by an average of 1.32%per year.Among the 31 WPR countries and territories,China had the highest number of incident cases,deaths,and DALYs for both cancers in 2021.Epidemiology change was the primary driver to the reduction of DALYs for SC,while population aging and population growth contributed to the increase of DALYs for CRC.Additionally,ASMR(r=-0.37,P=0.041)and ASDR(r=-0.43,P=0.016)of SC were negatively correlated with SDI in 2021,whereas positive correlations were observed between SDI and ASIR(r=0.74,P<0.001),ASMR(r=0.47,P=0.008),and ASDR(r=0.36,P=0.044)for CRC.Conclusions:SC and CRC continue to pose considerable public health threats in the WPR.Targeted prevention and control strategies should be prioritized,particularly in high-burden and resource-limited countries.展开更多
BACKGROUND Gastric cancer(GC)is a major global health challenge,and the treatment of proximal GC in particular presents unique clinical and surgical complexities.Currently,there is no consensus on whether proximal gas...BACKGROUND Gastric cancer(GC)is a major global health challenge,and the treatment of proximal GC in particular presents unique clinical and surgical complexities.Currently,there is no consensus on whether proximal gastrectomy(PG)or total gastrectomy(TG)should be used for advanced proximal GC,and the choice of postoperative gastrointestinal reconstruction method remains controversial.AIM To compare the short-term efficacy,long-term survival,and postoperative reflux outcomes of PG with tubular stomach reconstruction vs TG with Roux-en-Y re-construction in patients with proximal GC following neoadjuvant chemotherapy(NACT)in an effort to provide valuable insights for clinical decision-making regarding the optimal surgical approach.METHODS A multicenter retrospective cohort study was conducted at two Chinese medical centers between December,2012 and December,2022.Patients with histologically confirmed proximal GC who received NACT followed by either PG with tubular stomach reconstruction or TG with Roux-en-Y reconstruction were included.Propensity score matching(PSM)was performed to balance baseline characteristics,and the primary endpoint was 5-year overall survival(OS).Se-condary endpoints included recurrence-free survival(RFS),postoperative complications,and reflux severity.RESULTS After PSM,244 patients(122 PG,122 TG)were finally included and all baseline characteristics were comparable between groups.The PG group had a significantly shorter operation time compared to the TG group(189.50 vs 215.00 minutes,P<0.001),with no differences in intraoperative blood loss or postoperative complications(19.68%vs 14.75%,P=0.792).The 5-year OS rates were 52.7%vs 45.5%(P=0.330),and 5-year RFS rates were 54.3%vs 47.6%(P=0.356)for the PG and TG groups,respectively.Reflux symptoms(18.0%vs 31.1%,P=0.017)and clinically significant reflux based on gastroesophageal reflux disease questionnaire scores≥8(7.4%vs 21.3%,P<0.001)were significantly less frequent in the PG group.Multivariate analysis identified histological differentiation(HR=2.98,95%CI:2.03-4.36,P<0.001)and tumor size(HR=0.26,95%CI:0.17-0.41 for tumors≤4 cm,P<0.001)as independent prognostic factors.CONCLUSION PG with tubular stomach reconstruction is comparable to TG in terms of surgical safety and long-term oncological outcomes for proximal GC patients following NACT.Additionally,PG has the advantages of shorter operation time and lower rates of postoperative reflux,suggesting potential benefits for patient quality of life.Notably,the analysis of postoperative prognostic factors,including histological differentiation and tumor size,further informs clinical decision-making and highlights the importance of individualized treatment strategies.展开更多
Disseminated mucormycosis is a life-threatening fungal infection with high mortality,particularly in immunocompromised patients.Early diagnosis and prompt intervention are crutial but often delayed due to nonspecific ...Disseminated mucormycosis is a life-threatening fungal infection with high mortality,particularly in immunocompromised patients.Early diagnosis and prompt intervention are crutial but often delayed due to nonspecific presentations.Many studies have highlighted the challenges in emergency settings,where atypical symptoms may lead to misdiagnosis.We report a rare case of disseminated mucormycosis originating from the stomach in a pregnancy-induced thrombocytopenia(PITP)patient,emphasizing rapid gastroscopy examination,histopathological confi rmation,multidisciplinary management,and high-risk factors for hospital-acquired gastrointestinal mucormycosis infection.展开更多
基金funded by the National Key R&D Program of China(2022YFC2405904)the National Natural Science Foundation of China(52272284,32225028)+1 种基金Joint Research Unit Plan of the Chinese Academy of Sciences(121631ZYLH20240014)the Science and Technology Commission of Shanghai Municipality(24520750100)。
