Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway.

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected. We found through transcriptome sequencing that cell apoptosis and MAPK signaling pathway are the main potential pathways for DBP induced reproductive toxicity. Molecular biology analyses revealed a significant increase in the protein levels of JNK1(MAPK8) and BAX, as well as a significant increase in the BAX/BCL2 ratio after DBP exposure. Therefore, we propose that DBP induces reproductive toxicity by regulating JNK1 expression to activate the MAPK signaling pathway and induce reproductive cell apoptosis. In conclusion, our study provides the first evidence that the MAPK signaling pathway is involved in DBP-induced reproductive toxicity and highlights the importance of JNK1 as a potential target of DBP in inducing reproductive toxicity.

Optimized CAR-T therapy based on spatiotemporal changes and chemotactic mechanisms of MDSCs induced by hypofractionated radiotherapy.

Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of intratumoral myeloid-derived suppressor cells (MDSCs) and decreased infiltration of T cells in the tumor microenvironment (TME) of immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed in tumors from patients. RNA sequencing (RNA-seq) and cytokine profiling analysis revealed that HFRT induced the activation and proliferation of tumor-infiltrated MDSCs, which was mediated by the interactions of multiple chemokines and chemokine receptors. Further investigation showed that when combined with HFRT, CXCR2 blockade significantly inhibited MDSCs trafficking to tumors and effectively enhanced the intratumoral infiltration and treatment efficacy of CAR-T cells. Our study demonstrates that MDSCs blockade combined with HFRT is promising for CAR-T cell therapy optimization in solid tumors.

Acoustic Imaging Method for Gas Leak Detection and Localization Using Virtual Ultrasonic Sensor Array.

An acoustic imaging method for detecting and locating gas leaks based on a virtual ultrasonic sensor array is proposed and experimentally demonstrated. A scanning sensor array of only two sensors is used to collect the acoustic signals generated by the leakage hole. The matrix of the leakage signal is processed by the cross-power spectrum method to achieve time consistency, afterward, the location of the leakage source can be calculated by the virtual beamforming method. The influence of the number of sensors and the distance between adjacent sensors on the effect of the proposed method are compared and discussed. To verify the effectiveness and operability of the detection and localization method, several experiments were carried out. Furthermore, a series of experiments were conducted to assess the accuracy and stability of this method. The experimental results demonstrate that the proposed method based on a virtual sensor array can achieve highly accurate localization of gas leaks and performs well regarding stability.

Sensitivity-enhanced Fabry-Perot interferometric fiber-optic microphone using hollow cantilever.

Transducer components are crucial in optimizing the sensitivity of microphones. Cantilever structure is commonly used as a structural optimization technique. Here, we present a novel Fabry-Perot (F-P) interferometric fiber-optic microphone (FOM) using a hollow cantilever structure. The proposed hollow cantilever aims to reduce the effective mass and spring constant of the cantilever, thereby enhancing the sensitivity of the FOM. Experimental results demonstrate that the proposed structure outperforms the original cantilever design in terms of sensitivity. The sensitivity and minimum detectable acoustic pressure level (MDP) can reach 91.40 mV/Pa and 6.20 µPa/Hz at 1.7 kHz, respectively. Notably, the hollow cantilever provides an optimization framework for highly sensitive FOMs.

Study on the prognosis, immune and drug resistance of m6A-related genes in lung cancer.

BACKGROUND: Few studies have demonstrated that the relationship between m6A-related genes and the prognosis, tumor microenvironment and drug resistance of LC. METHODS: The main results were analyzed with bioinformatics methods. RESULTS: Hence, we found 10 m6A-related genes expressed less in tumor samples in comparison with normal ones. Using consensus clustering, all LC patients were grouped into 2 subgroups according to the overall expression of 10 differential expressed m6A-related genes. In two clusters, the OS and immune characteristics were different. We analyzed the predictive potential of 10 m6A-related genes in the prognosis of LC, and obtained a risk prognosis model on the strength of ZC3H13, CBLL1, ELAVL1 and YTHDF1 as the hub candidate genes through LASSO cox. The expression of 4 hub m6A-related genes was validated by IHC in the HPA database. The infiltration level of dendritic cell, CD4+ T cell and neutrophil that were affected by CNV level of m6A-related genes in LUAD and LUSC patients. Moreover, based on GSCALite database, we found that LUSC patients with hypermethylation tended to have a better overall survival. In terms of drug sensitivity, etoposide correlated negatively with ELAVL1, HNRNPC, RBM15B, YTHDF2 and CBLL1. ZC3H13 had positively association with afatinib, while HNRNPC was positively associated with dasatinib, erlotinib, lapatinib and TGX221. Crizotinib had a negative correlation with ELAVL1, CBLL1, HNRNPC and RBM15B. CONCLUSION: In conclusion, m6A-related genes are important participants in LC and the expression levels of ZC3H13, CBLL1, ELAVL1 and YTHDF1 are significant for prediction and treatment of LC. Researches of drug resistance based on m6A-related genes need to pay more attention for producing new therapeutic strategies of LC and CBLL1 may contribute to target treatment for further research.

