Clinicopathological analysis of metaplastic meningioma: report of 15 cases in Huashan Hospital

Objective： Metaplastic meningioma is a rare subtype of benign meningiomas, classified as WHO grade I with well prognosis. Here we presented our experiences on 15 cases of metaplastic meningioma, to investigate the clinicopathological features, therapies and prognosis of these cases. Methods： 15 patients underwent surgical treatment for intracranial metaplastic meningioma between 2001 and 2010 at Neurosurgery Department of Huashan Hospital, Shanghai, China. The clinical data, radiological manifestation, treatment strategy, pathological findings and prognosis of all patients were analyzed retrospectively. Results： Among the 15 cases （10 males and 5 females）, the age ranged from 22 to 74 years old （the mean age was 50.67-year old）. The clinical manifestations include headache, dizziness, seizure attack, vision decrease, and weakness of bilateral lower limbs. All the patients received surgical treatment, combined with radiotherapy in some cases. In the follow-up period, recurrence occurred in 2 cases, of which 1 patient died of other system complications. Conclusions： Metaplastic meningiomas are characterized by focal or widespread mesenchymal differentiation with formation of bone, cartilage, fat, and xanthomatous tissue elements. Surgical removal is the optimal therapy, and the overall prognosis is well. But recurrence may occur in some cases, thus radiotherapy is necessary for such kind of patients.

Clinical experience of 3T intraoperative magnetic resonance imaging integrated neurosurgical suite in Shanghai Huashan Hospital

Background Intraoperative magnetic resonance imaging （iMRI） dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI （〈1.0T）. This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital, Shanghai, China. Methods From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency. Results All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas （n=161） was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients （12.42%） suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients （3.16%）. Twenty-one of 161 patients （13.04%） had early speech deficit and late speech deficit was only observed in six of 158 patients （3.80%）. The ratio of gross total resection for pituitary adenomas （n=49） was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy. Conclusion The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.

Evaluation of retinal and choroidal thickness changes in overweight and obese adults without ocular symptoms by swept-source optical coherence tomography

AIM:To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography(SS-OCT).METHODS:According to the body mass index(BMI)results,the adults enrolled in the cross-sectional study were divided into the normal group(18.50≤BMI<25.00 kg/m^(2)),the overweight group(25.00≤BMI<30.00 kg/m^(2)),and the obesity group(BMI≥30.00 kg/m^(2)).The one-way ANOVA and the Chi-square test were used for comparisons.Pearson’s correlation analysis was used to evaluate the relationships between the measured variables.RESULTS:This research covered the left eyes of 3 groups of 434 age-and sex-matched subjects each:normal,overweight,and obesity.The mean BMI was 22.20±1.67,26.82±1.38,and 32.21±2.35 kg/m^(2) in normal,overweight and obesity groups,respectively.The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group(P<0.05 for all),while the retinal thickness of the three groups did not differ significantly.Pearson’s correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness,but no significant correlation was observed between BMI and retinal thickness.CONCLUSION:Choroidal thickness is decreased in people with overweight or obesity.Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.

Unraveling the enigma:A comprehensive review of solid pseudopapillary tumor of the pancreas

Solid pseudopapillary tumor of the pancreas(SPTP)is a rare neoplasm predom-inantly observed in young females.Pathologically,CTNNB1 mutations,β-catenin nuclear accumulation,and subsequent Wnt-signaling pathway activation are the leading molecular features.Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies.Surgical resection remains the mainstay treatment.Risk models,such as the Fudan Prognostic Index,show promise as predictive tools for assessing the prognosis of SPTP.Establishing three types of metachronous liver metastasis can be beneficial in tailoring individu-alized treatment and follow-up strategies.Despite advancements,challenges persist in understanding its etiology,establishing standardized treatments for unresectable or metastatic diseases,and developing a widely recognized grading system.This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology,clinical presentation,pathology,molecular characteristics,diagnostic methods,treatment options,and prognostic factors.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure:A multicenter study

BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Mechanism underlying the effects of exercise against type 2 diabetes:A review on research progress

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes(T2D)in certain nations.The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D.The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D,in addition to identify the limitations of the existing literature,thereby provide direction for future research in this field.

Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model

The rate of retear after surgical repair remains high.Mesenchymal stem cells(MSCs)have been extensively employed in regenerative medicine for several decades.However,safety and ethical concerns constrain their clinical application.Tendon Stem/Progenitor Cells(TSPCs)-derived exosomes have emerged as promising cellfree therapeutic agents.Therefore,urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms.In this study,TSPC-Exos were found to promote the proliferation,migration,and expression of fibrogenesis markers in BMSCs.Furthermore,TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization.In a rat model of rotator cuff repair,TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface,the biomechanical properties of the repaired tendon,and the function of the joint.Mechanistically,TSPC-Exos exhibited high expression of miR-21a-5p,which regulated the expression of PDCD4.The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation,migration,and fibrogenesis in BMSCs.This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies,potentially benefiting patients with rotator cuff tear in the future.

