HPV16-miRNAs exert oncogenic effects through enhancers in human cervical cancer.

BACKGROUND: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. METHODS: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. RESULTS: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. CONCLUSIONS: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

The accelerated design of the nanoantenna arrays by deep learning.

Nanoantenna fusion photonics and nanotechnology can manipulate light through the ultra-thin structure composed of sub-wavelength antennas, and meet the important requirements for miniaturized optical components, completely changing the field of optics. However, the device design process is still time-consuming and consumes computing resources. Besides, the professional knowledge requirements of engineers are also high. Relying on the algorithm's inference ability and excellent computing ability, artificial intelligence has great potential in the fields of material design, material screening, and device performance prediction. However, the deep learning (DL) requires a mass of data. Therefore, this article proposes a method for the forward and inverse design of nanoantenna based on DL. Compared with the previous work, the network uses a two-dimensional matrix as input, which has a simple structure and is more suitable for the advantages of deep netural network. Simultaneously, the small datasets can be used to achieve higher accuracy. In the forward prediction, 100% of the data error is less than 0.007; in the inverse prediction, the data with error less than 0.05 accounted for 90%, 99.8% and 100% of the length, height, and width's datasets. It demonstrates that the method can improve the automation of the design process and reduce the consumption of computer resources.

Prediction of electrical properties of FDSOI devices based on deep learning.

Fully depleted Silicon on insulator technology (FDSOI) is proposed to solve the various non-ideal effects when the process size of integrated circuits is reduced to 45 nm. The research of traditional FDSOI devices is mostly based on simulation software, which requires a lot of calculation and takes a long time. In this paper, a deep learning (DL) based electrical characteristic prediction method for FDSOI devices is proposed. DL algorithm is used to train the simulation data and establish the relationship between the physical parameters and electrical characteristics of the device. The network structure used in the experiment has high prediction accuracy. The mean square error of electrical parameters and transfer characteristic curve is only 4.34 × 10-4and 2.44 × 10-3respectively. This method can quickly and accurately predict the electrical characteristics of FDSOI devices without microelectronic expertise. In addition, this method can be extended to study the effects of various physical variables on device performance, which provides a new research method for the field of microelectronics.

Single event effects prediction of MOSFET device using deep learning.

Single event effect (SEE) is an important problem in the reliability research of integrated circuits. The study of SEE of traditional MOSFET devices is mainly based on simulation software, which is characterized by slow simulation speed, large computation and time-consuming. In this paper, a SEE research method based on deep learning is proposed. The method relies on 28 nm MOSFET. The complete drain transient current pulse, transient current peak value and total collected charge can be obtained in a short time by inputting relevant parameters that affect the SEE. The accuracy of the network for predicting transient current peak and total collected charge is 96.95% and 97.53% respectively, and the mean goodness of fit of the network for predicting the drain transient current pulse curve is 0.985. Compared with TCAD Sentaurus software, the simulation speed is increased by 5.89 × 103and 1.50 × 103times respectively. This method has good prediction effect and provides a new possibility for the study of SEE.

Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index.

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.

Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs.

OBJECTIVE: To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS: Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS: Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION: Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.

Strong selective oxidization on two-dimensional GaN: a first principles study.

Ab initio calculations were performed to investigate the chemical oxidation of two-dimensional (2D) gallium nitride (GaN). The nitrogen surface was found to form a metastable configuration under oxygen adsorption, while the gallium surface could be readily transformed to a more stable configuration of HO-GaN-H with an exceptionally low energy barrier. The results also revealed that the adsorption of oxygen adatoms resulted in the reduction of work-function and induced the change from 2D GaN to a new GaNO compound. Our findings indicate that we should pay attention to the oxidation effect of 2D GaN in practical device applications.

Human epithelial-type ovarian tumour marker beta-2-microglobulin is regulated by the TGF-ß signaling pathway.

BACKGROUND: Beta-2-microglobulin (B2M), a light chain subunit of the major histocompatibility complex (MHC) class I complex, has been implicated in tumorigenesis. However, whether it is expressed in different epithelial-type ovarian tumours remains unknown. This study was performed to examine the expression of B2M in different histopathological types of ovarian tumours, to explore the function of B2M in ovarian cancer (OC) cells and to investigate the mechanisms underlying the regulation of B2M by the TGF-ß signaling pathway. METHODS: B2M expression in normal ovarian tissues and epithelia-type ovarian tumours was detected by immunohistochemistry and Western blot, followed by the analysis of association with clinical features. OC cells were transfected with B2M-siRNA and cell proliferation, migration and invasion were determined by WST-1 assay, wound healing assay and Transwell invasion assay, respectively. The regulation of B2M by the TGF-ß signaling pathway in OC cells was examined by Western blot, ELISA and qRT-PCR. RESULTS: We found that B2M was overexpressed in ovarian borderline and malignant tumours compared with benign tumours and normal controls, but was not associated with age, tumour size, lymph node metastasis and clinical stage. Knocking down of B2M led to a decrease in OC cell proliferation, migration and invasion. The expression of B2M was downregulated by TGF-ß1 in OC cells, which was abolished in the presence of the inhibitor of TGF-ß type I receptor. CONCLUSION: Our findings suggest that B2M is a potential tissue biomarker and therapeutic target of borderline and malignant ovarian tumours and the dysregulation of B2M in these tumours may be mediated by the TGF-ß signaling pathway.

