Effect of fasting plasma glucose level in severe fever and thrombocytopenia syndrome patients without diabetes.

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0-11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS.

Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis.

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.

Ascitic microbiota alteration is associated with portal vein tumor thrombosis occurrence and prognosis in hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.

Identification and validation of hub genes expressed in ulcerative colitis with metabolic dysfunction-associated steatotic liver disease.

Objective: Ulcerative colitis (UC) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely intertwined; however, the precise molecular mechanisms governing their coexistence remain unclear. Methods: We obtained UC (GSE75214) and MASLD (GSE151158) datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired by the 'edgeR' and 'limma' packages of R. We then performed functional enrichment analysis of common DEGs. Hub genes were selected using the cytoHubba plugin and validated using GSE87466 for UC and GSE33814 for MASLD. Immunohistochemistry was employed to validate the hub genes' expression in clinical samples. Immune infiltration and gene set enrichment analyses of the hub genes were performed. Finally, we estimated the Spearman's correlation coefficients for the clinical correlation of the core genes. Results: Within a cohort of 26 differentially regulated genes in both UC and MASLD, pathways involving cytokine-mediated signaling, cell chemotaxis, and leukocyte migration were enriched. After further validation, CXCR4, THY1, CCL20, and CD2 were identified as the hub genes. Analysis of immune infiltration patterns highlighted an association between elevated pivotal gene expression and M1 macrophage activation. Immunohistochemical staining revealed widespread expression of pivotal genes in UC- and MASLD-affected tissues. Furthermore, significant correlations were observed between the increased expression of hub genes and biochemical markers, such as albumin and prothrombin time. Conclusion: This bioinformatics analysis highlights CXCR4, THY1, CCL20, and CD2 as crucial genes involved in the co-occurrence of UC and MASLD, providing insights into the underlying mechanisms of these two conditions.

Global burden and risk factors of gastritis and duodenitis: an observational trend study from 1990 to 2019.

In recent years, there has been a global trend of aging, which has resulted in significant changes to the burden of gastritis and duodenitis (GD). Using the global burden of disease (GBD) database spanning 1990 to 2019, we evaluated the temporal trends of age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized disability-adjusted life years (AS-DALYs) for GD using estimated annual percentage changes (EAPC). Additionally, we examined the burden of GD across various strata, including social demographic index (SDI), age, and sex. Finally, the risk factors linked to the incidence and mortality of GD, utilizing Pearson correlation analysis. In 2019, there were 31 million GD patients globally, a notable increase of 12 million from 1990, while the ASIR, ASDR, and AS-DALYs for GD all showed a decrease. Correlation analysis showed a significant negative relationship between ASIR and SDI. Factors like hand hygiene and vitamin A deficiency had significant positive correlations with ASIR and ASDR in 2019. Over the past thirty years, the burden of GD has increased alongside global population aging. Future efforts should focus on exploring prevention for GD, with special attention to the elderly population in low SDI regions.

Repetitive peripheral magnetic stimulation combined with transcranial magnetic stimulation in rehabilitation of upper extremity hemiparesis following stroke: a pilot study.

OBJECTIVE: To investigate the effect of combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation on upper extremity function in subacute stroke patients. DESIGN: Pilot study. SUBJECTS: Subacute stroke patients. METHODS: Included patients were randomized into 3 groups: a central-associated peripheral stimulation (CPS) group, a central-stimulation-only (CS) group, and a control (C) group. The CPS group underwent a new paired associative stimulation (combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation), the CS group underwent repetitive transcranial magnetic stimulation, and the C group underwent sham stimulation. All 3 groups received physiotherapy after the stimulation or sham stimulation. The treatment comprised 20 once-daily sessions. Primary outcome was the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score, and secondary outcomes were the Barthel Index and Comprehensive Functional Assessment scores, and neurophysiological assessments were mainly short-interval intracortical inhibition. A 3-group (CPS, CS, C) × 2-time (before, after intervention) repeated measures analysis of variance was conducted to determine whether changes in scores were significantly different between the 3 groups. RESULTS: A total of 45 patients were included in the analysis. Between-group comparisons on the FMA-UE demonstrated a significant improvement (group × time interaction, F2,42 = 4.86; p = 0.013; C vs CS, p = 0.020; C vs CPS, p = 0.016; CS vs CPS, p = 0.955). Correlation analysis did not find any substantial positive correlation between changes in FMA-UE and short-interval intracortical inhibition variables (C, r = -0.196, p = 0.483; CS, r = -0.169, p = 0.546; CPS, r = -0.424, p = 0.115). CONCLUSION: This study suggests that the real-stimulus (CS and CPS) groups had better outcomes than the control (C) group. In addition, the CPS group showed a better trend in clinical and neurophysiological assessments compared with the CS group.

Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank.

BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.

High CRP/PNI levels predict an unfavorable prognosis in severe fever with thrombocytopenia syndrome: A propensity score matching study.

BACKGROUND: This study aimed to identify a novel inflammatory index and construct a nomogram for predicting in-hospital mortality due to severe fever with thrombocytopenia syndrome (SFTS). METHODS: This cohort included 610 patients with SFTS hospitalized in Wuhan Union Hospital between March 2017 and November 2022. The ratio of C-reactive protein (CRP) to the prognostic nutritional index (PNI) was calculated and used to reflect patients' inflammatory status. Propensity score matching (PSM) was utilized to balance confounding factors between the low- and high-CRP/PNI groups. SFTS individuals from Jinyinhu Hospital were used as the validation cohort. RESULTS: Patients with SFTS and high CRP/PNI were significantly correlated with a higher percentage of severe and critical SFTS types and higher in-hospital mortality rates than those with low CRP/PNI. CRP/PNI was the potent risk indicator for in-hospital mortality in individuals with SFTS. The CRP/PNI nomogram showed a good predictive value for in-hospital mortality in patients with SFTS. After PSM, the predictive performance of CRP/PNI for 28-day mortality was excellent. Finally, the CRP/PNI could still assess patients with SFTS at different risks based on SFTS data from another medical center. CONCLUSION: The CPR/PNI ratio exhibited a strong positive correlation with the SFTS disease type and could predict in-hospital mortality in the early stages of SFTS. The CPR/PNI ratio could substantially help clinicians facilitate the early identification of patients with high-risk SFTS and the timely initiation of intensive therapy.

Evaporative cooling and reaction of carbon dioxide clusters by low-energy electron attachment.

Anionic carbonate CO3- has been found in interstellar space and the Martian atmosphere, but its production mechanism is in debate so far. To mimic the irradiation-induced reactions on icy micrograins in the Martian atmosphere and the icy shell of interstellar dust, here we report a laboratory investigation on the dissociative electron attachments to the molecular clusters of CO2. We find that anionic species (CO2)n-1O- and (CO2)n- (n = 2, 3, 4) are produced in the concerted reaction and further stabilized by the evaporative cooling after the electron attachment. We further propose a dynamics model to elucidate their competitive productions: the (CO2)n- yields survive substantially in the molecular evaporative cooling at the lower electron attachment energy, while the reactions leading to (CO2)n-1O- are favored at the higher attachment energy. This work provides new insights into physicochemical processes in CO2-rich atmospheres and interstellar space.

Direct production of molecular oxygen from carbon dioxide and helium ion collisions.

The prebiotic mechanism to produce molecular oxygen (O2) in carbon dioxide (CO2)-rich planetary atmospheres is of great importance in understanding astrochemical reactions and is potentially relevant to the origin of life on Earth. Here, we demonstrate that, aside from the direct productions of O2 by photodissociation and dissociative electron attachment, the low-energy ion-molecule reaction between cationic helium in solar winds and molecular CO2 is a noticeable mechanism. Branching ratios of the reaction channels are determined, and their absolute cross-sections are estimated accordingly. The present findings represent a further, indispensable step towards fully understanding the origins of atmospheric O2.

Using machine learning algorithms to predict 28-day mortality in critically ill elderly patients with colorectal cancer.

