Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

Development and performance evaluations of an HER-2 kit.

Objective To develop a kit for detecting human epidermal growth factor receptor 2 (HER-2) in the human body. Methods The HER-2 kit was evaluated based on an automated magnetic particle chemiluminescence platform. The kit was developed using the double antibody sandwich-complexation method. Results The kit showed a linear range of 0.01-800 ng/mL, with a linear R2 of >0.999. The limit of the blank was 0.0039 ng/mL, and the precision at 1.00 ng/mL was 9.4%. The recovery rate at 10.00 ng/mL was 97.81-101.81%. The negative serum reference range was 0-8.23 ng/mL. Conclusions The kit had a wide linear range, high accuracy, good precision, and high sensitivity, indicating that it has good application prospects.

Relationship between ambulatory arterial stiffness index and the severity of angiographic atherosclerosis in patients with H-type hypertension and coronary artery disease.

OBJECTIVE: To investigate coronary artery disease (CAD) and its correlation with the ambulatory arterial stiffness index (AASI) in patients with H-type hypertension (essential hypertension combined with hyper-homocysteinemia) and coronary heart disease (CHD). METHODS: Patients with essential hypertension and CHD who were undergoing coronary angiography were enrolled. The general clinical data, biochemical indicators, ambulatory blood pressure monitoring results and coronary angiography results of the selected patients were collected, and the AASI and Gensini scores were calculated. According to homocysteine (Hcy) levels, the patients were divided into two groups: a study group and a control group. The differences in general clinical data, biochemical indexes, AASI scores and degree of coronary artery lesions between the two groups were compared. The correlation between the AASI and the Gensini score and the relationship between the AASI and the Gensini score of CAD and various factors were analyzed. RESULTS: Compared with the control group, the Hcy level in the study group was significantly increased (8.16 ± 2.33 vs 19.20 ± 2.36, P = .001). The 24-h diastolic blood pressure (DBP) in the study group was significantly lower than that in the control group (76.38 ± 9.33 vs 79.91 ± 9.25, P = .002), and the AASI was significantly higher than in the control group (0.62 ± 0.81 vs 0.420 ± 0.70, P = .001). The number of patients having coronary stenoses with a Gensini score of ≤ 38 was significantly lower in the study group than in the control group (21.3% vs 49.4%, P < .001). The number of patients with a Gensini score of ≥ 51 in the study group was significantly higher than in the control group (22.0% vs 18.8%, P < .001). There was a significant positive correlation between the AASI and the Gensini score in the study group (R = 0.732, P < .001). Hypertension duration (ß = 0.168), diabetes history (ß = 0.236), 24-h SBP (ß = 0.122), 24-h DBP (ß = -0.131), low-density lipoprotein cholesterol (ß = 0.134) and Hcy (ß = 0.233) were the influencing factors for AASI (P < .05). Both Hcy * AASI (ß = 0.356) and Hcy × 24-h HR (ß = 0.331) had a synergistic effect on the Gensini score (P = .017), with Hcy * AASI having a more significant effect on the Gensini score (P < .001). CONCLUSION: The AASI was significantly increased in patients with H-type hypertension and CHD, which was associated with the severity of CAD. Therefore, Hcy levels and the AASI have a synergistic effect when evaluating the severity of CAD in patients with hypertensive CHD.

After-effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer's disease.

Repetitive anodal transcranial direct current stimulation (tDCS) in a rat model of Alzheimer's disease (AD) has been shown to have distinct neuroprotective effects. Moreover, the effects of anodal tDCS not only occur during the stimulation but also persist after the stimulation has ended (after-effects). Here, the duration of the after-effects induced by repetitive anodal tDCS was investigated based on our previous studies. Adult male Sprague-Dawley rats were divided into three groups: a sham group, a ß-amyloid (Aß) group (AD group) and a stimulation group (ATD group). Aß was injected into the bilateral hippocampi of the rats in the AD and ATD groups to produce the AD model. Rats in the ATD group underwent 10 sessions of anodal tDCS, and the after-effects of repetitive anodal tDCS were evaluated by behavioral and histological analyses. A Morris water maze (MWM) was utilized on a monthly basis to assess spatial learning and memory abilities. The ATD group showed shorter escape latencies and more platform region crossings than the AD group. Hippocampal choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) immunohistochemical analyses were carried out after the last MWM assessment. The immunohistochemistry results showed notable differences among the groups, particularly between the AD and ATD groups. This study reveals that repetitive anodal tDCS can not only improve cognitive function and memory performance but also has long-term after-effects that persist for 2 months.

