Marchiafava-Bignami disease (MBD) represents a rare neurological disorder predominantly associated with chronic ethanol consumption and thiamine insufficiency. However, its possible correlation with cobalamin deficiency resulting from anti-parietal cell antibodies (APCA) remained inadequately characterized in the literature. Timely diagnosis and therapeutic intervention were critical for optimizing clinical outcomes. This case suggested that APCA screening and vitamin B12 assessment should be considered in the diagnostic workup of MBD, especially in patients without classic thiamine deficiency.

Mitochondrial encephalomyopathy (ME) is clinically heterogeneous and frequently misdiagnosed as a single-organ disease. While recombinant human growth hormone (rhGH) is commonly used to treat short stature in children, its safety in patients with undiagnosed ME remains uncertain, with theoretical concerns that it may exacerbate multisystem disease progression. We described a genetically confirmed case of ME in a 24-year-old male patient over a decade. After receiving rhGH therapy at age 14 in 2015 for childhood short stature, he developed a cascade of multisystem manifestations: ptosis and cognitive decline emerged in 2017, followed by an acute metabolic crisis resembling heatstroke in 2018. Over the following years, he was diagnosed with a succession of conditions, including chronic sinusitis, sensorineural hearing loss, diabetes (HbA1c 7.25

To estimate the correlation between miRNA-338-3p/miRNA-1250-5p/miRNA-3065-5p clusters and ischemic stroke (IS). 83 hospitalized patients diagnosed with IS (experimental group) and 50 healthy subjects (control group) were enrolled in the Affiliated Hospital of North Sichuan Medical College from July 2020 to December 2020. The levels of miRNA-338-3p, miRNA-1250-5p, and miRNA-3065-5p in peripheral blood mononuclear cells (PBMCs) were measured by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). The expressions of miRNA-1250-5p and miRNA-3065-5p were significantly higher in the experimental group compared to the control group (2.04 ± 0.22 vs. 1.54 ± 0.33, P = 0.002, 6.41 ± 2.17 vs. 1.42 ± 0.24, P < 0.001, respectively) No significant difference in miRNA-338-3p expression was observed between the experimental and control groups (1.87 ± 0.22 vs. 1.25 ± 0.11, P = 0.309). The expression levels of miRNA-1250-5p increased after 24 h and no more than 7 days of disease progression but decreased after 7 days compared to baseline (P < 0.05). The expression levels of miRNA-3065-5p and miRNA-338-3p in patients with a discharge National Institutes of Health Stroke Scale (NIHSS) score greater than 33 were higher than those in the group with a score of 3 or less (P < 0.05). Additionally, the expression level of miRNA-3065-5p in patients with discharged mRS scores of 3 or higher was greater than in patients with discharged mRS scores of 2 or lower (P < 0.05). The miRNA-338-3p/miRNA-1250-5p/miRNA-3065-5p clusters showed a positive correlation with neutrophil percentage and a negative correlation with lymphocyte percentage (P < 0.05). Furthermore, miRNA-338-3p, miRNA-1250-5p, and miRNA-3065-5p significantly correlated in IS (P < 0.001). miRNA-1250-5p and miRNA-3065-5p may be associated with IS.

