Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification.

Purpose: Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment. Methods: SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein-Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment. Results: Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1ß, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1ß, and FAS were significantly higher than the sham group. Conclusion: CD14, FAS, and IL1ß may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.

Abnormal effective connectivity of reward network in first-episode schizophrenia with auditory verbal hallucinations.

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging. Group-level connection coefficients, between-group differences and correlation analysis between image measures and symptoms were performed. RESULT: DCM revealed weaker effective connectivity (EC) from right ventral striatum (RVS) to ventral tegmental area (VTA) in AVH compared to NAVH. AVH showed stronger EC from left anterior insula (AI) to RVS, stronger EC from RVS to anterior cingulate cortex (ACC), and stronger EC from VTA to posterior cingulate cortex (PCC) compared to NC. The correlation analysis results were mostly visible in the negative correlation between EC from right AI to ACC and positive sub-score, P1 sub-score, and P3 sub-score of PNASS in group-level. CONCLUSION: These findings suggest that neural causal interactions between the reward network associated with AVHs are disrupted, expanding the evidence for potential neurobiological mechanisms of AVHs. Particularly, dopamine-dependent salience attribution and top-down monitoring impairments and compensatory effects of enhanced excitatory afferents to ACC, which may provide evidence for a therapeutic target based on direct in vivo of AVHs in schizophrenia.

Nicotine plays a protective role in rats with induced viral pneumonia with polyinosinic-polycytidylic acid through α7nAChR.

Objective: To study the effect of nicotine in rat model of pneumonia induced by polyinosinic-polycytidylic acid [Poly (I:C)] and explore the underlying mechanism. Methods: Twenty-four healthy adult male Sprague-Dawley (SD) rats (200-250 g) were randomly divided into normal saline control group (NS group); Poly (I:C) group; nicotine group (NIC group); and α7 nicotinic acetylcholine receptor (α7nAChR) antagonist group (α-BGT group) (n = 6 each). Rats in the Poly (I: C), NIC, and α-BGT groups were administered 1.5 mg/mL 100 µL Poly (I:C) intranasally to establish pneumonia model. In α-BGT group, 1 µg/kg α-bungarotoxin (α-BGT) was intraperitoneally injected 45 min before intranasal Poly (I:C), and 400 µg/kg nicotine was intraperitoneally injected 15 min after α-BGT injection. The NIC group received an equal volume of NS in place of α-BGT while the other treatments were same. The Poly (I:C) group received equal volume of NS in place of nicotine while the other treatments were same as in NIC group. In the NS group, only NS was administered at all three time points. PaCO2, PaO2, and PaO2/FiO2 levels were determined 24 h after administration of Poly (I:C). After euthanization, rat lung tissues were extracted for pathological examination, and wet weight/dry weight (W/D ratio) was determined. Expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, and interferon (IFN)-γ in lung tissue was determined by ELISA. q-PCR was used to detect nuclear factor kappa-B P65 (NF-κBP65). Results: Compared with NS group, Poly (I:C) and α-BGT groups showed significantly increased W/D ratio, PaCO2, TNF-α, IL-6, IL-1ß, and IFN-γ content, NF-κB P65 expression, and reduced PaO2 and PaO2/FiO2 (p < 0.05), along with obvious signs of pathological injury. Nicotine pre-treatment reduced W/D ratio, PaCO2, proinflammatory cytokines, NF-κBP65 expression, and increased PaO2 and PaO2/FiO2 levels. The above effects were negated in α-BGT group. Conclusion: Pre-administration of nicotine improved Poly (I:C)-induced pneumonia by activating the cholinergic anti-inflammatory pathway.

Immunotherapy Combined with Chemotherapy in Relapse Metaplastic Breast Cancer.

