GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Changes in disease burden and global inequalities in bladder, kidney and prostate cancers from 1990 to 2019: a comparative analysis based on the global burden of disease study 2019.

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.

Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer.

Cervical cancer is the second leading cause of morbidity and mortality in women worldwide. Traditional treatment methods have become limited. Naringenin, a flavonoid abundant in various fruits and herbal medicines, has demonstrated anti-tumor properties among other effects. This research undertook to elucidate the mechanism of naringenin in the context of cervical cancer treatment by leveraging network pharmacology and performing experimental validation. Initial steps involved predicting potential naringenin targets and subsequently screening for overlaps between these targets and those related to cervical cancer, followed by analysis of their interrelationships. Molecular docking was subsequently utilized to verify the binding effect of the central target. Within the framework of network pharmacology, it was discovered that naringenin might possess anti-cancer properties specific to cervical cancer. Following this, the anti-tumor effects of naringenin on Hela cell viability, migration, and invasion were assessed employing CCK-8, transwell, wound healing assays, and western blotting. Experimental data indicated that naringenin attenuates the migration and invasion of Hela cells via downregulation EGFR/PI3K/AKT signaling pathway. Thus, our findings suggest that naringenin has therapeutic impacts on cervical cancer via multiple mechanisms, primarily by inhibiting the migration and invasion through the EGFR/PI3K/AKT/mTOR pathway. This study offers fresh insights for future clinical studies.

Synergistic binding mechanisms of co-contaminants in soil profiles: Influence of iron-bearing minerals and microbial communities.

In contaminated soil sites, the coexistence of inorganic and organic contaminants poses a significant threat to both the surrounding ecosystem and public health. However, the migration characteristics of these co-contaminants within the soil and their interactions with key components, including Fe-bearing minerals, organic matter, and microorganisms, remain unclear. This study involved the collection of a 4.3-m-depth co-contaminated soil profile to investigate the vertical distribution patterns of co-contaminants (namely, arsenic, cadmium, and polychlorinated biphenyls (PCBs)) and their binding mechanisms with environmental factors. The results indicated a notable downward accumulation of inorganic contaminants with increasing soil depth, whereas PCBs were predominantly concentrated in the uppermost layer. Chemical extraction and synchrotron radiation analysis highlighted a positive correlation between the abundance of reactive iron (FeCBD) and both co-contaminants and microbial communities in the contaminated site. Furthermore, Mantel tests and structural equation modeling (SEM) demonstrated the direct impacts of FeCBD and microbial communities on co-contaminants within the soil profile. Overall, these results provided valuable insights into the migration and transformation characteristics of co-contaminants and their binding mechanisms mediated by minerals, organic matter, and microorganisms.

Boosting the Cycle Performance of Iron Trifluoride Based Solid State Batteries at Elevated Temperatures by Engineering the Cathode Solid Electrolyte Interface.

Iron trifluoride (FeF3) is attracting tremendous interest due to its lower cost and the possibility to enable higher energy density in lithium-ion batteries. However, its cycle performance deteriorates rapidly in less than 50 cycles at elevated temperatures due to cracking of the unstable cathode solid electrolyte interface (CEI) followed by active materials dissolution in liquid electrolyte. Herein, by engineering the salt composition, the Fe3O4-type CEI with the doping of boron (B) atoms in a polymer electrolyte at 60 °C is successfully stabilized. The cycle life of the well-designed FeF3-based composite cathode exceeds an unprecedented 1000 cycles and utilizes up to 70% of its theoretical capacities. Advanced electron microscopy combined with density functional theory (DFT) calculations reveal that the B in lithium salt migrates into the cathode and promotes the formation of an elastic and mechanic robust boron-contained CEI (BOR-CEI) during cycling, by which the durability of the CEI to frequent cyclic large volume changes is significantly enhanced. To this end, the notorious active materials dissolution is largely prohibited, resulting in a superior cycle life. The results suggest that engineering the CEI such as tuning its composition is a viable approach to achieving FeF3 cathode-based batteries with enhanced performance.

Latest advances in the study of non-coding RNA-mediated circadian rhythm disorders causing endometrial cancer.

Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.

Hetrombopag plus recombinant human thrombopoietin for chemotherapy-induced thrombocytopenia in patients with solid tumors.