OBJECTIVE: To predict the 28-day mortality of critically ill, elderly patients with colorectal cancer (CRC) using five machine learning approaches. METHODS: Data were extracted from the eICU Collaborative Research Database (eICU-CRD) (version 2.0) for a training cohort and from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) and Wuhan Union hospital for validation cohorts. Clinical information (i.e., demographics; initial laboratory tests; vital signs; outcomes) were collected. Five machine learning algorithms (LightGBM, decision tree, XGBoost, random forest, and ensemble model) and a logistic regression were applied for the prediction of 28-day mortality. RESULTS: Overall, 693 patients were included from the eICU cohort, 181 patients from the MIMIC-IV cohort and 95 from the Wuhan Union cohort. Among the six machine learning models, the ensemble model exhibited the best predictive ability (AUC, 0.86), followed by random forest (AUC, 0.83) and LightGBM (AUC, 0.82) in the training cohort. The models also obtained the good predictive performance for the 28-day mortality in the validation cohorts. CONCLUSIONS: We showed that machine learning algorithms can be used for the 28-day mortality prediction in critically ill, elderly patients with CRC.

SHCBP1 Promotes the Proliferation of Breast Cancer Cells by Inhibiting CXCL2.

Breast cancer has the characteristics of high metastasis and recurrence and ranks first in incidence and mortality among female malignant tumors. Shc SH2-domain binding protein 1 (SHCBP1) is an important protein in intracellular signal transduction and cell division, but the role of SHCBP1 in breast cancers remains elusive. Here, we found that SHCBP1 deficiency inhibited the proliferation of breast cancer cells. Mechanistically, SHCPB1 significantly downregulates the mRNA level of CXCL2, which in turn activates the AKT and ERK signaling, while inactivates the p21 and p27 signaling. In addition, overexpression of SHCPB1 downregulates the protein levels of p21 and p27, which could be completely reversed by restoration of CXCL2 expression. Moreover, we analyzed the expression of both SHCPB1 and CXCL2, and found that SHCPB1 is highly expressed in breast cancer cells or tissues from breast cancer patients compared to normal breast cells or adjacent normal tissues, while CXCL2 is lowly expressed in breast cancer cells or tissues. Collectively, our study reveals that SHCBP1 plays an oncogenic role in breast cancer tumorigenesis partially through inhibiting the inflammatory response and ultimately activating the proliferation of breast cancers.

Incomplete radiofrequency ablation following transarterial chemoembolization accelerates the progression of large hepatocellular carcinoma.

Purpose: To examine post-operative progression and risk impact of insufficient radiofrequency ablation (RFA) following transarterial chemoembolization (TACE) for the prognosis of large hepatocellular carcinoma (HCC). Materials and Methods: From January 2014 to January 2021 were analyzed. A total of 343 patients with large HCC (diameter >5 cm) who received TACE combined with RFA were enrolled and were divided into two groups: complete ablation (CA, n = 172) and insufficient ablation (IA, n = 171). Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier curve and compared with the log-rank test. To find parameters influencing OS and PFS, clinicopathological variables underwent univariate and multivariate analysis. Results: The cumulative 1-, 3-, and 5-year OS and PFS rates of the CA group were significantly higher than that of the IA group (P < 0.001). 25 (41%) patients in local tumor progression (LTP), 36 (59%) in intrahepatic distant recurrence (IDR), and 0 (0%) in extrahepatic distant recurrence (EDR) in the CA group. 51 (32.1%) patients in LTP, 96 (60.4%) patients in IDR, and 12 (7.5%) cases in EDR in the IA group. The recurrence patterns of the two groups were statistically significant difference (P = 0.039). In multivariate analysis, inadequate ablation and conjunction with TKIs were both significant risk factors for OS and PFS. Apart from these, older age and >7 cm of tumor size were indicators of poor OS and multiple tumors were indicators of poor PFS. Conclusion: Insufficient ablation causes a poor survival outcome of TACE combined with RFA for large HCC, particularly, which can promote IDR.

Prohibitin1 facilitates viral replication by impairing the RIG-I-like receptor signaling pathway.

IMPORTANCE: Type I interferon (IFN-I), produced by the innate immune system, plays an essential role in host antiviral responses. Proper regulation of IFN-I production is required for the host to balance immune responses and prevent superfluous inflammation. IFN regulatory factor 3 (IRF3) and subsequent sensors are activated by RNA virus infection to induce IFN-I production. Therefore, proper regulation of IRF3 serves as an important way to control innate immunity and viral replication. Here, we first identified Prohibitin1 (PHB1) as a negative regulator of host IFN-I innate immune responses. Mechanistically, PHB1 inhibited the nucleus import of IRF3 by impairing its binding with importin subunit alpha-1 and importin subunit alpha-5. Our study demonstrates the mechanism by which PHB1 facilitates the replication of multiple RNA viruses and provides insights into the negative regulation of host immune responses.

