Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

Evaluation of the effectiveness of a segmented alternating shift pattern based on wearable vital signs monitoring devices during COVID-19: a cross-sectional study.

AIM: To explore the feasibility and effectiveness of an alternating shift pattern in two-hour segments in the state of emergency management of public health events. METHODS: A cross-sectional research design was conducted in our study. The nursing staff working in the admission ward of suspected or confirmed patients with COVID-19 in December 2022 were selected as subjects by the whole-group sampling method. We adopted a shift pattern of alternating shifts every two-hour in the isolation wards. The vital signs parameters were captured by uniformly wearing the multi-signs sensing devices, and the questionnaires collected the symptoms. RESULTS: Sixty-seven female participants, with a mean age of 33.09 ± 5.96 years, were included in this study. Measurements of body temperature (T), blood oxygen saturation (SpO2), respiratory rate (RR), and heart rate (HR) while wearing personal protective equipment (PPE) all remained within normal limits. None of the nurses reported sweating, dizziness, blurred vision, palpitations, or dyspnea. Statistical analysis showed significant differences between the critical care group and the non-critical care group in terms of age (P = 0.041), working duration (P = 0.036), and the total number of entries into isolation areas for nursing care (rounds) (P = 0.007). However, there were no statistically significant differences in vital signs based on age, work duration, or body mass index (BMI). The data indicated a notable increase in body temperature compared to other vital sign parameters with increasing work time while wearing PPE. Body temperature approached the upper limit when working close to 2 h long. CONCLUSIONS: The alternating shift pattern in two-hour segments can effectively maintain the physical well-being of nurses wearing PPE without increasing the burden on nursing staff or the wastage of protective materials. This approach is recommended for addressing similar public health events in the future.

Clinical characteristics of COVID-19 clusters in three schools in Beijing, China: A retrospective study.

Background: This retrospective analysis aims to investigate the clinical characteristics of students infected with the SARS-CoV-2 Omicron variant in three Beijing schools. Additionally, we explore the dynamic trends of nucleic acid cycle threshold values (Ct values) and serum antibody titers throughout the disease course. Methods: Demographic, clinical, nucleic acid Ct values, and antibody titer data were collected from cases in a COVID-19 cluster in Beijing Ditan Hospital, Capital Medical University, spanning from September 6 to October 1, 2022. Results: A total of 107 students infected with Omicron (BA.5.2 and BA.2.76) were identified across three schools. Primary clinical manifestations included fever and upper respiratory symptoms (85/107, 79.4 %), with the majority being classified as mild cases (96/107, 89.7 %). Notably, middle school students in the second school exhibited a higher peak body temperature compared to college students in the first and third schools (39.5 °C vs. 38.4 °C, adjusted P = 0.005; 39.5 °C vs. 38.6 °C, adjusted P = 0.002). Analysis of dynamic changes in Ct values revealed the lowest median Ct value in nasopharyngeal swabs on the third day of illness, reaching 35 after 9-11 days. Oropharyngeal swab nucleic acid median Ct value reached 35 approximately 3-5 days post-onset. Serum antibody detection showed continuous negativity of IgM antibody titers from days 1-10, while IgG antibody titers were positive on the first day and increased rapidly after one week. Conclusions: The three COVID-19 cluster school outbreaks primarily resulted from Omicron infections, with no severe or fatal cases observed. Clinically, the selection of different types of SARS-CoV-2 nucleic acid swabs for virus detection can be tailored based on the infection's course.

Development and validation of a prognostic nomogram to predict the recurrence of AFP-negative and DCP-positive hepatocellular carcinoma after curative resection.

Purpose: Approximately one-third of hepatocellular carcinoma (HCC) cases are characterized by alpha-fetoprotein (AFP) negativity (AFP-NHCC. Among these patients, around 60% exhibit des-gamma-carboxyprothrombin (DCP) positivity, and DCP-positive patients have a poorer prognosis. As a curative treatment, recurrence after liver resection poses significant challenges to the prognosis of HCC patients. Therefore, it is necessary to determine the relevant risk factors of these patients and provide timely treatment options. Methods: This study included 540 patients who underwent resection at Beijing You'an Hospital. 292 patients from 2014 to 2018 constituted the training cohort, while 248 patients from 2018 to 2020 constituted the validation cohort. All patients underwent routine follow-ups until December 2023. Variables were identified through Cox regression, and a nomogram was developed. The nomogram was evaluated using time-dependent receiver operating characteristic curves (ROC), calibration curves, Decision curve analysis (DCA), and Kaplan-Meier (KM) curve analysis. Results: We found that age, tumor number, tumor size, γ-glutamyl transpeptidase (γ-GT), and prothrombin time (PT) are independent risk factors for HCC recurrence, and a nomogram was developed and validated based on this result to predict recurrence-free survival (RFS) at 1, 2, and 3 years. The performance of the nomogram was further confirmed by the ROC curve, calibration curve, and DCA, all of which showed favorable results. The KM curve analysis clearly distinguishes between two groups of people with different risks in terms of prognosis in both the training and validation sets. Conclusion: In summary, we established and validated a novel nomogram by multivariate Cox regression analysis to predict recurrence in DCP-positive patients with AFP-NHCC after resection. The nomogram, including age, tumor number, tumor size, γ-GT, and PT, demonstrates better predictive ability for AFP-NHCC patients with DCP positive.

