Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.

BACKGROUND: Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined. AIM: To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism. METHODS: In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale. RESULTS: COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, ß = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, ß = -0.250, 95%CI: -0.495 to -0.004, P = 0.046). CONCLUSION: This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

A Terphenyllin Derivative CHNQD-00824 from the Marine Compound Library Induced DNA Damage as a Potential Anticancer Agent.

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls-a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core-has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative-CHNQD-00824-derived from the marine compound library as a potential anticancer agent. The cytotoxic activities of the CHNQD-00824 compound were evaluated against 13 different cell lines with IC50 values from 0.16 to 7.64 µM. Further study showed that CHNQD-00824 inhibited the proliferation and migration of cancer cells, possibly by inducing DNA damage. Acridine orange staining demonstrated that CHNQD-00824 promoted apoptosis in zebrafish embryos. Notably, the anti-cancer effectiveness was verified in a doxycin hydrochloride (DOX)-induced liver-specific enlargement model in zebrafish. With Solafinib as a positive control, CHNQD-00824 markedly suppressed tumor growth at concentrations of 2.5 and 5 µM, further highlighting its potential as an effective anticancer agent.

Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Management of liver transplantation perioperative period in acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.

Altered frequency-specific/universal amplitude characteristics of spontaneous brain oscillations in patients with bipolar disorder.

The human brain is a dynamic system with intrinsic oscillations in spontaneous neural activity. Whether the dynamic characteristics of these spontaneous oscillations are differentially altered across different frequency bands in patients with bipolar disorder (BD) remains unclear. This study recruited 65 patients with BD and 85 healthy controls (HCs). The entire frequency range of resting-state fMRI data was decomposed into four frequency intervals. Two-way repeated-measures ANCOVA was employed to detect frequency-specific/universal alterations in the dynamic oscillation amplitude in BD. The patients were then divided into two subgroups according to their mood states to explore whether these alterations were independent of their mood states. Finally, other window sizes, step sizes, and window types were tested to replicate all analyses. Frequency-specific abnormality of the dynamic oscillation amplitude was detected within the posterior medial parietal cortex (centered at the precuneus extending to the posterior cingulate cortex). This specific profile indicates decreased amplitudes in the lower frequency bands (slow-5/4) and no amplitude changes in the higher frequency bands (slow-3/2) compared with HCs. Frequency-universal abnormalities of the dynamic oscillation amplitude were also detectable, indicating increased amplitudes in the thalamus and left cerebellum anterior lobe but decreased amplitudes in the medial superior frontal gyrus. These alterations were independent of the patients' mood states and replicable across multiple analytic and parametric settings. In short, frequency-specific/universal amplitude characteristics of spontaneous oscillations were observed in patients with BD. These abnormal characteristics have important implications for specific functional changes in BD from multiple frequency and dynamic perspectives.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Metagenome Sequencing Reveals the Microbiome of Aedes albopictus and Its Possible Relationship With Dengue Virus Susceptibility.

Dengue fever virus (DENV) is a mosquito-borne flavivirus that poses a serious risk to human health. Aedes albopictus is a widely distributed vector of dengue fever in China. Based on the impact of physiological activity, the microbiome in A. albopictus will provide a novel environment-friendly approach to control DENV transmission. We performed metagenomic sequencing on A. albopictus before and after exposure to DENV blood meal to detect microbiome variation of A. albopictus with different susceptibilities to DENV. The dominant phyla in A. albopictus microbiome were Proteobacteria and Ascomycota, and the dominant genera were Aspergillus and Metarhizium. Gammaproteobacteria bacterium, Lactobacillus harbinensis, and Neurospora crassa differed significantly after DENV infection. There were 15 different microorganisms found to be involved in mosquito immunity and metabolism, such as Alphaproteobacteria bacterium, Methyloglobulus morosus, and Shigella sonnei, which might have an impact on the DENV susceptibility of A. albopictus. It was hypothesized that the lack of specific bacteria may lead to increased susceptibility of A. albopictus to DENV. Interventions in the microbiome composition or specific bacteria of A. albopictus may affect the susceptibility to DENV and control the mosquito-borne diseases efficiently.