Background To study the age‐adjusted Charlson comorbidity index (ACCI) scale, which is a comprehensive quantification of multimorbidity coexistence, for the assessment of the risk of acute myocardial infarction death in elderly people. Methods and Results A total of 502 older patients with acute myocardial infarction were studied at Qilu Hospital from September 2017 to March 2022. They were categorized on the basis of ACCI into low (≤5), intermediate (6, 7), and high (≥8) risk groups. Hospitalization duration was observed, with death as the end point. least absolute shrinkage and selection operator regression was used to screen variables, 10‐fold cross‐validation was performed to validate the screened variables, a Cox regression nomogram predicting the risk of patient death was prepared, hazard ratio with 95% CI was calculated, a nomogram calibration curve was constructed, and a receiver operating characteristic curve, decision curve analysis, and a clinical impact curve were established. From 62 potential factors in a least absolute shrinkage and selection operator regression, 12 were selected via 10‐fold cross‐validation. Retain variables with significant statistical differences in the Cox regression. A nomogram of the risk of death from acute infarction was constructed, and risk factors included ventricular tachycardia/fibrillation, atrial fibrillation, nicorandil, angiotensin‐converting enzyme inhibitors/angiotensin‐converting enzyme inhibitors, β blockers, and ACCI score, carbon dioxide combining power, and blood calcium concentration. Conclusions The ACCI score effectively assesses multimorbidity in the older patients. As ACCI rises, the death risk from acute myocardial infarction grows. The study's nomogram is valid and clinically applicable.

BackgroundWith the rapid growth of an aging global population and proportion, the prevalence of frailty is constantly increasing. Therefore, finding a frailty assessment tool suitable for clinical application by physicians has become the primary link in the comprehensive management of frailty in elderly patients. This study used the (fr)AGILE scale to investigate the frailty status of elderly patients from internal medicine wards and identified relevant factors that affect the severity of frailty.MethodIn this study, 408 elderly inpatients in internal medicine departments of Qilu Hospital of Shandong University from May 2021 to August 2022 were enrolled as research subjects, and a cross-sectional observational study was conducted. Researchers evaluated the frailty based on the (fr)AGILE scale score. The general condition, past medical history, physical examination, laboratory examination, nutrition control score, intervention and treatment measures and other elderly patient information was collected. Logistic regression analysis was used to analyze the relevant factors that affect the severity of frailty and hospitalization costs.ResultsAccording to the (fr)AGILE scale score, the elderly patients were divided into groups to determine whether they were frail and the severity of the frailty. Among them, 164 patients were in the prefrailty stage, which accounted for 40.2%. There were 188 cases of mild frailty that accounted for 46.1%, and 56 cases of moderate to severe frailty that accounted for 13.7%. Decreased grip strength, elevated white blood cell levels, and low sodium and potassium are independent risk factors affecting the severity of frailty. As the severity of frailty increases, the proportion of sodium, potassium, albumin supplementation as well as anti-infection gradually increases.ConclusionFrailty is a common elderly syndrome with a high incidence among elderly patients in internal medicine departments. The main manifestations of frailty vary with different severity levels. Inflammation, anemia, and poor nutritional status can lead to an increase in the severity of frailty as well as blood hypercoagulability, myocardial damage, and additional supportive interventions. This ultimately leads to prolonged hospitalization and increased hospitalization costs.

BACKGROUND AND PURPOSE:This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS:Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS:Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION:Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

The main clinical manifestation of Alzheimer's disease is progressive cognitive decline, and its pathological features are β-amyloid (Aβ) deposition, neurofibrillary tangles, synaptic dysfunction and neuron death. Neuroinflammation is an important reason for the occurrence and development of AD, which is mainly manifested by the accumulation of activated microglia and reactive astrocytes. Apolipoprotein E (ApoE) is one of the most important apolipoprotein in the brain, which is related to metabolism, aggregation and toxicity of Aβ. However, the underlying mechanism needs to be further explored. In this study, we studied the effect of ApoE mimetic peptide COG1410 on spatial learning and memory functions, deposition of Aβ in the dentate gyrus (DG) of APP/PS1 transgenic mice, and the different effects of A1 and A2 subtypes of reactive astrocytes. Administration of COG1410 effectively improved performance in spatial learning and memory of APP/PS1 mice, reduced Aβ deposition and significantly reverted the ratio of A1/A2 reactive astrocytes, which could be associated with BDNF/TrkB signaling pathway. On the whole, the present findings suggest new possibility of using apolipoprotein E mimetic peptide to treat AD with potential effectiveness.

