Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Gut microbiota and cognitive performance: A bidirectional two-sample Mendelian randomization.

PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer.

BACKGROUND: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. METHODS: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. RESULTS: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. CONCLUSIONS: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

[Comparison on anti-inflammatory activity of Gynostemma pentaphyllum processed with different methods].

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.

Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.

Background: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China. Methods: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses. Results: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss. Conclusions: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.

Numerical simulation of heat transfer properties of large-sized biomass particles during pyrolysis process.

During the pyrolysis process of large particles, the conduction between particles cannot be ignored. In the present work, a numerical simulation model for the pyrolysis of biomass particles was established, which takes into account the conduction within the particles. Based on this model, the temperature distribution inside the particle during the pyrolysis process was determined and the effects of particle size, moisture content, and gas velocity on heat transfer characteristics were analyzed. The results showed that the temperatures at different positions of the particles along the inflow direction were quite different, and the maximum temperature difference inside the particles was about 146.7 K for a particle diameter of 10 mm and a velocity of 0.2 m/s. During the pyrolysis process of biomass particles, there were two peaks of Nusselt number. The increase of moisture content prolonged the pyrolysis time. The pyrolysis. time of particles with moisture content of 15 % was about 1.5 times longer than that of dry particles when the particle diameter was 10 mm. Increasing the particle size decreased the difference between the two peaks and increased the time interval between the two peaks. Increasing the gas velocity can improve the heat transfer, but the effect of too high gas velocity on improving the heat transfer is limited. The present study is of great importance for a detailed understanding of the pyrolysis process of biomass particles.

Prognosis of spontaneously ruptured hepatocellular carcinoma: a propensity score matching study.

PURPOSE: Spontaneous rupture is a fatal complication of hepatocellular carcinoma (HCC). This study compared the prognosis of spontaneously ruptured HCC (srHCC) with that of non-ruptured HCC (nrHCC). METHODS: A total of 185 srHCC patients and 1085 nrHCC patients treated by hepatectomy between February 2005 and December 2017 at Zhongshan Hospital were retrospectively reviewed and enrolled. The overall survival (OS) and time to recurrence (TTR) were evaluated. A 1:2 propensity score matching (PSM) analysis was performed using the nearest neighbor matching with a caliper of 0.2. RESULTS: Before PSM, patients with srHCC who underwent hepatectomy (n = 185) had a poorer prognosis than those with nrHCC (n = 1085; 5-year OS, 39.1% vs 59.2%, P < 0.001; 5-year TTR, 83.8% vs 54.9%, P < 0.001). After PSM, patients with srHCC (n = 156) had higher 5-year TTR (83.2% vs 69.0%, P < 0.001) but comparable 5-year OS with those with nrHCC (n = 312, 44.0% vs 46.0%, P = 0.600). Univariate and multivariate analyses demonstrated spontaneous rupture as an independent risk factor for TTR (hazard ratio [HR], 1.681; 95% confidence interval [CI] 1.326-2.132; P < 0.001), but not for OS (HR: 1.074; 95% CI 0.823-1.401; P = 0.600). Further analysis revealed that srHCC was not appropriate to be assigned as T4 stage in American Joint Committee on Cancer classification. CONCLUSION: Spontaneous rupture of HCC is not a risk factor for survival. If resected eventually, srHCC may achieve comparable survival with nrHCC.

Advances in viral encephalitis: Viral transmission, host immunity, and experimental animal models.

Viral infections have led to many public health crises and pandemics in the last few centuries. Neurotropic virus infection-induced viral encephalitis (VE), especially the symptomatic inflammation of the meninges and brain parenchyma, has attracted growing attention due to its high mortality and disability rates. Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes. In this review, we summarize the common categories of neurotropic viruses, viral transmission routes in the body, host immune responses, and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection. This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Circulating immune index predicting the prognosis of patients with hepatocellular carcinoma treated with lenvatinib and immunotherapy.

Background: Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy. Methods: A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×109/L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated. Results: Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII > 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, P = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; P = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; P = 0.037) and disease control rate (89% vs 73%; P = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; P = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not. Conclusions: We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.

