Effect of remimazolam vs. propofol on hemodynamics during general anesthesia induction in elderly patients: Single-center, randomized controlled trial

The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in the propofol group(group P)or remimazolam at a rate of 6 mg/(kg·h)in the remimazolam group(group R)for the induction.A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug.We measured when patients entered the operating room(T_(0)),when the induction was successful(T_(1)),and when before(T_(2))and 5 min after successful endotracheal intubation(T_(3)).We found that mean arterial pressure(MAP)was lower at T_(1–3),compared with T_(0) in both groups,but higher at T_(2) in the group R,whileΔMAP_(T0–T2) andΔMAP_(max) were smaller in the group R(ΔMAP_(T0–T2):the difference between MAP at time point T_(0) and T_(2),ΔMAP_(max):the difference between MAP at time point T_(0) and the lowest value from T_(0) to T_(3)).Cardiac index and stroke volume index did not differ between groups,whereas systemic vascular resistance index was higher at T_(1–3) in the group R.These findings show that remimazolam,compared with propofol,better maintains hemodynamic stability during the induction,which may be attributed to its ability to better maintain systemic vascular resistance levels.

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

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.

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.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

Safety and effectiveness of butorphanol in epidural labor analgesia:A protocol for a systematic review and meta-analysis

BACKGROUND Epidural analgesia is the most effective analgesic method during labor.Butorphanol administered epidurally has been shown to be a successful analgesic method during labor.However,no comprehensive study has examined the safety and efficacy of using butorphanol as an epidural analgesic during labor.AIM To assess butorphanol's safety and efficacy for epidural labor analgesia.METHODS The PubMed,Cochrane Library,EMBASE,Web of Science,China National Knowledge Infrastructure,and Google Scholar databases will be searched from inception.Other types of literature,such as conference abstracts and references to pertinent reviews,will also be reviewed.We will include randomized controlled trials comparing butorphanol with other opioids combined with local anesthetics for epidural analgesia during labor.There will be no language restrictions.The primary outcomes will include the visual analog scale score for the first stage of labor,fetal effects,and Apgar score.Two independent reviewers will evaluate the full texts,extract data,and assess the risk of bias.Publication bias will be evaluated using Egger's or Begg's tests as well as visual analysis of a funnel plot,and heterogeneity will be evaluated using the Cochran Q test,P values,and I2 values.Meta-analysis,subgroup analysis,and sensitivity analysis will be performed using RevMan software version 5.4.This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)Protocols statement,and the PRISMA statement will be used for the systematic review.RESULTS This study provides reliable information regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.CONCLUSION To support clinical practice and development,this study provides evidence-based findings regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.

Functional dissection of parabrachial substrates in processing nociceptive information

Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.

Analgesic and anti-inflammatory activity of Cotinus coggygria Scop.extracts in vivo

Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples.Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively.“Pyruvate”“alpha-linolenic acid”and“2-oleoyl-1-palmitoy-snglycero-3-phosphocholine”are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine.Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

NECAB family of neuronal calcium-binding proteins in health and disease

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

Ultrasound-guided paravertebral nerve block anesthesia for percutaneous endoscopic laser unroofing treatment of symptomatic simple renal cysts—An innovative ambulatory surgery mode

Objective:This study was designed to evaluate the feasibility,efficacy,and safety of percutaneous ureteroscopy laser unroofing as an ambulatory surgery for symptomatic simple renal cysts under multilevel paravertebral nerve block anesthesia.Methods:From December 2015 to September 2017,33 simple renal cyst patients who had surgical indications were enrolled.Under ultrasound guidance,the T10/T11,T11/T12,and T12/L1 paravertebral spaces were identified,and 7-10 mL 0.5%ropivacaine was injected at each segment.Then a puncture needle was placed inside the cyst cavity under ultrasonic monitoring.A guidewire was introduced followed by sequential dilation up to 28/30 Fr.The extra parenchymal portion of the cyst wall was dissociated and incised using a thulium laser,and a pathological examination was performed.Results:Sensory loss to pinprick from T8 to L1 and sensory loss to ice from T6 to L2 were observed in all patients.None of the patients complained of pain during surgery.No serious complications occurred perioperatively.After the surgery,all patients recovered their lower limb muscle strength quickly,got out of bed,resumed oral feeding,and left the hospital within 24 h of admission.The pathologic diagnosis of all cyst walls was a simple renal cyst.The mean follow-up was 35.8 months.At the end of follow-up,the cyst units were reduced in size by more than 50%compared to the preoperative size,and no patient experienced a recurrence.Conclusion:Multi-level paravertebral nerve block for percutaneous ureteroscopy laser unroofing as an ambulatory surgery mode is feasible,safe,and effective for the treatment of simple renal cysts in selected patients.