Objective: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) had emerged as useful inflammatory biomarkers in multiple diseases. The study aimed to explore the possible relationships between NLR, PLR, MLR and methylamphetamine dependence, and explore their potential wider use in clinical research.Methods: 632 methylamphetamine-dependent patients and 325 controls were enrolled. The demographics, complication of de-pendence, and hematologic parameters were compared. The NLR, PLR, and MLR were estimated and compared between the two groups.Result: The count of white blood cell (WBC), neutrophil, monocyte, NLR, MLR, and PLR were significantly higher and the lym-phocyte count was significantly lower in methylamphetamine-dependent patients than controls (p < 0.05). Multivariate analysis showed that the NLR, MLR, monocyte, and platelet were screened as useful biomarkers to evaluate the inflammatory states of methylamphetamine dependence, respectively (NLR: OR (odds ratio) = 71.72, 95% CI (confidence interval) [27.63-186.19], p < 0.001. MLR: OR = 6.34, 95% CI [3.27-12.27], p < 0.001. Monocyte: OR = 26.34, 95% CI [3.44-206.11], p = 0.002. Platelets: OR = 3.71, 95% CI [1.97-7.02], p < 0.001). However, there were no significant differences in WBC, neutrophil cell, lymphocyte, and PLR (p > 0.05). Similar results were obtained after adjusting for age and gender. The receiver operating characteristic curve (ROC) analysis indicated that the NLR and MLR were useful parameters to identify the inflammatory states of methy-lamphetamine dependence (AUC (area under the curve): NLR = 0.89, MLR = 0.82, platelet = 0.64, monocyte = 0.77,p < 0.001). Furthermore, the NLR was significantly and positively associated with severity of dependence scale (SDS) score and hallucination in methylamphetamine-dependent patients (p < 0.05). However, the MLR was uncorrelated with those variables (p > 0.05).Conclusions: The NLR might serve as a useful clinical biomarker in inflammatory states of methylamphetamine dependence, and positively correlated with hallucination and severity of methylamphetamine dependence. [GRAPHICS]

BACKGROUND:Homocysteine (Hcy) is widely recognized as a significant risk factor for cardiovascular and cerebrovascular diseases. However, our research has uncovered a novel perspective, suggesting that elevated levels of Hcy could serve as an indicator for neurological diseases. This article presents a unique case of Subacute Combined Degeneration of the spinal cord(SCD), characterized by high homocysteine levels, yet normal vitamin B12 and imaging results. This discovery could facilitate early detection and ensure timely referral of patients to specialized departments for further treatment.

BackgroundPostoperative delirium (POD) presents as a serious neuropsychiatric syndrome in patients undergoing off-pump coronary artery bypass grafting (OPCABG) surgery. This is correlated with higher mortality, cognitive decline, and increased costs. The Age-adjusted Charlson Comorbidity Index (ACCI) is recognized as an independent predictor for mortality and survival rate. The purpose of our study is to estimate the predictive value of the ACCI on the POD in patients undergoing OPCABG surgery.MethodsThis prospective cohort study enrolled patients undergoing OPCABG surgery between December 2020 and May 2021 in Qilu Hospital. Patients were divided into the low-ACCI group (score, 0–3) and the high-ACCI group (score ≥4) according to their ACCI scores. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and CAM were used to diagnose POD within 7 days after surgery. The general, laboratory, and clinical data of the patients were recorded and collected. The characteristic ROC curve was applied to further assess the predictive value of the ACCI for POD in patients following OPCABG surgery.ResultsA total of 89 patients were enrolled, including 45 patients in the low-ACCI group and 44 patients in the high-ACCI group. The incidence of POD was higher in the high-ACCI group than in the low-ACCI group (45.5% vs. 15.6%, P = 0.003). Multivariate logistic regression analyses showed that the ACCI (OR, 2.433; 95% CI, 1.468–4.032; P = 0.001) was an independent risk factor for POD. The ACCI accurately predicted POD in patients following OPCABG surgery with an AUC of 0.738, and the Hosmer–Lemeshow goodness of fit test yielded X2 = 5.391 (P = 0.145).ConclusionThe high-ACCI group showed a high incidence of POD. The ACCI was an independent factor associated with POD in patients following OPCABG surgery. In addition, the ACCI could accurately predict POD in patients following OPCABG surgery. Clinical Trial RegistrationClinicalTrials.gov, identifier CHiCTR2100052811.