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common hematological complication in patients with cancer. Hetrombopag is a novel thrombopoietin receptor agonist that has shown an additive effect in stimulating platelet production when combined with recombinant human thrombopoietin (rhTPO). Objectives: This multicenter retrospective cohort study aimed to evaluate the efficacy and safety of hetrombopag plus rhTPO compared with rhTPO alone for CIT. Methods: A total of 294 patients with solid tumors and CIT (platelet count, <50 × 109/L) who received either rhTPO plus hetrombopag (146 patients) or rhTPO alone (148 patients) at 3 centers from January to December 2022 were included in the study. The primary outcome was a platelet count at least 50 × 109/L higher than the baseline value within 14 days. Chemotherapy dose reductions/delays, bleeding, and adverse events were reported. Results: One hundred twenty patients (82.2%) in the rhTPO-hetrombopag group vs 100 patients (67.6%) in the rhTPO group achieved the primary outcome (P = .005). This significant difference persisted in adjusted analysis (odds ratio, 2.01; 95% CI, 1.12-3.60). A total of 115 patients (78.8%) in the rhTPO-hetrombopag group and 101 patients (68.2%) in the rhTPO group avoided chemotherapy dose reductions/delays (P = .041). There was no significant difference in bleeding rates, and adverse events were mild and similar between the 2 groups. No deaths occurred. Conclusion: Compared to rhTPO alone, our findings suggest that the combination of hetrombopag and rhTPO is safe and more effective in patients with CIT.

Effects of treatment with stem cell-derived extracellular vesicles in preclinical rodent models of intrauterine adhesion: A meta-analysis.

Background: Intrauterine adhesion (IUA) results from serious complications of intrauterine surgery or infection and mostly remains incurable. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have emerged as a potential new approach for the treatment of IUA; however, their impact is not fully understood. Here, we performed a meta-analysis summarizing the effects of sEVs on IUA in preclinical rodent models. Methods: This meta-analysis included searches of PubMed, EMBASE, Cochrane, and the Web of Science databases from January 1, 1997, to April 1, 2022, to identify studies reporting the therapeutic effect of sEVs on rodent preclinical animal models of IUA. We compared improvements in endometrial thickness, endometrial gland number, fibrosis area, embryo number, vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGFß1), and leukemia inhibitory factor (LIF) levels after treatment. Results: Our search included 100 citations, of which 7 met the inclusion criteria, representing 231 animals. Compared with that in the control group, the fibrosis area in the sEV-treated group was significantly reduced (standardized mean difference (SMD) = -6.87，95 % confidence interval (CI) = -9.67 to -4.07). The number of glands increased after the intervention (95 % CI, 3.72-7.68; P = 0.000). Endometrial thickness was significantly improved in the sEV-treated group (SMD = 2.57, 95 % CI, 1.62-3.52). Conclusions: This meta-analysis is highlighting that sEV treatment can improve the area of endometrial fibrosis, as well as VEGF, and LIF level, in a mouse IUA model. This knowledge of these findings will provide new insights into future preclinical research.

Secular trends of morbidity and mortality of thyroid cancer in five Asian countries from 1990 to 2019 and their predictions to 2035.

BACKGROUND: The rising burden of thyroid cancer (TC) is a public health problem in Asia. Predicting the future burden of TC in Asian countries is essential for disease prevention. METHODS: Data were obtained from the Global Burden of Disease 2019 for five Asian countries. We applied Bayesian age-period-cohort models to predict morbidity and mortality to 2035 and calculated age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR). Furthermore, the estimated annual percentage change was calculated to evaluate the variation of ASIR and ASMR. RESULTS: By 2035, predictions suggest that cases of TC will reach 75.56 × 103 in China, 70.22 × 103 in India, 15.78 × 103 in the Republic of Korea, 9.01 × 103 in Japan and 5.55 × 103 in Thailand, respectively. Except Japan, a significant upward trend of ASIR of TC will be observed in five Asian countries. The deaths from TC will increase in five countries and India will become the highest reaching 14.07 × 103 . The ASMR will rise to 0.83/100 000 in India and 1.06/100 000 in the Republic of Korea, while it will drop to 0.35/100 000 in China, 0.43/100 000 in Japan and 0.50/100 000 in Thailand. In further predictions projected by sex, the growth rate of ASIR is reported higher in males than in females among most countries. ASMR of male will exceed that of females in China and Thailand by 2035. CONCLUSION: The disease burden caused by TC will further increase in five Asian countries, especially for men. It is necessary to develop more rational and timely disease prevention and manage strategies facing this disease trend.