Metaplastic breast cancer (MBC) is a rare disease, and there was rarely reported the treatment after recurrence and metastasis. Here, we report the treatment of an adult patient who suffered from MBC with lung, lymph nodes and left pleura metastasis after radical surgery. The next-generation sequencing result demonstrated that it had tumor mutational burden (TMB) of 12.0 Muts/Mb and microsatellite stability. The patient received sintilimab, an immune checkpoint inhibitor, plus chemotherapy and achieved partial response (PR). This is a report of a good outcome of metastatic MBC achieving 24 months of progression-free survival (PFS) and 39 months of overall survival (OS) with a combination therapy of immune checkpoint inhibitor and chemotherapy. Immuno-chemotherapy may have antitumor activity for relapse MBC. TMB may serve as a potential predictor associated with PD-1 inhibitors in MBC and help clinicians make an optimum treatment strategy.

LncRNA MEG3 promotes neuronal apoptosis in rats with ischemic cerebral infarction via the TGF-ß1 pathway.

To study the influence of long non-coding ribonucleic acid maternally expressed gene 3 (lncRNA MEG3) on the neuronal apoptosis in rats with ischemic cerebral infarction, and to analyze its regulatory effect on the transforming growth factor-beta 1 (TGF-ß1) pathway. A total of 36 Sprague-Dawley rats were randomly assigned into sham group, model group and low expression group. Ischemic cerebral infarction modeling was constructed in rats of the model group and low expression group. Corresponding adenoviruses were intracranially injected in rats of low expression group to knock down lncRNA MEG3 expression. At 24 h after the operation, the neurological function of rats was evaluated in each group, and the expression level of lncRNA MEG3 in cerebral tissues was determined using quantitative polymerase chain reaction (qPCR). The infarct size was measured via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The apoptosis level of neurons in cerebral tissues was determined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Besides, enzyme-linked immunosorbent assay (ELISA) was performed to determine the contents of inflammatory factors in cerebral tissues. Expression levels of apoptosis-associated proteins and vital genes in the TGF-ß1 signaling pathway in rat cerebral tissues were measured using Western blotting. Compared with the sham group, rats in the model group exhibited substantial increases in the neurological score and apoptosis level of neurons (p<0.01). Relative levels of lncRNA MEG3, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), Caspase-3, TGF-ß1, small mothers against decapentaplegic homolog 2 (Smad2) and Smad3 (p<0.01) were higher in a model group than those in sham group. Notable declines in the content of IL-10 (p<0.01) and the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl associated X protein (Bax) (p<0.01) were seen in the model group compared with the sham group. The abovementioned changes in the model group were partially abolished in the low expression group. LncRNA MEG3 is upregulated in the cerebral tissues of rats with ischemic cerebral infarction. It induces an inflammatory response, expands cerebral infarct size, and promotes neuronal apoptosis and impairment by activating the TGF-ß1 pathway.

Efficacy and safety of Lingnan surgery for the treatment of multi-quadrant acute incarcerated hemorrhoids: A retrospective study.

OBJECTIVE: In this study, we introduce a surgical procedure for multiple-quadrant hemorrhoid crisis, namely Lingnan surgery, and discuss its clinical efficacy and safety. METHODS: We performed a retrospective analysis of patients with acute incarcerated hemorrhoids who underwent Lingnan surgery at the Anorectal Department of Yunan County Hospital of Traditional Chinese Medicine of Guangdong Province from 2017 to 2021. The baseline data, preoperative condition, and postoperative condition of each patient were recorded in detail. RESULTS: A total of 44 patients were studied. There were no cases of massive hemorrhage, wound infection, wound nonunion, anal stenosis, abnormal anal defecation, recurrent anal fissure, or mucosal eversion within 30 days after surgery, and no recurrence of hemorrhoids and anal dysfunction occurred during the 6-month follow-up after surgery. The average operation time was 26.5 ± 6.2 min (17-43 min). The average length of hospital stay was 4.0 ± 1.2 days (2-7 days). In terms of postoperative analgesia, 35 patients took oral nimesulide, 6 did not use any analgesics, and 3 required nimesulide plus tramadol by injection. The mean Visual Analog Scale pain score was 6.8 ± 0.8 preoperatively and 2.9 ± 1.2, 2.0 ± 0.7, and 1.4 ± 0.6 at 1, 3, and 5 days postoperatively, respectively. The average basic activities of daily living score was 98.2 ± 2.6 (90-100) at discharge. CONCLUSION: Lingnan surgery is easy to perform and has obvious curative effects, providing an alternative to conventional procedures for acute incarcerated hemorrhoids.

