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.

Elevated remnant cholesterol is a risk factor for acute ischemic stroke.

OBJECTIVES: Remnant cholesterol (RC) is thought to be an important pathogenic risk factor for atherosclerosis, however, the relationship between RC and acute ischemic stroke (AIS) is still unclear. This study aimed to determine whether fasting blood RC level is an independent risk factor for AIS. MATERIALS AND METHODS: A retrospective analysis was performed on 650 patients with AIS and 598 healthy controls during the same time period. The association between RC and AIS was investigated using binary logistic regression, and the relationship between RC and AIS risk was demonstrated using Restricted Cubic Splines (RCS). RESULTS: RC was significantly higher in the AIS group compared with control group, and was an independent risk factor for AIS when the covariates were not adjusted;After adjusting some covariates, RC was still an independent risk factor for AIS. The RCS analysis found the risk was non-linear: when RC concentration was less than 0.69 mol/L, the risk of AIS increased with the elevation of RC, and when RC concentration was more than or equal to 0.69 mol/L, the risk of AIS was insignificant with the elevation of RC. Correlation analysis revealed that RC was associated with diabetes and fasting glucose. Further analysis revealed that the incidence of AIS in diabetic patients increased significantly with the increase of RC, and RCS analysis revealed that the risk of AIS in diabetic patients increased with the increase of RC when RC was more than 1.15 mol/L. CONCLUSIONS: This study confirms RC as an independent risk factor for AIS, which highlights a distinct non-linear association between RC levels and AIS risk. These findings suggest the need for targeted AIS risk assessment strategies, especially in diabetic patients, and underscore the relevance of RC as a biomarker in AIS risk stratification.

One-year follow-up of the effectiveness and mediators of cognitive behavioural therapy among adults with attention-deficit/hyperactivity disorder: secondary outcomes of a randomised controlled trial.

BACKGROUND: The long-term effectiveness of cognitive behavioural therapy (CBT) in medicated attention-deficit/hyperactivity disorder (ADHD) adults with residual symptoms needs to be verified across multiple dimensions, especially with respect to maladaptive cognitions and psychological quality of life (QoL). An exploration of the mechanisms underlying the additive benefits of CBT on QoL in clinical samples may be helpful for a better understanding of the CBT conceptual model and how CBT works in medicated ADHD. METHODS: We conducted a secondary analysis of a randomised controlled trial including 98 medicated ADHD adults with residual symptoms who were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M)-only group. Outcomes included ADHD-core symptoms (ADHD Rating Scale), depression symptoms (Self-rating Depression Scale), maladaptive cognitions (Automatic Thoughts Questionnaire and Dysfunctional Attitude Scale), and psychological QoL (World Health Organization Quality of Life-Brief Version-psychological domain). Mixed linear models (MLMs) were used to analyse the long-term effectiveness at one-year follow-up, and structural equation modeling (SEM) was performed to explore the potential mechanisms of CBT on psychological QoL. RESULTS: ADHD patients in the CBT + M group outperformed the M-only group in reduction of ADHD core symptoms (d = 0.491), depression symptoms (d = 0.570), a trend of reduction of maladaptive cognitions (d = 0.387 and 0.395, respectively), and improvement of psychological QoL (d = - 0.433). The changes in above dimensions correlated with each other (r = 0.201 ~ 0.636). The influence of CBT on QoL was mediated through the following four pathways: 1) changes in ADHD core symptoms; 2) changes in depressive symptoms; 3) changes in depressive symptoms and then maladaptive cognitions; and 4) changes firstly in depressive symptoms, maladaptive cognitions, and then ADHD core symptoms. CONCLUSIONS: The long-term effectiveness of CBT in medicated ADHD adults with residual symptoms was further confirmed. The CBT conceptual model was verified in clinical samples, which would be helpful for a deeper understanding of how CBT works for a better psychological QoL outcome. TRIAL REGISTRATION: ChiCTR1900021705 (2019-03-05).