The effects of childhood trauma on personality in unaffected first-degree relatives of patients with major depressive disorder.

ABSTRAC: OBJECTIVES: This study aimed to preliminarily and exploratorily examine the associations between childhood trauma (CT), its subtypes, and personality traits among unaffected first-degree relatives (FDR, children, or siblings) of patients with major depressive disorder (MDD). METHODS: The study sample included three subgroups: MDD patients (N = 85), Patients' FDRs (N = 35), and healthy control individuals (HC, N = 89). The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma and the Eysenck Personality Questionnaire was used to assess personality traits. RESULTS: Significant differences were found in a few personality traits (p < 0.05 for extraversion, neuroticism, and psychoticism) among MDD patients, FDR, and HC, and there were no significant differences between HC and FDR. In the FDR group, compared with those without CT, participants with CT scored significantly higher for neuroticism (N) (F = 3.246, p = 0.046). CT was significantly associated with N, psychoticism (P) and Lie (L), and the strongest association was between CT total score and N. Significantly positive correlations were found between N and sexual abuse (SA) (r = 0.344, p = 0.043), emotional neglect (EN) (r = 0.394, p = 0.019), physical neglect (PN) (r = 0.393, p = 0.019), and CTQ total score (r = 0.452, p = 0.006); between P and CTQ total score (r = 0.336, p = 0.049); and significant negative correlations were found between L and EN (r = -0.446, p = 0.007), CTQ total score (r = -0.375, p = 0.027). CONCLUSION: In unaffected FDRs, there were significant associations between childhood trauma and a few personality traits, including neuroticism, psychoticism, and lie, and emotional neglect was significantly associated with neuroticism.

Detection of Schizophrenia Cases From Healthy Controls With Combination of Neurocognitive and Electrophysiological Features.

Background: The search for a method that utilizes biomarkers to identify patients with schizophrenia from healthy individuals has occupied researchers for decades. However, no single indicator can be employed to achieve the good in clinical practice. We aim to develop a comprehensive machine learning pipeline based on neurocognitive and electrophysiological combined features for distinguishing schizophrenia patients from healthy people. Methods: In the present study, 69 patients with schizophrenia and 50 healthy controls participated. Neurocognitive (contains seven specific domains of cognition) and electrophysiological [prepulse inhibition, electroencephalography (EEG) power spectrum, detrended fluctuation analysis, and fractal dimension (FD)] features were collected, all these features were taken together to generate the identification models of schizophrenia by applying logistics, random forest, and extreme gradient boosting algorithm. The classification capabilities of these models were also evaluated. Results: Both the neurocognitive and electrophysiological feature sets showed a good classification effect with the highest accuracy greater than 85% and AUC greater than 90%. Specifically, the performances of the combined neurocognitive and electrophysiological feature sets achieved the highest accuracy of 93.28% and AUC of 97.91%. The extreme gradient boosting algorithm as a whole presented more stably and precisely in classification efficiency. Conclusion: The highest classification accuracy of 93.28% by combination of neurocognitive and electrophysiological features shows that both measurements are appropriate indicators to be used in discriminating schizophrenia patients and healthy individuals. Also, among three algorithms, extreme gradient boosting had better classified performances than logistics and random forest algorithms.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Comparison of the performance of SCORTEN and ABCD-10 in evaluating the prognosis of Stevens-Johnson syndrome/toxic epidermal necrolysis / 中华皮肤科杂志

