Unveiling the role of mtDNA in Liver-Kidney Crosstalk: Insights from trichloroethylene hypersensitivity syndrome.

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

Clinical implications and mechanism of CST1 in gastric carcinoma based on database screening.

Gastric cancer (GC) remains one of the most common malignant tumours worldwide, with extremely high morbidity and mortality rates. An in-depth understanding of the pathogenesis of GC is key to the future diagnosis and treatment of GC. In this study, we analysed the differentially expressed genes (DEGs) in gastric carcinoma (GC) through GEO database and their clinical implications, with the aim of providing clinical reference and guidance. We selected the GSE118916 dataset for bioinformatics analysis and identified a total of 3231 DEGs. Keywords, including extracellular region, vesicle, protein digestion and absorption, ECM-receptor interaction, etc., of DEGs can be seen by the GO and KEGG enrichment analysis. The online database determined up-regulated CST1 in GC and some other tumors, as well as a close connection between CST1 with patient prognosis. Subsequently, we collected a number of GC clinical cases and examined the expression of CST1, which was seen to be highly expressed in GC, with a favorable diagnostic effect on the occurrence of GC (P<0.05) and a strong correlation with TNM stage, tumor invasion, tumor diameter and differentiation (P<0.05). In other words, CST1 is closely related to the occurrence and development of GC, and has the potential to be a breakthrough in the diagnosis and treatment of GC in the future.

Effectiveness and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin for the therapy of locally advanced colorectal cancer: A retrospective study.

The goal of the present study was to appraise the efficacy and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin (XELOX) in patients with locally advanced colorectal cancer (CRC), as relevant data on its usage in this setting are lacking. A retrospective analysis was implemented on 100 patients with locally advanced CRC who received either neoadjuvant apatinib in combination with XELOX (N=50) or neoadjuvant XELOX alone (N=50). Radiological response and pathological complete response rates were evaluated. Furthermore, the researchers obtained data pertaining to disease-free survival (DFS), overall survival, as well as adverse events. The consequences of the present study indicated that the neoadjuvant apatinib in combination with XELOX treatment approach yielded higher rates of radiological objective response (86.0 vs. 68.0%, P=0.032) and major pathological response (46.0 vs. 22.0%, P=0.011) compared with XELOX alone. These findings were further confirmed through multivariate logistic regression analyses (P=0.037 and P=0.008, respectively). Interestingly, the neoadjuvant apatinib in combination with XELOX treatment approach significantly prolonged DFS when compared with XELOX alone (P=0.033). In summary, the administration of neoadjuvant apatinib in combination with XELOX demonstrates superiority over the use of XELOX alone in terms of achieving a more favorable pathological response and a longer duration of DFS in patients diagnosed with locally advanced CRC.

Investigation the existence and mechanism of Cu(II)-sulfamethoxazole co-pollution by road-deposited sediments in stormwater runoff.

In recent years, the escalating attention on Pharmaceutical and Personal Care Products (PPCPs) and Heavy Metals in urban stormwater runoff highlights the critical role of Road-deposited sediments (RDS) as a significant carrier for pollutant occurrence and transport in runoff. However, existing research has overlooked the composite characteristics of PPCPs and Heavy Metals, hampering a holistic understanding of their transformation in diverse forms within runoff. This limitation impedes the exploration of their subsequent migration and conversion properties, thereby obstructing coordinated strategies for the control of co-pollution in runoff. This study focuses on the typical PPCP sulfamethoxazole (SMX) and heavy metal Cu(II) to analyze their occurrence characteristics in the Runoff-RDS system. Kinetics and isotherm studies reveal that RDS effectively accumulates SMX and Cu(II), with both exhibiting rapid association with RDS in the early stages of runoff. The accumulation of SMX and Cu(II) accounts for over 80 % and 70 % of the total accumulation within the first 240 min and 60 min, respectively. Moreover, as runoff pH values decrease, the initially synergistic effect between the co-pollutant transforms into an antagonistic effect. In the composite system, varying pH values from 2.0 to 6.0 lead to an increase in SMX accumulation from 4.01 mg/kg to 6.19 mg/kg and Cu(II) accumulation from 0.43 mg/g to 3.39 mg/g. Compared to the single system, the composite system capacity for SMX and Cu(II) increases by 0.04 mg/kg and 0.33 mg/g at pH 4.0. However, at pH 3.0, the composite system capacity for SMX and Cu(II) decreases by 0.21 mg/kg and 0.36 mg/g, respectively. Protonation/deprotonation of SMX under different pH conditions influences electrostatic repulsion/attraction between SMX and RDS. The mechanism of RDS accumulation of SMX involves Electron Donor-Acceptor (EDA) interaction, hydrogen bond interaction, and Lewis acid-base interaction. Cu(II) enrichment on RDS includes surface complexation reaction, electrostatic interaction, and surface precipitation. Complex formation enhances the accumulation of both SMX and Cu(II) on RDS in runoff. This study elucidates the co-occurrence characteristics and mechanisms of SMX and Cu(II) co-pollution in runoff systems. The findings contribute valuable insights to understanding the existence patterns and mechanisms of co-pollution, providing a reference for investigating the migration and fate of co-pollutant in runoff. Moreover, these insights could offer guidance for the development of effective strategies to mitigate co-pollution in rainwater.