Prognostic nomogram based on the gamma-glutamyl transpeptidase-to-platelet ratio for patients with compensated cirrhotic hepatocellular carcinoma after local ablation.

Background: Hepatocellular carcinoma (HCC) patients with compensated cirrhosis typically face a high prevalence and unfavorable prognosis. However, there is currently a deficiency in prediction models to anticipate the prognosis of these patients. Therefore, our study included the Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in analysis and aimed to develop a nomogram for HCC patients with compensated cirrhosis after local ablation. Methods: Enrolling 669 patients who underwent local ablation at Beijing You'an Hospital during the period from January 1, 2014, to December 31, 2022, this study focused on individuals with compensated cirrhotic HCC. In a ratio of 7:3, patients were allocated to the training cohort (n=468) and the validation cohort (n=201). Lasso-Cox regression was employed to identify independent prognostic factors for overall survival (OS). Subsequently, a nomogram was constructed using these factors and was validated through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: GPR, age, and hemoglobin were identified by Lasso-Cox regression as independent prognostic factors of the nomogram. The area under the ROC curves (AUCs) for 3-, 5-, and 8-year OS (0.701, 0.755, and 0.768 for the training cohort; 0.684, 0.707, and 0.778 for the validation cohort), and C-indices (0.695 for training cohort; 0.679 for validation cohort) exhibited the excellent predictive ability of the nomogram. Calibration curves and DCA curves indicated favorable calibration performance and clinical utility. Patients were further stratified into two risk groups according to the median nomogram score. There existed an obvious distinction between the two groups both in the training cohort and validation cohort. Conclusion: In summary, this research established and validated a novel nomogram to predict OS, which had good predictive power for HCC patients with compensated cirrhosis after local ablation.

Validation of 12 Rapid Antigen Tests for the Detection of SARS-CoV-2.

The rapid identification SARS-CoV-2 virus has become the basis for the control of the COVID-19 outbreak. The rapid antigen tests for SARS-CoV-2 are quick, widely available, and inexpensive. Rapid antigen tests have gradually replaced the time-consuming and costly RT-PCR. Currently, although several RAT kits have been extensively used for the diagnosis of COVID-19, validity data are limited due to the inconsistent sensitivity and poor reproducibility. Meanwhile, WHO does not recommend specific commercial RAT kits. Therefore, it is crucial to establish a method to evaluate the effectiveness of different rapid antigen tests kits. This study aimed to develop an evaluation system for rapid antigen tests to provide an efficient and accurate technique for screening SARS-CoV-2 antigen detection kits. Given large number of rapid antigen tests kits available, this study only focused on those that are representative and commonely used in China. By minimzing biases through randomization, concealment, and blinding, we eventually found that the Test 1 had the lowest sensitivity and the Test VI had the highest sensitivity. This study provided an evaluation platform that can potentially serve as a reference for COVID-19 diagnostic strategies.

Recurrence of Hepatocellular Carcinoma in Patients with Low Albumin-Bilirubin Grade in TACE Combined with Ablation: A Random Forest Cox Predictive Model.

Purpose: The aim of our study was to investigate the relationship between albumin-bilirubin (ALBI) grade and recurrence in patients who underwent TACE sequential ablation. We developed and validated a nomogram to predict low levels of ALBI patients' recurrence. Patients and Methods: A total of 880 patients undergoing TACE combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were retrospectively enrolled, including 415 patients with L-ALBI (≤-2.6) and 465 patients with high levels (>-2.6) of ALBI (H-ALBI). L-ALBI patients were randomized in a 7:3 ratio into the training cohort (N=289) and validation cohort (N=126). Multivariate Cox regression followed by random survival forest was carried out to identify independent risk factors for prediction nomogram construction. An examination of nomogram accuracy was performed using the C-index, receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) curves. According to the nomogram, the patients were divided into low-risk, intermediate-risk, and high-risk groups. Kaplan-Meier (KM) curves were applied to compare the difference in recurrence-free survival (RFS) among the three groups. Results: The median RFS in L-ALBI patients was significantly longer than the H-ALBI patients (40.8m vs 20.1m, HR:1.71, 95% CI:1.44-2.04, P<0.0001). The nomogram was composed of five variables, such as age, Barcelona Clinic Liver Cancer (BCLC) stage, globulin, gamma-glutamyl transferase to lymphocyte ratio (GLR), and international normalized ratio (INR). The C-index (0.722 and 0.731) and 1-, 3-, and 5-year AUCs (0.725, 0.803, 0.870, and 0.764, 0.816, 0.798) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves demonstrated good consistency and good clinical utility. There were significant differences in RFS between the low-risk, intermediate-risk, and high-risk groups (P<0.0001). Conclusion: L-ALBI Patients who underwent TACE combined ablation had better recurrence-free survival than patients with H-ALBI. The nomogram developed and validated in our study had good predictive ability in recurrence for L-ALBI patients.