Objective:To compare the performance of the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) and ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area) scoring systems in predicting death in patients with Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) .Methods:Clinical data were collected from 85 patients with SJS/TEN who were hospitalized in Sichuan Provincial People′s Hospital from January 2010 to April 2021, and retrospectively analyzed. The predicted mortality and actual mortality were compared at each score level of SCORTEN and ABCD-10. The receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the predictive power and calibration of SCORTEN and ABCD-10 on mortality.Results:Among the 85 patients, 37 were males and 48 were females, and their ages were 52.36 ± 19.31 years (range, 14 - 88 years) . There were 61 cases of SJS, 6 of SJS/TEN overlap, and 18 of TEN. Ten patients died in hospital and the fatality rate was 11.76%. Among the SCORTEN and ABCD-10 components, age > 40 years or ≥ 50 years, epidermal exfoliation > 10% body surface area on the 1st day after admission, heart rate > 120 beats per minute, serum urea nitrogen level > 10 mmol/L and serum bicarbonate level < 20 mmol/L were significantly correlated with death ( χ2 = 4.46, 6.18, 25.50, 15.13, 7.59, 8.38, respectively, all P < 0.05) , while malignancies, serum glucose level > 14 mmol/L, and pre-hospital dialysis were not significantly correlated with death ( χ2 = 0.35, 0.10, 1.38, respectively, all P > 0.05) . There were no significant differences between the predicted mortality and actual mortality at every score level of SCORTEN and ABCD-10 (all P > 0.05) . The ROC curve showed that both SCORTEN and ABCD-10 had good predictive power for death (areas under the curve: 0.874 and 0.867, 95% CI: 0.758 - 0.990, 0.773 - 0.962, respectively) , but the model goodness-of-fit of SCORTEN was superior to that of ABCD-10 ( P = 0.944, 0.048, respectively) . Conclusion:Both SCORTEN and ABCD-10 scoring systems could accurately predict mortality of SJS/TEN patients at early stage, but SCORTEN showed more favourable predictive power and calibration.

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

The Neglect of Left-Behind Children in China: A Meta-Analysis.

OBJECTIVE: To evaluate the neglect of left-behind children (LBC) in China. METHOD: Participants: Children separated from one or both parents for at least 6 months. Intervention: Trauma of separation. Comparison: Non-left-behind children (NLBC). Outcomes: Neglect rates and severity. Only case-control studies were included. RESULTS: Thirteen studies were included; there were 18,688 LBC in a large sample (N = 42,003) of children aged 0-18 years in China. The overall neglect rate was significantly higher in LBC compared to NLBC (odds ratio [OR] = 1.58, 95% confidence interval [CI] = [1.50, 1.67], p < .01) based on the Chinese Rural Child Neglected Evaluation Model (CRCNEM) and the Parents-Child Conflict Tactics Scales (OR = 1.44, 95% CI [1.35, 1.54], p < .01). The overall neglect severity in LBC was also significantly higher than NLBC (SMD = 0.31, 95% CI [0.28, 0.33], p < .01). The same trends were observed in sex subgroups. With regard to subtypes, LBC were significantly more likely to have emotional neglect (OR = 2.29, 95% CI [1.88, 2.78], p < .01), medical neglect (OR = 1.79, 95% CI [1.62, 1.98], p < .01), physical neglect (OR = 1.75, 95% CI [1.60, 1.91], p < .01), security neglect (OR = 1.52, 95% CI [1.32, 1.75], p < .01), educational neglect (OR = 1.50, 95% CI [1.31, 1.72], p < .01), and social neglect (OR = 1.33, 95% CI [1.18, 1.51], p < .01). Furthermore, LBC had significantly higher severity in medical neglect (SMD = 0.31, 95% CI [0.27, 0.35], p < .01), emotional neglect (SMD = 0.28, 95% CI [0.24, 0.32], p < .01), physical neglect (SMD = 0.24, 95% CI [0.18, 0.29], p < .01), security neglect (SMD = 0.26, 95% CI [0.23, 0.29], p < .01), educational neglect (SMD = 0.25, 95% CI [0.20, 0.31], p < .01), and social neglect (SMD = 0.25, 95% CI [0.10, 0.40], p < .01). CONCLUSION: The neglect rates and severity in LBC in China were both significantly higher than those in NLBC. There was a strong association between neglect and LBC. Public policy changes are urgently needed to improve the dire situation and the well-being of the LBC.

Viral Metagenomics Analysis of Rodents From Two Border Provinces Located in Northeast and Southwest China.