AL amyloidosis with primary presentation of multiple serous cavity effusion and severe cholestasis: a case report and review of literature.

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis commonly affects the kidney or heart, but may also involve the liver at a histopathological level. Early diagnosis of AL amyloidosis is important for proper management with desirable outcome. We reported here an unusual case of AL amyloidosis, presenting primarily with multiple serous cavity effusion, accompanied with rapidly progressive cholestasis. CASE PRESENTATION: A previously healthy 63-year-old man presented with dysuria, frequent urination, oliguria and oedema of lower extremities for one month, accompanied with jaundice and hypoproteinemia. CT demonstrated multiple serous cavity effusion, focal hypodense lesions in the liver, and focal low-density in the spleen. Laparoscopy with liver biopsy revealed liver and spleen fibrosis with congestion, no visceral rupture, following haemorrhagic ascites from abdominocentesis. This patient was transferred to our (tertiary) hospital. The diagnosis of amyloidosis was confirmed with histopathology/immunohistochemistry. Haematopoietic stem cell transplantation was not applicable, however chemotherapy was advised, due to the patient's Mayo score 3. The patient declined chemotherapy and was self-discharged back to his hometown hospital with palliative care, however only lasted a further one-month. DISCUSSION: The lesson we have learnt from this case that any patients with multiple serous cavity effusion and isolated hepatic involvement, primary amyloidosis should be considered. Multiple serous cavity effusion may serve as an indicator for poor prognosis of hepatic AL amyloidosis.

The role of non-apoptotic cell death in the treatment and drug-resistance of digestive tumors.

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.

Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer.

BACKGROUND: EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. METHODS: All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. RESULTS: We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. CONCLUSIONS: Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.

Synergistic activation of persulfate by natural chalcocite and ferrous ions by promoting the cycling of Fe3+/Fe2+ couple for degradation of organic pollutants.

Natural chalcocite (NCC) was chosen as a co-catalyst for activation of persulfate (PS) to degrade organic contaminants in this study. A synergistic effect between NCC and ferrous ions (Fe2+) was found in catalyzing PS for degradation of orange G (OG). The main role of NCC in the NCC/Fe2+/PS system was to facilitate Fe3+ reduction back to Fe2+ and thus improve the stoichiometric efficiency of PS. The results of scavenging experiments and electron paramagnetic resonance tests proved that both sulfate and hydroxyl radicals were the primary reactive oxidants in the NCC/Fe2+/PS system. Twelve potential intermediate products of OG were identified, and the degradation pathway was proposed. Experiment parameters, such as NCC dose, Fe2+ concentration, initial pH, and the presence of anions (H2PO4‒ and Cl‒), all had important impacts on OG degradation. NCC had good reusability in synergistic activation of PS with Fe2+ for OG degradation for five cycles. This study demonstrated a natural sulfide mineral as an efficient co-catalyst towards PS activation for destruction of organic contaminants in water.

Photoacoustic trace gas detection of OCS using a 2.45 mL Helmholtz resonator and a 4823.3 nm ICL light source.