文摘Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines.Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies,which are incapable of repairing the pulpdentin complex defects.Although biomaterial-based strategies show remarkable progress in antibacterial,anti-inflammatory,and pulp regeneration,the important modulatory effects of nerves within pulp cavity have been greatly overlooked,making it challenging to achieve functional pulp-dentin complex regeneration.In this study,we propose an injectable bioceramicscontaining composite hydrogel in combination of Li-Ca-Si(LCS)bioceramics and gelatin methacrylate matrix with photocrosslinking properties.Due to the sustained release of bioactive Li,Ca and Si ions from LCS,the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells,odontogenic differentiation of dental pulp stem cells,and neurogenesis-odontogenesis couples in vitro.In addition,the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair.More importantly,LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers,leading to the re-innervation of pulp tissues.Taken together,the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair,offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
基金supported by NIH/NIAMS(P01 AG066603,R01 AR079171,R21 AR078919)NIH/NIDCR(R01 DE031488,R01 DE031028)+4 种基金Alex’s Lemonade Stand Foundation(22-26743)American Cancer Society(DBG-23-1155131-01-IBCD)the Maryland Stem Cell Research Foundation(2021-MSCRFD-5641),and Department of Defense(USAMRAA HT9425-24-1-0051)MC is supported by Merkin Peripheral Neuropathy and Nerve Regeneration Center(23-DF/C2/260)M.K.is supported by NIH(T32HD044355).
文摘Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金the Construction Program of Shanghai Medical Intensive Subject (Obstetrics and Gynaecology), No. 05-111-0165
文摘BACKGROUND： Studies have shown that abnormal innervation is an important factor impacting occurrence and development of pathological pain in endometriosis. OBJECTIVE： To observe uterine innervation of adenomyosis mice and to analyze the cause of innervation changes due to nerve growth factor （NGF） expression, inflammation, and vascularization. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Research Institute of Obstetrics and Gynecology Hospital, and Central Laboratory of Zhongshan Hospital, Fudan University from March to December 2008. MATERIALS： Tamoxifen was provided by Fudan Forward, China. Rabbit anti-mouse NGF was purchased from Santa Cruz Corporation, USA; rabbit anti-protein gene product 9.5 （PGP9.5） and rabbit anti-substance P （SP） were purchased from Chemicon, USA. METHODS： A total of 40 newborn ICR mice were randomly assigned to adenomyosis model and control groups, with 20 animals in each group. Mice in the adenomyosis model group were orally administrated 2.7 μmol/kg tamoxifen on days 2-5 after birth, while the controls were not treated. MAIN OUTCOME MEASURES： Both uteri from all mice were harvested at days 135-145 after birth Expressions of polyclonal PGP9.5 and SP were immunohistochemically detected to demonstrate pan- and sensory nerve fibers. Microvessel density was quantified in the endometrium and myometrium using immunochemical staining for polyclonal rabbit anti-CD31, which stained vessels. Gene expression for NGF, high-affinity tyrosine kinase receptor （trkA）, p75 neuretrophin receptor （p75NTR）, bradykinin receptor-1 （BKR-1）, and 2 （BKR-2）, as well as substance P receptor （neurokininl receptor, NK1-R）, were detected by reverse transcription-polymerase chain reaction. NGF-13 protein expression was detected by Western blot analysis. RESULTS： More nerve fibers were stained with PGP9.5 in the endometrium and myometrium, and with SP in the endometrium, in adenomyosis mice compared with controls （P 〈 0.01 and P 〈 0.05）. Microvessel density in the myometrium of adenomyosis mice was significantly greater than the controls （P 〈 0.01）. In the uterus of adenomyosis mice, mRNA expression of NGF and its two receptors （trkA and p75 NTR）, BKR-1, and NK1-R, as well as protein expression of NGF-β, were greater than the control mice （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Uterine innervation in the adenomyosis mice was increased compared with the controls. Moreover, NGF expression, inflammation, and vascularization, which have been shown to be impact factors of innervation, were abnormal in the uteri of adenomyosis mice.
基金Supported by Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant No. 16590139
文摘AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS： The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers （n = 10）. Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus （S. murinus） was examined employing whole mount immunohistochemistry.RESULTS： Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.CONCLUSION： The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.