Prognostic model for predicting outcome and guiding treatment decision for unresectable hepatocellular carcinoma treated with lenvatinib monotherapy or lenvatinib plus immunotherapy.

Background: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. Methods: 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. Results: Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P<0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II<600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II>600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II>600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. Conclusion: The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.

Efficacy and safety of lenvatinib for preventing tumor recurrence after liver transplantation in hepatocellular carcinoma beyond the Milan criteria.

Background: Lenvatinib is one of the first-line treatments for unresectable hepatocellular carcinoma (HCC). However, data are lacking on lenvatinib in the postoperative setting. Methods: This retrospective analysis enrolled 242 patients with HCC who underwent liver transplantation (LTx). Eligible patients were divided into 2 groups according to their use of adjuvant lenvatinib following LTx (lenvatinib, n=42; control, n=200). The primary outcome measures were overall survival (OS), time to recurrence (TTR), and safety. Kaplan-Meier analysis was applied to calculate the OS, while a competing risk model was used to estimate the cumulative incidence of recurrence. Results: The lenvatinib group showed more advanced tumors and a higher proportion of HCC beyond the Milan criteria (P<0.001) than the control group. There were no significant differences in both the OS and TTR between the 2 groups. After focusing on the patients with HCC beyond the Milan criteria, baseline characteristics were similar in the lenvatinib group (n=38) and the control group (n=102). Competing risk analysis showed lenvatinib significantly prolonged TTR after LTx versus the control group [sub-hazard ratio (sHR), 0.40; 95% confidence interval (CI): 0.17 to 0.93; P=0.031]. In the multivariate competing risk model, adjuvant lenvatinib was an independent protective factor for tumor recurrence after LTx in patients with HCC beyond the Milan criteria (sHR, 0.33; 95% CI: 0.13 to 0.83; P=0.018). The rate of early recurrence within t2 years after LTx was also significantly decreased in the lenvatinib group (15.8% vs. 33.3%, P=0.041). However, the lenvatinib group exhibited comparable OS with the control group in patients with HCC beyond the Milan criteria. Treatment-related adverse events (TRAEs) and Grade ≥3 TRAEs occurred in 40 (95.2%) and 13 (31%) patients who received adjuvant lenvatinib, respectively. No treatment-related death was reported. Conclusions: Postoperative lenvatinib administration may provide clinical benefits and is well tolerated in patients with HCC beyond the Milan criteria who undergo LTx.

Stabilizing Li-Rich Layered Cathode Materials Using a LiCoMnO4 Spinel Nanolayer for Li-Ion Batteries.

Lithium-rich cathodes have excess lithium in the transition metal layer and exhibit an extremely high specific capacity and good energy density. However, they still have some disadvantages. Here, we propose LiCoMnO4, a new nanolayer coating material with a spinel structure, to modify the surface of lithium cathode oxide (Li7/6Mn1/2Ni1/6Co1/6O2) with a layered structure. The designed cathode with nanolayer spinel coating delivers an excellent reversible capacity, outstanding rate capability, and superior cycling ability whilst exhibiting discharge capacities of 300, 275, 220, and 166 mAh g-1 at rates of 0.1 C at 2.0-4.8 V formation and 0.1, 1, and 5 C, respectively, between 2.0 and 4.6 V. The cycling ability and voltage fading at a high operational voltage of 4.9 V were also investigated, with results showing that the nanolayer spinel coating can depress the surface of the lithium cathode oxide layer, leading to phase transformation that enhances the electrochemical performance.

Metagenomic Next-Generation Sequencing Versus Traditional Laboratory Methods for the Diagnosis and Treatment of Infection in Liver Transplantation.