Multi-joint protective effects of lumbar brace on lumbar, hip, knee, and ankle in parachute landing with backpack load.

There were high injury risks on lumbar and lower limb joints in parachuting landing, and the lumbar brace could protect lumbar. Besides, a backpack load was necessary in parachute landing and increased the injury risk. This study aimed to evaluate multi-joints protective effects of the lumbar brace on lumbar and lower limb joints in parachuting landing with the backpack load. Seven participants landed from a 120 cm height platform without and with a lumbar brace and without and with a 5-kg backpack load, respectively. Infrared makers were pasted on trunk, pelvis, and lower limb in order to build a multi-rigid-body model for calculating kinematic and kinetic parameters. The joint angular displacements of lumbar and ankle and the peak vertical ground reaction force were significantly decreased from 29.2 ± 9.2°, 45.2 ± 7.8°, and 14.7 ± 2.0 bodyweight to 21.6 ± 4.9° (p < 0.05), 39.0 ± 10.1° (p < 0.05) and 10.7 ± 1.3 bodyweight (p < 0.05) respectively by the lumbar brace with no backpack load, and the joint angular displacement of hip was significantly increased from 52.6 ± 7.2° to 68.3 ± 12.5° (p < 0.05). The joint angular displacement of lumbar and ankle were significantly decreased from 29.0 ± 5.0° and 53.8 ± 5.1° to 25.1 ± 5.2° (p < 0.05) and 48.5 ± 2.5° (p < 0.05) respectively by the lumbar brace with the backpack load, and the joint angular displacement of hip and knee were significantly increased from 60.1 ± 8.2° and 110.1 ± 9.3° to 69.7 ± 13.2° (p < 0.05) and 116.8 ± 5.8° (p < 0.05), respectively. The lumbar brace could provide the multi-joint protective effect by decreasing injuries of lumbar and ankle in landing both without and with the backpack load.

Identification of Critical Biomarkers and Mechanisms of Fructus Ligustri Lucidi on Vitiligo Using Integrated Bioinformatics Analysis.

Objective: Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Fructus Ligustri Lucidi (FLL) has been used for premature graying of hair since ancient China and is currently used to treat vitiligo. However, the key biomarkers and mechanisms underlying FLL in vitiligo remain unclear. This study aimed to identify the potential biomarkers and mechanisms of FLL in vitiligo using network pharmacology analysis. Methods: The expression profiles of GSE65127 and GSE75819 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the vitiligo and healthy samples. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs were performed using R analyses. We performed R to further understand the functions of the critical targets. Cytoscape tools have facilitated network topology analysis. Molecular docking was performed using Auto Dock Vina software. Results: The results showed that 13 DEGs were screened in vitiligo. Based on bioinformatics, network pharmacology and Western blot, we found that the critical targets of melanoma antigen recognized by 5,6-dihydroxyindole-2-carboxylic acid oxidase (TYRP1) may be related to the mechanism of action of FLL in the treatment of vitiligo. Conclusion: TYRP1, as a melanocyte molecular biomarker, may be closely related to the underlying mechanism of FLL in the treatment of vitiligo via the inhibition of melanocyte death.

Restraint stress promotes monobenzone-induced depigmentation in mice via the activation of glucocorticoid receptor/macrophage migration inhibitory factor signaling pathway.

Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.

Prediction of HER2 status via random forest in 3257 Chinese patients with gastric cancer.