Aims: Deep vein thrombosis (DVT) is a prevalent cardiovascular condition. Endothelial-derived extracellular vesicles (EVs) may play a crucial role in platelet-dependent DVT development via platelet activation, but the mechanism is not clear yet. This research aims to understand how platelets and endothelial-derived EVs work in DVT. Methods: The interaction between protein disulfide isomerase (PDI) and glucose-regulated protein 94 (GRP94) was founded by molecular docking. Inferior vena cava stasis–induced mice received PDI and GRP94 inhibitor treatments. Platelet activation, endothelial-derived EVs, and PDI were measured using flow cytometry. The expression of PDI and dimetric GRP94 in platelets co-cultured with hypoxic endothelial cells was confirmed by Western blot or native PAGE. The fluorescence resonance energy transfer assay shows conformational changes in GPIIb/IIIa on platelet surfaces. A tracking experiment was performed using PKH26, which labelled endothelial-derived EVs, and the endocytosis of EVs by platelets was tracked by confocal microscope. Results: In a DVT mouse model, platelets enhance venous thrombus formation in a coagulation-independent manner, instead, platelet activation and the length of the thrombus are related to PDI and GRP94 activity. Next, we found that the expression level of endothelial-derived EVs carrying PDI is significantly increased in plasma. Endothelial-derived EVs carrying PDI are endocytosed by platelets, in which the content of GRP94 dimer is elevated, and consequently increases the expression of surface GPIIb/IIIa. In addition, PDI allosterically interacts with GPIIb/IIIa, which is re-configurated into an activated form. Conclusion: Endothelial-derived EVs carrying PDI induce DVT via interplay with GRP94 and GPIIb/IIIa in platelets. These findings emphasize the significance of platelets in DVT formation, and PDI may be a suitable target in DVT prevention.

BackgroundExcision repair cross-complementing group 1 (ERCC1) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke.MethodsA total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism (RFLP-PCR) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed.ResultsThe ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group (P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group (P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076–1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744–3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028–1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087–3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype (P < 0.05).ConclusionIt was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.

This prospective randomized controlled study was intended to assess the effects of different doses of clopidogrel plus early rehabilitation therapy on motor function and inflammatory factors in patients with ischemic stroke. Between August 2018 and October 2020, 90 cases of ischemic stroke treated in the Second People’s Hospital of Yibin were randomized at a ratio of 1 : 1 to receive either oral 50 mg/d clopidogrel plus early rehabilitation therapy (low-dose group) or oral 75 mg/d clopidogrel plus early rehabilitation therapy (high-dose group), with 45 cases in each group. The outcome measures including the Barthel Index (BI), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer simplified scale, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and occurrence of adverse events were collected. After treatment, the high-dose group had higher BI results than the low-dose group. All eligible patients showed significantly declined NIHSS scores, and the high-dose group had markedly lower results ( P < 0.05 ). After treatment, the Fugl-Meyer scores of both upper and lower extremities of the high-dose group were significantly higher than those in the low-dose group. The high-dose group achieved a greater decrease in inflammatory factor levels after treatment versus the low-dose group. The two groups showed a similar incidence of adverse events. High-dose clopidogrel plus early rehabilitation outperforms the low-dose treatment for patients with ischemic stroke by effectively mitigating the inflammatory response in the body, promoting the restoration of neurological function, improving the level of motor function, and enhancing the patient’s quality of life, with manageable safety.