Background: Metagenomic next-generation sequencing (mNGS) has emerged as an effective method for the noninvasive and precise detection of infectious pathogens. However, data are lacking on whether mNGS analyses could be used for the diagnosis and treatment of infection during the perioperative period in patients undergoing liver transplantation (LT). Methods: From February 2018 to October 2018, we conducted an exploratory study using mNGS and traditional laboratory methods (TMs), including culture, serologic assays, and nucleic acid testing, for pathogen detection in 42 pairs of cadaveric liver donors and their corresponding recipients. Method performance in determining the presence of perioperative infection and guiding subsequent clinical decisions was compared between mNGS and TMs. Results: The percentage of liver donors with mNGS-positive pathogen results (64.3%, 27/42) was significantly higher than that using TMs (28.6%, 12/42; P<0.05). The percentage of co-infection detected by mNGS in liver donors was 23.8% (10/42) significantly higher than 0.0% (0/42) by TMs (P<0.01). Forty-three pathogens were detected using mNGS, while only 12 pathogens were identified using TMs. The results of the mNGS analyses were consistent with results of the TM analyses in 91.7% (11/12) of donor samples at the species level, while mNGS could be used to detect pathogens in 66.7% (20/30) of donors deemed pathogen-negative using TMs. Identical pathogens were detected in 6 cases of donors and recipients by mNGS, among which 4 cases were finally confirmed as donor-derived infections (DDIs). For TMs, identical pathogens were detected in only 2 cases. Furthermore, 8 recipients developed early symptoms of infection (<7 days) after LT; we adjusted the type of antibiotics and/or discontinued immunosuppressants according to the mNGS results. Of the 8 patients with infections, 7 recipients recovered, and 1 patient died of severe sepsis. Conclusions: Our preliminary results show that mNGS analyses can provide rapid and precise pathogen detection compared with TMs in a variety of clinical samples from patients undergoing LT. Combined with symptoms of clinical infection, mNGS showed superior advantages over TMs for the early identification and assistance in clinical decision-making for DDIs. mNGS results were critical for the management of perioperative infection in patients undergoing LT.

Integration of Inflammation-Immune Factors to Build Prognostic Model Predictive of Prognosis and Minimal Residual Disease for Hepatocellular Carcinoma.

Background: Tumor recurrence after hepatectomy is high for hepatocellular carcinoma (HCC), and minimal residual disease (MRD) could be the underlying mechanism. A predictive model for recurrence and presence of MRD is needed. Methods: Common inflammation-immune factors were reviewed and selected to construct novel models. The model consisting of preoperative aspartate aminotransferase, C-reactive protein, and lymphocyte count, named ACLR, was selected and evaluated for clinical significance. Results: Among the nine novel inflammation-immune models, ACLR showed the highest accuracy for overall survival (OS) and time to recurrence (TTR). At the optimal cutoff value of 80, patients with high ACLR (> 80) had larger tumor size, higher Edmondson's grade, more vascular invasion, advanced tumor stage, and poorer survival than those with low ACLR (≤ 80) in the training cohort (5-year OS: 43.3% vs. 80.1%, P < 0.0001; 5-year TTR: 74.9% vs. 45.3%, P < 0.0001). Multivariate Cox analysis identified ACLR as an independent risk factor for OS [hazard ratio (HR) = 2.22, P < 0.001] and TTR (HR = 2.36, P < 0.001). Such clinical significance and prognostic value were verified in validation cohort. ACLR outperformed extant models, showing the highest area under receiver operating characteristics curve for 1-, 3-, and 5-year OS (0.737, 0.719, and 0.708) and 1-, 3-, and 5-year TTR (0.696, 0.650, and 0.629). High ACLR correlated with early recurrence (P < 0.001) and extremely early recurrence (P < 0.001). In patients with high ACLR, wide resection margin might confer survival benefit by decreasing recurrence (median TTR, 25.5 vs. 11.4 months; P = 0.037). Conclusions: The novel inflammation-immune model, ACLR, could effectively predict prognosis, and the presence of MRD before hepatectomy and might guide the decision on resection margin for patients with HCC.