[Systematic review and Meta-analysis of efficacy and safety of Shumian Capsules in treatment of insomnia].

This study aims to assess the safety and efficacy of Shumian Capsules in the treatment of insomnia. Randomized controlled trial(RCT) about Shumian Capsules for insomnia were retrieved from databases. RevMan 5.4 was used for statistical analysis. A total of 23 articles were included, involving 2 621 patients. Meta-analysis showed that Shumian Capsules had advantages in the treatment of insomnia(RR=1.07, 95%CI[1.03, 1.10], P=0.000 2) and insomnia with depression(RR=1.13, 95%CI[1.02, 1.25], P=0.02) in terms of total response rate. Shumian Capsules had advantages in the treatment of insomnia(MD=-0.75, 95%CI[-1.33,-0.17], P=0.01) and insomnia with depression(MD=-2.51, 95%CI[-2.96,-2.06], P<0.000 01) in terms of PSQI score. The incidence of adverse events in the Shumian Capsules(RR=0.33, 95%CI[0.24, 0.46], P<0.000 01) and Shumian Capsules + conventional western medicine(RR=0.71, 95%CI[0.54, 0.95], P=0.02) was lower than that in the conventional wes-tern medicine alone. In addition, Shumian Capsules had an advantage in treating insomnia complicated with depression in terms of HAMD score(P<0.000 1) and reducing the serum levels of 5-HT, TSH, T3, and T4 in insomnia patients(P<0.05). The quality of evidence was mostly medium or low. The studies demonstrate that Shumian Capsules is effective and safe for treating insomnia, which may be related to the mechanism of lowering the levels of 5-HT, TSH, T3, and T4 in the serum. In view of the quality of evidence, the application of Shumian Capsules should be considered after comprehensive evaluation in clinical practice.

Mapping multi-omics characteristics related to short-term PM2.5 trajectory and their impact on type 2 diabetes in middle-aged and elderly adults in Southern China.

The relationship between PM2.5 and metabolic diseases, including type 2 diabetes (T2D), has become increasingly prominent, but the molecular mechanism needs to be further clarified. To help understand the mechanistic association between PM2.5 exposure and human health, we investigated short-term PM2.5 exposure trajectory-related multi-omics characteristics from stool metagenome and metabolome and serum proteome and metabolome in a cohort of 3267 participants (age: 64.4 ± 5.8 years) living in Southern China. And then integrate these features to examine their relationship with T2D. We observed significant differences in overall structure in each omics and 193 individual biomarkers between the high- and low-PM2.5 groups. PM2.5-related features included the disturbance of microbes (carbohydrate metabolism-associated Bacteroides thetaiotaomicron), gut metabolites of amino acids and carbohydrates, serum biomarkers related to lipid metabolism and reducing n-3 fatty acids. The patterns of overall network relationships among the biomarkers differed between T2D and normal participants. The subnetwork membership centered on the hub nodes (fecal rhamnose and glycylproline, serum hippuric acid, and protein TB182) related to high-PM2.5, which well predicted higher T2D prevalence and incidence and a higher level of fasting blood glucose, HbA1C, insulin, and HOMA-IR. Our findings underline crucial PM2.5-related multi-omics biomarkers linking PM2.5 exposure and T2D in humans.

Surficial engineering of active hydroxyls for ambient formaldehyde oxidation via enhanced Lewis acidity over Zr-doped cryptomelane materials.