A miniaturized photoacoustic spectroscopy-based gas sensor is proposed for the purpose of detecting sub-ppm-level carbonyl sulfide (OCS) using a tunable mid-infrared interband cascade laser (ICL) and a Helmholtz photoacoustic cell. The tuning characteristics of the tunable ICL with a center wavelength of 4823.3 nm were investigated to achieve the optimal driving parameters. A Helmholtz photoacoustic cell with a volume of ∼2.45 mL was designed and optimized to miniaturize the measurement system. By optimizing the modulation parameters and signal processing, the system was verified to have a good linear response to OCS concentration. With a lock-in amplifier integration time of 10 s, the 1σ noise standard deviation in differential mode was 0.84 mV and a minimum detection limit (MDL) of 409.2 ppbV was achieved at atmospheric pressure and room temperature.

Difficulty in differentiating liver injury from an immune checkpoint inhibitor from chemotherapy.

This study investigated the potential of immune checkpoint inhibitors (ICIs) combined with chemotherapy as a promising treatment approach for malignancies. This report focuses on a patient with drug-induced liver injury (DILI) following the administration of chemotherapy and ICIs. A 63-year-old patient with non-small cell lung adenocarcinoma (NSCLC) initially underwent γ-knife treatment and subsequently received a combination of chemotherapy comprising bevacizumab and camrelizumab. Due to liver abnormalities, both chemotherapy and ICIs were stopped on day 21. The patient's liver function improved within a month after methylprednisolone treatment. Subsequently, the patient received carboplatin, pemetrexed, and bevacizumab without complications. This finding supported the notion that DILI was likely triggered by the ICI. This case series details a complex instance of DILI resulting from the use of ICIs and pemetrexed/carboplatin. The alignment of the pathological findings and clinical presentation strongly suggested ICI-induced DILI, which was further supported by the definitive response to steroid treatment. This information is important for clinicians, as it emphasizes the importance of closely monitoring liver function and being aware of potential adverse effects associated with ICIs. Such insights contribute to more effective patient care.

Liver fibrosis is closely linked with metabolic-associated diseases in patients with autoimmune hepatitis.

BACKGROUND: This cross-sectional study aimed to investigate the impact of metabolic-associated diseases (MADs) on patients with autoimmune hepatitis (AIH). METHODS: The study analyzed the clinical characteristics of 283 AIH patients who underwent liver biopsy between January 2016 and February 2022 in Ruijin Hospital, Shanghai, China. RESULTS: Among the identified AIH patients (n = 283), 87.3%, 23.0%, or 43.1% had MADs, non-alcoholic fatty liver disease (NAFLD), or severe fibrosis, respectively. The proportion of diabetes mellitus (DM) was significantly higher in patients with severe liver fibrosis than in those with mild or moderate fibrosis in the AIH cohort (31.1% vs. 18.0%, p < 0.05). Fibrosis was also more severe in patients with NAFLD than in those without (53.8% vs. 39.9%, p < 0.05). Age, Plts, IgG and the presence with MADs were identified as independent predictors of the severity of inflammation in AIH patients. Moreover, severe liver fibrosis (stages 3 to 4) was independently associated with male (OR, 2.855; p = 0.025), γ-GT (OR, 0.997; p = 0.007), and combination with MADs (OR, 4.917; p = 0.006). Furthermore, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients (OR, 2.445, p = 0.038). CONCLUSIONS: Concurrent MADs, common in AIH patients, is an independent risk factor for severe fibrosis or inflammation; of note, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients. While managing with AIH, routine assessment of co-existing MADs, especially DM, is also important.

Cost-effectiveness analysis of durvalumab plus tremelimumab as first-line therapy in patients with unresectable hepatocellular carcinoma.

Background: The HIMALAYA trial found that durvalumab plus tremelimumab significantly prolonged progression-free survival and overall survival in patients with unresectable hepatocellular carcinoma (HCC) compared with sorafenib. Objective: This study aimed to investigate the cost-effectiveness of durvalumab plus tremelimumab compared with sorafenib in the first-line HCC setting. Design: A Markov model-based cost-effectiveness analysis. Methods: We created a Markov model to compare healthcare costs and clinical outcomes of HCC patients treated with durvalumab plus tremelimumab in the first-line setting compared with sorafenib. We estimated transition probabilities from randomized trials. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated for first-line durvalumab plus tremelimumab compared with sorafenib from a US payer's perspective. Results: In the base case, first-line durvalumab plus tremelimumab was associated with an improvement of 0.29 QALYs compared with sorafenib. While both treatment strategies were associated with considerable lifetime expenditures, first-line durvalumab plus tremelimumab was less expensive than sorafenib ($188,405 vs $218,584). The incremental net monetary benefit for durvalumab plus tremelimumab versus sorafenib was $72,762 (valuing QALYs at $150,000 each). The results of durvalumab plus tremelimumab were better in terms of costs and health outcomes in patients with HBV-related HCC and high alpha-fetoprotein levels. Conclusion: First-line durvalumab plus tremelimumab was estimated to be dominant for the treatment of unresectable HCC compared with sorafenib from a US payer's perspective.