Multiple cystic echinococcosis in abdominal and pelvic cavity treated by surgery with a 4-year follow-up: a case report.

We report a case of a male patient who presented with multiple abdominal and pelvic echinococcosis. The patient had been diagnosed with hepatic echinococcosis for 7 years and developed intermittent distension and discomfort in the upper abdomen after an accidental fall. In recent years, the patient's abdominal distention increased gradually. Computed tomography revealed multiple hydatid cysts in the liver, spleen, abdominal cavity, and pelvic cavity. Abdominal organs were severely compressed, such that he could not eat normally except for a liquid diet. The patient underwent radical surgical resection based on the multi-disciplinary treatment (MDT) and the operation lasted 10 h, nearly 100 hydatid cysts were excised, about 18 liters of cyst fluid and cyst contents were removed, and the patient lost 20 kg of weight after surgery. The operation was successful, but there were still some postoperative complications such as hypovolemic shock, postoperative ascites, postoperative bile leakage. Treatment measures for the patient were anti-infection, antishock, clamping the abdominal drainage tube, and negative pressure abdominal puncture drainage. At follow up the patient's quality of life had been significantly improved with 15 kg weight gain compared to before.

The investigation of the binding ability between sodium dodecyl sulfate and Cu (II) in urban stormwater runoff.

The simultaneous presence of heavy metals and surfactants in runoff induces complexation and ecological harm during migration. However, interactions between these pollutants are often overlooked in past studies. Thus, investigating heavy metal-surfactant complexes in runoff is imperative. In this work, Cu (II) and sodium dodecyl sulfate (SDS) were selected to investigate the interaction between heavy metals and surfactants due to the higher detected frequency in runoff. Through 1H NMR and FTIR observation of hydrogen atom nuclear displacement and functional group displacement of SDS, the change of SDS and Cu (II) complexation was obtained, and then the complexation form of Cu (II) and SDS was verified. The results showed that solution pH values and ionic strength had significant effects on the complexation of Cu (II). When the pH values increase from 3.0 to 6.0, the complexation efficiency of SDS with Cu (II) increased by 12.12% at low concentration of SDS, which may be attributed to the excessive protonation in the aqueous solution at acidic condition. The increase of ionic strength would inhibit the complexation reaction efficiency by 19.57% and finally reached the platform with concentration of NaNO3 was 0.10 mmol/L, which was mainly due to the competitive relationship between Na (I) and Cu (II). As a general filtering material in stormwater treatment measures, natural zeolite could affect the interaction between SDS and Cu (II) greatly. After the addition of SDS, the content of free Cu (II) in the zeolite-SDS-Cu (II) three-phase mixed system was significantly reduced, indicating that SDS had a positive effect on the removal of Cu (II) from runoff. This study is of great significance for investigating the migration and transformation mechanism of SDS and Cu (II) in the future and studying the control technology of storm runoff pollution.

EEG microstate analysis reveals large-scale brain network alterations in depressed adolescents with suicidal ideation.