[Monitoring of gastrointestinal dysfunction by near-infrared spectroscopy in children with sepsis: a prospective study]. / åº”ç”¨è¿‘çº¢å¤–å ‰è°±æŠ€æœ¯ç›‘æµ‹è„“æ¯’ç—‡æ‚£å„¿èƒƒè‚ åŠŸèƒ½éšœç¢çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence and mortality of gastrointestinal dysfunction in children with sepsis, the application of near-infrared spectroscopy (NIRS) in monitoring mesenteric regional tissue oxygen saturation (rSO2), and the association between rSO2 and gastrointestinal dysfunction. METHODS: In this prospective study, 79 children with sepsis in the pediatric intensive care unit (sepsis group) and 40 children who underwent physical examination in the Department of Child Healthcare (healthy control group) from January to December, 2021 were enrolled as subjects. The related medical data were collected, including general information on admission and at discharge, treatment during hospitalization, and laboratory examination results. NIRS was used to measure mesenteric rSO2. Clinical characteristics were compared between the patients with and without gastrointestinal dysfunction. RESULTS: For the 79 children with sepsis, the incidence rate of gastrointestinal dysfunction was 49% (39/79), and the mortality rate of the children with gastrointestinal dysfunction was 26% (10/39). The children with gastrointestinal dysfunction had a longer duration of mechanical ventilation and a higher 28-day mortality rate (P<0.05). The children with gastrointestinal dysfunction had a significantly lower median rSO2 (64%) than the children without gastrointestinal dysfunction (72%) and the healthy control group (78%) (P<0.05). CONCLUSIONS: There are high incidence and mortality rates of gastrointestinal dysfunction in children with sepsis, and the reduction in rSO2 may be associated with the development of gastrointestinal dysfunction.

The treatment strategy and outcome for spontaneously ruptured hepatocellular carcinoma: a single-center experience in 239 patients.

PURPOSE: There exist no treatment guidelines for spontaneously ruptured hepatocellular carcinoma (srHCC) and its prognosis remains controversial. METHODS: Patients were retrospectively enrolled and grouped based on hemodynamics and tumor resectability. The 30-day mortality, 5-year overall survival (OS), progression-free survival (PFS), peritoneal metastasis (PM) and intrahepatic metastasis (IM) rates were compared. RESULTS: In general, 239 patients were classified into four groups: patients with stable hemodynamics underwent semi-elective hepatectomy (n = 119), and those with unstable hemodynamics received emergent hepatectomy (n = 17), sequential hemostatic-transcatheter arterial chemoembolization (TACE)/-laparotomy with late hepatectomy (n = 49), or TACE only (n = 54). Hepatectomy was safer and provided better OS and PFS than TACE both before and after propensity score matching. Emergent hepatectomy was associated with higher 30-day mortality (6.2%, P < 0.05) and poorer prognosis whereas semi-elective hepatectomy and sequential treatment had comparable mortality (both 0%) and survival (36.3% vs 45.2%, P > 0.05). Compared with hemostatic TACE in the sequential treatment group, early surgical intervention (semi-elective hepatectomy, emergent hepatectomy, and sequential laparotomy with late hepatectomy) decreased PM (13.6% vs 34.2%, P = 0.003) whereas had higher IM (68.0% vs 50.0%, P = 0.039), but neither procedure had affected OS. In srHCC patients with high risk of recurrence (multiple tumors, micro- and macro-vascular invasion), postoperative adjuvant TACE improved OS. CONCLUSION: Hepatectomy could provide better prognosis than TACE for srHCC patients while semi-elective hepatectomy and sequential hemostatic-TACE with staged hepatectomy are viable options for srHCCs with stable and unstable hemodynamics, respectively.

Development of an Eight-gene Prognostic Model for Overall Survival Prediction in Patients with Hepatocellular Carcinoma.

BACKGROUND AND AIMS: The overall survival (OS) of hepatocellular carcinoma (HCC) remains dismal. Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision. This study aimed to develop a prognostic gene model for HCC. METHODS: GSE14520 was retrieved as a training set to identify differential expressed genes (DEGs) between tumor and adjacent liver tissues in HCC patients with different OS. A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model. The area under the receiver operating characteristic curve (AUC) and hazard ratio (HR) of the model for OS were calculated. A model-based nomogram was established and verified. RESULTS: In the training set, differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation. After univariate Cox and LASSO regression, eight genes (LPCAT1, DHRS1, SORBS2, ALDH5A1, SULT1C2, SPP1, HEY1 and GOLM1) were selected to build the prognostic model. The AUC for 1-, 3- and 5-year OS were 0.779, 0.736, 0.754 in training set and 0.693, 0.689, 0.693 in the TCGA-LIHC validation set, respectively. The AUC for 1- and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set. Multivariate analysis confirmed the model was an independent prognostic factor (training set: HR=4.422, p<0.001; TCGA-LIHC validation set: HR=2.561, p<0.001; ICGC-LIRI validation set: HR=3.931, p<0.001). Furthermore, a nomogram combining the model and AJCC stage was established and validated, showing increased OS predictive efficacy compared with the prognostic model (p=0.035) or AJCC stage (p<0.001). CONCLUSIONS: Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.

Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation.

Background: This study aimed to evaluate the role of plasma microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) for prediction and surveillance of early tumor recurrence in hepatocellular carcinoma (HCC) patients who had undergone liver transplantation (LT). Methods: The expression of plasma microRNA panel was assayed in 193 HCC patients (training cohort, n =151; validation cohort, n = 42). Sensitivity and specificity for detecting post-transplant HCC recurrence, and the relationship of microRNA panel expression with clinical characteristics were analyzed accordingly. The prognostic value of microRNA panel was compared with that of AFP (alpha-fetoprotein) and DCP (Des-gamma-carboxyprothrombin). Cox regression analyses were used to evaluate independent prognostic factors. Results: In the training cohort, the rate of positive plasma microRNA panel status at 7-14 days after LT (late phase; 44.2%) decreased than that before (76.2%, P < 0.001) and 1-6 days after LT (early phase; 78.5%, P < 0.001). At late phase, positive microRNA panel status correlated with higher early tumor recurrence rate (one year after LT) than negative status (45.9% vs 10.7%; P < 0.001). Patients with persistent positive microRNA panel status both before and after LT had the highest early tumor recurrence rate in this cohort (54.9%, P < 0.001). The results were consistent in the validation cohort. Cox regression analysis found that positive plasma microRNA panel status at late phase was the only independent risk factor for early recurrence (HR: 4.903, 95% CI = 2.195 - 10.951; P < 0.001). Dynamic monitoring demonstrated plasma microRNA panel status changed from negative to positive earlier than AFP and DCP upon recurrence, and the median time between positivity of plasma microRNA and imaging evidence of recurrence was 2.4 (0.5-10.0) months. Conclusions: Plasma microRNA panel could be a noninvasive biomarker for prediction and surveillance of early tumor recurrence in HCC patients who have undergone LT.

Boson-peak-like anomaly caused by transverse phonon softening in strain glass.

Strain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.

A novel preoperative predictive model of 90-day mortality after liver resection for huge hepatocellular carcinoma.

BACKGROUND: Hepatectomy for huge hepatocellular carcinoma (HCC) (diameter ≥10 cm) is characterized by high mortality. This study aimed to establish a preoperative model to evaluate the risk of postoperative 90-day mortality for huge HCC patients. METHODS: We retrospectively enrolled 1,127 consecutive patients and prospectively enrolled 93 patients with huge HCC who underwent hepatectomy (training cohort, n=798; validation cohort, n=329; prospective cohort, n=93) in our institute. Based on independent preoperative predictors of 90-day mortality, we established a logistic regression model and visualized the model by nomogram. RESULTS: The 90-day mortality rates were 9.6%, 9.2%, and 10.9% in the training, validation, and prospective cohort. The α-fetoprotein (AFP) level, the prealbumin levels, and the presence of portal vein tumor thrombosis (PVTT) were preoperative independent predictors of 90-day mortality. A logistic regression model, AFP-prealbumin-PVTT score (APP score), was subsequently established and showed good performance in predicting 90-day mortality (training cohort, AUC =0.87; validation cohort, AUC =0.91; prospective cohort, AUC =0.93). Using a cut-off of -1.96, the model could stratify patients into low risk (≤-1.96) and high risk (>-1.96) with different 90-day mortality rates (~30% vs. ~2%). Furthermore, the predictive performance for 90-day mortality and overall survival was significantly superior to the Child-Pugh score, the model of end-stage liver disease (MELD) score, and the albumin-bilirubin (ALBI) score. CONCLUSIONS: The APP score can precisely predict postoperative 90-day mortality as well as long-term survival for patients with huge HCC, assisting physician selection of suitable candidates for liver resection and improving the safety and efficacy of surgical treatment.