Optimizing prediction models for pancreatic fistula after pancreatectomy:Current status and future perspectives

Postoperative pancreatic fistula(POPF)is a frequent complication after pancre-atectomy,leading to increased morbidity and mortality.Optimizing prediction models for POPF has emerged as a critical focus in surgical research.Although over sixty models following pancreaticoduodenectomy,predominantly reliant on a variety of clinical,surgical,and radiological parameters,have been documented,their predictive accuracy remains suboptimal in external validation and across diverse populations.As models after distal pancreatectomy continue to be pro-gressively reported,their external validation is eagerly anticipated.Conversely,POPF prediction after central pancreatectomy is in its nascent stage,warranting urgent need for further development and validation.The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance.Moreover,there is potential for the development of personalized prediction models based on patient-or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF.In the future,prospective multicenter studies and the integration of novel imaging technologies,such as artificial intelligence-based radiomics,may further refine predictive models.Addressing these issues is anticipated to revolutionize risk stratification,clinical decision-making,and postoperative management in patients undergoing pancre-atectomy.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in 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.

Epidemiology of insertional and midportion Achilles tendinopathy in runners:A prospective cohort study

Background:Achilles tendinopathy(AT)is a common problem among runners.There is only limited evidence for risk factors for AT,and most studies have not defined the AT subcategories.No study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered distinct.This study aimed to assess incidence and risk factors of AT based on data from a large prospective cohort.The secondary aim was to explore differences in risk factors between insertional and midportion AT.Methods:Participants were recruited from among registered runners at registration for running events.Questionnaires were completed at baseline,1 month before the event,1 week before the event,and 1 month after the event.Information concerning demographics,training load,registered events,and running-related injuries were collected at baseline.The follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional AT.The primary outcome was the incidence of AT.Multivariable logistic regression analysis was applied to identify risk factors for the onset.Results:We included 3379 participants with a mean follow-up of 20.4 weeks.The incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion AT.Men had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.94-1.00).Conclusion:The incidence of new-onset AT among recreational runners was 4.2%.The proportion of insertional and midportion AT was 27.7%and 63.8%,respectively.AT in the past 12 months was the predominant risk factor for the onset of AT.Risk factors varied between insertional and midportion AT,but we could not identify clinically relevant differences between the 2 subtypes.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.

Recurrence scoring system predicting early recurrence for patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy and portomesenteric vein resection

BACKGROUND Pancreatectomy with concomitant portomesenteric vein resection(PVR)enables patients with portomesenteric vein(PV)involvement to achieve radical resection of pancreatic ductal adenocarcinoma,however,early recurrence(ER)is frequently observed.AIM To predict ER and identify patients at high risk of ER for individualized therapy.METHODS Totally 238 patients undergoing pancreatectomy and PVR were retrospectively enrolled and were allocated to the training or validating cohort.Univariate Cox and LASSO regression analyses were performed to construct serum recurrence score(SRS)based on 26 serum-derived parameters.Uni-and multivariate Cox regression analyses of SRS and 18 clinicopathological variables were performed to establish a Nomogram.Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy.Survival analysis was performed using Kaplan-Meier method and log-rank test.RESULTS Independent serum-derived recurrence-relevant factors of LASSO regression model,including postoperative carbohydrate antigen 19-9,postoperative carcinoembryonic antigen,postoperative carbohydrate antigen 125,preoperative albumin(ALB),preoperative platelet to ALB ratio,and postoperative platelets to lymphocytes ratio,were used to construct SRS[area under the curve(AUC):0.855,95%CI:0.786–0.924].Independent risk factors of recurrence,including SRS[hazard ratio(HR):1.688,95%CI:1.075-2.652],pain(HR:1.653,95%CI:1.052-2.598),perineural invasion(HR:2.070,95%CI:0.827-5.182),and PV invasion(HR:1.603,95%CI:1.063-2.417),were used to establish the recurrence nomogram(AUC:0.869,95%CI:0.803-0.934).Patients with either SRS>0.53 or recurrence nomogram score>4.23 were considered at high risk for ER,and had poor long-term outcomes.CONCLUSION The recurrence scoring system unique for pancreatectomy and PVR,will help clinicians in predicting recurrence efficiently and identifying patients at high risk of ER for individualized therapy.