[Analysis on composition principles of Tibetan medicine containing Terminalia chebula by data mining].

This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis.

Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis.

BACKGROUND: The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis. METHODS: The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis. RESULTS: Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers. CONCLUSIONS: nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers.

Emergence of human-like H3N2 influenza viruses in pet dogs in Guangxi, China.

BACKGROUND: After the 1968 H3N2 pandemic emerged in humans, H3N2 influenza viruses continuously circulated and evolved in nature. An H3N2 variant was circulating in humans in the 1990s and subsequently introduced into the pig population in the 2000s. This virus gradually became the main subtype of swine influenza virus worldwide. However, there were no reports of infections in dogs with this virus. FINDINGS: In 2013, 35 nasal swabs from pet dogs were positive for Influenza A virus by RT-PCR. Two viruses were isolated and genetically characterized. In the phylogenetic trees of all gene segments, two H3N2 canine isolates clustered with Moscow/10/99 and most H3N2 swine influenza viruses. These results indicated that two H3N2 CIVs possessed high homology with human/swine influenza viruses, which at the same time exhibited some amino acid substitutions in NA, polymerase basic protein 1 (PB1), and nucleoprotein (NP), which probably were related to the interspecies transmission. CONCLUSIONS: These two viruses share the highest homology with swine H3N2, Moscow/99-like viruses, which indicated that these viruses might originate from swine viruses.

Celecoxib attenuates hepatic cirrhosis through inhibition of epithelial-to-mesenchymal transition of hepatocytes.

BACKGROUND AND AIM: The epithelial-mesenchymal transition (EMT) of hepatocytes is a key step for hepatic fibrosis and cirrhosis. Long-term administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, can ameliorate hepatic fibrosis. This research aimed to examine the effect of celecoxib on the EMT of hepatocytes during the development of liver cirrhosis. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). Thirty-six rats were randomly assigned to control, TAA, and TAA + celecoxib groups. Hepatic expressions of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), COX-2, prostaglandin E2 (PGE2 ), matrix metalloproteinase (MMP)-2 and -9, transforming growth factor-ß1 (TGF-ß1), Phospho-Smad2/3, Snail1, α-smooth muscle actin (α-SMA), vimentin, collagen I, fibroblast-specific protein (FSP-1), E-cadherin and N-cadherin were quantitated. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and Ishak's scoring system. RESULTS: Exposed to TAA treatment, hepatocytes underwent the process of EMT during hepatic fibrosis. Compared with those in TAA group, celecoxib significantly downregulated the hepatic expressions of TNF-α, IL-6, COX-2, PGE2 , MMP-2, MMP-9, TGF-ß1, Phospho-Smad2/3, Snail1, α-SMA, FSP-1, and vimentin while greatly restoring the levels of E-cadherin. The fibrotic areas and collagen I levels of TAA + celecoxib group were much lower than those in TAA group. CONCLUSIONS: Celecoxib could ameliorate hepatic fibrosis and cirrhosis in TAA-rat model through suppression of the mesenchymal biomarkers in the hepatocytes while restoring the levels of their epithelial biomarkers. The inhibitory effect of celecoxib on the EMT of hepatocytes is associated with reduction of intrahepatic inflammation, preservation of normal basement matrix, and inhibition of TGF-ß1/Smad pathway.

Advancements in Ultrasound Techniques for Evaluating Intracranial Pressure through Optic Nerve Sheath Diameter Measurement.

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage (ICH), and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and non-nervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising non-invasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP.

[Effect and mechanism of gene therapy of lentivirus mediated RhoA shRNA on ovarian cancer xenograft in vivo].