Short- and long-term outcomes of Roux-en-Y and Billroth II with Braun reconstruction in total laparoscopic distal gastrectomy: a retrospective analysis.

BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Risk Factors for Granulomatous Mastitis and Establishment and Validation of a Clinical Prediction Model (Nomogram).

Background: This study aimed to explore the risk factors and clinical characteristics of granulomatous mastitis (GM) using a case-control study and establish and validate a clinical prediction model (nomogram). Methods: This retrospective case-control study was conducted in three hospitals in China from June 2017 to December 2021. A total of 1634 GM patients and 186 healthy women during the same period were included and randomly divided into the modeling and validation groups in a 7:3 ratio. To identify the independent risk factors of GM, univariate and multivariate logistic analyses were conducted and used to develop a nomogram. The prediction model was internally and externally validated using the Bootstrap technique and validation cohort. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical significance of the model. Results: The average age of GM patients was 33.14 years (mainly 20-40). The incidence was high within five years from delivery and mainly occurred in the unilateral breast. The majority of the patients exhibited local skin alterations, while some also presented with systemic symptoms. On multivariate logistic analysis, age, high prolactin level, sex hormone intake, breast trauma, nipple discharge or invagination, and depression were independent risk factors for GM. The mean area under the curve (AUC) in the modeling and validation groups were 0.899 and 0.889. The internal and external validation demonstrated the model's predictive ability and clinical value. Conclusion: Lactation-related factors are the main risk factors of GM, leading to milk stasis or increased ductal secretion. Meanwhile, hormone disorders could affect the secretion and expansion of mammary ducts. All these factors can obstruct or injure the duct, inducing inflammatory reactions and immune responses. Additionally, blunt trauma, depressed mood, and diet preference can accelerate the process. The nomogram can effectively predict the risk of GM.

Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy.

BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.

Predisposing Factors for Granulomatous Lobular Mastitis: A Case-Control Study.

Background: Despite the rising incidence rate of granulomatous lobular mastitis (GLM), uncertainties persist about its etiologic and predisposing factors to guide clinical treatment and early prevention. The objective of this study is to explore the predisposing factors for GLM. Patients and methods: This case-control study was conducted from 2018 to 2021 at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients with GLM (cases) were matched with healthy examinees (controls) in a 1:1 ratio according to gender and living area. We analyzed their demographic features and investigated 75 factors that may be relevant to GLM using a standard questionnaire. Univariate and multivariable binary conditional logistic regression analyses were used to compare the differences between the two groups and evaluate the predisposing factors that may induce GLM. Results: There were 594 female GLM patients and 594 matched controls included in the study. The average age of the cases was 32.78 years (mainly 20 to 40). The incidence was high within five years after childbirth, and lesions were mainly in the unilateral breast. Univariate and multivariable conditional logistic regression analyses obtained six relevant factors and six high-risk factors. The six relevant factors included age, marriage, emotional abnormality, high prolactin, psychiatric drug intake, and sex hormone intake. Additionally, the independent high-risk factors for GLM included gestation, nipple invagination, blunt trauma, non-iatrogenic massage, lactation disorder, and nipple discharge (odds ratio (OR)=17.378, 8.518, 4.887, 3.116, 2.522, 1.685, P<0.05). Menopause was an independent protective factor (OR=0.249, P<0.05). Conclusion: The factors that increase milk and secretion production in the mammary duct are the main risk factors of GLM, especially when the nipples are invaginated. These factors can obstruct the duct and induce inflammation. Additionally, hormonal disorders, extrinsic trauma, and emotional abnormalities can accelerate the occurrence of GLM.

Comparison of proximal gastrectomy with double-flap technique and double-tract reconstruction for proximal early gastric cancer: a meta-analysis.