Safety and immunogenicity of inactivated COVID-19 vaccine CoronaVac and the RBD-dimer-based COVID-19 vaccine ZF2001 in chronic hepatitis B patients.

Background and aims: Although COVID-19 vaccination is recommended for the patients with chronic liver disease, the clinical outcomes of COVID-19 vaccinated in patients with chronic hepatitis B (CHB) has not been well characterized. The study aimed to explore the safety and specific antibody responses following COVID-19 vaccination among CHB patients. Methods: Patients with CHB were included. All patients were vaccinated with two doses of inactivated vaccine (CoronaVac) or three doses of adjuvanted protein subunit vaccine (ZF2001). The adverse events were recorded and neutralizing antibody (NAb) were determined 14 days following the whole-course vaccination. Results: A total of 200 patients with CHB were included. Specific NAb against SARS-CoV-2 were positive in 170 (84.6%) patients. The median (IQR) concentrations of NAb were 16.32 (8.44-34.10) AU/ml. Comparison of immune responses between CoronaVac and ZF2001 vaccines showed no significant differences in neither the concentrations of NAb nor the seropositive rates (84.4 vs. 85.7%). Moreover, we observed lower immunogenicity in older patients and in patients with cirrhosis or underlying comorbidities. The incidences of adverse events were 37 (18.5%) with the most common adverse event as injection side pain [25 (12.5%)], followed by fatigue [15 (7.5%)]. There were no differences in the frequencies of adverse between CoronaVac and ZF2001 (19.3% vs. 17.6%). Almost all of the adverse reactions were mild and self-resolved within a few days after vaccination. Severe adverse events were not observed. Conclusions: COVID-19 vaccines, CoronaVac and ZF2001 had a favorable safety profile and induced efficient immune response in patients with CHB.

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB.

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs). Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy. Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child-Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs. Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.

The 20 years transition of clinical characteristics and metabolic risk factors in primary liver cancer patients from China.

Background: The clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated. Methods: It was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients. Results: The average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitis-related PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) < 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT > 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P<0.05). Conclusions: It was gradually increased that age, the proportion of females, non-viral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs.

Lenvatinib Plus Pembrolizumab vs. Chemotherapy in Pretreated Patients With Advanced Endometrial Cancer: A Cost-Effectiveness Analysis.

Background: In the international, randomized, open-label, phase 3 study 309-KEYNOTE-775 trial, lenvatinib plus pembrolizumab (LP) showed improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in pretreated patients with advanced endometrial cancer. This study aimed to investigate whether LP is cost-effective compared with chemotherapy. Materials and Methods: The clinical data for this model was derived from the 309-KEYNOTE-775 trial. Costs and utilities were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced endometrial cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether LP is cost-effective in patients with mismatch repair-proficient (pMMR) disease. Results: Lenvatinib plus pembrolizumab provided an incremental 0.64 quality-adjusted life years (QALYs) with an incremental cost of $241,278.18, compared with chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $378,251.44/QALY, which exceeded the willingness to pay (WTP) threshold. While in the pMMR subgroup, the ICER increased to $413,256.68/QALY. The variance of the utility of PFS state, the cost of LP, and the utility of the progressive disease state were the most influential factors in the sensitivity analysis. Conclusion: Under the current WTP threshold, LP is not cost-effective compared with chemotherapy in pretreated patients with advanced endometrial cancer.

Margetuximab Versus Trastuzumab in Patients With Advanced Breast Cancer: A Cost-effectiveness Analysis.

