The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair.

Arterial calcification is a hallmark of vascular pathology in the elderly and in individuals with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs), after attaining a senescent phenotype, are implicated in the calcifying process. However, the underlying mechanism remains to be elucidated. Here, we reveal an aberrant upregulation of transcriptional factor GATA6 in the calcified aortas of humans, mice with CKD and mice subjected to vitamin D3 injection. Knockdown of GATA6, via recombinant adeno-associated virus carrying GATA6 shRNA, inhibited the development of arterial calcification in mice with CKD. Further gain- and loss-of function experiments in vitro verified the contribution of GATA6 in osteogenic differentiation of VSMCs. Samples of human aorta exhibited a positive relationship between age and GATA6 expression and GATA6 was also elevated in the aortas of old as compared to young mice. Calcified aortas displayed senescent features with VSMCs undergoing premature senescence, blunted by GATA6 downregulation. Notably, abnormal induction of GATA6 in senescent and calcified aortas was rescued in Sirtuin 6 (SIRT6)-transgenic mice, a well-established longevity mouse model. Suppression of GATA6 accounted for the favorable effect of SIRT6 on VSMCs senescence prevention. Mechanistically, SIRT6 inhibited the transcription of GATA6 by deacetylation and increased degradation of transcription factor Nkx2.5. Moreover, GATA6 was induced by DNA damage stress during arterial calcification and subsequently impeded the Ataxia-telangiectasia mutated (ATM)-mediated DNA damage repair process, leading to accelerated VSMCs senescence and osteogenic differentiation. Thus, GATA6 is a novel regulator in VSMCs senescence. Our findings provide novel insight in arterial calcification and a potential new target for intervention.

Prevalence and factors associated with dyslipidemia in patients with first hospitalization for major depressive disorder: a large sample cross-sectional study.

BACKGROUND: Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients' clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. METHODS: In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. RESULTS: A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. CONCLUSION: The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL.

Gender differences in prevalence and associated factors of metabolic syndrome in first-treatment and drug-naïve schizophrenia patients.

BACKGROUND: Metabolic syndromes (MetS) are clinical syndromes involving multiple pathological states with distinct gender-specific clinical patterns. As a serious disorder associated with psychiatric conditions, the prevalence of MetS is significantly higher in the population with schizophrenia (Sch). The aim of this paper is to report gender differences in the prevalence, associated factors and severity-related factors of MetS in first-treatment and drug-naïve (FTDN) patients with Sch. METHODS: A total of 668 patients with FTDN Sch were included in this study. We collected socio-demographic and general clinical information on the target population, measured and evaluated common metabolic parameters and routine biochemical indicators, and assessed the severity of psychiatric symptoms using Positive and Negative Symptom Scale (PANSS). RESULTS: In the target group, the prevalence of MetS was significantly higher in women (13.44%, 57/424) than in men (6.56%, 16/244). In the males, waist circumference (WC), fasting blood glucose (FBG), diastolic blood pressure (DBP), and triglycerides (TG) were risk factors for MetS, while systolic blood pressure (SBP), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and platelet (PLT) were risk factors for the females. More importantly, for the females, we found that age, LDL-C, PANSS scores and blood creatinine (CRE) were risk factors for higher MetS scores, while onset age and hemoglobin (HGB) were protective factors. CONCLUSION: There are significant gender differences in the prevalence of MetS and its factors among patients with FTDN Sch. The prevalence of MetS is higher and the factors that influence MetS are more numerous and extensive in females. The mechanisms of this difference need further research and clinical intervention strategies should be formulated with gender differences.

BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease.

Amyloid beta (Aß) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting ß-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aß production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aß production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.

SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.

Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and ß-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.

Cleavage of GSK-3ß by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK-3ß activity induced by H2O2.