OBJECTIVE: To investigate treatment effects of lentivirus mediated RhoA short hairpin RNA (shRNA) on xenograft tumor of ovarian cancer in nude mice in vivo and the underlying mechanism. METHODS: Human ovarian cancer cell line HO8910 were inoculated to establish subcutaneous xenograft model of human ovarian cancer. Tumor-bearing nude mice were assigned randomizely to three groups: Lenti-RhoA-sh group, Lenti- negative control (NC) group and phosphate buffered saline (PBS) group.lentivirus mediated RhoA shRNA, negative control lentivirus and PBS were respectively injected in the three groups. Effects of treatment were observed by tumor growth curve, tumor volume, tumor weight, and tumor inhibition rate. Xenograft tissues and liver, spleen, lung, and renal tissues were examined by hematoxylin and eosin (HE) staining or were detected by streptavidin-perosidase(SP)immunochemical method. The changes of RhoA gene expression in xenograft tissues after lentivirus mediated RhoA shRNA treated were also detected by real-time qPCR, immunochemistry and Western blot assay. Cell apoptosis in xenograft tissues were examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and apoptotic index (AI) were counted. RESULTS: Compared with Lenti-NC group and PBS group, the growth speed of xenograft in Lenti-RhoA-sh group delayed significantly after injection 9 days (P < 0.01) . Tumor volume (338 ± 114) mm(3) decreased significantly in the Lenti-RhoA-sh group when compared with those in Lenti-NC group (1190 ± 332) mm(3) and PBS group (1101 ± 396) mm(3) (P < 0.01) . Tumor weight (0.23 ± 0.11) g decreased significantly in the Lenti-RhoA-sh group when compared with Lenti-NC group (0.79 ± 0.19) g and PBS group (0.74 ± 0.17) g (P < 0.01) . Real-time qPCR result shown that the expression of RhoA mRNA (0.30 ± 0.05) decreased significantly in the Lenti-RhoA-sh group compared with Lenti-NC group (0.95 ± 0.06) and PBS group(1.00 ± 0.11; P < 0.01) .Western blot result showed that the expression level of RhoA protein decreased significantly in the Lenti-RhoA-sh group (0.14 ± 0.06) compared with those in Lenti-NC group(0.78 ± 0.14) and PBS group (0.75 ± 0.13;P < 0.01). TUNEL staining displayed that AI significantly increased in the Lenti-RhoA-sh group (20.9 ± 3.4) % compared with those in Lenti-NC group (5.2 ± 2.0) % and PBS group (6.0 ± 2.1) % (P < 0.01). CONCLUSION: Lentivirus mediated RhoA shRNA may be effectively down-regulate of the expression of RhoA, inhibit the growth of subcutaneous xenograft tumor of ovarian cancer in nude mice by increasing the cell apoptosis.

Updates on global epidemiology, risk and prognostic factors of gastric cancer.

Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.

Phylogenetic and Morphological Evidence Reveal Five New Species of Boletes from Southern China.

Fungi of the order Boletales are extremely important in both ecology and economy, since most of them are ectomycorrhizal fungi, which play vital roles in maintaining forest ecosystems, water and soil protection, vegetation restoration and so on. Although previous studies have shown that this order has a very high species diversity in China, there are few reports on the species diversity of boletes in Jiangxi Province, China. Based on morphological (macroscopic and microscopic morphological characteristics) and phylogenetic analyses (ITS, LSU, and TEF1-α sequences), in this study, the wild boletes in Jiangxi Province were investigated, and five new species are described: Austroboletus albus, Xanthoconium violaceipes, Xanthoconium violaceofuscum, Xerocomus rutilans and Xerocomus subsplendidus. Descriptions and hand drawings of the new species are presented.

Gastric epithelial histology and precancerous conditions.

