Vibration-reduced anxiety-like behavior relies on ameliorating abnormalities of the somatosensory cortex and medial prefrontal cortex

Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder

Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

Association between abnormal default mode network homogeneity and sleep disturbances in major depressive disorder

Background Sleep disturbance is a common comorbidity of major depressive disorder(MDD).However,network homogeneity(NH)changes of the default mode network(DMN)in MDD with sleep disturbances are unclear.Aims The purpose of this study was to probe the abnormal NH in the DMN in MDD with sleep disturbances and to reveal the differences between MDD with or without sleep disturbances.Methods Twenty-four patients with MDD and sleep disturbances(Pa_s),33 patients with MDD without sleep disturbances(Pa_ns)and 32 healthy controls(HCs)were recruited in this study.Resting-state functional imaging data were analysed using NH.Results Compared with Pa_ns and HCs,Pa_s showed decreased NH in the left superior medial prefrontal cortex and increased NH in the right precuneus.There was a negative correlation between NH in the left superior medial prefrontal cortex and sleep disturbances(r=−0.42,p=0.001)as well as a positive correlation between NH in the right precuneus and sleep disturbances(r=0.41,p=0.002)in patients with MDD.Conclusions MDD with sleep disturbances is associated with abnormal NH in the DMN,which could differentiate pa_s from pa_ns.The DMN may play a crucial role in the neurobiological mechanisms of MDD with sleep disturbances.

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.

Science, History, Fiction: The Facetious Mediality of Lu Xun's Old Stories Retold

This paper examines the performance significance of Lu Xun's historical short stories collected in Gushi xinbian(Old stories retold,1936)by focusing on the mediality of his idiosyncratic writing,which he himself called"facetious."It revisits the young Lu Xun's uneasy en gageme nt with medical science as student documented in his lecture notebooks bearing corrections by his teacher as well as his early essays?This provides an analytical framework for discussing the stakes of his historical fiction as a critique of the discourse of scientific historiography which was increasingly gaining currency in May Fourth China.Lu Xun's historical fiction is conspicuously not meant to function as a stable medium between the past and the present but betrays its opaque and even arbitrary mediality,which disrupts identity in historical representation and thus critiqques ideological,"cultural"power inherent in scientific discourse that tries to establish that identity.The paper then reads Gushi xinbian as attempts at recovering history from such power and envisioning new possibilities of historical transmission in the midst of an aporetic search of a prehistory of Chinese modernity—attempts hinged on anachronistic textual moments whose meanings circulate in defiance of any identity of time with itself,thereby bespeaking an alternative power to"make"history.

Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.

Epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study

BACKGROUND Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types:Supracondylar(SC),lateral condyle(LC),and medial epicondyle(ME)fractures.AIM To evaluate the epidemiology of pediatric distal humerus fractures(SC,LC,and ME)from an American insurance claims database.METHODS A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC,LC and ME fractures based on the IBM Truven MarketScan®Commercial and IBM Truven MarketScan Medicare Supplemental databases.Patients from 2015 to 2020 were queried for treatments,patient age,sex,length of hospitalization,and comorbidities.RESULTS A total of 1133 SC,154 LC,and 124 ME fractures were identified.SC fractures had the highest percentage of operation at 83%,followed by LC(78%)and ME fractures(41%).Male patients were,on average,older than female patients for both SC and ME fractures.CONCLUSION In the insurance claims databases used,SC fractures were the most reported,followed by LC fractures,and finally ME fractures.Age was identified to be a factor for how a pediatric distal humerus fractures,with patients with SC and LC fractures being younger than those with ME fractures.The peak age per injury per sex was similar to reported historic central tendencies,despite reported trends for younger physiologic development.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood

The molecular pathology of stress-related disorders remains elusive.Our brain multiregion,multiomic study of posttraumatic stress disorder(PTSD)and major depressive disorder(MDD)included the central nucleus of the amygdala,hippocampal dentate gyrus,and medial prefrontal cortex(mPFC).Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.Pathways pointed to immune function,neuronal and synaptic regulation,and stress hormones.Multiomic factor and gene network analyses provided the underlying genomic structure.