Tracking the Evolution of Polymer Interface Films during the Process of Thermal Annealing at the Domain and Single Molecular Levels using Scanning Tunneling Microscopy.

Structural evolution of polymer (NTZ12) interface films during the process of annealing is revealed at the domain and single molecular levels using the statistical data measured from scanning tunneling microscopy images and through theoretical calculations. First, common features of the interface films are examined. Then, mean values of surface-occupied ratio, size and density of the domain are used to reveal the intrinsic derivation of the respective stages. Formation of new domains is triggered at 70 °C, but domain ripening is not activated. At 110 °C, the speed of formation of new domains is almost balanced by the consumption due to the ripening process. However, formation of new domains is reduced heavily at 150 °C but restarted at 190 °C. At the single molecular level, the ratio of the average length of linear to curved backbones is increased during annealing, whereas the ratios of the total length and the total number of linear to curved skeletons reaches a peak value at 150 °C. The two major conformations of curved backbones for all samples are 120° and 180° bending, but the ripening at 150 °C reduces 180° folding dramatically. Molecular dynamic simulations disclose the fast relaxing process of curved skeletons at high temperature.

Natural course and predictors of consciousness recovery in children with prolonged disorder of consciousness.

Prolonged disorder of consciousness (DoC) is a rising challenge. Pediatric data on diagnosis and prognosis of prolonged DoC were too limited and heterogeneous, making it difficult to define the natural course and evaluate the prognosis. The present study explored the emergence from the Minimally Conscious State (eMCS) incidence at different months postinjury drawing the natural course, and detected the predictors of the incidence in children with prolonged DoC. A hospital-based prospective cohort study was conducted. Kaplan-Meier curves, as well as univariate and multivariate COX regression analysis, were performed. The study enrolled 383 pediatric DoC individuals, including 220 males (57.4%), with an average age of 3.9 (1.9-7.3) years. The median duration between onset and rehabilitation is 30.0 (21.0-46.0) days. At enrollment, the ratio of vegetative state/unresponsive wakefulness syndrome (VS/WUS) to MCS is 78.9%-21.1%. Traumatic brain injury and infection are the major etiologies (36.8% and 37.1%, respectively), followed by hypoxia cerebral injury (12.3%). For children with prolonged DoC, the cumulative incidence of eMCS at months 3, 6, 12, and 24 was 0.510, 0.652, 0.731, 0.784 VS 0.290, 0.418, 0.539, 0.603 in the traumatic VS non-traumatic subgroup, respectively. For children in a persistent vegetative state (PVS), the cumulative incidence of emergence at months in 3, 6, 12, 24, 36 and 48 was testified as 0.439, 0.591, 0.683, 0.724, 0.743 and 0.743 in the traumatic subgroup, and 0.204, 0.349, 0.469, 0.534, 0.589 and 0.620 in the non-traumatic subgroup. Participants who exhibit any of the following four demographical and/or clinical characteristics-namely, older than 4 years at onset, accepted rehabilitation within 28 days of onset, remained MCS at enrollment, or with etiology of traumatic brain injuries-had a significantly positive outcome of consciousness recovery (eMCS). Moreover, both prolongation of the central somatosensory conductive time (CCT) (level 2) and absence of N20 (level 3) independently predict a negative outcome. In children with prolonged DoC, we found that 12 months postinjury was critical to eMCS, and a preferred timepoint to define chronic vegetative state (VS). The characteristics including age, etiology, time before rehabilitation, consciousness state, and SEP results were useful predictors of conscious recovery.Trial registration Registered 06/11/2018, the registration number is chiCTR1800019330 (chictr.org.cn). Registered prospectively.

Biomarker cystatin B expression correlates with pathogenesis in cervical cancer.

OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic malignancies worldwide. Although rapid improvements have been made regarding its prevention and treatment, little is known about disease pathogenesis and the clinical relevance of reliable biomarkers. The present study evaluated the expression of cystatin B (CSTB) as a potential biomarker of CC. METHODS: Tissue microarray analysis and immunohistochemical staining were performed to detect CSTB expression, while CSTB mRNA and protein expression levels of freshly isolated CC tissue were measured by quantitative real-time PCR and western blot, respectively. Bioinformatics were used to analyze the CSTB co-expression network and functional enrichments. RESULTS: We observed high CSTB mRNA and protein expression levels in CC tissues, which was confirmed by tissue microarray in a comparison with paired adjacent non-cancerous cervical tissue samples. CSTB gene enrichments and associations with co-expressed genes were also observed. Further analysis showed that elevated CSTB expression was associated with pathological progress in CC. CONCLUSION: Our data demonstrate that CSTB has the potential to be used as a tissue biomarker with clinical value in patients with CC, which may aid the development of intervention strategies.

COL5A1 overexpression correlates with poor prognosis in human cervical cancer.