Glycogen synthase kinase-3 beta (GSK-3ß) dysfunction may play an essential role in the pathogenesis of psychiatric, metabolic, neurodegenerative diseases, in which oxidative stress exists concurrently. Some studies have shown that GSK-3ß activity is up-regulated under oxidative stress. This study evaluated how oxidative stress regulates GSK-3ß activity in human embryonic kidney 293 (HEK293)/Tau cells treated with hydrogen peroxide (H2O2). Here, we show that H2O2 induced an obvious increase of GSK-3ß activity. Surprisingly, H2O2 dramatically increased phosphorylation of GSK-3ß at Ser9, an inactive form of GSK-3ß,while there were no changes of phosphorylation of GSK-3ß at Tyr216. Moreover, H2O2 led to a transient [Ca²âº](i) elevation, and simultaneously increased the truncation of GSK-3ß into two fragments of 40 kDa and 30 kDa, whereas inhibition of calpain decreased the truncation and recovered the activity of GSK-3ß. Furthermore, tau was hyperphosphorylated at Ser396, Ser404, and Thr231, three most common GSK-3ß targeted sites after 100 µM H2O2 administration in HEK293/Tau cells, whereas inhibition of calpain blocked the tau phosphorylation. In addition, we found that there were no obvious changes of Cyclin-dependent kinase 5 (CDK5) expression (responsible for tau phosphorylation) and of p35 cleavage, the regulatory subunit of CDK5 in H2O2-treated HEK293/Tau cells. In conclusion, Ca²âº-dependent calpain activation leads to GSK-3ß truncation, which counteracts the inhibitory effect of Ser9 phosphorylation, up-regulates GSK-3ß activity, and phosphorylates tau in H2O2-treated HEK293/Tau cells.

Preventing postoperative cognitive dysfunction using anesthetic drugs in elderly patients undergoing noncardiac surgery: a systematic review and meta-analysis.

Postoperative cognitive dysfunction (POCD) is a common neurological system disorder in surgical patients. The choice of anesthetic can potentially reduce POCD. The authors performed this network meta-analysis to compare different anesthetic drugs in reducing the incidence of POCD for elderly people undergoing noncardiac surgery. We searched MEDLINE, EMBASE, the Cochrane Library, and the Web of Science for randomized controlled trials comparing the different anesthetic drugs for noncardiac surgery in elderly from inception until July, 2022. The protocol was registered on the PROSPERO database (CRD#42020183014). A total of 34 trials involving 4314 patients undergoing noncardiac surgery in elderly were included. The incidence of POCD for each anesthetic drug was placebo (27.7%), dexmedetomidine (12.9%), ketamine (15.2%), propofol (16.8%), fentanyl (23.9%), midazolam (11.3%), sufentanil (6.3%), sevoflurane (24.0%), and desflurane (28.3%). Pairwise and network meta-analysis showed dexmedetomidine was significantly reducing the incidence of POCD when compared with placebo. Network meta-analysis also suggested dexmedetomidine was significantly reducing the incidence of POCD when compared with sevoflurane. Sufentanil and dexmedetomidine ranked the first and second in reducing the incidence of POCD with the surface under the cumulative ranking curve value of 87.4 and 81.5%. Sufentanil and dexmedetomidine had the greatest possibility to reduce the incidence of POCD for elderly people undergoing noncardiac surgery.

Incidence and Factors Associated with Hyperglycemia in Patients with First Hospitalization for Major Depression Disorder: A Large Cross-Sectional Sample.

Purpose: Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times. Patients and Methods: A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients' clinical symptoms. Results: The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor. Conclusion: The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.

Single-nucleus transcriptome profiling of prefrontal cortex induced by chronic methamphetamine treatment.

Background: Methamphetamine (METH) addiction causes a huge burden on society. The prefrontal cortex (PFC), associated with emotion and cognitive behaviours, is also involved in addiction neurocircuitry. Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC, the impact on different cell types remains unknown. Aims: To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders. Methods: We performed single-nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of 20 465 nuclei isolated from the PFC of chronic METH-treated and control mice. Main cell types and differentially expressed genes (DEGs) were identified and confirmed by RNA fluorescence in situ hybridization(FISH). Results: Six main cell types were identified depending on the single-cell nucleus sequencing; of particular interest were the mature oligodendrocytes in the PFC. The DEGs of mature oligodendrocytes were enriched in the myelin sheath, adenosine triphosphate (ATP) metabolic process, mitochondrial function and components, and so on. The messenger RNA levels of Aldoc and Atp5l (FISH) and the protein level of the mitochondrial membrane pore subunit TOM40 (immunofluorescence) decreased in the mature oligodendrocytes. Fast blue staining and transmission electron microscopy image indicated myelin damage, and the myelin thickness decreased in METH brains. Conclusions: snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment, underscoring potential relationships with psychiatric disorders.

