Disentangled Dynamic Deviation Transformer Networks for Multivariate Time Series Anomaly Detection.

Graph neural networks have been widely used by multivariate time series-based anomaly detection algorithms to model the dependencies of system sensors. Previous studies have focused on learning the fixed dependency patterns between sensors. However, they ignore that the inter-sensor and temporal dependencies of time series are highly nonlinear and dynamic, leading to inevitable false alarms. In this paper, we propose a novel disentangled dynamic deviation transformer network (D3TN) for anomaly detection of multivariate time series, which jointly exploits multiscale dynamic inter-sensor dependencies and long-term temporal dependencies to improve the accuracy of multivariate time series prediction. Specifically, to disentangle the multiscale graph convolution, we design a novel disentangled multiscale aggregation scheme to better represent the hidden dependencies between sensors to learn fixed inter-sensor dependencies based on static topology. To capture dynamic inter-sensor dependencies determined by real-time monitoring situations and unexpected anomalies, we introduce a self-attention mechanism to model dynamic directed interactions in various potential subspaces influenced by various factors. In addition, complex temporal correlations across multiple time steps are simulated by processing the time series in parallel. Experiments on three real datasets show that the proposed D3TN significantly outperforms the state-of-the-art methods.

Fine particulate matter-induced lung inflammation is mediated by pyroptosis in mice.

BACKGROUND: Exposure to ambient air-borne fine particulate matter (PM2.5) increases respiratory morbidity and mortality. The mechanisms underlying PM2.5-induced adverse effects remain unclear. This study aimed to uncover the molecular mechanisms of PM2.5-induced lung toxicity using a mouse model. METHODS: Scanning electron microscopy and inductively coupled plasma mass spectrometry were used to examine and analyze PM2.5 morphology and element compositions, respectively. Twenty four male mice were randomly divided into three groups: control (PBS), PM2.5 (4.0 mg/kg b.w.), and PM2.5 + Z-YVAD-FMK. In the latter group, the pan-caspase inhibitor (Z-YVAD-FMK) was intraperitoneally injected into mice at a dose of 12.5 mg/kg body weight prior to intratracheal instillation of PM2.5 (4.0 mg/kg b.w.) every other day for a total of 3 times (n = 8 in each group). Bronchoalveolar lavage fluids (BALFs) were collected 24 h after the last instillation of PM2.5. Levels of total proteins (TP), lactate dehydrogenase (LDH), IL-1ß and IL-18 were analyzed for biomarkers of cell injury and inflammation. Additionally, histological alterations of lung tissues were assessed by hematoxylin-eosin staining. mRNA and protein expression of Caspase1, NLRP3 and GSDMD were examined by real-time fluorescent quantitative PCR and immunohistochemical staining. RESULTS: Exposure to PM2.5 increased levels of TP, LDH, IL-1ß, IL-18 and inflammatory cell counts in lung. The mRNA and protein expression of Caspase1, NLRP3 and GSDMD were increased. Inhibition of the NALRP3/Caspase-1 signaling pathway ameliorated PM2.5-induced lung injury and inflammation, partially through suppressing pyroptosis in lung. CONCLUSION: PM2.5 exposure induces lung injury and inflammation, which is mediated by the NALRP3/Caspase-1 signaling pathway.

Fine particulate matter exposure exacerbated nasal mucosal damage in allergic rhinitis mice via NLRP3 mediated pyroptosis.

