N6-methyladenosine(m6A)modification is one of the most abundant epitranscriptomic modifications in eukaryotic mRNA,with dynamic and reversible properties.This modification process is coordinated by methyltransferases,demethylases,and related m6A binding proteins,which in turn affect mRNA metabolism and function.Increasing evi-dence has indicated that the m6A RNA modification plays an important role in the occurrence and development of athero-sclerosis(As)and other related diseases.This paper provide a comprehensive review of the relationship between m6A RNA modification and As.The entire manuscript summarizes the m6A RNA modification mechanism and its roles in As-related cells including endothelial cells,macrophages,and smooth muscle cells,and discusses the association of m6A RNA modification with risk factors of As such as high-fat diet,ischemia/hypoxia,oscillatory stress,and hypertension.Finally,this review summarizes researches on drug intervention targeting m6A RNA methylation to mitigate As.These studies pro-vide important references for exploring new targets for early diagnosis and treatment of As.

Lactic acid bacteria(LAB)were isolated and cultivated from the intestinal contents of rabbits by MRS-CaCO3 solid medium.Identification was achieved through morphological observa-tion,Gram staining,physiological and biochemical characterisation,16S rDNA sequence analysis,and ERIC-PCR analysis.Strains displaying typical Lactobacilli characteristics were exanimated for their biological characteristics,resistance properties,adherence capacity in vitro,colonization abili-ty in vivo,and safety profile.In this study,a total of four strains of Lactobacillus reuteri were iso-lated from rabbits,all of which exhibited typical biological characteristics of LAB.These strains demonstrated inhibitory effects on common pathogenic bacteria in the gastrointestinal tract,with the primary inhibitory substance being bacteriocin.Furthermore,they showed sensitivity to chlor-amphenicol,rifampicin,and erythromycin,and displayed a degree of tolerance to gastrointestinal conditions and high temperature.These stains were capable of successful colonization in rabbits with a higher degree of safety.This study lays a foundation for the development of LAB prepara-tions for the prevention and treatment of rabbit intestinal diseases.

Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95％CI:1.532～2.499),length of ICU stay (P=0.000,OR=2.561,95％CI:1.728～3.794),number of operations (P=0.015,OR=1.814,95％CI:1.124～2.927),spinal fixation (P=0.004,OR=0.370,95％CI:0.189～0.724),restrictive position (P=0.000,OR=21.269,95％CI:5.276～85.740),platelet count (P=0.000,OR=1.553,95％CI:1.236～1.951),D-dimer level (P=0.000,OR=1.600,95％CI:1.376～1.860)and prothrombin time (P=0.025,OR=2.756,95％CI:1.138～6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM),SAP model group (SAP),and Chaihuang Qingyi Huoxue Granule (CH)group,with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5％ sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage,while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation,eight rats from each group were sacrificed to collect abdominal aortic blood,pancreatic and ileal tissues for analysis. Ascites,pancreatic and ileal tissues were observed. Serum amylase(AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points,the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels,pancreatic and ileal histopathological scores increased,and Claudin-1 protein expression in ileal tissue markedly decreased (all P<0.05). The differences in abundance of microbial community increased,while the evenness of community composition reduced. The microbial richness showed no significant change (P>0.05),but the microbial diversity decreased(P<0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 decreased,whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced,and the evenness of community composition increased. The microbial richness showed no significant change(P>0.05),but the microbial diversity increased (P<0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 increased,whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH,pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group(P<0.05). The differences in abundance of microbial community reduced,and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP,which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

With the development of neuroimaging technology, cerebral small vessel disease has become a hot research topic in recent years. It has been clearly related to cognitive decline, dementia and gait instability. However, recent studies have found that small cerebral vascular disease with white matter hyperintensities is the main cause of chronic dizziness in the elderly, but the pathogenesis is not completely clear, which may be related to brain neural network disconnection, visual dependence, eye movement disorder caused by abnormal brain tissue structure, oxidative stress regulation disorder, cerebral blood flow self-regulation disorder, and the interaction mechanism between vestibular system and emotional disorder.