血管性认知损害(VCI)是由各种脑血管病或其危险因素引起的不同程度认知损害的临床综合征.随着全球老龄化程度的不断加重,VCI发病率也与日俱增,但VCI的发病机制尚不明确,因而缺乏有效的治疗策略.微小RNA(microRNA,micRNA)是一类转录后靶向调控基因表达的非编码小RNA,参与众多疾病的发生发展,在VCI发病机制中亦发挥重要作用.文中就miRNA在VCI突触可塑性、炎症反应、血脑屏障通透性及神经元死亡等不同分子机制进行综述.

Objective: Amphetamine-type stimulant (ATS) and opioid dependencies are chronic inflammatory diseases with similar symptoms and common genomics. However, their coexpressive genes have not been thoroughly investigated. We aimed to identify and verify the coexpressive hub genes and pathway involved in the pathogenesis of ATS and opioid dependencies.Methods: The microarray of ATS- and opioid-treatment mouse models was obtained from the Gene Expression Omnibus database. GEO2R and Venn diagram were performed to identify differentially expressed genes (DEGs) and coexpressive DEGs (CDEGs). Functional annotation and protein-protein interaction network detected the potential functions. The hub genes were screened using the CytoHubba and MCODE plugin with different algorithms, and further validated by receiver operating characteristic analysis in the GSE15774 database. We also validated the hub genes mRNA levels in BV2 cells using qPCR.Result: Forty-four CDEGs were identified between ATS and opioid databases, which were prominently enriched in the PI3K/Akt signaling pathway. The top 10 hub genes were mainly enriched in apoptotic process (CD44, Dusp1, Sgk1, and Hspa1b), neuron differentiation, migration, and proliferation (Nr4a2 and Ddit4), response to external stimulation (Fos and Cdkn1a), and transcriptional regulation (Nr4a2 and Npas4). Receiver operating characteristic (ROC) analysis found that six hub genes (Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, and Nr4a2) have an area under the curve (AUC) of more than 0.70 in GSE15774. The mRNA levels of Fos, Dusp1, Sgk1, Ddit4, Cdkn1a, PI3K, and Akt in BV2 cells and GSE15774 with METH and heroin treatments were higher than those of controls. However, the Nr4a2 mRNA levels increased in BV2 cells and decreased in the bioinformatic analysis.Conclusions: The identification of hub genes was associated with ATS and opioid dependencies, which were involved in apoptosis, neuron differentiation, migration, and proliferation. The PI3K/Akt signaling pathway might play a critical role in the pathogenesis of substance dependence.

AbstractPurposeTo review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2O) abuse, and analyze the factors that affect outcomes.MethodsPatients with N2O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow‐up was conducted to determine the outcomes.ResultsThe average age of the 110 patients with N2O abuse was 21.4 ± 4.2 years (range: 14–33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow‐up was completed for 51 patients. Thirty‐four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients.ConclusionThe recreational use of N2O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2O abuse. The therapeutic administration of vitamin B12 supplementation and N2O withdrawal can make the overall prognosis good, especially for female patients.