BACKGROUND: The incidence of nasal allergy/allergic rhinitis (AR) is rising worldwide, which has become a serious public health problem. Epidemiological studies point that exposure to environmental PM2.5 is closely linked to AR aggravation, however, the exactly mechanism is not clear. This study was performed to reveal molecular mechanisms of PM2.5 -induced AR deterioration. METHODS: Morphology and element analysis of PM2.5 was examined by scanning electron microscopy (SEM) and Energy Dispersive Spectrometer (EDS). A total of 24 female C57BL/6 mice were divided into three groups (control group, AR group, and PM2.5 + AR group, each group contains 8 mice). Mice from AR group and PM2.5 + AR group were intraperitoneally injected with OVA suspension (0.004% OVA+3% aluminum hydroxide) on days 1, 7, and 14. 0.2 mL /kg B.W. for sensitization; then the same mice were intranasal instilled with 5% OVA solution daily for 7 days to established AR mice model (each nostril for 10 µl, day 15-21). The mice were intranasal instilled PBS (control group and AR group, each nostril for 10 µl) or PM2.5 (AR + PM2.5 group, 4.0 mg/kg b.w., each nostril for 10 µl) at the same way from day 23-29. The nasal symptoms were evaluated after the last instillation of PM2.5. Pathological changes and ultrastructure of nasal mucosa were observed by HE staining and SEM. Goblet cells hyperplasia was performed by Periodic acid-Schiff (PAS) staining. NLRP3, Caspase-1, GSDMD and IL-1ß protein expression were assessed by immunohistochemical (IHC) staining. RESULTS: Exposure to PM2.5 aggravated rhinitis symptom, promoted the secretion of serum IgE level and destroyed ultrastructural of nasal mucosa. Interestingly, NLRP3, Caspase-1 GSDMD and IL-1ß protein expression were obviously elevated. NLRP3 /Capase-1/ GSDMD meditated cell pyroptosis participated in the process of AR exacerbation. However, macrophage is not the main effector cell. CONCLUSION: PM2.5 exposure induces aggravation of allergic rhinitis, which is related to NLRP3 inflammasome meditated caspase-1 activation and cell pyroptosis in nasal mucosal.

New Authentication Scheme for Wireless Body Area Networks Using the Bilinear Pairing.

Due to the development of information technologies and network technologies, healthcare systems have been employed in many countries. As an important part of healthcare systems, the wireless body area network (WBAN) could bring convenience to both patients and physicians because it could help physicians to monitor patients' physiological values remotely. It is essential to ensure secure communication in WBANs because patients' physiological values are very sensitive. Recently, Liu et al. proposed an efficient authentication scheme for WBANs. Unfortunately, Zhao pointed out that their scheme suffered from the stolen verifier-table attack. To improve security and efficiency, Zhao proposed an anonymous authentication scheme for WBANs. However, Zhao's scheme cannot provide real anonymity because the users' pseudo identities are constant value and the attack could tract the users. In this paper, we propose a new anonymous authentication scheme for WBANs. Security analysis shows that the proposed scheme could overcome weaknesses in previous scheme. We also use the BAN logic to demonstrate the security of the proposed scheme.

Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy.

Duchenne/Becker muscular dystrophies are the most frequent inherited neuromuscular diseases caused by mutations of the dystrophin gene. However, approximately 30% of patients with the disease do not receive a molecular diagnosis because of the complex mutational spectrum and the large size of the gene. The introduction and use of next-generation sequencing have advanced clinical genetic research and might be a suitable method for the detection of various types of mutations in the dystrophin gene. To identify the mutational spectrum using a single platform, whole dystrophin gene sequencing was performed using next-generation sequencing. The entire dystrophin gene, including all exons, introns and promoter regions, was target enriched using a DMD whole gene enrichment kit. The enrichment libraries were sequenced on an Illumina HiSeq 2000 sequencer using paired read 100 bp sequencing. We studied 26 patients: 21 had known large deletion/duplications and 5 did not have detectable large deletion/duplications by multiplex ligation-dependent probe amplification technology (MLPA). We applied whole dystrophin gene analysis by next-generation sequencing to the five patients who did not have detectable large deletion/duplications and to five randomly chosen patients from the 21 who did have large deletion/duplications. The sequencing data covered almost 100% of the exonic region of the dystrophin gene by ≥10 reads with a mean read depth of 147. Five small mutations were identified in the first five patients, of which four variants were unreported in the dmd.nl database. The deleted or duplicated exons and the breakpoints in the five large deletion/duplication patients were precisely identified. Whole dystrophin gene sequencing by next-generation sequencing may be a useful tool for the genetic diagnosis of Duchenne and Becker muscular dystrophies.

[Analysis of clinical features, metabolic profiling and gene mutations of patients with ornithine transcarbamylase deficiency].

OBJECTIVE: To analyze the clinical features, metabolic profiling and gene mutations of patients with ornithine transcarbamylase deficiency (OTCD) and explore the molecular pathogenesis of OTCD in order to provide a solution for molecular diagnostics and genetic counseling. METHODS: Clinical data of 3 neonates were analyzed. The amino acids level in blood was analyzed with mass spectrum technology. PCR was used to amplify all the 10 exons of OTC gene. The PCR products were directly sequenced to detect the mutations. RESULTS: All of the 3 cases had neonatal onset and showed poor reaction, feeding difficulty, convulsion and neonatal infection. Citrulline levels were significantly decreased. Case 1 had a missense mutation of Y183C. Case 2 showed a missense mutation of V339G in exon 10. And a missense mutations of W332S in exon 9 was detected in case 3. CONCLUSION: Analysis of OTC gene sequences can be used for the diagnosis of OTCD and screening of asymptomatic carriers. Mutation analysis is important for prenatal diagnosis of individuals with a positive family history and genetic counseling. The V339G and W332S mutations have been discovered for the first time. Patients with such mutations may have onset of the disease during neonatal period.