Surgical resection is the main treatment for proximal gastric cancer, but there is no consensus on its reconstruction. We carried out a meta-analysis to evaluate the effects of double-tract reconstruction (DTR) and double-flap technique (DFT) on postoperative quality of life in patients with proximal gastric cancer. Systematic searches of PubMed, Web of Science, EBSCO, and the Cochrane Library were performed. Literature for the last 5 years was searched without language restrictions. The cutoff date for the search was 12 April 2023. Literature and research searches were conducted independently by two researchers and data were extracted. Statistical analyses were performed using Review Manager (Revman) 5.4 software. Fixed models were used when heterogeneity was small and random-effects models were used for meta-analysis when heterogeneity was large. The study was registered with PROSPERO, CRD 42023418520. Surgical time was significantly shorter in the DTR group than in the DFT group (P = 0.03). There were no significant differences between DFT and DTR in terms of age, gender, pathological stage, preoperative body mass index, surgical bleeding, and perioperative complications. There was no statistically significant difference between the two groups in terms of reflux esophagitis and PPI intake, but DFT was superior to DTR in weight improvement at 1 year after surgery (P < 0.0001). Compared with DTR, DFT reconstruction is more demanding and time-consuming, but its postoperative nutritional status is better, so it should be the first choice for GI reconstruction in most patients with early proximal gastric cancer. However, DTR should be the best choice for patients who have difficulty operating.

A deep learning approach based on multi-omics data integration to construct a risk stratification prediction model for skin cutaneous melanoma.

PURPOSE: Skin cutaneous melanoma (SKCM) is a highly aggressive melanocytic carcinoma whose high heterogeneity and complex etiology make its prognosis difficult to predict. This study aimed to construct a risk subtype typing model for SKCM. METHODS: The study proposes a deep learning framework combining early fusion feature autoencoder (AE) and late fusion feature AE for risk subtype prediction of SKCM. The deep learning framework integrates mRNA, miRNA, and DNA methylation data of SKCM patients from The Cancer Genome Atlas (TCGA), and clusters the screened multi-omics features associated with survival prognosis to identify risk subtypes. Differential expression analysis and functional enrichment analysis were performed between risk subtypes, while SVM classifiers were constructed between differentially expressed genes (DEGs) obtained by Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression screening and risk subtype labels inferred from multi-omics data, and the predictive robustness of risk subtypes inferred from the risk subtype classification prediction model was validated using two independent datasets. RESULTS: The deep learning framework that combined early fusion feature AE with late fusion feature AE distinguished the two best risk subtypes compared to the multi-omics integration approach with single strategy AE or PCA. A promising C-index (C-index = 0.748) and a significant difference in survival (log-rank P value = 4.61 × 10-9) were found between the identified risk subtypes. The DEGs with the top significance values together with differentially expressed miRNAs provided the biological interpretation of risk subtypes on SKCM. Finally, the framework was applied to predict risk subtypes in two independent test datasets of SKCM patients, all of which showed good predictive power (C-index > 0.680) and significant survival differences (log-rank P value < 0.01). CONCLUSION: The SKCM risk subtypes identified by integrating multi-omics data based on deep learning can not only improve the understanding of the molecular mechanisms of SKCM, but also provide clinicians with assistance in treatment decisions.

The burden of chronic kidney disease associated with dietary exposure to cadmium in China, 2020.

Cadmium (Cd) exposure increases the risk of chronic kidney disease (CKD). But the contribution of dietary Cd intake, the primary exposure route of Cd in humans, to the CKD burden remains to be evaluated in China. Concentrations of Cd in foods and population glomerular filtration rate (GFR) were retrieved from studies published between January 2000 and February 2023 in China. Daily food consumption in adults aged ≥35 years old was obtained from two nationwide Chinese surveys. Dietary Cd intake and its contribution rate among total Cd exposure from diet, inhalation, smoking and water were evaluated. Urinary Cd (UCd) was estimated using the toxicokinetic (TK) model based on dietary Cd intake. The effect of Cd on kidney function has been quantified with the previously published dose-response relationship between UCd and GFR. The incidence and disability-adjusted life years (DALYs) of CKD attributable to dietary Cd intake were derived considering the contribution rate of dietary Cd intake at the national and provincial levels. The national average dietary Cd intake was 0.6891 µg/kg bw/day, contributing 63.69% of total Cd exposure. The Cd exposure through foods resulted in 2.34 (95% uncertainty interval, UI: 1.54-3.40) stage 4 CKD and 0.37 (95% UI: 0.20-0.59) stage 5 CKD cases per 100,000 persons/year in mainland China, 2020. The corresponding DALYs loss associated with stage 4 and stage 5 CKD due to dietary Cd intake were 5.14 (95% UI: 3.24-7.67) and 4.78 (95% UI: 2.32-8.30) per 100,000 persons/year, together accounting for 2% of total DALYs of CKD. Greater dietary Cd intake and corresponding burden of late-stage CKD were observed in Southern areas than in Northern areas. Diet remains the primary exposure to Cd in Chinese adults. Efforts to reduce dietary Cd exposure would positively impact public health, especially in Southern provinces with high Cd exposure.