Background: Venous thromboembolism (VTE) is a major global health problem with high incidence and mortality. Vein endothelial cell (VEC) dysfunction is the primary cause of VTE. MicroRNAs (miRNAs) assist in the regulation of VEC functional pathways. Our objective was to identify potential miRNA target genes associated with VTE. Materials and Methods: To explore the association between mRNAs and miRNAs in VTE, we performed an mRNA or miRNA microarray analysis and experiments in vitro. In addition, five online bioinformatics tools identified the target genes of differentially expressed miRNAs, and a miRNA-gene network was constructed. As a result, hub miRNA and mRNA were confirmed. Finally, wound healing assay and transwell migration assay were performed to elucidate the effect of hub miRNA in VEC. Luciferase reporter assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to decide the role of miRNA in the expression of hub mRNA. Results: Screening identified eight overlapping dysregulated genes in patients with VTE, three of which demonstrated a significantly decreased expression of miR-200a-5p. Low expression miR-200a-5p in VTE patients is confirmed by a receiver operating characteristic analysis (AUC = 0.800, P = 0.023) and binary logistic regression (OR = 0.359, 95% confidence interval: 0.605-0.995). RT-qPCR results showed that the miR-200a-5p level was decreased in hypoxia VEC (P= 0.038). MiR-200a-5p significantly promoted the migration ability of VEC. The result of Dual-luciferase reporter assay showed that cytochrome coxidase VIIc (COX7C) directly inhibit the miR-200a-5p expression by binding 5'UTR of miR-200a-5p (P = 0.011). Conclusions: We anticipate that the miR-200a-5p-COX7C pair might be involved in the progression of VTE. Moreover, miR-200a-5p might be a therapeutic target for VTE.

Abstract Purposes: MicroRNAs (miRNAs) and their single nucleotide polymorphisms may be involved in the pathophysiological process of acute ischemic stroke (AIS), of which miRNA-146a is one of the most concerned miRNAs. This experiment is aimed to investigate the association of miRNA-146a and its single nucleotide polymorphism (SNP) with AIS and its susceptibility in a Chinese population. Methods A case-control study including 137 AIS patients and 100 controls were enrolled. The relative miRNA-146a expression in PBMCs was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR). And the SNP of miRNA-146a rs2910164 was genotyped using DNA extraction kit and TaqMan-MGB probe real-time PCR, and its relevance to AIS susceptibility was evaluated. Results The relative miRNA-146a expression in the experimental group (1.65 ± 0.11) was significantly higher than that in the control group (1.13 ± 0.09, P = 0.002). In subgroup analysis, the relative expression level of miRNA-146a in AIS with a course longer than 3 days was significantly higher than that less than or equal to 3 days and the control group (P < 0.05). Difference of the distribution of allele frequencies of the rs2910164C/G polymorphism was failed to found between the experimental and control groups (P = 0.703, OR = 0.930, 95% CI = 0.641–1.349). However, the GG genotype frequency was higher in AIS patients with other causes (SOE) than that in controls according to the TOAST subtype analysis. (P = 0.00, OR: 4.825, 95% CI: 2.720–8.562). Conclusions The findings suggested that miRNA-146a may be involved in the pathophysiological process of AIS. But the miRNA-146a rs2910164C/G polymorphism may not be associated with AIS genetic susceptibility, although the rs2910164GG genotype may increase the risk of SOE AIS.