Objective: Wild animal pathogen surveillance will help to understand the next possible pandemic in advance. Rodents, which have close contact with humans, are generally regarded as a key factor for zoonotic disease control. Given the variation in rodent virus composition in diverse ecologies, we conducted a study on the viral infection of rodents of diverse species in different typical environments of Heilongjiang and Yunnan Provinces, located in northeastern and southwestern China, respectively. Methods: Viral metagenomics sequencing and bioinformatic analysis were performed to determine the different distributions of rodent-borne viruses in typical environments of Heilongjiang and Yunnan Provinces, China. After viral culture and PCR confirmation, genomic and phylogenetic quantitative analysis was performed on the detected hantaviruses (HVs) and Beilong viruses (BeiVs). Results: Nineteen rodents from three species and 35 rodents from five species of rodents were collected from Heilongjiang and Yunnan Provinces, respectively. Although the number and number of species of rodents trapped in the northeast were fewer than those in the southwest, viruses annotated from rodents in Heilongjiang were more diverse than those in Yunnan. Rodents carried 22 virus families in Heilongjiang and 13 families in Yunnan. Sequences assembled from Rattus norvegicus were annotated to the M, L, and S segments of HV, and all were clustered within the Seoul-type hantavirus (SEOV). There were 2 (R81Q, S698T) and 4 (K153R, M168I, I279S, and R1790K) amino acid site substitutions in M and L compared with the versions in the most homologous strains. Two BeiV isolates from Rattus norvegicus were closely related to BeiV from brown rats in Hong Kong, with high bootstrap values of >90% in the N segment and > 95% in the L segment. They were further clustered with Tailam virus, forming a distinct group in Paramyxoviridae. Conclusion: The rodents from Heilongjiang and Yunnan located in northeast and southwest China, respectively, had different viral spectra, and only one-third (10/32) of virus families were detected in both areas. The predominant viruses were HV and BeiV in the Hantaviridae and Paramyxoviridae families, respectively. Rodent-borne viruses in the same species were similar in different geographic disparate areas owing to their similar close contact with human habitats and human activities. Additional attention should be given to the monitoring of neglected rodent-borne viruses, especially opportunistic viruses with currently low loads.

Low expression S100 calcium ion binding protein A6 promoting the proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells / 解剖学报

Objective To explore the effect of S100 calcium ion binding protein A6 (S100A6) on proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells. Methods Lenti viruses were used to construct stable transfected cell lines (shNC and shS100A6). Real-time PCR was used to detect the mRNA expression of S100A6. The inverted microscope and MTT were used to detect cell proliferation. The Transwell assay was used to detect cell migration. Western blotting was used to detect the expression of S100A6, p-ERK, p-Akt and its downstream molecular involved in proliferation and migration. Using U0126 ( inhibitor of MER1/2) and LY294002 ( inhibitor of PI3K) to detect the effect of these two inhibitors on cell proliferation and migration and the expression of p-ERK, p-Akt and its downstream molecular involved in proliferation and migration in shS100A6 cells. Results Stable cell lines of knockdown S100A6 were constructed. Knockdown S100A6 promoted cell proliferation and migration. Western blotting result displayed that in shS100A6 cells, the levels of p-Akt and p-ERK increased, p21 decreased, cyclinDl increased, and the expression of β-catenin and vimentin, increased. U0126 and LY294002 inhibited the migration of shS100A6 cells. U0126 had no effect on the proliferation of shS100A6 cells, however LY294002 could inhibit the proliferation of shS100A6 cells. U0126 treatment on shS100A6 cells could decrease p-ERK and β-catenin expression. After shS100A6 cells treated with LY294002, p-Akt and β-catenin expression decreased, p21 expression increased and the expression of cyclinDl decreased. Conclusion Low expression of S100A6 promotes cell proliferation and migration, which may be mediated by activation of p-Akt regulating cell cycle progression to promote cell proliferation and by activation of p-Akt/p-ERK to regulate β-catenin to promote cell migration.