BACKGROUND: Accumulating evidence showed abnormalities in brain network connectivity in depressive individuals with suicidal ideation (SI). We aimed to investigate the large-scale brain network dynamics in adolescents with SI and major depressive disorder (MDD). METHODS: We recruited 47 first-episode drug-naïve adolescents with MDD and SI, 26 depressed adolescents without SI (noSI), and 26 age-matched healthy controls (HC). The Columbia Suicidal Ideation Severity Scale (C-SSRS) was utilized to assess suicide ideation. We acquired 64-channel resting-state EEG recordings from all subjects and used microstate analysis to investigate the large-scale brain network dynamics. RESULTS: We observed a significant reduction in the occurrence and coverage of microstate B within the SI group when contrasted with the noSI group. Conversely, there was a significant increase in the occurrence and coverage of microstate A in the SI group as compared to the HC group. Additionally, we observed heightened transition probabilities from microstates D and C to microstate A in the SI group; meanwhile, transitions from microstate D to B were more prevalent in the noSI group. Furthermore, the noSI group exhibited a significant decline in the transition probabilities from microstate D to microstate C. LIMITATIONS: The cross-sectional nature limits the capacity to determine whether microstate dynamics have prognostic significance for SI. CONCLUSION: We provided evidence that depressed adolescents with SI have a distinct pattern in microstate dynamics compared to those without SI. These findings suggest that microstate dynamics might serve as a potential neurobiomarker for identifying SI in depressed adolescents.

Validation of non-invasive indicators in the screening of metabolic dysfunction-associated fatty liver disease: a cross-sectional study among Uighurs in rural Xinjiang.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in China. Our study aimed to evaluate the screening value of the fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Zhejiang University index (ZJU), as well as other single indicators for MAFLD. We aimed to find the optimal screening tool and its appropriate cut-off values for rural Uyghur adults. METHODS: We completed a survey of 14,321 Uyghur adults in 51 groups in Kashgar, Xinjiang, in 2016 using a typical sampling method, with 12,794 patients ultimately included in statistical analyses. Fatty liver was diagnosed using ultrasonography. RESULTS: The prevalence of fatty liver disease (FLD) and MAFLD was 16.73% and 16.55%, respectively, and the FLI, HSI, LAP, VAI, and ZJU were all independently associated with an increased risk of MAFLD. The areas under the receiver operating characteristic curves (AUCs) of the FLI for diagnosing MAFLD in men and women were 0.853 and 0.847, respectively. The AUCs of the body mass index (BMI) for diagnosing MAFLD in men and women were 0.850 and 0.852, respectively. Compared with other metabolic-related markers, FLI had the largest AUC. In men, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 84.83%, specificity 69.57%) and 27.4 (sensitivity 78.47%, specificity 76.30%), respectively. In women, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 80.11%, specificity 74.23%) and 28.0 (sensitivity 79.56%, specificity 75.41%), respectively. In men and women, an FLI score of < 30 ruled out MAFLD, while a score of ≥ 50 was a basis for diagnosis. CONCLUSION: FLI and BMI had good screening ability for MAFLD and were superior to HSI, LAP, VAI, and ZJU in both sexes.

The mediating effect of depression on the relationship between osteoarthritis and cardiovascular disease mortality: A cohort study.

BACKGROUND: To explore the mediator role of depression in the association of osteoarthritis (OA) and cardiovascular disease (CVD) mortality based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Totally 19,605 adults from NHANES 2009-2018 were included in this cohort study ultimately. The outcome was considered as the CVD related mortality in this study. The follow-up duration was 81.09 ± 1.05 months. Weighted univariate and multivariate linear regressions were used to explore the association between OA and depression. Weighted univariate and multivariate COX regressions were performed to assess the relationship of OA and CVD related mortality. Also, we analyzed the mediating role of depression on the association between OA and CVD mortality through the Sobel Test. RESULTS: The CVD related mortality in this study was 2.57 %. After adjusting age, gender, physical activity, history of CVD, history of hypertension and eGFR, OA was positively correlated with depression [ß = 0.78, 95 % confidence interval (CI) = 0.54-1.02], and OA was associated the death risk of CVD [hazard ratio (HR): 1.35, 95%CI, 1.09-1.68]. Additionally, depression slightly mediated the association between OA and CVD related mortality in this study, with this mediating variable accounting for 5.61 % of the association. CONCLUSION: OA was associated with depression and CVD related mortality, respectively. Additionally, the increased risk of CVD related mortality in OA patients may be slightly mediated by depression. These results serve as a reminder that giving careful attention to and effectively managing mental health may be beneficial to prevent CVD related mortality, especially for those with OA.