Media, Mediation, and Transmediality: The Multivalence of "Storyworlds" in 20^th Century China

In media studies,the term transmediality is frequently used to mark the huge success of cross-platform franchises such as Batman,Star War,The Lord of the Rings,and Tombs Raiders.1 The term underscores the signifycance of a new phenomenon in our internet and smart-phone world where a story can be seamlessly relaunched in different media platforms to create a"media ecology"to attract maximum viewers,subscription and sponsorship.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Unhappy triad of the knee:What are the current concepts and opinions?

The association between injuries to the anterior cruciate ligament,medial collateral ligament,and medial meniscus(MM)has been known to orthopedic surgeons since 1936;O’Donoghue first used the term"unhappy triad"of the knee to describe this condition in 1950.Later studies revealed that involvement of the lateral meniscus is more common than MM in these cases,leading to a change in the definition.Recent studies have revealed that this triad may be primarily linked to knee anterolateral complex injuries.Although there is not a definite management protocol for this triad,we try to mention the most recent concepts about it in addition to expert opinions.

Deep magnetic stimulation targeting the medial prefrontal and anterior cingulate cortices for methamphetamine use disorder:a randomised,double-blind,sham-controlled study

Craving is a key component of substance use disorders(SUDs).1 In recent decades,repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising treatment for individuals with SUDs by reducing their drug cravings and drug-associated cues,including methamphetamine,heroin,cocaine,nicotine and alcohol.2–7 Recently,the transdiagnostic consistency of the medial prefrontal cortex(MPFC)8 and anterior cingulate cortex(ACC)9 as neural substrates underlying cue reactivity was proposed.

Mechanism of hepatocytes differentiation and dedifferentiation in liver regeneration:Process and exploration

The liver has roles in many processes,including metabolism,synthesis,and biotransformation.It is unique among all visceral organs,as it even can regenerate after injury.A common research model of liver regeneration is the 2/3 partial hepatectomy(PHx)model in animals,like rodents,in which the left lateral,left medial,and right medial hepatic lobes are surgically removed[1].More-over,with the ability of hepatocyte hypertrophy and hyperplasia,within 7-10 days,the rest liver regenerates to its original size[2].Jo and colleagues[3]reported that splanchnic vasoactive agents could decrease portal vein pressure to facilitate the liver regenera-tion after 70%hepatectomy.However,liver regeneration and func-tion maintenance need adequate mass of future remnant liver.In-adequate mass of future remnant liver results in liver failure which loses the opportunity for the liver to regenerate and therefore,it is important to keep an adequate future remnant liver to avoid post-hepatectomy liver failure[4].

Combined medial patellofemoral ligament and medial patellotibial ligament reconstruction in recurrent patellar instability:A systematic review and meta-analysis

BACKGROUND The medial patellofemoral ligament(MPFL),along with the medial patellotibial ligament(MPTL)and medial patellomeniscal ligament,aid in the stabilization of the patellofemoral joint.Although the MPFL is the primary stabilizer and the MPTL is a secondary limiter,this ligament is critical in maintaining joint stability.There have been few studies on the combined MPFL and MPTL reconstruction and its benefits.AIM To look into the outcomes of combined MPFL and MPTL reconstruction in frequent patellar instability.METHODS By May 8,2022,four electronic databases were searched:Medline(PubMed),Scopus,Web of Science,and Google Scholar.General keywords such as"patellar instability,""patellar dislocation,""MPFL,""medial patellofemoral ligament,""MPTL,"and"medial patellotibial ligament"were co-searched to increase the sensitivity of the search.RESULTS The pooled effects of combined MPFL and MPTL reconstruction for Kujala score(12-mo followup)and Kujala score(24-mo follow-up)were positive and incremental,according to the findings of this meta-analysis.The mean difference between the Cincinnati scores was also positive,but not statistically significant.The combination of the two surgeries reduces pain.According to cumulative meta-analysis,the trend of pain reduction in various studies is declining over time.CONCLUSION The combined MPFL and MPTL reconstruction has good clinical results in knee function and,in addition to providing good control to maintain patellofemoral joint balance,the patient's pain level decreases over time,making it a valid surgical method for patella stabilization.