Effect of hydrogen on activation of A1 astrocytes in hippocampus of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the effect of hydrogen on activation of A1 astrocytes in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:A total of 164 clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=41 each) using a random number table method: sham operation group (group Sham), sham operation plus hydrogen group (group Sham+ H 2), group SAE and SAE plus hydrogen group (group SAE+ H 2). The SAE model was established by cecal ligation and perforation.Group Sham+ H 2 and group SAE+ H 2 inhaled 2% hydrogen starting from 1 and 6 h after operation, respectively.Twenty mice in each group were selected to observe the 7-day survival rate after operation.The remaining mice were sacrificed at 12 h after operation, and brain tissues were removed for examination of the pathological changes in hippocampal CA1 region (with a light microscope) and for determination of the apoptosis in neurons (by TUNEL), co-expression of hippocampal glial fibrillary acidic protein (GFAP) and complement C3 (by immunofluorescence staining), expression of A1 astrocyte marker C3 (by Western blot), and contents of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) (by enzyme-linked immunosorbent assay). The abnormal cell ratio and apoptosis rate were calculated.Six mice in each group were selected at 7 days after operation to perform Y-Maze paradigm. Results:Compared with group Sham, the 7-day survival rate after operation was significantly decreased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were increased, the contents of TNF-α, IL-6 and HMGB1 were increased, the expression of C3 was up-regulated, the number of cells coexpressing GFAP and C3 was increased, the exploration time spent in the novel arm in Y-Maze paradigm was shortened, and the preference index was decreased in group SAE ( P<0.05). Compared with group SAE, the 7-day survival rate after operation was significantly increased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were decreased, the contents of TNF-α, IL-6 and HMGB1 were decreased, the expression of C3 was down-regulated, the number of cells coexpressing GFAP and C3 was decreased, the exploration time spent in the novel arm in Y-Maze paradigm was prolonged, and the preference index was increased in group SAE+ H 2 ( P<0.05). There was no significant difference in each parameter mentioned above between Sham group and Sham+ H 2 group ( P>0.05). Conclusion:The mechanism by which hydrogen improves SAE may be related to inhibiting activation of A1 type astrocytes in mice.

The predictive value of red blood cell distribution width in predicting the prognosis of patients with Extracorporeal Membrane Oxygenation / 中华急诊医学杂志

Objective:To explore the predictive value of Red Blood Cell Distribution Width (RDW) in predicting the prognosis of patients with Extracorporeal Membrane Oxygenation (ECMO).Methods:The clinical data of patients undergoing ECMO admitted to Intensive Care Unit of Sichuan Provincial People’s Hospital from January 2015 to January 2020 were retrospectively analyzed. Patients were divided into the survival group and death group according to the prognosis during ICU hospitalization. The patients' basic data , acute physiology and chronic health score system Ⅱ (APACHE Ⅱ), RDW and activated partial thromboplastin time (APTT) at 72 hours after treatment with ECMO were compared between the two groups. Univariate and Logistic regression multivariate analyses were used to analyze the prognostic factors of patients with ECMO, predictive models and death warning scores were established. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficacy of RDW and death warning scores for the prognosis of patients with ECMO.Results:A total of 71 patients with ECMO who met the inclusion criteria were included, including 38 patients in the death group and 33 patients in the survival group. The age, APACHE-Ⅱscore, 72 h RDW and 72 h APTT in the death group were higher than those in the survival group. Respectively, the hospitalization time of ICU in the death group was significantly lower than that in the survival group ( P< 0.05). Logistic regression analysis showed that APACHE-Ⅱscore ( OR=1.117, P=0.047)、72 h RDW( OR=1.102, P=0.029) and 72 h APTT ( OR=1.049, P=0.029) were independent risk factors for death in patients with ECMO. ROC curve analysis showed that the area under ROC curve (AUC) of the APACHE-Ⅱ, score 、72 h RDW and 72 h APTT were 0.691, 0.691 and 0.632( P<0.05), Respectively, the combined AUC was 0.764, the sensitivity was 0.526, and the specificity was 0.909. The death warning score of patients with ECMO was established according to the Predictive model , which is less than 2 points with low risk of death and more than 2 points with high risk of death. The area under the ROC curve of death warning score is 0.8, the sensitivity is 0.607 and the specificity is 0.923. Conclusions:The RDW at 72 hours after treatment with ECMO has a good value in predicting the prognosis of patients with ECMO. Besides, a greater predictive value for the prognosis of patients with ECMO by combining 72 hours RDW, 72 hours APTT with APACHE-Ⅱscore than that of any separate indicator.