Effect Analysis of WeChat Platform Combined with PBL Teaching Method for Standardized Training of Residents in Anesthesiology Department

Objective: To explore and analyze the effect of the WeChat platform combined with the PBL teaching method in the standardized training of anesthesia residents. Methods: 120 anesthesiology residents from January 2018 to the end of December 2019 were selected, and divided into a control group and an observation group of 60 each according to the time sequence of admission. The control group adopted the conventional teaching mode, and the observation group adopted the WeChat platform combined PBL teaching method. The scores of theoretical knowledge and anesthesia skills operation after training, the scores of the teaching interest survey, and the satisfaction with the teaching mode between the two groups were compared. Results: The scores of theoretical knowledge and anesthesia skills operation in the observation group were significantly higher than those in the control group, and the indicators of teaching interest in the observation group were also higher than those in the control group. The differences were statistically significant (P < 0.05). The satisfaction degree of the observation group was significantly higher than that of the control group, and the difference was also statistically significant (P < 0.05). Conclusion: The WeChat platform combined with the PBL teaching method is beneficial to improve the training effect of anesthesiology residents, stimulating autonomous learning ability, ensuring the effective practice of theoretical knowledge, and promoting them to move towards a higher standard of anesthesia skills.

Postoperative accurate pain assessment of children and artificial intelligence: A medical hypothesis and planned study

Although the pediatric perioperative pain management has been improved in recent years,the valid and reliable pain assessment tool in perioperative period of children remains a challenging task.Pediatric perioperative pain management is intractable not only because children cannot express their emotions accurately and objectively due to their inability to describe physiological characteristics of feeling which are different from those of adults,but also because there is a lack of effective and specific assessment tool for children.In addition,exposure to repeated painful stimuli early in life is known to have short and long-term adverse sequelae.The short-term sequelae can induce a series of neurological,endocrine,cardiovascular system stress related to psychological trauma,while long-term sequelae may alter brain maturation process,which can lead to impair neurodevelopmental,behavioral,and cognitive function.Children’s facial expressions largely reflect the degree of pain,which has led to the developing of a number of pain scoring tools that will help improve the quality of pain mana-gement in children if they are continually studied in depth.The artificial inte-lligence(AI)technology represented by machine learning has reached an unprecedented level in image processing of deep facial models through deep convolutional neural networks,which can effectively identify and systematically analyze various subtle features of children’s facial expressions.Based on the construction of a large database of images of facial expressions in children with perioperative pain,this study proposes to develop and apply automatic facial pain expression recognition software using AI technology.The study aims to improve the postoperative pain management for pediatric population and the short-term and long-term quality of life for pediatric patients after operational event.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients:A meta-analysis

BACKGROUND Remimazolam is characterized by rapid action and inactive metabolites.It is used as the general anesthetic for many clinical surgeries.In this study,we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients.AIM To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults.METHODS The PubMed,Web of Science,the Cochrane Library databases were queried for the relevant key words"remimazolam,""and propofol,""and gastrointestinal endoscopy or gastroscopy."The search scope was"Title and Abstract,"and the search was limited to human studies and publications in English.Seven studies wherein remimazolam and propofol were compared were included for the metaanalysis.RESULTS We selected seven randomized controlled trials involving 1445 cases for the analysis.Remimazolam reduced the hypotension(relative risk,RR=0.44,95%CI:0.29-0.66,P=0.000),respiratory depression(RR=0.46,95%CI:0.30-0.70,P=0.000),injection pain(RR=0.12,95%CI:0.05-0.25,P=0.000),bradycardia(RR=0.37,95%CI:0.24-0.58,P=0.000),and time to discharge[weighted mean difference(WMD)=-0.58,95%CI:-0.97 to-0.18,P=0.005],compared to those after propofol administration.No obvious differences were observed for postoperative nausea and vomiting(RR=1.09,95%CI:0.97-1.24,P=0.151),dizziness(RR=0.77,95%CI:0.43-1.36,P=0.361),successful sedation rate(RR=0.96,95%CI:0.93-1.00,P=0.083),or the time to become fully alert(WMD=0.00,95%CI:-1.08-1.08,P=0.998).CONCLUSION Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults.However,further studies are required to confirm these findings.

Percutaneous antegrade management of large proximal ureteral stones using non-papillary puncture

Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL.Depending on stone size,in-toto stone removal or lithotripsy using the Lithoclast®Trilogy(EMS Medical,Nyon,Switzerland)was performed.Perioperative parameters including operative time(from start of puncture to the skin suturing),stone extraction time(from the first insertion of the nephroscope to the extraction of all stone fragments),and the stone-free rate were evaluated.Results:Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi.The median age and stone size of treated patients were 58(interquartile range[IQR]:51-69)years and 19.3(IQR:18.0-22.0)mm,respectively.The median operative time and stone extraction time were 25(IQR:21-29)min and 8(IQR:7-10)min,respectively.One case(2.7%)of postoperative bleeding and two cases(5.4%)of prolonged fever were managed conservatively.The stone-free rate at a 1-month follow-up was 94.6%.Conclusion:The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter.Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.