Profiling of viral load, antibody and inflammatory response of people with monkeypox during hospitalization: a prospective longitudinal cohort study in China.

BACKGROUND: The dynamics of viral shedding and the specific humoral response against monkeypox virus (MPXV) have not been well characterized in patients across their disease course during hospitalisation. The aim of this study was to determine the viral load and the levels of antibodies against MPXV using longitudinal paired-collected samples from hospitalized patients. METHODS: Patients who were hospitalised with mpox were recruited at Beijing Ditan Hospital Capital Medical University in China between June 2 and September 23, 2023. Paired samples, including samples from skin lesions, the oropharynx, saliva, faeces, urine, plasma, and serum, were serially collected at days 1, 3, 7, and 14 after admission until discharge. Not all of the patients had samples obtained at all of the timepoints. All the samples were analysed via quantitative PCR. Virus isolation was performed by using clinical samples and Vero cells. The presence of IgM, IgA, IgG, and neutralising antibodies (NAbs) against MPXV was evaluated. The first collected plasma sample was taken when the patient was hospitalised, and the levels of cytokines and chemokines were measured in the sample. The demographic data, smallpox vaccination status, history of known exposure to MPVX, HIV status and other clinical data were collected using a standard case report form. FINDINGS: A total of 510 specimens were serially collected from 39 recruited people with mpox. Among all the samples, the skin lesions had the highest viral DNA detection rates and viral loads, and the saliva samples had the second highest rates and viral loads. One day before discharge, 85% of the dry scrabs (median Ct 28.2, range 19.0-38.3) and 70% of the saliva samples (median Ct 32.4, range 24.5-38.1) were positive for viral DNA, Of which, 23.1% of dry scrabs were positive in viral culture. The rate of viral DNA detection in the oropharyngeal, saliva, and faecal samples decreased with time, while the rates in the plasma, serum, and urine samples increased quickly before 10 days post symptom onset (PSO). The median days of appearance of MPXV-IgM, MPXV-IgA, MPXV-IgG, and NAb were at 8 (interquartile range [IQR] 7-9), 9 (7-10), 12 (9-15), and 12 (9-15) PSO, respectively. The IgM, IgA, IgG, and NAb titres increased with time. Between days 11 and 21 PSO, the NAb titres were lower in people living with HIV (PWH) than in people living without HIV (PWOH). Increased NAb titres were associated with decreased viral loads in the saliva (r = 0.28, p = 0.025), faeces (r = 0.35, p = 0.021), plasma (r = 0.30, p = 0.0044), and serum samples (r = 0.37, p = 0.001). Compared with PWOH, PWH had higher plasma levels of MIP-1α, MIP-1ß, G-CSF, IL-4, and FGF-basic. INTERPRETATION: The high positive viral culture rate of clinical samples of patients when they are discharged from the hospital indicates that effective public health management strategies are needed for people with mpox. The low NAb titres and high levels of cytokines in PWH shows that earlier treatment is needed to control inflammation in high-risk populations. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences, Fundamental Research Funds for the Central Universities for Peking Union Medical College, National Key R&D Program of China.

Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

Introduction: This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. Methods: We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. Results: The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Conclusion: Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents.

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

Incorporating Inflammatory Markers and Clinical Indicators into a Predictive Model of Single Small Hepatocellular Carcinoma Recurrence After Primary Locoregional Treatments.

Purpose: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence. Patients and Methods: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram. Results: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P<0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P<0.0001). Conclusion: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.

Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis.

Introduction: This study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram. Methods: Data from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You'an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves. Results: The nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell's concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703-0.785) and 0.724 (95% CI: 0.644-0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram's reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram's efficacy in distinguishing varying recurrence risks. Conclusion: This study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.

Nomogram built based on machine learning to predict recurrence in early-stage hepatocellular carcinoma patients treated with ablation.