Co-prescription of aripiprazole on prolactin levels in long-term hospitalized chronic schizophrenic patients with co-morbid type 2 diabetes: A retrospective clinical study.

Background: One of the most frequent side effects of atypical antipsychotics is hyperprolactinemia (HPRL), and metformin or aripiprazole co-prescription is regarded as an effective therapy option for reducing prolactin (PRL) levels. However, whether either of the two drugs can reduce PRL levels in patients with long-term hospitalized chronic schizophrenia with co-morbid type 2 diabetes (T2DM) has not been adequately reported. Methods: In our study, long-term hospitalized chronic schizophrenia patients with co-T2DM who were prescribed olanzapine or risperidone as the primary antipsychotic medication were enrolled. A total of 197 of these cases with co-prescribed aripiprazole were set up as the study group (co-Ari group), and the other 204 cases without co-prescribed aripiprazole were set up as the control group (non-Ari group). The two groups' variations in each target parameter were compared, and the variables affecting PRL levels were examined. Results: Compared to the non-Ari group, fasting blood glucose (FBG), blood uric acid (UA), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the co-Ari group, but there was no difference in PRL levels. Co-prescribing aripiprazole had no impact on PRL levels in all patients with co-T2DM, and aripiprazole dose had no impact on PRL levels in the clinical subgroup of the co-Ari group. Conclusion: Aripiprazole not only worsened the severity of index disturbances associated to metabolism in long-term hospitalized chronic schizophrenia patients with co-T2DM on metformin-based hypoglycemic medications but also failed to lower PRL levels.

Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection.

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Defective mitophagy and the etiopathogenesis of Alzheimer's disease.

Accumulation of impaired mitochondria and energy metabolism disorders are non-negligible features of both aging and age-related neurodegeneration, including Alzheimer's disease (AD). A growing number of studies suggest that mitophagy disorders play an important role in AD occurrence and development. The interaction between mitophagy deficits and Aß or Tau pathology may form a vicious cycle and cause neuronal damage and death. Elucidating the molecular mechanism of mitophagy and its role in AD may provide insights into the etiology and mechanisms of AD. Defective mitophagy is a potential target for AD prevention and treatment.

Plasma Exosome miRNAs Profile in Patients With ST-Segment Elevation Myocardial Infarction.

Background: Circulating microRNAs (miRNAs) have been found to have different expressions in different phases of acute myocardial infarction. The profiles of plasma exosome miRNAs in patients with ST-segment elevation myocardial infarction (STEMI) at 3-6 months postinfarction are unknown. Objective: The aim of this study was to assess the profiles of plasma exosome miRNAs in patients with STEMI in comparison with healthy volunteers and to select specific exosome miRNAs related to pathophysiological changes post-STEMI. Methods: Plasma and echocardiography parameters were collected from 30 patients 3-6 months after STEMI and 30 healthy volunteers. Plasma exosome miRNAs were assessed by using high-throughput sequence (Illumina HiSeq 2500) and profile of the plasma exosome miRNAs was established in 10 patients and 6 healthy volunteers. The specific exosome miRNAs related to heart diseases were selected according to the TargetScan database. The specificity of the selected exosome miRNAs was evaluated in additional 20 post-STEMI patients and 24 healthy volunteers by using quantitative PCR (qPCR). Left ventricular remodeling (LVR) was defined using the European Association of Cardiovascular Imaging criteria according to echocardiography examination. Correlations between expression of the specific miRNAs and echocardiography parameters of LVR were assessed using the Spearman correlation analysis. Results: Twenty eight upregulated miRNAs and 49 downregulated miRNAs were found in patients 3-6 months after STEMI (p < 0.01) in comparison with the healthy volunteers. The two least expressed and heart-related exosome miRNAs were hsa-miR-181a-3p (0.64-fold, p < 0.01) and hsa-miR-874-3p (0.50-fold, p < 0.01), which were further confirmed by using qPCR and demonstrated significant specificity in another 20 patients with post-STEMI comparing to 24 healthy volunteers [area under the curve (AUC) = 0.68, p < 0.05; AUC = 0.74, p < 0.05]. The expression of hsa-miR-181a-3p was downregulated in patients with LV adverse remodeling in comparison with patients without LV adverse remodeling and healthy volunteers. Conclusion: Circulating exosome miR-874-3p and miR-181a-3p were downregulated in patients with STEMI postinfarction. Exosome hsa-miR-181a-3p might play a potential role in the development of LVR in patients with post-STEMI.