BACKGROUND: In the international, randomized, open-label, phase III study SOPHIA trial, margetuximab plus chemotherapy showed improved progression-free survival (PFS), and overall survival (OS) compared with trastuzumab plus chemotherapy. This study aimed to investigate whether margetuximab plus chemotherapy is cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer. MATERIALS AND METHODS: The clinical data for this model was derived from the SOPHIA trial. Costs and utility were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced breast cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether margetuximab is cost-effective in CD16A-158F allele carriers. RESULTS: Margetuximab plus chemotherapy provided an incremental 0.04 QALYs with an incremental cost of $66,109.78, compared with the trastuzumab plus chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $1,486,442.35/QALY, which exceeded the willingness to pay (WTP) threshold. While in the CD16A-158F allele carriers subgroup, the ICER decreased to $592,669.73/QALY. The variance of the utility of PFS state, costs of margetuximab, and utility of progressive disease state were the most influential factors in the sensitivity analysis. CONCLUSION: Under current WTP threshold, margetuximab plus chemotherapy is not cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer. Selecting CD16A-158F allele carriers might be a considerable option to optimize the cost-effectiveness of margetuximab.

A deep learning algorithm based on 1D CNN-LSTM for automatic sleep staging.

BACKGROUND: Sleep staging is an important part of sleep research. Traditional automatic sleep staging based on machine learning requires extensive feature extraction and selection. OBJECTIVE: This paper proposed a deep learning algorithm without feature extraction based on one-dimensional convolutional neural network and long short-term memory. METHODS: The algorithm can automatically divide sleep into 5 phases including awake period, non-rapid eye movement sleep period (N1 ∼ N3) and rapid eye movement using the electroencephalogram signals. The raw signal was processed by the wavelet transform. Then, the processed signal was directly input into the deep learning algorithm to obtain the staging result. RESULTS: The accuracy of staging is 93.47% using the Fpz-Cz electroencephalogram signal. When using the Fpz-Cz and electroencephalogram signal, the algorithm can obtain the highest accuracy of 94.15%. CONCLUSION: These results show that this algorithm is suitable for different physiological signals and can realize end-to-end automatic sleep staging without any manual feature extraction.

A novel model based on qAnti-HBc and conventional biomarkers for identifying significant liver injury among CHB patients with ALT ≤ ULN.

BACKGROUND: Antiviral therapy is not routinely recommended for CHB patients with ALT ≤ ULN (CHB-NALT), based on current international guidelines. However, it is debatable if antiviral treatment should be offered for CHB-NALT patients, because significant liver injury is observed from liver biopsy of some CHB-NALT patients. Quantification of anti-HBc (qAnti-HBc) can predict antiviral response in CHB patients, while its role in CHB-NALT patients remains to be explored. AIM: To determine if it is reliable that the novel non-invasive model based mainly on qAnti-HBc and other conventional biomarkers for providing objective value among CHB-NALT patients with antiviral therapy, in direct comparison with liver biopsy. METHODS: 542 or 110 liver biopsied CHB-NALT patients from 2015 to 2020 or in 2021 were included in training set or validation set. Circulating IL-1ß, IL-2, IL-4, IL-12p70, IL-17, TNF and IFNα were determined in the training set. A non-invasive model was developed based on qAnti-HBc and other conventional biomarkers. RESULTS: Among 423/542 (78%) patients with significant liver injury in the training set, 47% were in grey-zone. Circulating IL-1ß, IL-12p70, IL-17 in the CHB-NALT patients with liver injury was significantly higher than these without liver injury in the training set (p < 0.01). No significant difference of IL-1ß, IL-12p70, IL-17 was observed between CHB-NALT patients with significant liver injury and active CHB with elevated ALT in the training set. There was inverse correlation between liver injury grades and IFNα, IL-4, or IL-2 in these patients (p < 0.05). Serum qAnti-HBc level was significantly higher with CHB-NALT patients with liver injury than these without in the training set (P < 0.01). ALT/ULN, AST, PLT and qAnti-HBc were identified as independent predictors for significant liver injury. Furthermore, our current model demonstrated a good performance in predicting significant liver injury, i.e. AUROCs of 0.95 or 0.86 in training set or validation set. The model cut-off value for anti-viral therapy at ≥1.471. CONCLUSIONS: qAnti-HBc appears to be well correlated with the hepatic damage, in direct comparison with liver biopsy from CHB-NALT patients. The novel model developed seems to be reliable for predicting liver injury in CHB-NALT patients. Such model also provides objective value for decision making of antiviral therapy.