Lewis acids of solid catalysts have been featured for a pivotal role in promoting various reactions. Regarding the oxidation protocol to remove formaldehyde, the inherent drawback of the best-studied MnO2 materials in acidic sites has eventually caused deficiency of active hydroxyls to sustain low-temperature activity. Herein, the cryptomelane-type MnO2 was targeted and it was tuned via incorporation of Zr metal, exhibiting great advances in not only the complete HCHO-to-CO2 degradation but also cycling performance. Zr species were existent in doping state in the MnO2 lattice, rendering lower crystallinity and breaking the regular growth of MnO2 crystallites, which thereby tripled surface area and created larger volume of smaller mesopores. Meantime, the local electronic properties of Mn atoms were also changed by Zr doping, i.e., more low-valence Mn species were formed due to the electron transfer from Zr to Mn. The results of infrared studies demonstrate the higher possession of Lewis acid sites on ZrMn, and this high degree of electrophilic agents favored the production of hydroxyl species. Furthermore, the reactivity of surface hydroxyls, as investigated by CO temperature programmed reduction and temperature programmed desorption of adsorbed O2, was obviously improved as well after Zr modification. It is speculated jointly with the characterizations of the post-reaction catalysts that the accelerated production of active hydroxyls helped rapidly convert formaldehyde into key intermediate-formate, which was then degraded into CO2, avoiding the side reaction path with undesired intermediate-hydrocarbonate-over the pristine MnO2, where active sites were blocked and formaldehyde oxidation was inhibited. Additionally, Zr decoration could stabilize Lewis acidity to be more resistant to heat degeneration, and this merit brought about advantageous thermal recyclability for cycled application.

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.

N-containing phenolic compounds from Periplaneta americana with triple negative breast cancer inhibitory activity.

Eight previously undescribed compounds comprising pyrrole-2-carboxaldehyde derivatives, namely periplanpyrroles A-D (1-4), spirooxindole derivatives perispirooxindoles A (5) and B (6), and the phenolic compounds periplanetols G (7) and H (8), along with eight known compounds were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. In addition, all compounds were evaluated for their activities against triple negative breast cancer in vitro. The wound healing assay revealed that 7, 9, and 11 significantly inhibit the migration of BT549 and MDA-MB-231 cells. Further observations made in Western blotting experiments showed that 7 could dose-dependently decrease the protein level of vimentin and N-cadherin in MDA-MB-231 and BT549 cells.

Study on neutron energy spectrum unfolding algorithm with EJ309 liquid scintillation detector.

Proton recoil method can be used to experimentally measure fast neutron energy spectrum of non-pulsed neutron sources. The neutron energy spectrum unfolding algorithms based on the MLEM method, the GOLD deconvolution method, the Direct-D method, have been developed by using the EJ309 liquid scintillation detector. The degree of iteration by the mean square error (MSE) is proposed as a judgment criterion by according to the iterative accuracy, convergence speed and iteration efficiency. The developed neutron energy spectrum unfolding algorithms can unfolding the standard simulated mono-energetic neutron spectrum (2.5 MeV), 252Cf neutron spectrum, Am-Be neutron spectrum and the experimentally measured D-D neutron spectrum with higher precision as well as fewer iterations. The unfolded neutron spectra are in good agreement with the standard simulated neutron spectra and evaluated D-D neutron spectrum, which is revealed that the developed unfolding algorithms can unfolding neutron energy spectrum with reasonable accuracy.

Real-World Clinical Characteristics, Management, and Outcomes of 44 Paediatric Patients with Hypopigmented Mycosis Fungoides.

Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned populations, and a predominance of CD8+ T cells. Due to the rarity and heterogeneous presentation of hypopigmented mycosis fungoides, there are no criteria that clearly define the clinical characteristics and treatment regimens for this condition. This retrospective study of 44 paediatric patients with hypopigmented mycosis fungoides aimed to summarize their epidemiological and clinical characteristics and assess the effectiveness and safety of different treatment regimens. Clinical manifestations were further classified into 3 morphological groups: hypopigmented lesions, papules overlying hypopigmented lesions, and erythematous plaques overlying hypopigmented lesions. In addition, the results of this study suggest that interferon alpha might be an effective and well-tolerated therapy that could shorten the treatment time to complete response compared with other treatments. Maintenance therapy and long-term follow-up reduced the recurrence rate.

Bidirectional associations between maladaptive cognitions and emotional symptoms, and their mediating role on the quality of life in adults with ADHD: a mediation model.

Background/objectives: Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions. Methods: 299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson's correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL. Results: More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p < 0.01) in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication. Conclusion: Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome.