A resting-state electroencephalographic microstates study in depressed adolescents with non-suicidal self-injury.

Neuroimaging studies have revealed abnormal brain activities in depressed teenagers who engage in non-suicidal self-injury (NSSI). We used resting-state electroencephalography (EEG) microstate analysis, which indicates the brief overlap of brain network activation for exploring the characteristics of large-scale cortical activities in depressed adolescents engaged with NSSI to clarify the underlying temporal mechanism. A modified k-means cluster algorithm was used to segment 64-channel resting-state EEG data into microstates. Data from 27 healthy adolescents, 37 adolescents with major depressive disorder (MDD), and 53 adolescents with both MDD and NSSI were examined in this study. The resting-state microstate parameters were compared among groups using the one-way ANOVA and Spearman correlation. Then the associations between significantly different microstate parameters and the depressive severity and self-harming data in the patient groups were further analyzed. The MDD group had higher contribution (p < 0.01), occurrence (p < 0.01) of microstate A, and higher microstate E→A transition (p < 0.05) than the HC and the NSSI group. The MDD group showed a distinctly longer duration (p < 0.05) of microstate A and microstate A→C transition than the HC. The transition probability from B to C was increased in the NSSI group compared to the HC. In the MDD group, the HAMD correlated with the duration of microstate A (Spearman's rho = 0.34, p = 0.044), as the PHQ-9 correlated with its occurrence (Spearman's rho = 0.37, p = 0.028). This research revealed that whereas depressive adolescents with NSSI and MDD displayed similar patterns with healthy controls in EEG microstate, the MDD group did not. Additionally, the non-random transition from microstate E→A may protect against recent self-harm in adolescents with MDD.

Effects of Bio-Aging on Mechanical Properties and Microbial Behavior of Different Resin Composites.

Under challenging oral environments, the overall performance of resin composites is affected by bio-aging. This study investigated the effects of saliva biofilm-induced bio-aging on the mechanical properties and microbial behavior of composites with different filler types. Microhybrid, nanohybrid, nano-filled and nano-filled flowable composites were bio-aged with saliva biofilm for 30 days. Surface morphology, roughness, mechanical and aesthetic properties were determined. A 48 h saliva biofilm model was used to evaluate the microbial behavior of different composites in vitro. Biofilm metabolic activity, lactic acid production and live/dead bacterial staining were tested. Six volunteers were selected to wear intra-oral appliances with composite slabs for 24 h and biofilms were collected and analyzed using 16S rRNA sequencing to assess the biofilm formation over those materials in situ. Although there were increasing trends, surface roughness, water resorption and material solubility had no significant changes for all groups after bio-aging (p > 0.05). There were no significant changes in elastic modulus for all groups after aging (p > 0.05). However, a decrease in flexural strength in all groups was observed (p < 0.05), except for the nanoflow composite group (p > 0.05). The Vickers hardness remained stable in all groups after aging (p > 0.05), except for the nano-filled group (p < 0.05). The nanoflow composite showed distinct color changes compared to the micro-hybrid group after aging (p < 0.05). Biofilm metabolic activity and lactic acid production in vitro increased slightly after bio-aging in all groups, but with no statistical significance (p > 0.05). The Shannon index diversity of biofilms in situ decreased after aging (p < 0.05), while no significant difference was shown in species composition at the genus level in all groups (p > 0.05). Resin composites with different sized fillers displayed a relatively stable mechanical performance and uncompromised microbial behavior both in vitro and in situ after 30 days of bio-aging. Based on the results, composites with different filler types can be selected flexibly according to clinical needs. However, a longer time for bio-aging is still needed to confirm the mechanical properties and microbial behaviors of composites in the long run.

Probing the Effect of Photovoltaic Material on Voc in Ternary Polymer Solar Cells with Non-Fullerene Acceptors by Machine Learning.