Introduction: To analyze the risk factors affecting recurrence in early-stage hepatocellular carcinoma (HCC) patients treated with ablation and then establish a nomogram to provide a clear and accessible representation of the patients' recurrence risk. Methods: Collect demographic and clinical data of 898 early-stage HCC patients who underwent ablation treatment at Beijing You'an Hospital, affiliated with Capital Medical University from January 2014 to December 2022. Patients admitted from 2014 to 2018 were included in the training cohort, while 2019 to 2022 were in the validation cohort. Lasso and Cox regression was used to screen independent risk factors for HCC patients recurrence, and a nomogram was then constructed based on the screened factors. Results: Age, gender, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, globulin (Glob) and γ-glutamyl transpeptidase (γ-GT) were finally incorporated in the nomogram for predicting the recurrence-free survival (RFS) of patients. We further confirmed that the nomogram has optimal discrimination, consistency and clinical utility by the C-index, Receiver Operating Characteristic Curve (ROC), calibration curve and Decision Curve Analysis (DCA). Moreover, we divided the patients into different risk groups and found that the nomogram can effectively identify the high recurrence risk patients by the Kaplan-Meier curves. Conclusion: This study developed a nomogram using Lasso-Cox regression to predict RFS in early-stage HCC patients following ablation, aiding clinicians in identifying high-risk groups for personalized follow-up treatments.

Machine learning-based characterization of the gut microbiome associated with the progression of primary biliary cholangitis to cirrhosis.

BACKGROUND: Primary biliary cholangitis (PBC) is associated closely with the gut microbiota. This study aimed to explore the characteristics of the gut microbiota after the progress of PBC to cirrhosis. METHOD: This study focuses on utilizing the 16S rRNA gene sequencing method to screen for differences in gut microbiota in PBC patients who progress to cirrhosis. Then, we divided the data into training and verification sets and used seven different machine learning (ML) models to validate them respectively, calculating and comparing the accuracy, F1 score, precision, and recall, and screening the dominant intestinal flora affecting PBC cirrhosis. RESULT: PBC cirrhosis patients showed decreased diversity and richness of gut microbiota. Additionally, there are alterations in the composition of gut microbiota in PBC cirrhosis patients. The abundance of Faecalibacterium and Gemmiger bacteria significantly decreases, while the abundance of Veillonella and Streptococcus significantly increases. Furthermore, machine learning methods identify Streptococcus and Gemmiger as the predominant gut microbiota in PBC patients with cirrhosis, serving as non-invasive biomarkers (AUC = 0.902). CONCLUSION: Our study revealed that PBC cirrhosis patients gut microbiota composition and function have significantly changed. Streptococcus and Gemmiger may become a non-invasive biomarker for predicting the progression of PBC progress to cirrhosis.

A Novel Nomogram to Predict Prognosis in Elderly Early-Stage Hepatocellular Carcinoma Patients After Ablation Therapy.

Purpose: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Early diagnosis is crucial for improving prognosis. Elderly HCC patients often have underlying liver diseases such as chronic hepatitis and cirrhosis, leading to impaired liver function and suboptimal liver reserve. Radiofrequency ablation (RFA) has rapidly become one of the most important methods for treating early-stage hepatocellular carcinoma (EHCC) due to its advantages, including minimal trauma, short operation time, less intraoperative bleeding, quick postoperative recovery, cost-effectiveness, and few postoperative-complications. However, the prognostic model for early recurrence after local ablation in elderly EHCC patients has not been widely evaluated. We have developed a prognostic model for the recurrence of local RFA in elderly EHCC patients. This is expected to provide a new early warning system for preventing early recurrence in elderly EHCC patients, prolonging patient's life, and improving overall quality of life. Methods: In this study, we included 661 EHCC patients who underwent local ablation, dividing them into a Primary cohort and a Validation cohort in a 7:3 ratio. We characterized the cohorts and utilized the primary cohort to develop a prognostic nomogram model for recurrence after local ablation in elderly EHCC patients. Additionally, the validation cohort was used to assess the potential of the nomogram as a non-invasive biomarker for post-ablation recurrence in EHCC. Results: The user-friendly nomogram incorporates common clinical variables including gender, BCLC stage, tumor number, tumor size, red blood cell (RBC), gamma-glutamyl transferase (GGT), and prothrombin time activity (PTA). The nomogram constructed using the identified seven variables exhibits robust discriminatory capabilities, favorable predictive performance, and noteworthy clinical utility. Conclusion: We developed a user-friendly nomogram based on the BCLC stage classification, which may provide prognostic assessments for elderly EHCC patients at 1, 3, and 5 years post-RFA.

GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation.

BACKGROUND: Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC. METHODS: This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility. CONCLUSION: This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

Construction and validation of a machine learning-based nomogram to predict the prognosis of HBV associated hepatocellular carcinoma patients with high levels of hepatitis B surface antigen in primary local treatment: a multicenter study.

Background: Hepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment. Method: This study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram. Result: After PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P<0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P<0.001). Conclusion: High levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.

Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device.

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1.

The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.