USP10 deubiquitinates Tau, mediating its aggregation.

Normal Tau promotes the assembly and stabilization of microtubules, thus, maintaining axon transport. In Alzheimer's disease (AD), Tau aggregation causes it to lose these above-mentioned functions. However, the molecular mechanism leading to Tau aggregation in AD remains ambiguous. Here, we report that USP10, one of the important deubiquitinases (DUBs), is involved in Tau aggregation. We found that USP10 is upregulated in postmortem human AD and APP/PS1 mice brains, but not in P301S mice brains. Moreover, in primary neuronal cultures, Aß42 induces a dose-dependent USP10 upregulation, an increase in the levels of both total and phosphorylated Tau, as well as a markedly elevated Tau binding with USP10, that is accompanied by a significantly decreased Tau ubiquitination. In addition, overexpression of USP10 directly causes an increase in the levels of total and phosphorylated Tau, induces Tau aggregation, and delays in Tau degradation. Results from mass spectrometry, reciprocal immunoprecipitation, and immunofluorescence assays strongly prove Tau's interaction with USP10. This is further supported by the Tau307-326K and Tau341-378K peptides' competitive inhibition of Tau binding with USP10, attenuating Tau hyperphosphorylation and Tau deubiquitination. Together, our data strongly indicate that USP10 plays a critical role in mediating Tau aggregation via downregulating its ubiquitination and thus slowing down Tau turnover. Inhibition of USP10-Tau interaction might be therapeutically useful in the management of AD and related tauopathies.

Atypical location of primary cardiac lymphoma in the left heart with atypical clinical presentation: A case report and literature review.

Background: Primary cardiac lymphoma (PCL) is a rare and aggressive cardiac tumor with very poor prognosis that occurs mostly in the right cardiac cavity. Early diagnosis and treatment may improve its prognosis. In the present report, we describe the diagnosis and treatment of a primary cardiac diffuse large B-cell lymphoma (PC-DLBCL) with atypical location and clinical presentation. Additionally, a literature review was conducted to summarize the current knowledge of the disease. Case Presentation: A 71-year-old man visited his local hospital because of syncope, recurrent chest tightness, shortness of breath, palpitations, and profuse sweating for more than 20 days. Chest radiography revealed a mediastinal mass. Cardiac computed tomography (CT) showed multiple enlarged mediastinal lymph nodes. Transthoracic echocardiography (TTE) showed a cardiac mass in the posterior-inferior wall of the left atrium. He was then transferred to our hospital for positron emission tomography-CT (PET-CT) which showed active uptake of fluorodeoxyglucose both in the cardiac mass and in the multiple enlarged mediastinal lymph nodes. Biopsy of the enlarged mediastinal lymph nodes was carried out by using video-assisted thoracic surgery (VATS) technique, and pathological examination confirmed the subtype of PC-DLBCL, Stage IV, NCCN IPI 3. Therefore, the patient received a combination of chemotherapy and immunotherapy with R-CDOP (rituximab, cyclophosphamide, liposome doxorubicin, vincristine, and prednisone). After four courses of treatment in 4 months, the cardiac lymphoma and the enlarged mediastinal lymph nodes achieved complete remission with mild side effects of the chemotherapy. Conclusion: Early diagnosis and a precise choice of chemotherapy and immunotherapy based on cardiac imaging and pathological examination may improve the prognosis of PC-DLBCL in an atypical location.

Altered fecal microbiota composition in individuals who abuse methamphetamine.

As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.

Oral Microbiota Profile of Individuals Who Abuse Methamphetamine.