Environmental profiles, hazard identification, and toxicological hallmarks of emerging tire rubber-related contaminants 6PPD and 6PPD-quinone.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and ozone exposure. This practice extends the lifespan of rubber products, including tires, by preventing cracking, aging, and deterioration. However, the environmental consequences of waste generated during rubber product use, particularly the formation of 6PPD-quinone (6PPD-Q) through the reaction of 6PPD with ozone, have raised significant concerns due to their detrimental effects on ecosystems. Extensive research has revealed the widespread occurrence of 6PPD and its derivate 6PPD-Q in various environmental compartments, including air, water, and soil. The emerging substance of 6PPD-Q has been shown to pose acute mortality and long-term hazards to aquatic and terrestrial organisms at concentrations below environmentally relevant levels. Studies have demonstrated toxic effects of 6PPD-Q on a range of organisms, including zebrafish, nematodes, and mammals. These effects include neurobehavioral changes, reproductive dysfunction, and digestive damage through various exposure pathways. Mechanistic insights suggest that mitochondrial stress, DNA adduct formation, and disruption of lipid metabolism contribute to the toxicity induced by 6PPD-Q. Recent findings of 6PPD-Q in human samples, such as blood, urine, and cerebrospinal fluid, underscore the importance of further research on the public health and toxicological implications of these compounds. The distribution, fate, biological effects, and underlying mechanisms of 6PPD-Q in the environment highlight the urgent need for additional research to understand and address the environmental and health impacts of these compounds.

Reference intervals for serum thyroid hormones in preterm hospitalized infants.

OBJECTIVE: In our study, the reference intervals of serum thyroid hormones were established in 247 hospitalized preterm infants from 28 to 36 weeks of gestation at 8-15 postnatal days. The thyroid hormones were serum triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxine (FT4), and thyrotropin (TSH). METHODS: Electrochemiluminescence immunoassay was used to examine the thyroid hormone levels of serum samples from 247 preterm infants, who were grouped on sampling by gestational age. SPSS 16.0 was used to calculate the population-based reference intervals, in comparison to the manufacturer's suggested reference intervals. RESULTS: Kruskal-Wallis H tests could not determine the difference in TSH levels among groups, which allowed us to develop a single interval for the study population. ANOVA determined the differences in T3, FT3, T4, and FT4 levels among groups, which allowed us to define reference intervals for preterm infants according to their gestational age. CONCLUSION: Developed reference intervals are useful for clinical diagnosis; however, there is a lack of consensus. These values could be used to assess the thyroid status of preterm infants and provide a foundation for clinical therapy. The results emphasized the importance of establishing gestational age-based reference intervals for the clinical laboratory.

Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis.

OBJECTIVE: Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication. RESULTS: Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05). CONCLUSION: Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.

[Genetic analysis of a supernumerary derivative chromosome 15].

OBJECTIVE: To detect and analyze a supernumerary derivative chromosome 15 with combined cytogenetic and molecular techniques, and to discuss the correlation between genomic copy number variations (CNVs) and clinical phenotypes. METHODS: G-banded chromosome analysis and multiplex ligation-dependent probe amplification (MLPA) were carried out. The whole genome of the patient was also analyzed with array-comparative genome hybridization(array-CGH). RESULTS: G-banding analysis indicated that the patient has a karyotype of 47, XY, + mar, with the supernumerary chromsome derived from 15q11-13 region spanning 9.8 Mb from locus 20477397 to 30298155. CONCLUSION: CNVs of 15q11-13 are associated with mental retardation, language development delay and autistic disorder. Conventional cytogenetic analysis with array-CGH may provide a platform for accurate detection of chromosomal aberrations, which can faciliate the study of genome rearrangement underlying various diseases.

[Clinical and molecular genetic analysis for a patient with glycogen storage disease â a].