基金Supported by the National Natural Science Foundation of China(No.81470609 No.81870632)+4 种基金the Youth National Natural Science Foundation of China(No.81700800 No.81800800 No.81500695)Natural Science Foundation of Shandong Province(No.ZR2017MH008 No.ZR2017BH025)
文摘AIM: To characterize changes in the cornea nerve and pain responses in fungal keratitis(FK).METHODS: A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57 BL/6 mice were infected with Aspergillus fumigatus. Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7 d post infection(p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin(β-EP) and μ receptor protein expression was detected through Western blotting.RESULTS: Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1 d p.i., reaching a minimum at 5 d p.i. Clinical scores rose at 1 d p.i., peaked at 3 d p.i., and decreased at 5 d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and μ receptor protein expression increased after infection.CONCLUSION: Corneal nerve density is lower in FK patients and Aspergillus fumigatus-infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and μ receptor proteins are both upregulated in infected mouse corneas.
基金Claudia Machado(Instituto de Investigacao e Inovacao em Saude)for her help in preparing the bone slides for the immunohistochemistryThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation(POCI),Portugal 2020,and by Portuguese funds through FCT/MCTES in the framework of the project SproutcORE—Inervagao patologica em metastases osseas:OSTEOCLASTOS,o que estao a fazer?(PTDC/MED-PAT/30158/2017,POCI-01-0145-FEDER-030158)+1 种基金D.M.S.is a recipient of a Post-Doc fellowship(SFRH/BPD/115341/2016)L.L.and F.C.are recipients of Ph.D.fellowships(SFRH/BD/109686/2015 and SFRH/BD/128771/2017,respectively).
文摘Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.
文摘Liver innervation comprises sympathetic,parasympathetic and peptidergic nerve fibers,organized as either afferent or efferent nerves with different origins and roles.Their anatomy and physiology have been studied in the past 30 years,with different results published over time.Hepatocytes are the main cell population of the liver,making up almost 80%of the total liver volume.The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways.In this short review,we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population,how it influences their metabolism and functions,and how different receptors and transmitters are involved in this complex process.
基金supported by a grant from the Tianjin“Project+Team”Key Cultivation Program(XC202034)a Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A).
文摘Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive lethal malignancy,characterized by late diagnosis,aggressive growth,and therapy resistance,leading to a poor overall prognosis.Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape.The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets.In this review,we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC,summarize the potential signaling pathways modulating the neuronal-cancer interaction,and discuss the current and future therapeutic possibilities for this condition.
文摘Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the in- jured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber＇s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.
基金Supported by Ministry of Education, Culture, Sports, Science and Technology of Japan Grant, No. 14570008
文摘AIM： To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS： The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount imm unohistochemistry. RESULTS： The innervation of the pyloric region in humans involved three routes： One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION： There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy （PPPD）. However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries （the right gastroepiploic and gastroduodenal arteries）, and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.
基金supported by NIH grants R21OD017244(to OZ)the National Center for Research Resources UL1RR025755(to OZ and AL)+5 种基金UL1TR001070(to OZ and AL)NCIP30CA16058(OSUCCC)(to OZ and AL)the NIH Roadmap for Medical Research(to OZ and AL)supported by the SEED Grant from College of Education and Human EcologyAccelerator Grant from Office for Technology and CommercializationBrain Injury program from the Ohio State University(to OZ and AL)
文摘White adipose tissue(WAT) stores energy and also plays an important endocrine role in producing adipokines for communication with the peripheral and central nervous system. WAT consists of the major lipogenic unilocular adipocytes and the minor populations of beige and brite multilocular adipocytes. These multilocular adipocytes express thermogenic genes and have phenotypic similarity with thermogenic brown adipose tissue. According to a current paradigm, multilocular adipocytes have a thermogenic function in WAT. In this mini review, we discuss data revealing heterogeneity among multilocular cell subsets in WAT and their functions beyond thermogenesis. We propose a hypothetical neuroendocrine role for multilocular adipocytes subsets in the formation of adaptive sensory-sympathetic circuits between the central nervous system and adipose tissue, which activate lipolysis and thermogenesis in WAT in high energy demand situations.
基金the National Natural Science Foundation of China, No. 30571907the Grant from the Science and Technology Commission of Shanghai, No. 05QMH1409
文摘In the present study, the oculomotor nerves were sectioned at the proximal （subtentorial） and distal （superior orbital fissure） ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that the regenerating nerve fibers following oculomotor nerve injury in the superior orbital fissure had a high level of specificity for innervating extraocular muscles. The level of functional recovery of extraocular muscles in rats in the superior orbital fissure injury group was remarkably superior over that in rats undergoing oculomotor nerve injuries at the proximal end （subtentorium）. Horseradish peroxidase retrograde tracing through the right superior rectus muscle showed that the distribution of neurons in the nucleus of the oculomotor nerve was directly associated with the injury site, and that crude fibers were badly damaged. The closer the site of injury of the oculomotor nerve was to the extraocular muscle, the better the recovery of neurological function was. The mechanism may be associated with the aberrant number of regenerated nerve fibers passing through the injury site.