The poor oral health condition of individuals who abuse methamphetamine (MA) is well known. The roles of the oral and fecal microbiomes in addiction and nervous system diseases have been the focus of many studies. However, changes in the microbiota composition of MA users have not been reported. This was addressed in the present study in 20 MA users and 14 sex-matched healthy subjects. Saliva samples were collected and high-throughput 16S rRNA sequencing and bioinformatic analysis were performed to evaluate oral microbiome profiles. The results showed that species richness was significantly lower in the MA group than in the control group. Bacterial taxa that are known to be related to oral diseases such as Negativicutes, Veillonellaceae, Veillonella, and Selenomonadales had higher relative abundance in the MA group than in the control group, and the relative abundance of Prevotella melaninogenica-a putative etiologic agent of periodontal disease-was also higher. Avoiding MA use and improving oral hygiene practices over a short term (i.e., during hospitalization for 2 weeks) did not alter the oral microbiota composition of MA users. Although the causal relationship between changes in oral microbiome profile and MA abuse remains to be determined, our results suggest that oral disease prevention and treatment strategies are important for MA users.

Construction of the gene expression subgroups of patients with coronary artery disease through bioinformatics approach.

Coronary artery disease (CAD) is a heterogeneous disease that has placed a heavy burden on public health due to its considerable morbidity, mortality and high costs. Better understanding of the genetic drivers and gene expression clustering behind CAD will be helpful for the development of genetic diagnosis of CAD patients. The transcriptome of 352 CAD patients and 263 normal controls were obtained from the Gene Expression Omnibus (GEO) database. We performed a modified unsupervised machine learning algorithm to group CAD patients. The relationship between gene modules obtained through weighted gene co-expression network analysis (WGCNA) and clinical features was identified by the Pearson correlation analysis. The annotation of gene modules and subgroups was done by the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Three gene expression subgroups with the clustering score of greater than 0.75 were constructed. Subgroup I may experience coronary artery disease of an in-creased severity, while subgroup III is milder. Subgroup I was found to be closely related to the upregulation of the mitochondrial autophagy pathway, whereas the genes of subgroup II were shown to be related to the upregulation of the ribosome pathway. The high expression of APOE, NOS1 and NOS3 in the subgroup I suggested that the patients had more severe coronary artery disease. The construction of genetic subgroups of CAD patients has enabled clinicians to improve their understanding of CAD pathogenesis and provides potential tools for disease diagnosis, classification and assessment of prognosis.

Minimum heart rate and mortality in critically ill myocardial infarction patients: an analysis of the MIMIC-III database.

BACKGROUND: Low minimum heart rate (MHR) is common in critically ill myocardial infarction (MI) patients. However, the association between MHR and the mortality of critically ill MI patients remains unclear. METHODS: In this retrospective cohort study, a total of 2,031 critically ill MI patients were enrolled from the Medical Information Mart for Intensive Care (MIMIC)-III database. Patients were divided into a low MHR group [MHR <60 beats per minute (bpm)] and a high MHR group (MHR ≥60 bpm). A Cox proportional hazard model was used to elucidate the association between these two groups and the mortality of MI patients. The association between mortality and MHR as a continuous variable was analyzed non-parametrically using restricted cubic splines. Sensitivity analyses were conducted to determine the impact of different admission heart rate, hypertension, atrial fibrillation, and vasopressor use on our results. RESULTS: MI patients in the low MHR group had higher 30-day and 1-year mortality than those in the high MHR group (20.59% vs. 10.91%, P<0.001 and 29.76% vs. 19.31%, P<0.001, respectively). After adjustment, the low MHR group was significantly correlated with 30-day mortality [hazard ratio, 1.779, 95% confidence interval (CI), 1.400-2.261, P<0.001] and 1-year mortality (hazard ratio, 1.537, 95% CI, 1.272-1.859, P<0.001). This correlation remained remarkable in patients with low or high admission heart rate, with or without hypertension, and with or without atrial fibrillation. An apparent L-curve relationship was observed between the 30-day mortality or 1-year mortality and MHR as a continuous variable. CONCLUSIONS: MHR under 60 bpm may be associated with a higher risk for both 30-day and 1-year mortality in critically ill MI patients. These findings highlight the possibility of MHR as an early risk indicator and potential therapeutic target for mortality in critically ill MI patients, which warrants further investigation.