OBJECTIVE: To investigate the mutation of glucose-6-phosphatase gene (G6PC gene) in a patient with glycogen storage disease Ⅰa. METHODS: PCR was used to amplify all five exons of G6PC gene. The PCR products were directly sequenced to detect the mutations. RESULTS: A heterozygous 743G>A mutation was found in the patient and his mother, resulting in the substitution of glycine (G) by arginine (R) in codon 222(G222R) in the putative membrane-spanning domain in human G6Pase, but not in his father and his sister. CONCLUSIONS: G222R mutation in G6PC gene was first identified in a patient with glycogen storage disease Ⅰa in mainland China.

[Value of methylation-specific mutiplex ligation-dependent probe in the diagnosis of Prader-Willi syndrome].

OBJECTIVE: Prader-Willi syndrome (PWS) with different pathogenesis has different clinical manifestations, prognosis and genetic risks. Pathogenesis of the disease cannot be explained by conventional diagnostic method MS-PCR. This study employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for the diagnosis of PWS in order to explore the role of this method in the diagnosis and assessment of pathogenesis of PWS. METHODS: A system antithetical method was employed. Peripheral blood samples were collected from 30 children for MS-PCR. Of the 30 children, 16 were diagnosed with PWS by MS-PCR and the other 14 showed negative MS-PCR. MS-MLPA kit Me028 was used to detect DNA extracted from the 30 samples. RESULTS: The results showed by MS-MLPA and MS-PCR were identical. MS-MLPA demonstrated that 4 cases were maternal uniparental disomy and 12 cases were paternal dfeletion in 15q11-q13 region. CONCLUSIONS: MS-MLPA is a reliable method of genetic testing for PWS which can distinguish pathogenesis of PWS.

An integrated remote sensing and model approach for assessing forest carbon fluxes in China.

Forest plays an important role in reducing pressure on the natural environment, weaking the influence of greenhouse effects, and sequestrating atmospheric carbon dioxide. So far, due to the lack of complete understanding of forest ecosystem processes and the limitations on the scope of application of evaluation methods, there are still great uncertainties in the researches on carbon fluxes of forest ecosystems in China at the national level. In this study, an individual tree species FORCCHN model, which could flexibly use the inventory data as the initial field (more accurately) or use the remote sensing information to inverse initial field was applied. The dynamics of key carbon cycle fluxes (net primary productivity (NPP) and net ecosystem productivity (NEP)) and carbon sequestration of forest ecosystems in China from 1982 to 2019 were simulated based on remote sensing data and FORCCHN model. The results showed that forest ecosystems in China had great carbon sequestration potential over the past 39 years. From 1982 to 2019, the NPP of Chinese forests presented a fluctuated increase. Total NPP from 2011 to 2019 ranged from 0.91 PgC·a-1 to 1.14 PgC·a-1. Annual average NEP of forest ecosystems in China from 2011 to 2019 was 0.199 PgC·a-1 (1Pg = 1015 g). Influenced by climate, soil and vegetation, carbon sequestration potential in Chinese forest ecosystems presented obvious regional differences in space. The spatial distribution of NEP gradually increased from Northwest to Southeast China. From 2011 to 2019, forests in Yunnan Province had the strongest carbon storage capacity (72.79 TgC·a-1, 1Tg = 1012 g), followed by forests in Guangxi (18.49 TgC·a-1) and forests in Guangdong (10.01 TgC·a-1). Our results not only address concerns about carbon sequestration but also reflect the importance of Chinese forest resources in the development of the national economy and society.

Prevalence and clinical characteristics of COVID-19 in inpatients with schizophrenia in Wuhan, China.