Fever burden within 24 h after hematoma evacuation predicts early neurological deterioration in patients with intracerebral hemorrhage: a retrospective analysis.

Background: Early neurological deterioration after hematoma evacuation is closely associated with a poor prognosis in patients with intracerebral hemorrhage. However, the relationship between body temperature after hematoma evacuation and early neurological deterioration remains unclear. Therefore, this study aims to explore the possible relationship between body temperature and early neurological deterioration in patients with intracerebral hemorrhage after hematoma evacuation. Methods: We retrospectively collected data from patients with cerebral hemorrhage at our institute between January 2017 and April 2022. The Student's t-test, Mann-Whitney U-test, and χ2 Test and Fisher's exact test were used to analyze the clinical baseline data. A univariate logistic regression model was used to evaluate the association between the body temperature indices and early neurological deterioration. The predictive power was assessed using the area under the Receiver Operating Characteristic (ROC) curve. The secondary outcome was a poor functional outcome. Results: Among 2,726 patients with intracerebral hemorrhage, 308 who underwent hematoma evacuation were included in the present analysis. A total of 82 patients (22.6%) developed early neurological deterioration. Univariate analysis showed that sex (p = 0.041); body temperature at 6 h (p = 0.005), 12 h (p = 0.01), and 24 h (p = 0.008) after surgery; duration of fever (p = 0.008); and fever burden (p < 0.001) were associated with early neurological deterioration. Multivariate logistic regression showed that fever burden was independently associated with early neurological deterioration (OR = 1.055 per °C × hour, 95%CI 1.008-1.103, p = 0.020). ROC showed that fever burden (AUC = 0.590; 95%CI: 0.514-0.666) could predict the occurrence of early neurological deterioration. Conclusion: Fever burden is associated with early neurological deterioration in intracerebral hemorrhage patients undergoing hematoma evacuation. Our findings add to previous evidence on the relationship between the fever burden and the occurrence of early neurological deterioration in patients with intracerebral hemorrhage. Future studies with larger sample sizes are required to confirm these findings.

Screening and detection of multivalent human papillomavirus antibodies using a high-throughput liquid chip fluoroimmunoassay system.

Immunoassays are commonly used in disease diagnosis and vaccine evaluation but can be costly and time-consuming when confronted with multivalent targets, such as antisera containing antibodies to human papillomavirus (HPV), because of their limited ability to discriminate between multiple analytes in a single reaction well. This study describes the development of a high-throughput liquid chip system that combines immunoassay techniques and magnetic beads to allow the simultaneous screening and quantitative detection of antibodies to four types of HPV using the Luminex fluoroimmunoassay system. Groups of beads embedded with fluorescent dyes at various ratios were coated with optimized HPV capture antigens and demonstrated excellent dose-dependent response to four monoclonal antibodies used as reference standards. This assay is sensitive, accurate, repeatable, and simple to perform, enabling multiplex antibody detection with a high degree of orthogonality. The performance of the Luminex system was compared with conventional immunoassays for quantitative detection of quadrivalent HPV antibodies in antisera of mice immunized with five lots of HPV vaccines, verifying the accuracy and detection efficiency of the assay. This strategy is a promising approach to characterizing antibodies present in polyclonal antisera and has promising applications in research, clinical, and industrial settings, for example, streamlining vaccine efficacy trials and vaccine lot inspection and release procedures.