Objective:To investigate the efficacy and safety of daratumumab in the treatment of systemic light chain amyloidosis.Methods:The clinical data of 24 patients with systemic light chain amyloidosis who received daratumumab-based regimens in Sichuan Provincial People's Hospital from January 2020 to November 2022 were retrospectively analyzed. The treatment process of patients was summarized and the therapeutic efficacy was evaluated. Kaplan-Meier method was used to make survival analysis and the adverse reactions were analyzed.Results:All 24 patients included 2 cases (8.33%) of Mayo 2004 stageⅠ, 2 cases (8.33%) of Mayo 2004 stage Ⅱ and 20 cases (83.33%) of Mayo 2004 stage Ⅲ. All patients were treated with daratumumab-based regimen, and 17 patients had evaluable efficacy. In the chemotherapy regimens, 15 patients received DVd (daratumumab + bortezomib + dexamethasone) regimen, 7 patients received DVCd (daratumumab + bortezomib + cyclophosphamide + dexamethasone) regimen, 1 patient received DRd (daratumumab + lenalidomide + dexamethasone) regimen, and 1 patient received DTd (daratumumab +thalidomide + dexamethasone) regimen. After 1 course of daratumumab-based regimens in 17 cases with evaluable efficacy, the strict complete remission (sCR) rate was 41.18% (7/17), the overall response rate (ORR) was 88.24% (15/17). Among 17 patients who received daratumumab-based chemotherapy regimen as the first-line treatment, sCR rate of 11 cases with evaluable efficacy was 36.36% (4/11) after 1 course of treatment ORR was 90.90% (10/11). Among 5 relapsed/refractory patients, sCR rate of 4 cases with evaluable efficacy was 50.00% (2/4) after 1 course of treatment; ORR was 75.00% (3/4). Among 24 patients, renal involvement was found in 17 patients at the initial diagnosis. After 1 course of daratumumab-based chemotherapy regimen, ORR of 7 cases with evaluable efficacy was 85.71% (6/7), among which 42.86% (3/7) patients with renal involvement had an assessed renal response of very good partial remission (VGPR) or above. At the initial diagnosis, 19 cases had cardiac involvement; ORR of 14 cases with evaluable efficacy was 85.71% (12/14), among which 42.86% (6/14) patients had cardiac response to VGPR or above. After daratumumab-based chemotherapy regimen, the main adverse reactions were infusion-related adverse reactions, myelosuppression and infection, all of which were tolerated by the patients. The median follow-up time of 24 patients was 7.0 months (0.5- 16.5 months), the median progression-free survival time was 7.0 months (0.5-16.5 months) and the median overall survival time was 7.0 months (0.5-35.0 months).Conclusions:Daratumumab-based chemotherapy regimen has good efficacy and safety in the treatment of systemic light chain amyloidosis.

White matter hyperintensity (WMH) is one of the major imaging markers of cerebral small vascular disease, which is prevalent in the elderly. At present, the pathogenesis of WMH is not clear, most of the previous studies focused on the arterial system, but the role of the venous system in WMH is attracting more and more attention. Small venous collagen hyperplasia, downstream intracranial venous dilatation and internal jugular venous reflux may be involved in the formation and development of white matter hyperintensity.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Objective:To explore any effect of mechanical vibration on the expression of estrogen and brain-derived neurotrophic factor (BDNF) in ovariectomized rats with an osteoporotic fracture.Methods:Thirty 3-month-old female Wistar rats were divided randomly into a control group, an ovariectomy group and a vibration group, each of 10. Fractures were induced in the rats of all three groups. Twenty minutes of whole-body vertical vibration was applied to the vibration group at a frequency of 35Hz, 5 days a week for 6 weeks. After 2 and 6 weeks the fracture healing of each group was evaluated using X-rays, the levels of hippocampal estrogen were measured using enzyme-linked immunosorbent assays and fracture-end BDNF was quantified by immunoblotting.Results:After 2 and 6 weeks of vibration the average fracture healing in the vibration group was significantly greater than in the other 2 groups. The average estrogen content in the hippocampus of the vibration group was significantly higher than in the other 2 groups after both 2 and 6 weeks, while the average BDNF content in their fracture ends was significantly lower. The BDNF expression at the fracture end was significantly correlated with the fracture healing.Conclusion:Mechanical vibration can promote the expression of estrogen and BDNF in the hippocampus and accelerate fracture healing in osteoporotic rats.