Background: The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin’s lymphoma. However, the cardiotoxicity and efficacy of the (R)-CDOP regimen compared with conventional anthracyclines have not been demonstrated in the general population. Therefore, this systematic review and meta-analysis evaluated the risk of cardiotoxicity and efficacy associated with the (R)-CDOP regimen in patients with non-Hodgkin’s lymphoma.Methods: PubMed, Embase, Cochrane Library, CNKI, WanFang Database, and VIP were searched. The search covered the period from the start of the clinical use of (R)-CDOP to April 2022. We searched the literature for cardiovascular adverse events associated with (R)-CDOP in non-Hodgkin’s lymphoma. The data were analyzed using R 4.2.0 and Stata 12.0.Results: From the included studies, the important findings were as follows: total cardiovascular event rate, 7.45% (95% confidence interval [CI] = 4.86%–10.44%); non-serious cardiovascular adverse event rate, 6.48% (95% CI = 3.70%–9.8%); serious cardiovascular adverse event rate, 0.67% (95% CI = 0.00%–2.12%); heart failure rate, 0.55% (95% CI = 0.00%–1.93%); rate of treatment discontinuation attributable to left ventricular dysfunction or heart failure, 0.02% (95% CI = 0.00%–0.57%); and cardiovascular death rate, 0.00% (95% CI = 0.00%–0.37%). Compared with the (R)-CHOP regimen, the (R)-CDOP regimen reduced the risk of cardiovascular events, including total cardiovascular adverse events (odds ratio [OR] = 0.161, 95% CI = 0.103–0.251, p < 0.001, and NNT = 3.7), non-serious cardiovascular adverse events (OR = 0.171, 95% CI = 0.093–0.314, p < 0.001, and NNT = 3.6), serious cardiovascular adverse events (OR = 0.252, 95% CI = 0.119–0.535, p < 0.001, and NNT = 6.8), and heart failure (OR = 0.294, 95% CI = 0.128–0.674, p = 0.004, and NNT = 9.5). To evaluate the survival benefits, we compared (R)-CDOP and (R)-CHOP regimens. We found that the (R)-CDOP regimen was no less efficacious, including complete remission (CR) (OR = 1.398, 95% CI = 0.997–1.960, and p = 0.052), partial response (PR) (OR = 1.631, 95% CI = 1.162–2.289, and p = 0.005), objective response rate (ORR) (OR = 2.236, 95% CI = 1.594–3.135, and p < 0.001), stable disease (SD) (OR = 0.526, 95% CI = 0.356–0.776, and p = 0.001), and progressive disease (PD) (OR = 0.537, 95% CI = 0.323–0.894, and p = 0.017).Conclusion: Our findings suggested that the (R)-CDOP regimen had a lower risk of cardiovascular adverse events in non-Hodgkin’s lymphoma than the (R)-CHOP regimen, demonstrating its safety with regard to cardiotoxicity. In addition, this study found the (R)-CDOP regimen was no less efficacious than the (R)-CHOP regimen in the treatment of non-Hodgkin’s lymphoma. These findings need to be validated by higher-quality research because of the limited number and quality of included studies.

Abstract Background The quinone oxidoreductase 1 (NQO1) gene was involved in the pathophysiological process of illicit drugs abuse, and its polymorphisms might be associated with methamphetamine (METH) dependence susceptibility. The purpose of this study was to examine the NQO1 mRNA and protein levels and to analyze the 609C/T polymorphism (rs1800566) between METH‐dependent patients and controls. Methods A total of 392 METH‐dependent patients (cases) and 669 healthy controls (controls) were enrolled in the study. The quantitative real‐time polymerase chain reaction (RT‐qPCR) and enzyme‐linked immunosorbent assay (ELISA) were used to detect the relative expressions of NQO1 mRNA in PBMCs and protein levels in plasma, respectively. PCR‐restriction fragment length polymorphism (RFLP‐PCR) and direct‐sequencing genotyping were used to detect the alleles and genotypes of NQO1 609C/T polymorphism. Results The levels of NQO1 mRNA in cases (3.2650 ± 2.2943) was significantly higher than in controls (1.0125 ± 0.7959) (p < 0.001), the plasma protein in cases (0.2368 ± 0.1486) was significantly lower than in controls (0.5844 ± 0.1742) (p < 0.001). The T allele of the 609C/T polymorphism significantly increased the risk of METH dependence (p = 0.032, OR = 1.214, 95%CI = 1.017–1.450). The TC and TC/TT genotypes of 609C/T were observed significantly more frequently in cases than in controls, respectively (TC vs CC: p = 0.012, OR = 1.457, 95% CI = 1.087–1.952; TC/TT vs CC: p = 0.008, OR = 1.460, 95% CI = 1.102–1.935). Similar results were obtained after adjusting for age and sex. We failed to find that any genotype of 609C/T polymorphism affected the mRNA or plasma protein levels in controls, respectively (p > 0.05). Conclusion The findings suggested that NQO1 might play an important role in the pathophysiological process of METH dependence, and the 609C/T polymorphism might contribute to the susceptibility to METH dependence in a Chinese Han population.