Molecular and Morphological Identification of Monilia yunnanensis Causing Brown Rot on Chinese Quince and Peach in Yunnan, China.

More than 30% of fruits of Chinese Quince (Chaenomeles speciosa) and peach (Prunus persica) showed circular, water-soaked and brown spots in July 2022 in Kunming, Yunnan, China. The center of these spots was covered by a large number of earthy brown and oblate sporogeneous mycelium containing conidiophore and conidia, which were one-celled, limoniform, hyaline (13.73 to 22.77 x 8.17 to 12.84 µm, n=50). By September 2022, almost 100% of fruits showed symptoms. Later, most of them fell or a few stiff, black and mummified fruits were left on the trees. Fungal isolates were isolated by single-spore technique on Potato Dextrose agar (PDA) from the diseased fruits, and incubated at room temperature (20-28 °C) in darkness for 14 days. The colony was gray, smooth at margins, 7.6-8.0 cm in diameter. To fullfill Koch's postulates, mycelial plugs of one representative isolate YHD611 from Chinese Quince and another YHD610 from peach were used to inoculate three wounded and three non-wounded surface-disinfected fruits of both hosts at room temperature (19-27 °C), respectively. Three wounded and three non-wounded fruits inoculated with sterile PDA plugs served as the control. The wounded peaches appeared water-soaked and had brown lesions after three days of inoculation, then completely decayed after nine days, while non-wounded fruits showed symptoms after five days. The wounded fruits of Chinese Quince developed similar symptoms after eight days of inoculation, and completely decayed after 13 days, while non-wounded fruits showed obvious symptoms after 15 days. In a subsequent study, isolate YHD611 was inoculated to peach while isolate YHD610 was inoculated to Chinese Quince to understand host specificity of the isolates. The results showed that when peaches were infected with YHD611, symptoms were observed on wounded fruits after three days while on non-wounded fruits after five days. When Chinese Quince was infected with YHD610, symptoms were observed on wounded fruits after 14 days while on non-wounded fruits after 21 days. Fungal isolates from symptomatic fruits were identical to the original isolates. There were no symptoms on the control fruits of both hosts. Molecular identification was confirmed based on the sequences of internal transcribed spacer (ITS, primers ITS1 and ITS4) and ß-tubulin (TUB2, primers Bt2a and Bt2b) genes (Niu et al. 2016). BLASTn analysis of the ITS (OQ15519and OQ155196) and TUB2 (OQ185202 and OQ185201) of YHD611 and YHD610 revealed a 100% sequence identity, respectively, to Monilia yunnanensis AH7-2 (KT735924.1 for ITS, KT736008.1 for TUB2). In the phylogenetic analyses based on ITS and TUB2 sequence data, the isolates YHD611 and YHD610 belonged to the M. yunnanensis clade. Based on morphological and molecular identification, both isolates were identified as M. yunnanensis, which was reported as the pathogen causing brown rot of plum, peach, apple and pear in Yunnan, China (Hu et al. 2011; Yin et al. 2015). To our knowledge, this is the first report of M. yunnanensis causing brown rot on the fruits of Chinese Quince in Yunnan, China. This study also reports that M. yunnanensis from Chinese Quince can infect peach, and the pathogen from peach can infect Chinese Quince. These findings suggest that M. yunnanensis can transfer from one host to another and causing serious economic losses in multiple fruit crops in Yunnan, China. References: Hu, M. J., et al. 2011. PLoS One. 6:e24990. Niu, C. W., et al. 2016. Mycosystema, 35(10):1. Yin, L. F., et al. 2015. Plant Dis. 99:1775.

Formulating the Li sites of Li-CoOx composites for achieving high-efficiency oxidation removal of formaldehyde over the Ag/Li-CoOx catalyst under ambient conditions.