文摘The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes.The experimental rabbits were killed after 6,8,10, 12weeks.Corneal innervation was studied by histochemical techniques and transimission electron microscopy.The results revealed that in diabetic rabbits,from 6 weeks,the density of nerve-nets was markedly sparser,the fibers were thinner and the activity of nerves was lower than those of the control group.Ultrastructural changes showed swelling of axons,irregular distribution of fibril and degeneration of mitochondria of varying degree.With the progress of disease the above changes were becoming more marked gradually.It may be assumed that these changes are related to hyperglycemia.
文摘Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.
文摘Background: Altered myocardial sympathetic innervation activity (AMSI) is known to be present in systolic heart failure patients (SHF) and recently SPECT imaging using I-123 mIBG heart to mediastinum (H/M) ratio <1.6 has been shown to predict MACE in the ADMIRE-HF trial. Left ventricular mechanical dyssynchrony (LVMD) is known to be present in a substantial number of SHF patients and has been studied mainly to guide CRT therapy. Recently gated SPECT has shown promise to provide an accurate assessment of LVMD. It remains unclear how the combination of AMSI and LVMD collectively affect clinical outcomes and other cardiovascular parameters. Objectives: The objectives are to examine the clinical characteristics and incremental prognostic value for MACE of LVMD determined by SPECT in SHF patients with or without abnormal cardiac MIBG uptake (H/M ratio < 1.6). Methods: Out of 30 SHF patients who participated from our institution in the ADMIRE-HF trial studying MIBG based AMSI, we included 22 patients with abnormal MIBG H/M ratio of <1.6. We performed gated SPECT LVMD analysis on these patients using the Emory Cardiac Toolbox. The 2 SPECT variables for LVMD assessed were histogram bandwidth and phase standard deviation both of which assess the extent of dispersion of LV activation during contraction as a marker of LVMD. Patients were followed up for a mean period of 6 years. The primary end point was mortality from any cause and secondary end point was heart failure admission or myocardial infarction or ICD shock. Results: 2 Groups were defined: Group A: n = 17 with H/M MIBG ratio < 1.6 and +LVMD and Group B, n = 5 H/M MIBG ratio −LVMD. Baseline characteristics, cardiac risk factors and medications were comparable between both groups. LVEF was lower and RBBB was less common in Group A. There was no statistical difference in achievement of primary or secondary end points in the two groups including death heart failure readmissions, ICD shocks or MI. Conclusions: In our pilot study, we did not find definitive value of adding SPECT based LVMD to abnormal cardiac MIBG imaging in SHF patients with regards to predicting outcomes. Although our sample size is too small to make any definitive conclusions, it is possible that LVMD works independently through different pathways in the progression of SHF and hence may not necessarily add incremental value to AMSI determination using MIBG.
基金Grant Agency of Masaryk University,Grant/Award Number:MUNI/11/SUP/01/2020 and MUNI/A/1457/2021。
文摘Background:Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation.Although dual innervation approaches using two neurotizers have shown promise,there is a lack of evidence-based comparison in the literature.Furthermore,no animal model of dual reinnervation has yet been published.This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats.Methods:Fifteen Wistar rats were divided into four experimental groups and one control group.The sural nerve was exposed and used as a cross-face nerve graft(CFNG),which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead.The CFNG,the masseteric nerve(MN),and the recipient nerve were coapted in one or two stages.The length and width of the utilized structures were measured under an operating microscope.Return of whisker motion was visually confirmed.Results:Nine out of the eleven rats that underwent surgery survived the procedure.Whisker motion was observed in all experimental animals,indicating successful reinnervation.The mean duration of the surgical procedures did not differ significantly between the experimental groups,ensuring similar conditions for all groups.Conclusions:Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible,with a high success rate,and shows good prospects for future experiments.