Prognostic roles of hematological indicators for the efficacy and prognosis of immune checkpoint inhibitors in patients with advanced tumors: a retrospective cohort study.

BACKGROUND: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy. METHODS: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis. RESULTS: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively. CONCLUSIONS: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy.

The Impact of COVID-19 Pandemic Lockdown on Emergency Department Visits in a Tertiary Hospital.

Purpose: This study aimed to highlight the impact of the COVID-19 pandemic lockdown on emergency department (ED) visits of non-COVID-19 patients in a tertiary hospital and evaluate protocol development during this period. Patients and Methods: Clinical data of patients who visited the ED of Foshan Hospital of Traditional Chinese Medicine during the first-level response in Foshan, Guangdong province in 2020 (from January 23 to February 24) and the same period in 2019 and 2021 were collected. A retrospective cross-sectional analysis was performed to understand the characteristics of critically ill patients and compare the proportion of hospitalizations, deaths, and emergency ambulance calls (EACs). Results: The number of patients presenting to the ED was significantly decreased, with a 37.75% reduction in 2020 (6196) compared to the same period in 2019 (9954). A rise in patient ED presentations was observed in the same period in 2021 (10,503). This decline was mostly in the 15-45 age group. In 2019, 2020, and 2021, critically ill patients treated by the ED totaled 568 (5.706%), 339 (5.495%), and 590 (5.617%), respectively. Compared to the same period in 2019 and 2021, the proportion of critically ill patients with respiratory system involvement, severe trauma, and poisoning decreased most significantly in 2020 (P<0.05). In contrast, the rates of EACs, hospitalizations, and deaths increased significantly (P<0.05). Conclusion: The number of ED visits to hospitals was decreased during the 2020 lockdown, while the rates of EACs, hospitalizations, and deaths increased significantly though there were no documented COVID-19 cases. Optimizing emergency medical resources and ensuring the safety of healthcare providers and patients were essential to provide efficient emergency diagnosis and treatment during the lockdown.

Impaired large-scale cortico-hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia.

Background and objective: The cortico-hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico-hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition. Methods: A total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico-hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores. Results: Compared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico-hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico-hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC). Conclusion: Schizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico-hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Dachaihu decoction ameliorates septic intestinal injury via modulating the gut microbiota and glutathione metabolism as revealed by multi-omics.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu decoction (DCH), a classic formula for Yangming and Shaoyang Syndrome Complex recorded in "Treatise on Cold Damage", has been widely used in treating intestinal disorders and inflammatory diseases with few side effects in China. However, the mechanism of DCH on septic intestinal injury (SII) remains to be explored. AIM OF THE STUDY: This study aimed to clarify the mechanism of DCH on SII. MATERIALS AND METHODS: SII model of rat, established by cecal ligation and puncture (CLP), was used to study the effect of DCH on SII. 24 h mortality was recorded. Histological changes were observed by H&E staining. The expression of tight junction protein ZO-1 (ZO-1) and mucin2 (MUC2) was determined by immunohistochemical analysis. Secretory IgA (sIgA), diamine oxidase (DAO) and intestinal fatty acid binding protein (iFABP) were determined by enzyme-linked immunosorbent assay (ELISA). IL-1ß, IL-6 and TNF-α were measured by ELISA and quantitative Real-time PCR (RT-qPCR). The gut microbiota was analyzed by 16S rRNA sequencing. The potential targets and pathways of DCH in treating SII were analyzed by integrative analysis of transcriptomic and metabolomic methods. Total glutathione (T-GSH), GSH, GSSG (reduced form of GSH), GSH peroxidase (GPX), superoxide dismutase (SOD), malonaldehyde (MDA) and indicators of hepatic and renal function were measured by biochemical kits. RESULTS: Medium dose of DCH improved 24 h mortality of SII rats, reduced the pathological changes of ileum, and increased the expression levels of ZO-1, MUC2 and sIgA. DCH decreased DAO, iFABP of serum and IL-1ß, IL-6, TNF-α of ileum. DCH improved α- and ß-diversity and modulated the structure of gut microbiota, with Escherichia_Shigella decreased and Bacteroides and Ruminococcus increased. GSH metabolism was identified as the key pathway of DCH on SII by integrative analysis of transcriptome and metabolome. GSH/GSSG and the most common indicators of oxidative stress, were validated. Antioxidative T-GSH, GSH, GPX and SOD were increased, while MDA, the mark of lipid peroxidation was downregulated by DCH. Eventually, DCH was proved to be safe and hepato- and nephro-protective. CONCLUSION: DCH ameliorated septic intestinal injury possibly by modulating the gut microbiota and enhancing glutathione metabolism of SII rats, without hepatotoxicity and nephrotoxicity.