The power conversion efficiency (PCE) of ternary polymer solar cells (PSCs) with non-fullerene has a phenomenal increase in recent years. However, improving the open circuit voltage (Voc) of ternary PSCs with non-fullerene still remains a challenge. Therefore, in this work, machine learning (ML) algorithms are employed, including eXtreme gradient boosting, K-nearest neighbor and random forest, to quantitatively analyze the impact mechanism of Voc in ternary PSCs with the double acceptors from the two aspects of photovoltaic materials. In one aspect of photovoltaic materials, the doping concentration has the greatest impact on Voc in ternary PSCs. Furthermore, the addition of the third component affects the energy offset between the donor and acceptor for increasing Voc in ternary PSCs. More importantly, to obtain the maximum Voc in ternary PSCs with the double acceptors, the HOMO and LUMO energy levels of the third component should be around (-5.7 ± 0.1) eV and (-3.6 ± 0.1) eV, respectively. In the other aspect of molecular descriptors and molecular fingerprints in the third component of ternary PSCs with the double acceptors, the hydrogen bond strength and aromatic ring structure of the third component have high impact on the Voc of ternary PSCs. In partial dependence plot, it is clear that when the number of methyl groups is four and the number of carbonyl groups is two in the third component of acceptor, the Voc of ternary PSCs with the double acceptors can be maximized. All of these findings provide valuable insights into the development of materials with high Voc in ternary PSCs for saving time and cost.

Research on an Identification Method for Wheelset Coaxial Wheel Diameter Difference Based on Trackside Wheelset Lateral Movement Detection.

The wheelset coaxial wheel diameter difference is one of the most common wheel faults of railway vehicles. The existence of the wheelset coaxial wheel diameter difference may lead to the off-load operation of vehicles, resulting in abnormal wheel tread wear, leading to the deterioration of the wheel-rail contact relationship, resulting in the deterioration of the vehicle's operating stability and comfort, and even leading to an increase in the derailment coefficient, affecting the running safety. In order to monitor the freight car wheelset coaxial wheel diameter difference online, a vehicle-track coupling dynamics model based on a trackside detection method was established, and the response of rail lateral displacement under the condition of the wheelset coaxial wheel diameter difference was analyzed. The results show that the existence of the wheelset coaxial wheel diameter difference can lead to a deviation in the vehicle's run, with an increase in the wheelset coaxial wheel diameter difference and an increase in the lateral offset of wheelset increases. The impact of vehicle unbalance loading on the lateral movement of the wheelset is much smaller than that of the wheelset coaxial wheel diameter difference. The existence of the wheelset coaxial wheel diameter difference can be better reflected by detecting the wheelset's lateral displacement. On straight line, the variation of lateral displacement has no infection of vehicle speed, but shows a quadratic growth trend with the wheelset coaxial wheel diameter difference. Based on this, the mapping relationship between the wheelset coaxial wheel diameter difference and wheelset lateral displacement can be obtained. Through a mapping relationship, the size of the wheelset coaxial wheel diameter difference can be reversed precisely through the detection of a trackside lateral movement monitoring system. The reliability of the identification method was verified with a specific test on the trackside monitoring system.

Neurophysiological biomarkers for depression classification: Utilizing microstate k-mers and a bag-of-words model.

Microstates are analogous to characters in a language, and short fragments consisting of several microstates (k-mers) are analogous to words. We aimed to investigate whether microstate k-mers could be used as neurophysiological biomarkers to differentiate between depressed patients and normal controls. We utilized a bag-of-words model to process microstate sequences, using k-mers with a k range of 1-10 as terms, and the term frequency (TF) with or without inverse-document-frequency (IDF) as features. We performed nested cross-validation on Dataset 1 (27 patients and 26 controls) and Dataset 2 (34 patients and 30 controls) separately and then trained on one dataset and tested on the other. The best area under the curve (AUC) of 81.5% was achieved for the model with L1 regularization using the TF of 4-mers as features in Dataset 1, and the best AUC of 88.9% was achieved for the model with L1 regularization using the TF of 9-mers as features in Dataset 2. When Dataset 1 was used as the training set, the best AUC of predicting Dataset 2 was 74.1% for the model with L2 regularization using the TF-IDF of 9-mers as features, while the best AUC of predicting Dataset 1 was 70.2% for the model with L1 regularization using the TF of 8-mers as features. Our study provided novel insights into the potential of microstate k-mers as neurophysiological biomarkers for individual-level classification of depression. These may facilitate further exploration of microstate sequences using natural language processing techniques.

