Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Cerebral ischemia-reperfusion injury can lead to secondary brain damage through com-plex pathological processes such as ion imbalance,inflammation,mitochondrial dysfunction,oxidative stress,and increased vascular permeability,serious-ly affecting the prognosis and quality of life of isch-emic stroke patients.How to effectively reduce and prevent neurological damage caused by CIRI has become a key and hot topic in CIS research.In re-cent years,many studies have confirmed that the active ingredients of traditional Chinese medicine can alleviate oxidative stress,inhibit autophagy,regulate cell apoptosis,control neuroinflammation,reduce cell apoptosis index,alleviate neuronal his-topathological damage,promote neuronal survival,enhance synaptic plasticity,and play a therapeutic role in CIRI through the PI3K/Akt signaling pathway.In summary,this article provides a review of the PI3K/Akt signaling pathway and its role in CIRI,as well as the research on the regulation of PI3K/Akt signaling by active ingredients in traditional Chi-nese medicine for the treatment of CIRI.The aim is to provide a theoretical basis for the clinical use of active ingredients in traditional Chinese medicine to alleviate CIRI damage.

BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Objective To investigate the effects of body weight and length of SD rats on the carotid artery balloon injury-induced vascular stenosis model in order to provide a reference for replicating an ideal vascular stenosis mod-el.Methods Male rats were divided into three groups based on body weight and length.The CONQUEROR? SC PTCA balloon catheter was employed,with a fixed balloon inflation volume of 0.2 mL to induce injury in the left common carotid artery,while the right side served as a control.As soon as surgery operation,one rat from each group was selected for Evans Blue dye verification.Fourteen days later,the injured and contra lateral common ca-rotid arteries from remaining rats were harvested for HE staining to check the extent of stenosis.Based on these find-ings,six rats within the optimal range of body weight and length were selected for further validation.Results Rats with body weights ranging from 280 to 380 g(corresponding body lengths of 21.0-26.5 cm)underwent balloon catheter injury,resulting in endothelial detachment and varying degrees of stenosis in the common carotid artery.In rats weighing 280-300 g(body lengths of 21.0-22.5 cm)had severe stenosis or occlusion of the common carotid artery with thrombosis.In rats weighing 320-340 g(body lengths of 23.0-24.5 cm),the internal and external elastic plates of the common carotid artery were ruptured and the vascular morphology was abnormal.Conversely,rats weighing 360-380 g(body lengths of 25.0-26.5 cm)did not show any ruptured elastic laminae or thrombus formation in the common carotid artery,and the extent of vascular stenos in rats with a body weight of 360 g was moderate and uniform.The results of the repeated validation experiments were consistent.Conclusions Rats with a body weight range of 360 g(corresponding body length of 25.0-26.5 cm)are suitable for development of an ideal vascular stenosis model.

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

Objective To compare the effects of desflurane inhalation anesthesia versus propofol total intravenous anesthesia on postoperative recovery quality in patients undergoing endoscopic transnasal pituitary adenoma resection,and to provide evidence-based recommendations for optimizing anesthetic management in this surgical population.Methods This single-center,prospective,randomized controlled trial enrolled 112 patients scheduled for endoscopic transnasal pituitary adenoma resection,who were randomly assigned to either the desflurane group(n=56)or the propofol group(n=56).The desflurane group received desflurane[0.7-1.0 minimum alveolar concentration(MAC)]combined with remifentanil for anesthesia maintenance,whereas the propofol group received propofol(4-6 mg·kg-1·h-1)with remifentanil.The primary outcome was defined as the time from discontinuation of anesthetics to achieving an Aldrete score of 9.Secondary outcomes included emergence time,extubation time,and incidences of postoperative agitation and vomiting.Results Patients receiving desflurane achieved an Aldrete score of 9 significantly faster than those in the propofol group(13.0 min vs 16.5 min,P=0.003).Similarly,both emergence time(14.0 min vs 16.5 min,P=0.009)and extubation time(13.0 min vs 16.5 min,P=0.003)were significantly shorter in the desflurane group.However,the desflurane group had higher incidences of postoperative agitation(17.9%vs 3.6%,P=0.015)and vomiting(19.6%vs 5.4%,P=0.022).No significant difference was observed in severe agitation rates or 24 h postoperative recovery quality[Quality of Recovery-15(QoR-15)scores]between groups.Conclusion Desflurane anesthesia significantly accelerates postoperative recovery in patients undergoing endoscopic transnasal pituitary adenoma resection,however,it may increase risks of mild agitation and vomiting.In clinical applications,it is necessary to balance recovery benefits against potential adverse effects,and take targeted prophylactic measures.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.

Objective:To screen and analyze the carcinogenesis-related differential expression profile of long non-coding RNAs(LncRNAs)in oral lichen planus(OLP)mucosa tissue,and preliminarily analyze their functions,to explore their possible role in the development of OLP.Methods:High-throughput sequencing technology was used to construct differential expression profile from 5 cases of erosive OLP lesions and 5 of normal oral mucosa.LncRNAs that are closely related to the carcinogenesis of OLP were ob-tained by bioinformatics analysis.Results:400 LncRNAs associated with OLP were screened,of which 250 were up-regulated and 150 were down-regulated,and 5 LncRNAs were obtained with differential expression associated with OLP carcinogenesis:LncRNA 54055,100128560,399717,378825 and 100130231.Conclusion:400 LncRNAs are differentially expressed in the mucosa of erosive OLP lesions,and 5 of them are related to the incidence and carcinogenesis tendency of OLP.

Objective·To detect the active brain regions in patients experiencing pain associated with temporomandibular disorder under anxiety emotion stimulation by using functional magnetic resonance imaging(fMRI).Methods·A total of 30 temporomandibular disorder patients with spontaneous pain were included,who visited the Department of Stomatology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,from November 2021 to September 2023.A task program consisting of negative and medium pictures chosen from the International Affective Picture System(IAPS)was used to stimulate anxiety in the volunteers during fMRI scanning.The activated brain regions were identified by processing the data with the general linear model using FSL 5.0.6 software.The pain levels and anxiety levels of the subjects before and after anxiety stimulation were recorded by using the Visual Analogue Scale(VAS)and State-Trait Anxiety Inventory(STAI).Paired t-tests were then conducted by using SPSS 20.0 software.Results·After stimulation with negative pictures,the anxiety levels of the subjects with temporomandibular disorder significantly increased(P＜0.001),and the pain levels also worsened(P＜0.001).The degree of temporomandibular joint pain aggravated with the stimulation of negative emotional pictures and improved with the neutral pictures.The main brain regions activated during the task included amygdala,hippocampus,anterior cingulate gyrus,thalamus,occipital cortex,and insula.Among them,the occipital cortex,anterior cingulate gyrus,and amygdala were the main brain regions activated after removing neutral control stimulation.Conclusion·The aggravation of anxiety can increase the temporomandibular joint pain level in patients with temporomandibular disorder.There is significant activation in the brain regions related to the hippocampus-centered hyperalgesia reaction and the thalamic-limbic system and the thalamic-limbic system,which are involved in pain and emotion regulation networks.