Identification of shared and distinct patterns of brain network abnormality across mental disorders through individualized structural covariance network analysis.

BACKGROUND: Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders. METHODS: Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed. RESULTS: Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network. CONCLUSIONS: These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

Altered static and dynamic functional connectivity of habenula in first-episode, drug-naïve schizophrenia patients, and their association with symptoms including hallucination and anxiety.

Background and objective: The pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study. Methods: A total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed. Results: Compared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole. Conclusion: This study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.

The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study.

OBJECTIVES: Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. METHODS: This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. RESULTS: Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. CONCLUSIONS: Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.

Nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity: A fMRI study of interaction effects.

BACKGROUND: Nicotine addiction and overweight often co-exist, but the neurobiological mechanism of their co-morbidity remains to be clarified. In this study, we explore how nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity. METHODS: This study included 54 overweight people and 54 age-, sex-, and handedness-matched normal-weight individuals, who were further divided into four groups based on nicotine addiction. We used a two-way factorial design to compare intrinsic neural activity (calculated by the fALFF method) in four groups based on resting-state functional magnetic resonance images (rs-fMRI). Furthermore, the correlation between fALFF values and PET- and SPECT-derived maps to examine specific neurotransmitter system changes underlying nicotine addiction and overweight. RESULTS: Nicotine addiction and overweight affect intrinsic neural activity by themselves. In combination, they showed antagonistic effects in the interactive brain regions (left insula and right precuneus). Cross-modal correlations displayed that intrinsic neural activity changes in the interactive brain regions were related to the noradrenaline system (NAT). CONCLUSION: Due to the existence of interaction, nicotine partially restored the changes of spontaneous activity in the interactive brain regions of overweight people. Therefore, when studying one factor alone, the other should be used as a control variable. Besides, this work links the noradrenaline system with intrinsic neural activity in overweight nicotine addicts. By examining the interactions between nicotine addiction and overweight from neuroimaging and molecular perspectives, this study provides some ideas for the treatment of both co-morbidities.

Altered time-varying local spontaneous brain activity pattern in patients with high myopia: a dynamic amplitude of low-frequency fluctuations study.