基金supported by the National Natural Science Foundation of China(No.72441022)the Tsinghua University Initiative Scientific Research Program of Precision Medicine(No.2022ZLA001)。
文摘Objective:This study aimed to describe the updated disease burden and temporal trends of stomach cancer(SC)and colorectal cancer(CRC),and to explore potential influence factors of the two cancers in the Western Pacific region(WPR).Methods:Estimates of incidence,deaths,and disability-adjusted life years(DALYs)for SC and CRC were obtained from the Global Burden of Disease Study 2021.Trends in age-standardized incidence rates(ASIR),agestandardized mortality rates(ASMR),and age-standardized DALY rates(ASDR)were assessed.A decomposition analysis was conducted to quantify the role of three factors(i.e.,population aging,population growth,and epidemiological change)driving DALY changes between 2000 and 2021.Pearson correlation analysis was used to examine the association between cancer burden and Socio-demographic Index(SDI)at the national level in 2021.Results:In 2021,the WPR accounted for 61.77%of global incident SC cases and 43.07%of global incident CRC cases.From 2000 to 2021,the ASIR,ASMR,and ASDR of SC and the ASMR and ASDR of CRC decreased,whereas the ASIR of CRC increased by an average of 1.32%per year.Among the 31 WPR countries and territories,China had the highest number of incident cases,deaths,and DALYs for both cancers in 2021.Epidemiology change was the primary driver to the reduction of DALYs for SC,while population aging and population growth contributed to the increase of DALYs for CRC.Additionally,ASMR(r=-0.37,P=0.041)and ASDR(r=-0.43,P=0.016)of SC were negatively correlated with SDI in 2021,whereas positive correlations were observed between SDI and ASIR(r=0.74,P<0.001),ASMR(r=0.47,P=0.008),and ASDR(r=0.36,P=0.044)for CRC.Conclusions:SC and CRC continue to pose considerable public health threats in the WPR.Targeted prevention and control strategies should be prioritized,particularly in high-burden and resource-limited countries.
基金Supported by Special Fund for the Beijing Hope Marathon of the China Cancer Foundation,No.LC2019 L05and the Capital Health Development Research Special Fund Project,No.2024-2-4026.
文摘BACKGROUND Gastric cancer(GC)is a major global health challenge,and the treatment of proximal GC in particular presents unique clinical and surgical complexities.Currently,there is no consensus on whether proximal gastrectomy(PG)or total gastrectomy(TG)should be used for advanced proximal GC,and the choice of postoperative gastrointestinal reconstruction method remains controversial.AIM To compare the short-term efficacy,long-term survival,and postoperative reflux outcomes of PG with tubular stomach reconstruction vs TG with Roux-en-Y re-construction in patients with proximal GC following neoadjuvant chemotherapy(NACT)in an effort to provide valuable insights for clinical decision-making regarding the optimal surgical approach.METHODS A multicenter retrospective cohort study was conducted at two Chinese medical centers between December,2012 and December,2022.Patients with histologically confirmed proximal GC who received NACT followed by either PG with tubular stomach reconstruction or TG with Roux-en-Y reconstruction were included.Propensity score matching(PSM)was performed to balance baseline characteristics,and the primary endpoint was 5-year overall survival(OS).Se-condary endpoints included recurrence-free survival(RFS),postoperative complications,and reflux severity.RESULTS After PSM,244 patients(122 PG,122 TG)were finally included and all baseline characteristics were comparable between groups.The PG group had a significantly shorter operation time compared to the TG group(189.50 vs 215.00 minutes,P<0.001),with no differences in intraoperative blood loss or postoperative complications(19.68%vs 14.75%,P=0.792).The 5-year OS rates were 52.7%vs 45.5%(P=0.330),and 5-year RFS rates were 54.3%vs 47.6%(P=0.356)for the PG and TG groups,respectively.Reflux symptoms(18.0%vs 31.1%,P=0.017)and clinically significant reflux based on gastroesophageal reflux disease questionnaire scores≥8(7.4%vs 21.3%,P<0.001)were significantly less frequent in the PG group.Multivariate analysis identified histological differentiation(HR=2.98,95%CI:2.03-4.36,P<0.001)and tumor size(HR=0.26,95%CI:0.17-0.41 for tumors≤4 cm,P<0.001)as independent prognostic factors.CONCLUSION PG with tubular stomach reconstruction is comparable to TG in terms of surgical safety and long-term oncological outcomes for proximal GC patients following NACT.Additionally,PG has the advantages of shorter operation time and lower rates of postoperative reflux,suggesting potential benefits for patient quality of life.Notably,the analysis of postoperative prognostic factors,including histological differentiation and tumor size,further informs clinical decision-making and highlights the importance of individualized treatment strategies.
基金supported by a grant from Guangdong Provincial Natural Science Foundation of China(2023A15115012665).
文摘Disseminated mucormycosis is a life-threatening fungal infection with high mortality,particularly in immunocompromised patients.Early diagnosis and prompt intervention are crutial but often delayed due to nonspecific presentations.Many studies have highlighted the challenges in emergency settings,where atypical symptoms may lead to misdiagnosis.We report a rare case of disseminated mucormycosis originating from the stomach in a pregnancy-induced thrombocytopenia(PITP)patient,emphasizing rapid gastroscopy examination,histopathological confi rmation,multidisciplinary management,and high-risk factors for hospital-acquired gastrointestinal mucormycosis infection.