Bone marrow edema in a postpartum female following ankle sprain: a case report

Bone marrow edema(BME)is characterized by an accumulation of interstitial fluid within the bone marrow,the cancellous,hematopoietic compartment within bones.[1]BME is divided into two principal categories:idiopathic or primary BME,with an unknown etiology,and secondary BME,which occurs as a result of an identifiable underlying pathology.[2]Although the prevalence of BME is not limited to specific demographic parameters,it shows a predilection for males or individuals assigned male at birth,predominantly aged between the ages of 30 and 60 years,especially in cases of bone marrow edema syndrome(BMES),a rare idiopathic variant.[3]The etiological spectrum of BME is diverse,including oncological entities(such as acute myeloid leukemia and osteosarcoma),degenerative diseases(such as osteoarthritis),infectious processes(osteomyelitis),ischemic conditions(avascular necrosis),metabolic dysfunctions(osteoporosis),inflammatory disorders(rheumatoid arthritis),and traumatic injuries(such as stress fractures).[1,2]Clinically,BME primarily manifests as localized pain,often accompanied by joint effusion and warmth near the affected joint.Diagnostic protocols typically include physical examination,serological assays,bone marrow biopsies,dual-energy X-ray absorptiometry(DEXA)scans,magnetic resonance imaging(MRI),and ultrasonography,with computed tomography(CT)scans and radiographs being less effective.

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Lactiplantibacillus plantarum AR113 alleviates microbiota dysbiosis of tongue coating and cerebral ischemia/reperfusion injury in rat

Stroke is one of the leading causes of death and disability worldwide.However,information on stroke-related tongue coating microbiome(TCM)is limited,and whether TCM modulation could benefit for stroke prevention and rehabilitation is unknown.Here,TCM from stroke patients(SP)was characterized using molecular techniques.The occurrence of stroke resulted in TCM dysbiosis with significantly reduced species richness and diversity.The abundance of Prevotella,Leptotrichia,Actinomyces,Alloprevotella,Haemophilus,and TM7_[G-1]were greatly reduced,but common infection Streptococcus and Pseudomonas were remarkably increased.Furthermore,an antioxidative probiotic Lactiplantibacillus plantarum AR113 was used for TCM intervention in stroke rats with cerebral ischemia/reperfusion(I/R).AR113 partly restored I/R induced change of TCM and gut microbiota with significantly improved neurological deficit,relieved histopathologic change,increased activities of antioxidant enzymes,and decreased contents of oxidative stress biomarkers.Moreover,the gene expression of antioxidant-related proteins and apoptosis-related factors heme oxygenase-1(HO-1),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),nuclear factor erythroid 2-related factor 2(Nrf2),NAD(P)H:quinone oxidoreductase-1(NQO-1),and Bcl-2 was significantly increased,but cytochrome C,cleaved caspase-3,and Bax were markedly decreased in the brain by AR113 treatment.The results suggested that AR113 could ameliorate cerebral I/R injury through antioxidation and anti-apoptosis pathways,and AR113 intervention of TCM may have the application potential for stroke prevention and control.

Prediction of single cell mechanical properties in microchannels based on deep learning

Traditional methods for measuring single-cell mechanical characteristics face several challenges,including lengthy measurement times,low throughput,and a requirement for advanced technical skills.To overcome these challenges,a novel machine learning(ML)approach is implemented based on the convolutional neural networks(CNNs),aiming at predicting cells'elastic modulus and constitutive equations from their deformations while passing through micro-constriction channels.In the present study,the computational fluid dynamics technology is used to generate a dataset within the range of the cell elastic modulus,incorporating three widely-used constitutive models that characterize the cellular mechanical behavior,i.e.,the Mooney-Rivlin(M-R),Neo-Hookean(N-H),and Kelvin-Voigt(K-V)models.Utilizing this dataset,a multi-input convolutional neural network(MI-CNN)algorithm is developed by incorporating cellular deformation data as well as the time and positional information.This approach accurately predicts the cell elastic modulus,with a coefficient of determination R^(2)of 0.999,a root mean square error of 0.218,and a mean absolute percentage error of 1.089%.The model consistently achieves high-precision predictions of the cellular elastic modulus with a maximum R^(2)of 0.99,even when the stochastic noise is added to the simulated data.One significant feature of the present model is that it has the ability to effectively classify the three types of constitutive equations we applied.The model accurately and reliably predicts single-cell mechanical properties,showcasing a robust ability to generalize.We demonstrate that incorporating deformation features at multiple time points can enhance the algorithm's accuracy and generalization.This algorithm presents a possibility for high-throughput,highly automated,real-time,and precise characterization of single-cell mechanical properties.

Impact of Air Pollutants on Lung Function and Inflammatory Response in Asthma in Shanghai

Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study monitored 27 asthma outpatients for a year,collecting data on weather,patient self-management[daily asthma diary,peak expiratory flow(PEF)monitoring,medication usage],spirometry and serum markers.To explore the potential mechanisms of any effects,asthmatic mice induced by ovalbumin(OVA)were exposed to PM_(2.5).Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma.Acute exposure showed a correlation between PEF and levels of ozone(O_(3))and nitrogen dioxide(NO_(2)).Chronic exposure indicated that interleukin-5(IL-5)and interleukin-13(IL-13)levels correlated with PM_(2.5)and PM_(10)concentrations.In asthmatic mouse models,exposure to PM_(2.5)increased cytokine levels and worsened lung function.Additionally,PM_(2.5)exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways.Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation.Specifically,PM_(2.5)significantly contributes to these adverse effects.Further research is needed to elucidate the mechanisms by which PM_(2.5)impacts asthma.