Impaired behavioral inhibitory control of self-injury cues between adolescents with depression with self-injury behavior and those without during a two-choice oddball task: an event-related potential study.

Background: This study aimed to objectively evaluate the severity of impulsivity [behavior inhibitory control (BIC) impairment] among adolescents with depression. In particular, those involved in non-suicidal self-injury (NSSI) behaviors, compared with those engaged in suicidal behaviors and adolescents without any self-injury behavior, using event-related potentials (ERPs) and event-related spectral perturbation (ERSP) within the two-choice oddball paradigm. Methods: Participants with a current diagnosis of major depressive disorder (MDD) engaged in repetitive NSSI for five or more days in the past year (n = 53) or having a history of at least one prior complete suicidal behavior (n = 31) were recruited in the self-injury group. Those without self-injury behavior were recruited in the MDD group (n = 40). They completed self-report scales and a computer-based two-choice oddball paradigm during which a continuous electroencephalogram was recorded. The difference waves in P3d were derived from the deviant minus standard wave, and the target index was the difference between the two conditions. We focused on latency and amplitude, and time-frequency analyses were conducted in addition to the conventional index. Results: Participants with self-injury, compared to those with depression but without self-injury, exhibited specific deficits in BIC impairment, showing a significantly larger amplitude. Specifically, the NSSI group showed the highest value in amplitude and theta power, and suicidal behavior showed a high value in amplitude but the lowest value in theta power. These results may potentially predict the onset of suicide following repetitive NSSI. Conclusion: These findings contribute to substantial progress in exploring neuro-electrophysiological evidence of self-injury behaviors. Furthermore, the difference between the NSSI and suicide groups might be the direction of prediction of suicidality.

Changes in microstates of first-episode untreated nonsuicidal self-injury adolescents exposed to negative emotional stimuli and after receiving rTMS intervention.

Background: Nonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%-60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents. Methods: Sixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12-17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed post-treatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed. Results: Our results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS. Conclusion: MDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Changes in emotion-related EEG components and brain lateralization response to negative emotions in adolescents with nonsuicidal self-injury: An ERP study.

Nonsuicidal self-injury (NSSI) is a serious risk behavior in adolescents and is a high risk factor for suicide, while negative emotions can lead to increased NSSI behaviors. In this study, we investigated the altered behavioral performance and neural reactivity of adolescents with NSSI by using a two-choice oddball paradigm when exposed to negative emotional stimuli, and analyzed the brain lateralization effect. Our data indicated that adolescents with NSSI exhibit more pronounced N250, P300, and LPP components during negative emotional face stimulation, as evidenced by a smaller N250 wave amplitude, larger P300 wave amplitude, steeper LPP waveform, and faster fallback baseline; and the presence of brain lateralization responses in both the N250 component and the LPP component. These results suggested that adolescents with NSSI showed significant alterations in cognitive EEG components associated with emotional processing during negative emotional face stimulation, particularly in EEG components representing inhibitory control, and there was a lateralization effect on emotional processing in the brain, with different processing stages and different dominance of the left and right brain.

Gallbladder disease is associated with the risk of cardiovascular disease among Uyghurs in Xinjiang: a prospective cohort study.

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

MixGradient: A gradient-based re-weighting scheme with mixup for imbalanced data streams.

A challenge for contemporary deep neural networks in real-world problems is learning from an imbalanced data stream, where data tends to be received chunk by chunk over time, and the prior class distribution is severely imbalanced. Although many sophisticated algorithms have been derived, most of them overlook the importance of gradient information. From this perspective, the difficulty of learning from imbalanced data streams lies in the fact that the gradient estimated on an uneven class distribution is not informative enough to reflect the critical pattern of each class. To this end, we propose to assign higher weights on the training samples whose gradients are close to the gradient of corresponding typical samples, thus highlighting the important samples in minority classes and suppressing the noisy samples in majority classes. Such an idea can be combined with Mixup, which exploits the interpolation information of data to further compensate for the information of sample space that the typical samples do not provide and expand the role of the proposed re-weighting scheme. Experiments on artificially induced long-tailed CIFAR data streams and long-tailed MiniPlaces data stream show that the resulting method, termed MixGradient, boosts the generalization performance of DNNs under different imbalance ratios and achieves up to 10% accuracy improvement.