The accurate evaluation of human epidermal growth factor receptor 2 (HER2) is crucial for successful trastuzumab-based therapy in individuals with gastric cancer (GC). The present study, involving a retrospective cohort (N = 2865) from Wuhan Union Hospital and a prospective cohort (N = 392) from Renmin Hospital of Wuhan University, evaluated the benefits of clinical features using random forest and logistic regression models for the detection of HER2 status in patients with GC. Patients from the Union cohort were randomly assigned to either a training (N = 2005) or an internal validation (N = 860) group. Data processing and feature selection were done in Python, which was also used to build random forest and logistic regression models for the prediction of HER2 overexpression. The Renmin cohort (N = 392) was used as the external validation group. Ten features were closely correlated with HER2 overexpression, including age, albumin/globulin ratio, globulin, activated partial thromboplastin time, tumor stage, node stage, tumor node metastasis stage, tumor size, tumor differentiation, and neuron-specific enolase (NSE). Random forest and logistic regression had areas under the curve (AUC) of 0.9995 and 0.6653 in the training group and 0.923 and 0.667 in the internal validation group, respectively. When the two predictive models were validated using data from the Renmin cohort, random forest and logistic regression had AUCs of 0.9994 and 0.627, respectively. This is the first multicenter study to predict HER2 overexpression in individuals with GC, based on clinical variables. The random forest model significantly outperformed the logistic regression model.

Correlation Analysis Between Disease Activity and Anxiety, Depression, Sleep Disturbance, and Quality of Life in Patients with Inflammatory Bowel Disease.

Objective: To explore the correlation between disease activity and anxiety, depression, sleep quality, and quality of life in patients with inflammatory bowel disease (IBD). Methods: The disease activity of IBD patients was evaluated by 66 gastroenterologists from 42 hospitals in 22 provinces in China from September 2021 to May 2022. Anxiety, depression, sleep quality and quality of life of IBD patients were investigated and statistically analyzed by different scales, including Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Quality-of-Life Questionnaire (IBD-Q). Results: A total of 2478 IBD patients were included, of which 1532 (61.8%) were in active stage and 946 (38.2%) were in remission. The proportions of active IBD with anxiety, depression, sleep disturbance, and poor quality of life were 29.5%, 29.7%, 71.1%, and 50.1%, respectively, while the proportions of remission IBD with anxiety, depression, sleep disturbance, and poor quality of life were 19.1%, 24.4%, 69.3%, and 17.4%, respectively. IBD patients who also had anxiety, depression, sleep disturbances and poor quality of life had 80 cases (8.46%) in remission and 114 cases (7.44%) in active stage, with 54 cases (9.18%) in mild activity, 51 cases (6.95%) in moderate activity and 9 cases (4.49%) in severe activity. IBD patients with different disease activity levels differed in GAD-7 scores, PHQ-9 scores, PSQI scores, and IBD-Q scores (all P<0.001). In IBD patients, anxiety, depression, and sleep disturbance, which interact with each other, can further aggravate their disease activity (all P<0.001). Conclusion: Anxiety, depression, sleep disturbances, and quality of life are strongly correlated with disease activity in IBD patients, and IBD patients with psychological disturbances are most often in the active stage and have a poor quality of life.

Apoprotein E methylation is correlated with immune microenvironment in hepatocellular carcinoma.

BACKGROUND: We aimed to evaluate the correlation of apoprotein E (APOE) transcription and its methylation with immune microenvironment in HCC patients. MATERIAL AND METHODS: The expression profiles of APOE transcription, APOE methylation, and APOE protein were investigated via comprehensive bioinformatic analyses. After that, the association between the immune activation of HCC and APOE transcription and methylation were analyzed. Finally, the prognostic role and immune correlation of the APOE protein in 92 HCC individuals was determined. RESULTS: Based on data from TCGA, GEO, and ICGC datasets, the APOE mRNA was differentially expressed in HCC tissues compared with normal liver tissues. Further, APOE methylation was down-regulated in HCC tissues compared to normal liver tissues. APOE methylation was negatively correlated with APOE transcription in HCC (r=-0.52, p < 0.0001). Based on APOE methylation, the HCC patients were stratified into hypermethylation and hypomethylation subgroups as they exhibited different immune activation statuses. Further, HCC individuals with APOE hypermethylation had a closer immune correlation than those with hypomethylation. Notably, APOE transcription was associated with weak immune infiltrates and activation. Finally, over-expression of the APOE protein was correlated with better survival outcomes, but not correlated with PD-1 or CTLA4 protein in HCC revealed by immunohistochemistry. CONCLUSION: APOE methylation had a closer correlation with immune cells than APOE mRNA, indicating that APOE methylation might play an important role in immune regulation in HCC.