PURPOSE: To investigate the abnormal time-varying local spontaneous brain activity in patients with high myopia (HM) on the basis of the dynamic amplitude of low-frequency fluctuations (dALFF) approach. METHODS: Age and gender matching were performed based on resting-state functional magnetic resonance imaging data from 86 HM patients and 87 healthy controls (HCs). Local spontaneous brain activities were evaluated using the time-varying dALFF method. Support vector machine combined with the radial basis function kernel was used for pattern classification analysis. RESULTS: Inter-group comparison between HCs and HM patients has demonstrated that dALFF variability in the left inferior frontal gyrus (orbital part), left lingual gyrus, right anterior cingulate and paracingulate gyri, and right calcarine fissure and surrounding cortex was decreased in HM patients, while increased in the left thalamus, left paracentral lobule, and left inferior parietal (except supramarginal and angular gyri). Pattern classification between HM patients and HCs displayed a classification accuracy of 85.5%. CONCLUSION: In this study, the findings mentioned above have suggested the association between local brain activities of HM patients and abnormal variability in brain regions performing visual sensorimotor and attentional control functions. Several useful information has been provided to elucidate the mechanism-related alterations of the myopic nervous system. In addition, the significant role of abnormal dALFF variability has been highlighted to achieve an in-depth comprehension of the pathological alterations and neuroimaging mechanisms in the field of HM.

Association of the Timeless Gene with Prognosis and Clinical Characteristics of Human Lung Cancer.

(1) Background: As the most common malignant tumor type worldwide, it is necessary to identify novel potential prognostic biomarkers to improve the poor prognosis of lung cancer. The Timeless gene, a circadian rhythm-related gene, is associated with several types of cancer. However, studies analyzing the clinical significance of the Timeless gene in patients with lung cancer are currently limited. (2) Methods: In the present study, the expression levels and prognostic potential of the Timeless gene and its co-expressed genes in different subtypes of lung cancer were explored using multiple bioinformatics approaches. The correlations between the Timeless gene and its co-expressed genes were validated using A549 and NCI-H226 cells by transfecting them with expression vectors and analyses using Western blot and reverse transcription-quantitative PCR. (3) Results: The Oncomine and GEPIA database analyses indicated that the expression of the Timeless gene was significantly higher in lung cancer as compared to that in the normal tissue. Using the UALCAN database, significant differences in Timeless gene expression were determined among different stages of lung cancer and between genders. A Kaplan-Meier plotter analysis indicated that high expression of the Timeless gene was associated with poor overall survival (OS) and progression-free survival (PFS) of patients with lung cancer. In the cBioPortal and GEPIA database analyses, extra spindle pole bodies like 1 (ESPL1) was the top correlated gene of Timeless in patients with lung cancer. Similar to the Timeless gene, high expression of the ESPL1 gene was also associated with poor OS and PFS. Of note, overexpression of the Timeless gene increased the expression level of ESPL1 at both the mRNA and protein levels. (4) Conclusion: The present study explored the clinical significance of the Timeless gene and its correlated gene ESPL1 in patients with lung cancer, thereby providing a potential therapeutic target for lung cancer.

Combination of Serum Test and Questionnaire in Early Gastric Cancer Screening.

Background: We aimed to analyze the predictive role of serum test and questionnaire in Early Gastric Cancer in The First Affiliated Hospital of Xingtai Medical College, Hebei Province from 2019 to 2020. Methods: In this prospective study, 280 medical examiners underwent questionnaire, serum test and gastroscopy. They were divided into Gastric cancer (GC) and Non-Gastric cancer (NGC) group. NGC group was divided into Low-grade intraepithelial neoplasia (LGIN), Chronic atrophic gastritis (CAG) and Non-chronic atrophic gastritis (NCAG) group. Results: Age, drinking, sex and Gastrin-17(G-17) was respectively independent risk factors for GC. Age, drinking and G-17 was independent risk factors for GC in men. G-17 of GC group was higher than that of LGIN and NCAG group (P<0.05). Pepsinogen I/II ratio (PGR) of GC was lower than that of NCAG group (P<0.05). There was no significant difference between Pepsinogen I (PGI) and Pepsinogen II (PGII) in the four groups. Helicobacter pylori-immunoglobulin G antibodies (H. pylori-IgG) of LGIN group was significantly higher than that of CAG and NCAG group in gastritis group (P<0.008). G-17≥42.95 pmol/L, age≥69years, male and drinking can predict GC. Conclusion: Older, drinking, men and high G-17 could respectively predict GC. Especially in men, older, drinking and high G-17 could affect the occurrence of GC. G-17, age, drinking and sex used respectively to screen high-risk populations for GC were more efficient than combined screening. GC had a higher serum G-17 and a lower PG than other gastric diseases.