The most common histological type of gastric cancer (GC) is gastric adenocarcinoma arising from the gastric epithelium. Less common variants include mesenchymal, lymphoproliferative and neuroendocrine neoplasms. The Lauren scheme classifies GC into intestinal type, diffuse type and mixed type. The WHO classification includes papillary, tubular, mucinous, poorly cohesive and mixed GC. Chronic atrophic gastritis (CAG) and intestinal metaplasia are recommended as common precancerous conditions. No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended. Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus. Presently, the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis, treatment and surveillance. Management of precancerous conditions promotes the early detection and treatment of early GC, and even prevent the occurrence of GC. In the review, precancerous conditions including CAG, metaplasia, foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded, based on the overview of gastric epithelial histological organization and its renewal.

Effects of 3, 4-divanillyltetrahydrofuran from Urtica fissa on sexual dysfunction in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica fissa E. Pritz. are important herbs and have been traditionally used as ethnic medicine to treat rheumatism, inflammation, diabetes, and benign prostatic hyperplasia by the Han, Uighur, and other minorities in China, and also as an aphrodisiac in Uighur medicine. AIMS OF THE STUDY: To determine the effect and potential mechanism of 3, 4-divanillyltetrahydrofuran (DVTF), one of the main active components isolated from U. fissa on hypogonadism in diabetic mice. MATERIALS AND METHODS: The active compound DVTF was extracted and separated from the roots of U. fissa and identified using mass spectrometry and nuclear magnetic resonance spectroscopy. A mouse model of diabetes was established using high fat and sugar diet combined with streptozotocin. In the treatment groups, mice were received different doses of DVTF for 4 weeks. Fasting blood glucose levels, physiological and biochemical indices, and the mating behavior of DM mice were analyzed. Changes in testicular morphology were assessed using light microscopy and transmission electron microscopy. The expression of testosterone synthesis-related signaling proteins was detected using western blotting. Molecular docking was used to determine the binding ability of DVTF to Nur77. RESULTS: In diabetic mice, body weight and fasting blood glucose levels decreased. Mating behavior, including mount latency, mount number, and intromission number, was improved following DVTF treatment. Plasma total testosterone, free testosterone, and insulin resistance were positively associated with the recovery of testicular pathological structures in diabetic mice. DVTF treatment increased the expression of Nur77, StAR, and P450scc in the testes of diabetic mice. DVTF and Nur77 formed chemical bonds at five sites. CONCLUSION: As one of the main active components of U. fissa, DVTF exert potential therapeutic effects on testicular injury and hypogonadism caused by diabetes through activating the expression of Nur77 and testosterone synthesis related proteins. Our result will provide new insight for the clinical application of Urtica fissa E. Pritz., especially DVTF, as a potential drug candidate in the treatment of hypogonadism in diabetes.

Altered static functional network connectivity predicts the efficacy of non-steroidal anti-inflammatory drugs in migraineurs without aura.

Brain networks have significant implications for the understanding of migraine pathophysiology and prognosis. This study aimed to investigate whether large-scale network dysfunction in patients with migraine without aura (MwoA) could predict the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs). Seventy patients with episodic MwoA and 33 healthy controls (HCs) were recruited. Patients were divided into MwoA with effective NSAIDs (M-eNSAIDs) and with ineffective NSAIDs (M-ieNSAIDs). Group-level independent component analysis and functional network connectivity (FNC) analysis were used to extract intrinsic networks and detect dysfunction among these networks. The clinical characteristics and FNC abnormalities were considered as features, and a support vector machine (SVM) model with fivefold cross-validation was applied to distinguish the subjects at an individual level. Dysfunctional connections within seven networks were observed, including default mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), dorsal attention network (DAN), visual network (VN), and auditory network (AN). Compared with M-ieNSAIDs and HCs, patients with M-eNSAIDs displayed reduced DMN-VN and SMN-VN, and enhanced VN-AN connections. Moreover, patients with M-eNSAIDs showed increased FNC patterns within ECN, DAN, and SN, relative to HCs. Higher ECN-SN connections than HCs were revealed in patients with M-ieNSAIDs. The SVM model demonstrated that the area under the curve, sensitivity, and specificity were 0.93, 0.88, and 0.89, respectively. The widespread FNC impairment existing in the modulation of medical treatment suggested FNC disruption as a biomarker for advancing the understanding of neurophysiological mechanisms and improving the decision-making of therapeutic strategy.