BACKGROUND: In contrast to many Western countries, China has maintained its large psychiatric hospitals. The prevalence and clinical characteristics of coronavirus disease 2019 (COVID-19) in inpatients with schizophrenia (SCZ) are unclear. AIM: To assess the prevalence of COVID-19 among inpatients with SCZ and compare the infected to uninfected SCZ patients in a Wuhan psychiatric hospital. METHODS: We retrospectively collected demographic characteristics and clinical profiles of all SCZ patients with COVID-19 at Wuhan's Youfu Hospital. RESULTS: Among the 504 SCZ patients, 84 had COVID-19, and we randomly sampled 174 who were uninfected as a comparison group. The overall prevalence of COVID-19 in SCZ patients was 16.7%. Among the 84 SCZ patients with confirmed COVID-19, the median age was 54 years and 76.2% were male. The most common symptom was fever (82%), and less common symptoms were cough (31%), poor appetite (20%), and fatigue (16%). Compared with SCZ patients without COVID-19, those with COVID-19 were older (P = 0.006) and significantly lighter (P = 0.002), and had more comorbid physical diseases (P = 0.001). Surprisingly, those infected were less likely to be smokers (< 0.001) or to be treated with clozapine (P = 0.03). Further logistic regression showed that smoking [odds ratio (OR) = 5.61], clozapine treated (OR = 2.95), and male (OR = 3.48) patients with relatively fewer comorbid physical diseases (OR = 0.098) were at a lower risk for COVID-19. SCZ patients with COVID-19 presented primarily with fever, but only one-third had a cough, which might otherwise be the most common mode of transmission between individuals. CONCLUSION: Two unexpected protective factors for COVID-19 among SCZ inpatients are smoking and clozapine treatment.

MicroRNA expression profile in hyperoxia-exposed newborn mice during the development of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm neonates; the underlying pathogenesis is not fully understood. MicroRNAs (length 21-25 nucleotides) are ribonucleic acid (RNA) molecules that have important functions in development, cellular differentiation, apoptosis, proliferation, and migration; very little is known regarding their role in developmental lung diseases. METHODS: We exposed neonatal mice to either room air or 60% oxygen, beginning at birth, and we used microRNA microarray and real-time polymerase chain reaction on lung samples. RESULTS: The hyperoxia-exposed mice developed a lung injury that mimicked human BPD. Fifty-one microRNAs shared similar profiles in the hyperoxia-exposed BPD lungs and the normal lungs, which indicates that those microRNAs might play a protective role during the septation process. In the BPD lungs, compared to the control lungs, 14 microRNAs were up-regulated, and 7 microRNAs were down-regulated, which indicates that these microRNAs might play an important role in the development of BPD. Some of the candidate microRNAs can regulate cell proliferation. CONCLUSIONS: To our knowledge, this study is the first to identify microRNAs associated with BPD development, which provides a clue for further investigation of their function in BPD development.

[Chromosome analysis in 92 children with congenital mental retardation].

OBJECTIVE: To explore the chromosome karyotypes in children with mental retardation. METHODS: The peripheral blood lymphocytes from 92 children with congenital mental retardation were cultured and analysed by the G-band technique. RESULTS: Of the 92 cases, 43 cases (47%) showed chromosome abnormalities. Autosomal abnormalities were found in 35 cases (38%) and sex chromosome abnormalities were found in 8 cases (9%). A novel abnormal karyotype 45, XX, psu dic (11;9) (p15;p24) was found in a child. CONCLUSIONS: Chromosome abnormalities may be important cytogenetic factors for congenital mental retardation. Cytogenetic chromosome karyotypic analysis appears to be an important method for genetic screening of congenital mental retardation.

Metabarcoding Analysis of Harmful Algal Bloom Species in the Western Pacific Seamount Regions.

The Western Pacific is the most oligotrophic sea on Earth, with numerous seamounts. However, the plankton diversity and biogeography of the Western Pacific in general and the seamount regions in particular remains largely unexplored. In this project, we quantitatively analyzed the composition and distribution patterns of plankton species in the Western Pacific seamount regions by applying metabarcoding analysis. We identified 4601 amplicon sequence variants (ASVs) representing 34 classes in seven protist phyla/divisions in the Western Pacific seamount regions, among which Dinoflagellata was by far the most dominant division. Among the 336 annotated phytoplankton species (including species in Dinoflagellata), we identified 36 harmful algal bloom (HAB) species, many of which displayed unique spatial distribution patterns in the Western Pacific seamount regions. This study was the first attempt in applying ASV-based metabarcoding analysis in studying phytoplankton and HAB species in the Western Pacific seamount regions, which may facilitate further research on the potential correlation between HABs in the Western Pacific seamount regions and coastal regions.

Single-Atom Ru Implanted on Co3 O4 Nanosheets as Efficient Dual-Catalyst for Li-CO2 Batteries.