Oxide supported noble metals are extensively investigated for ambient formaldehyde oxidation, and the Ag-CoOx complex is one promising combination in terms of cost and activity. Further, we previously observed that cooperating Ag with Li + greatly boosted formaldehyde degradation on CoOx. Yet, there is still room for improvement in removal efficiency, mineralization capacity and resistance to severe conditions. These objectives could be realized via strategically formulating the Li+ sites of Li-CoOx composite in this sister study. Three samples with Li + ---Co3+-O2- connections (L-CO), spinel Li+ (LCO-S) and layered Li+ (LCO-L) were obtained at low (300 °C), moderate (500 °C) and high (700 °C) temperatures, respectively. The specific Li+ positions and componential interaction were demonstrated by Hyperspectral imaging (HSI), XRD, SEM, TEM, HAADF mapping, UV-vis DRS and XPS. Moreover, the effect of reactive oxygen exposure on catalytic oxidation of formaldehyde (330-350 mg/m3) was disclosed through CO-TPR and O2-TPD. Compared with the LCO-S and LCO-L, L-CO exhibited dominant formaldehyde degradation due to the larger content of surface oxygen. After Ag decoration, the Li+---Co3+-O2- connections uniquely caused a strong binding of Ag species with catalyst host, which boosted the amount of reactive oxygen and finally resulted in an even higher elimination of ∼73% (CO2 yield = âˆ¼21%), 47% higher than that of the L-CO (CO2 yield = âˆ¼6%). But in contrast, the Ag@LCO-S only achieved ∼53% removal (CO2 yield = âˆ¼9%) and Ag modification was powerless in altering the inertness of LCO-L, demonstrating that the chemical environment of alkali metal is crucial to effectively tuning the catalyst activity. The advantage of Ag@L-CO in formaldehyde depollution was further reflected from its much better resistance to moisture and aromatic compound omnipresent in indoor air. For the first time, this study extended the understanding of the alkali-metal-promoted formaldehyde oxidation reaction to an in-depth level.

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta-analysis.

Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1-year/2-year progression-free survival [PFS], and overall survival [OS]) and safety (vaccine-related grade 3-5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non-small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6-17.0%) and 34.6% (95%CI, 24.1-45.9%). The estimates for 1-year and 2-year PFS were 38.4% (95%CI, 24.8-53.0%) and 20.0% (95%CI, 10.4-31.7%), respectively. The estimates for 1-year and 2-year OS were 75.3% (95%CI, 62.4-86.3%) and 45.5% (95%CI, 34.0-57.2%), respectively. The estimate for vaccine-related grade 3-5 AEs was 1.0% (95%CI, 0.2-2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3-5 AEs.

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.

Epidemiological and clinical features of hypertrophic scar and keloid in Chinese college students: A university-based cross-sectional survey.

Background: Hypertrophic scar (HS) and keloid (KD) are common dermal fibroproliferative growth caused by pathological wound healing. HS's prevalence is currently undetermined in China. Though it primarily occurs in dark-skinned individuals, KD can develop in all races, and its prevalence among Chinese people is poorly documented. Objective: To explore the present epidemiological status of them in Chinese college students. Methods: We conducted a university-based cross-sectional study at one university in Fujian, China. A total of 1785 participants aged 16-34 years (mean age, 20.0 ± 2.0; 58.7% female) were enrolled and statistical analyses were performed. Results: HS and KD were observed in 5.2% (95% confidence interval [CI]: 4.2-6.2) and 0.6% (95% CI: 0.3-1.0) of the population respectively. There was a significant difference by sex in HS (P < 0.05), but not in KD. The prevalence of HS and KD both showed a significant difference by age (P < 0.05), but not in ethnic and native place distribution. The occurrence of HS and KD were both concentrated in individuals 9-20 years old (HS: 77.2%; KD: 81.8%). They were mainly distributed in the upper limbs (52.1%; 64.3%), and the main cause was trauma (51.0%; 35.7%). In addition, male sex was a risk factor for HS (adjusted P < 0.001), and KD was associated with age ≥22 years and family history (adjusted P < 0.050). Conclusion: HS and KD are common in Chinese college students, and more attention and research is warranted.

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.