BACKGROUND: Cervical cancer is the most prevalent malignant tumor in women. This study aims to detect collagen type V α1 chain (COL5A1) expression and its clinical relevance in the prognosis of patients with cervical cancer. METHODS: Cervical cancer tissues and their paired adjacent normal tissues were prepared for tissue microarray. The expression of COL5A1 protein and the scores of the expression were evaluated by immunohistochemistry (IHC) staining. The prognostic value of COL5A1 was analyzed by R software version 4.2.1 with "survival, survminer, ggplot2" packages and Gene Expression Profiling Interactive Analysis (GEPIA). The cBioPortal database was utilized for the analysis of COL5A1 gene mutations. RESULTS: COL5A1 protein was overexpressed in human cervical cancer tissues compared to their paired adjacent normal tissues detected by IHC (P < 0.001). High expression of COL5A1 tends to be in elderly patients with cervical cancer. Survival analyses of clinical data of patients with cervical cancer showed that a high level of COL5A1 expression was significantly correlated with shorter overall survival (P = 0.031) and disease-free survival (P = 0.042) of patients. Further analyses of The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and the GEPIA survival datasets confirmed the association of high COL5A1 expression with poor overall survival of patients (P = 0.040 and P = 0.018, respectively). The analysis of genomic alterations of COL5A1 using the cBioPortal tool revealed that the COL5A1 gene was altered in 4% of cervical cancer patients and COL5A1 corresponding protein alterations with post-translational modifications were hydroxylation. CONCLUSION: COL5A1 is a tissue biomarker correlated with the poor prognosis of patients with cervical cancer, which may lead to a new clinical application.

The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

GaN JBS Diode Device Performance Prediction Method Based on Neural Network.

GaN JBS diodes exhibit excellent performance in power electronics. However, device performance is affected by multiple parameters of the P+ region, and the traditional TCAD simulation method is complex and time-consuming. In this study, we used a neural network machine learning method to predict the performance of a GaN JBS diode. First, 3018 groups of sample data composed of device structure and performance parameters were obtained using TCAD tools. The data were then input into the established neural network for training, which could quickly predict the device performance. The final prediction results show that the mean relative errors of the on-state resistance and reverse breakdown voltage are 0.048 and 0.028, respectively. The predicted value has an excellent fitting effect. This method can quickly design GaN JBS diodes with target performance and accelerate research on GaN JBS diode performance prediction.

Matrine improves the hepatic microenvironment and reverses epithelial-mesenchymal transition in hepatocellular carcinoma by inhibiting the Wnt-1/ß-catenin signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.

Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.

BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

Reliability and validity of the PedsQL™ Generic Core Scales 4.0 for Chinese children with epilepsy.

This investigation examines the reliability and validity of the Chinese version of the PedsQL 4.0 Generic Core Scales for prognostic measures of pediatric epilepsy. The study comprised 163 parents whose children, between the ages of 2 and 18 years, were diagnosed with epilepsy. The parents were given a questionnaire to be completed on behalf of the child. Reliability was assessed by Cronbach's alpha analysis. Validity was assessed by the exploratory factor analysis and intercorrelation analysis between the four subscales as well as Student's t-test. The internal consistency reliability for Total Scale Score was 0.94 by Cronbach's alpha test. Four major factors were extracted by factor analysis. The scores from all sub-scales derived from healthy children were significantly higher than children with epilepsy (P<0.001). The reliability and validity of the parent proxy-report scales from the Chinese version of the PedsQL™ 4.0 Generic Core Scales effectively matched the original version and could be used to evaluate the health-related quality of life of children with epilepsy.

Sarcopenia and Systemic Inflammation Response Index Predict Response to Systemic Therapy for Hepatocellular Carcinoma and Are Associated With Immune Cells.

Background: Systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states. Methods: We reviewed 160 patients with HCC treated with TKIs and ICIs. The patients' psoas muscle size was measured on axial computed tomography scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients' clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated. Results: Sarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group. Conclusion: Sarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

Implementation of early rehabilitation for critically ill children in China: A survey and narrative review of the literature.

Introduction: The focus of this survey was to understand the current status of implementation of early rehabilitation for critically ill children in China. We also reviewed the available literature on this topic for further insights to inform its future development. Materials and methods: We used a cross-sectional study design to survey tertiary hospitals nationwide. Questionnaires were distributed via the social media platform "WeChat Questionnaire Star" within the framework of the Rehabilitation Group of the Pediatrics Branch of the Chinese Medical Association. A narrative literature review on the implementation of the early rehabilitation for critically ill pediatric and/or adult patients was carried out. Results: A total of 202 valid questionnaires were received. About half (n = 105, 52.0%) of respondent hospitals reported that they implement early rehabilitation for critically ill children. Among these 105 hospitals, 28 implemented a continuous chain of early rehabilitation. A total of 24 hospitals had set up permanent specialized centralized early rehabilitation units for critically ill children. Implications and future directions: Early rehabilitation for critically ill children is not widely available in China and only a minority of hospitals implement a continuous chain of early rehabilitation. To improve this undesirable situation, we suggest creating a two-level integrated system comprising centralized early rehabilitation units and surrounding early rehabilitation networks within a region.