Explore the effects of overweight and smoking on spontaneous brain activity: Independent and reverse.

Accumulating evidence suggested that overweight and smoking often co-exist. However, current neuroimaging researches have almost always studied smoking or overweight status separately. Here we sought to investigate the neurobiological mechanisms of this comorbid association, by detecting spontaneous brain activity changes associated with smoking and weight status separately and collectively. We used 2 × 2 factorial design and included the following four groups: overweight/normal-weight smokers (n = 34/n = 30) and overweight/normal-weight non-smokers (n = 22/n = 24). The spontaneous brain activity among the four groups was comparable using an amplitude of low-frequency fluctuation (ALFF) method based on resting-state fMRI (rs-fMRI). Furthermore, correlation analyses between brain activity changes, smoking severity and BMI values were performed. A main effect of smoking was discovered in the default mode network (DMN) and visual network related brain regions. Moreover, overweight people had high ALFF value in the brain regions associated with reward and executive control. More importantly, smoking and overweight both affected brain activity of the middle temporal gyrus (MTG), but the effect was opposite. And the brain activity of MTG was negatively correlated with smoking years, pack year and BMI value. These results suggest that smoking and overweight not only affect spontaneous brain activity alone, but also paradoxically affect spontaneous brain activity in the MTG. This suggests that we need to control for weight as a variable when studying spontaneous brain activity in smokers. Besides, this interaction may provide a neurological explanation for the comorbidity of overweight and smoking and a target for the treatment of comorbid populations.

Altered dynamic functional connectivity of auditory cortex and medial geniculate nucleus in first-episode, drug-naïve schizophrenia patients with and without auditory verbal hallucinations.

Background and objective: As a key feature of schizophrenia, auditory verbal hallucination (AVH) is causing concern. Altered dynamic functional connectivity (dFC) patterns involving in auditory related regions were rarely reported in schizophrenia patients with AVH. The goal of this research was to find out the dFC abnormalities of auditory related regions in first-episode, drug-naïve schizophrenia patients with and without AVH using resting state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 107 schizophrenia patients with AVH, 85 schizophrenia patients without AVH (NAVH) underwent rs-fMRI examinations, and 104 healthy controls (HC) were matched. Seed-based dFC of the primary auditory cortex (Heschl's gyrus, HES), auditory association cortex (AAC, including Brodmann's areas 22 and 42), and medial geniculate nucleus (MGN) was conducted to build a whole-brain dFC diagram, then inter group comparison and correlation analysis were performed. Results: In comparison to the NAVH and HC groups, the AVH group showed increased dFC from left ACC to the right middle temporal gyrus and right middle occipital gyrus, decreased dFC from left HES to the left superior occipital gyrus, left cuneus gyrus, left precuneus gyrus, decreased dFC from right HES to the posterior cingulate gyrus, and decreased dFC from left MGN to the bilateral calcarine gyrus, bilateral cuneus gyrus, bilateral lingual gyrus. The Auditory Hallucination Rating Scale (AHRS) was significantly positively correlated with the dFC values of cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus, and posterior cingulate gyrus) using left AAC seed, cluster 2 (right middle temporal gyrus and right middle occipital gyrus) using left AAC seed, cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus and posterior cingulate gyrus) using right AAC seed and cluster 2 (posterior cingulate gyrus) using right HES seed in the AVH group. In both AVH and NAVH groups, a significantly negative correlation is also found between the dFC values of cluster 2 (posterior cingulate gyrus) using the right HES seed and the PANSS negative sub-scores. Conclusions: The present findings demonstrate that schizophrenia patients with AVH showed multiple abnormal dFC regions using auditory related cortex and nucleus as seeds, particularly involving the occipital lobe, default mode network (DMN), and middle temporal lobe, implying that the different dFC patterns of auditory related areas could provide a neurological mechanism of AVH in schizophrenia.