Treatment of proximal humeral fractures accompanied by medial calcar fractures using fibular autografts:A retrospective,comparative cohort study

BACKGROUND Severe proximal humerus comminuted fractures are often accompanied by medial calcar comminuted fractures and loss of medial support,which are important factors that lead to internal fixation failure.The appropriate treatment for proximal humerus comminuted fractures has not been established.Therefore,this study assessed the outcomes of using a fibular autograft with locking plates to treat severe proximal humerus comminuted fractures.AIM To investigate the outcomes of using a fibular autograft with locking plates to treat severe proximal humerus comminuted fractures.METHODS This retrospective,comparative cohort study included two groups of patients.Group 1 comprised 22 patients and group 2 comprised 25 patients with complete follow-up data.Group 1 was treated with a fibular autograft with open reduction and locking plates to enable internal fixation.Group 2 was treated with open reduction and locking plates to enable internal fixation.The intraoperative blood loss volume from the shoulder wound,operative time,shoulder wound pain,bone fracture healing time,Constant-Murley score of the shoulder joint,preoperative Holden walking function score,Mallet score of the shoulder joint,and humeral neck-shaft angle during surgery of the two groups were compared,and the differences were analysed using an independent sample t-test.RESULTS Group 1 had a shorter mean operative time than group 2(2.25±0.30 h vs 2.76±0.44 h;P=0.000).Group 1 had a lower shoulder wound pain score on the first day after surgery than group 2(7.91±1.15 points vs 8.56±1.00 points;P=0.044).Group 1 had a shorter fracture healing time than group 2(2.68±0.48 mo vs 3.64±0.64 mo;P=0.000).Group 1 had higher Constant-Murley scores of the shoulder joint at 3,6,and 12 mo after surgery than group 2(76.64±4.02 points vs 72.72±3.02 points,86.36±3.53 points vs 82.96±3.40 points,and 87.95±2.77 points vs 84.68±2.63 points,respectively;P=0.000,0.002,and 0.000,respectively).Group 1 had higher Mallet scores of the shoulder joint at 3,6,and 12 mo after surgery than group 2(10.32±0.57 points vs 9.96±0.54 points,13.36±1.00 points vs 12.60±0.87 points,and 13.91±0.75 points vs 13.36±0.70 points,respectively;P=0.032,0.007,and 0.013,respectively).CONCLUSION Using locking plates with a fibular autograft can recreate medial support,facilitate fracture healing,and improve shoulder function;therefore,this may be an effective treatment option for severe proximal humerus comminuted fractures.

Assessment of Calf Skeletal Muscle Stiffness in Diabetic Nephropathy Patients with Medial Tibial Stress Syndrome by Two-Dimensional Shear Wave Elastography

Objective:To explore the feasibility of two-dimensional shear wave elastography in evaluating calf skeletal muscle stiffness in diabetic nephropathy patients with medial tibial stress syndrome.Methods:A total of 48 diabetic nephropathy patients with medial tibial stress syndrome from January 2020 to December 2022 were included as the study group,and 48 patients with diabetic nephropathy during the same period were included as the control group.Both groups were detected by two-dimensional shear wave elastography with ultrasonic equipment,and Young‘s modulus of the tibialis anterior muscle,tibialis posterior muscle,and gastrocnemius muscle were observed and analyzed in the two groups.Results:The Young‘s modulus values of tibialis anterior muscle,tibialis posterior muscle,and gastrocnemius muscle in the study group were significantly lower than those in the control group(P<0.05).Conclusion:Two-dimensional shear wave elastography is feasible for the evaluation of calf skeletal muscle stiffness in diabetic nephropathy patients with medial tibial stress syndrome,and has high accuracy and repeatability.This technique can be used to diagnose,treat and monitor muscle lesions in patients with diabetic nephropathy,and can also be used to assess muscle fatigue and exercise capacity,which has broad application prospects.

The selective 5-HTIA receptor antagonist WAY-100635 inhibits neuronal activity of the ventromedial prefrontal cortex in a rodent model of Parkinson's disease

Objective The ventral part of the medial prefrontal cortex（mPFC）plays an important role in initiation and control of voluntary movement,mood and cognition.However,after the degeneration of the nigrostriatal pathway,the neuronal activity of the ventral mPFC and the role of serotonin1A（5-hydroxytryptamine,5-HT1A）receptors in the firing of the neurons are still unknown.The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT1Areceptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine（6-OHDA）-lesioned rats.Methods Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesiond rats in vivo.Results 6-OHDA lesion of the substantia nigra pars compacta（SNc）significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats.Systemic administration of WAY-100635（0.1 mg/kg,i.v.）did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats.In contrast,WAY-100635 signifi- cantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.Conclusion These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT1Areceptor.