Li-CO2 battery has attracted extensive attention and research due to its super high theoretical energy density and its ability to fix greenhouse gas CO2 . However, the slow reaction kinetics during discharge/charge seriously limits its development. Hence, a simple cation exchange strategy is developed to introduce Ru atoms onto a Co3 O4 nanosheet array grown on carbon cloth (SA Ru-Co3 O4 /CC) to prepare a single atom site catalyst (SASC) and successfully used in Li-CO2 battery. Li-CO2 batteries based on SA Ru-Co3 O4 /CC cathode exhibit enhanced electrochemical performances including low overpotential, ultra high capacity, and long cycle life. Density functional theory calculations reveal that single atom Ru as the driving force center can significantly enhance the intrinsic affinity for key intermediates, thus enhancing the reaction kinetics of CO2 reduction reaction in Li-CO2 batteries, and ultimately optimizing the growth pathway of discharge products. In addition, the Bader charge analysis indicates that Ru atoms as electron-deficient centers can enhance the catalytic activity of SA Ru-Co3 O4 /CC cathode for the CO2 evolution reaction. It is believed that this work has important implications for the development of new SASCs and the design of efficient catalyst for Li-CO2 batteries.

Influencing Factors of Hospital-Acquired Pneumonia Infection in the Middle-Aged and Elderly Patients With Schizophrenia.

Introduction: Pneumonia is an important cause of death in patients with schizophrenia. It is critical to understand the risk factors of hospital-acquired pneumonia (HAP) and determine prevention strategies to reduce HAP. The aim of this study is to elucidate the risk factors for HAP in the middle-aged and elderly hospitalized patients with schizophrenia. Methods: We retrospectively reviewed the medical records of 2,617 the middle-aged and elderly patients (age ≥ 50) with schizophrenia who were admitted for the first time to a large-scale psychiatric hospital between 2016 and 2020. The factors related to the incidence of HAP in patients were analyzed, including personal characteristics, antipsychotics, and non-antipsychotics. Results: The HAP infection rate of hospitalized the middle-aged and elderly patients with schizophrenia was 7.8%. Chi-square analyses showed that older age, male, and ≥60 days of hospitalization were risk factors for HAP infection (χ2 = 94.272, p < 0.001; χ2 = 22.110, p < 0.001; χ2 = 8.402, p = 0.004). Multivariate logistic regression showed that quetiapine, clozapine, and olanzapine significantly increased the incidence of HAP (OR = 1.56, 95% CI = 1.05-2.32, p = 0.029; OR = 1.81, 95% CI = 1.26-2.60, p = 0.001; OR = 1.68, 95% CI = 1.16-2.42, p = 0.006). Antipsychotic drugs combined with aceglutamide had an effect on HAP (OR = 2.19, 95% CI = 1.38-3.47, p = 0.001). Conclusion: The high HAP infection rate in hospitalized the middle-aged and elderly patients with schizophrenia may be related to the increase of age and the use of antipsychotic drugs. The types and dosages of antipsychotic drugs should be minimized while paying attention to the mental symptoms of patients.

Inactivation of PI3k/Akt signaling pathway and activation of caspase-3 are involved in tanshinone I-induced apoptosis in myeloid leukemia cells in vitro.

Tanshinone I (Tan I), a diterpene quinone extracted from herbal medicine Salvia miltiorrhiza Bunge, has recently been reported to have antitumor effects. As the mechanism of its proapoptotic effects on human myeloid leukemia cells has not been extensively studied, we performed an in-depth evaluation of the effects of Tan I on apoptosis in human K562 and HL-60 cells. The results revealed that Tan I could inhibit the growth of leukemia cells and cause apoptosis in a time- and dose-dependent manner. Apoptosis was observed clearly by flow cytometry and Hoechst 33258 staining, as well as DNA fragmentation analysis. After treatment by Tan I for 48 h, the percentage of disruption of mitochondrial membrane potential (Δψm) was increased in a dose-dependent manner. Western blotting analysis demonstrated the cleavage of caspase-3 zymogen protein and a dose-dependent cleavage of poly-(ADP-ribose) polymerase. Tan I-induced apoptosis was accompanied by a significant decrease in survivin and an increase in Bax. Moreover, Tan I treatment remarkably downregulated the phosphorylation of both P85/PI3K and Akt in a time-dependent manner, and the PI3K/AKT-specific inhibitor (LY294002) mimicked the apoptosis-inducing effects of Tan I. We therefore conclude that the induction of apoptosis by Tan I in these leukemia cells is mainly related to the disruption of Δψm, the upregulation of Bax expression, and the activation of caspase-3. This process is highly correlated with the inactivation of PI3K/Akt/survivin signaling pathways. The results indicate that Tan I may serve as an effective adjunctive reagent in the treatment of leukemia.