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What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment?This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate.Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups.The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

In recent years, numerous neurosurgical multimodal techniques have been utilized to maximize tumor resection safely and effectively. However, the synergetic effects of neurosurgical multimodalities on the survival of glioblastoma patients remain unclear. This study evaluated the role of intraoperative utilization of multimodalities in glioblastoma patients.Data of 912 adult patients with glioblastoma were obtained from the Huashan Glioma Registry. The utilization of fewer than 2 (multimodality value 2) intraoperative multimodal techniques was defined as the nonmultimodal group. In contrast, the utilization of 2 or more (multimodality value ≥ 2) intraoperative multimodal techniques was regarded as the multimodal group. The prognosis of the 2 cohorts was compared and further stratified based on the diagnosis date (2010-2014 or 2015-2019) to reveal the role of the application of multimodal techniques.The median overall survival (OS) and progression-free survival of glioblastoma patients were 17.70 months and 12.03 months, respectively. The OS time of the multimodal group was noticeably longer than that of the nonmultimodal group (21.0 months vs. 16.0 months, P 0.001). Multimodal techniques were more frequently applied in surgery in the 2015-2019 group than in the 2010-2014 group. The popularity of multimodal techniques contributed to significant improvement in the prognosis of glioblastoma patients from 2010-2014 to 2015-2019 (OS, 16.0 months vs. 22.0 months, P 0.001).This study indicated that the utilization of intraoperative multimodal techniques improved the extent of resection and elevated the survival for adult glioblastoma patients.

HLA-A*02:937 has one nucleotide change compared with HLA-A*02:07:01:01 in codon 182 of exon 3 (ACGGCG).

Remifentanil combined with sevoflurane is a standard protocol for obstetric general anesthesia (GA).In this study, we performed a randomized clinical trial to evaluate whether remifentanil has an effect on the median effective concentration (EC50) of sevoflurane and compare anesthetic outcomes of them in cesarean section with Supreme™ laryngeal mask airway (SLMA) under narcotrend monitoring. Ninety parturients with singleton births undergoing elective cesarean delivery (CD) with initial inhaled 1.0 minimum alveolar concentration (MAC) sevoflurane for anesthesia maintenance were assigned to three groups randomly and evenly: Group A (0.05 µg·kg-1·min-1 remifentanil combined with sevoflurane), Group B (0.1 µg·kg-1·min-1 remifentanil combined with sevoflurane), and Group C (normal saline combined with sevoflurane). Narcotrend was used to monitor the depth of anesthesia during the operation, with the level of anesthesia depth controlled within the D-E stage. The EC50 of sevoflurane was determined by Dixon's sequential method. The Narcotrend index, amount of bleeding, neonatal Apgar score, and corresponding treatment measures in the three groups were recorded.The results showed that the estimated EC50 of sevoflurane for obstetric GA was 0.80 MAC (95% CI: 0.63-0.95 MAC) in group A, 0.82 MAC (95% CI: 0.63-0.96 MAC) in group B, and 0.80 MAC (95% CI: 0.63-0.95 MAC) in group C. There was no statistically significant difference in the estimated EC50 of sevoflurane, time to wakefulness, Apgar score, amount of intraoperative bleeding, and postoperative bleeding within 24 hours between the three groups (all P0.05).The addition of remifentanil at 0.05-0.1 µg·kg-1·min-1 did not change the EC50 of sevoflurane and anesthetic quality. The concentration of inhaled anesthetics can be minimized with Narcotrend monitoring.Chinese Clinical Trial Registry ChiCTR2000034512.

Purpose To study and investigate the synergistic benefit of incorporating both conventional handcrafted and learning-based features in disease identification across a wide range of clinical setups. Methods and materials In this retrospective study, we collected 170, 150, 209, and 137 patients with four different disease types associated with identification objectives : Lymph node metastasis status of gastric cancer (GC), 5-year survival status of patients with high-grade osteosarcoma (HOS), early recurrence status of intrahepatic cholangiocarcinoma (ICC), and pathological grades of pancreatic neuroendocrine tumors (pNETs). Computed tomography (CT) and magnetic resonance imaging (MRI) were used to derive image features for GC/HOS/pNETs and ICC, respectively. In each study, 67 universal handcrafted features and study-specific features based on the sparse autoencoder (SAE) method were extracted and fed into the subsequent feature selection and learning model to predict the corresponding disease identification. Models using handcrafted alone, SAE alone, and hybrid features were optimized and their performance was compared. Prominent features were analyzed both qualitatively and quantitatively to generate study-specific and cross-study insight. In addition to direct performance gain assessment, correlation analysis was performed to assess the complementarity between handcrafted features and SAE features. Results On the independent hold-off test, the handcrafted, SAE, and hybrid features based prediction yielded area under the curve of 0.761 versus 0.769 versus 0.829 for GC, 0.629 versus 0.740 versus 0.709 for HOS, 0.717 versus 0.718 versus 0.758 for ICC, and 0.739 versus 0.715 versus 0.771 for pNETs studies, respectively. In three out of the four studies, prediction using the hybrid features yields the best performance, demonstrating the general benefit in using hybrid features. Prediction with SAE features alone had the best performance in the HOS study, which may be explained by the complexity of HOS prognosis and the possibility of a slight overfit due to higher correlation between handcrafted and SAE features. Conclusion This study demonstrated the general benefit of combing handcrafted and learning-based features in radiomics modeling. It also clearly illustrates the task-specific and data-specific dependency on the performance gain and suggests that while the common methodology of feature combination may be applied across various studies and tasks, study-specific feature selection and model optimization are still necessary to achieve high accuracy and robustness.

BackgroundCOVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain.MethodsThe pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group.ResultsIn the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (pConclusionsAmong the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

BackgroundOrgan donation has been claimed as a prosocial behavior to prolong the recipient's life and deliver great love. However, the supply-demand ratio of organs in China is highly unbalanced. Being entangled with multiple factors derived from individual and supra-individual levels, organ donation in China is important but sensitive. Previous scholars usually depended on obtrusive approaches to explore the facilitators and hindrances of organ donation, which is hard to discover genuine perceptions toward organ donation. Besides, relatively limited scholarly attention has been paid to what hampers organ donation in China.ObjectiveWe intended to excavate the diversified social representations and perceived barriers to organ donation in China over the past decade.MethodTwo kinds of text analysis methods—semantic network analysis and conventional content analysis, were applied to 120,172 posts from ordinary users on the Sina Weibo platform to address the research questions.ResultsRegarding social representations, the “hope, understanding, and acceptance” of organ donation was the most pronounced one (34% of the whole semantic network), followed by “family story” (26%), “the procedure of organ donation in NGOs” (15%), “the practical value of organ donation” (14%), and “organ donation in the medical context” (11%). Regarding perceived barriers, a four-layer framework was constructed, including (1) the individual level, mainly about the fear of death and postmortem autopsy; (2) the familial level, which refers to the opposition from family members; (3) the societal level, which alludes to distrust toward medical institutions and the general society; (4) the cultural level, which covers religious-cultural concerns about fatalism.ConclusionIn concordance with prior works on social representations regarding organ donation, the current study also uncovered the coexistence of antithetical representations about organ donation—the longing for survival and the fear of death. This representation pair serves as the foundation of Chinese people's ambivalence. Besides, family-related narratives were dispersed over various representations, demonstrating the critical position of family support in organ donation. Moreover, the four-layer framework concerning donation barriers affords a reference for future empirical studies. The practical implications of this work are further discussed.

Background: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression. Methods: Expression of ETV6 was first examined in two American and three Chinese tissue microarrays. The correlation between ETV6 staining intensity and patient survival was calculated, followed by validation using public databases—TCGA and REMBRANDT. The effect of ETV6 knockdown on glioma cell proliferation (EdU), viability (AnnexinV labeling), clonogenic growth (colony formation), and migration/invasion (transwell assays) in GBM cells was tested. RNA sequencing and Western blot were performed to elucidate the underlying molecular mechanisms. Results: ETV6 was highly expressed in GBM and associated with an unfavorable prognosis. ETV6 silencing in glioma cells led to increased apoptosis or decreased proliferation, clonogenicity, migration, and invasion. RNA-Seq-based gene expression and pathway analyses revealed that ETV6 knockdown in U251 cells led to the upregulation of genes involved in extracellular matrix organization, NF-κB signaling, TNF-mediated signaling, and the downregulation of genes in the regulation of cell motility, cell proliferation, PI3K-AKT signaling, and the Ras pathway. The downregulation of the PI3K-AKT and Ras-MAPK pathways were further validated by immunoblotting. Conclusion: Our findings suggested that ETV6 was highly expressed in GBM and its high expression correlated with poor survival. ETV6 silencing decreased an aggressive in vitro phenotype probably via the PI3K-AKT and Ras-MAPK pathways. The study encourages further investigation of ETV6 as a potential therapeutic target of GBM.

Objective Glioblastoma is the most common and fatal primary brain tumor in adults. Even with maximal resection and a series of postoperative adjuvant treatments, the median overall survival (OS) of glioblastoma patients remains approximately 15 months. The Huashan Hospital glioma bank contains more than 2000 glioma tissue samples with long-term follow-up data; almost half of these samples are from glioblastoma patients. Several large glioma databases with long-term follow-up data have reported outcomes of glioblastoma patients from countries other than China. We investigated the prognosis of glioblastoma patients in China and compared the survival outcomes among patients from different databases. Methods The data for 967 glioblastoma patients who underwent surgery at Huashan Hospital and had long-term follow-up records were obtained from our glioma registry (diagnosed from 29 March 2010, through 7 June 2017). Patients were eligible for inclusion if they underwent surgical resection for newly diagnosed glioblastomas and had available data of survival and personal information. Data of 778 glioblastoma patients were collected from three separate online databases (448 patients from The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov), 191 from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) database (GSE108476) and 132 from data set GSE16011(Hereafter called as the French database). We compared the prognosis of glioblastoma patients from records among the different databases and the changes in survival outcomes of glioblastoma patients from Huashan Hospital over an 8-year period. Results The median OS of glioblastoma patients was 16.3 (95% CI: 15.4-17.2) months for Huashan Hospital, 13.8 (95% CI: 12.9-14.9) months for TCGA, 19.3 (95% CI: 17.0-20.0) months for the REMBRANDT database, and 9.1 months for the French database. The median OS of glioblastoma patients from Huashan Hospital improved from 15.6 (2010-2013, 95% CI: 14.4-16.6) months to 18.2 (2014-2017, 95% CI: 15.8-20.6) months over the study period (2010-2017). In addition, the prognosis of glioblastoma patients with total resection was significantly better than that of glioblastoma patients with sub-total resection or biopsy. Conclusions Our study confirms that treatment centered around maximal surgical resection brought survival benefits to glioblastoma patients after adjusting to validated prognostic factors. In addition, an improvement in prognosis was observed among glioblastoma patients from Huashan Hospital over the course of our study. We attributed it to the adoption of a new standard of neurosurgical treatment on the basis of neurosurgical multimodal technologies. Even though the prognosis of glioblastoma patients remains poor, gradual progress is being made.

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high incidence, high malignancy, and low survival rate. Cuproptosis is a novel form of cell death mediated by lipoylated TCA cycle proteins-mediated novel cell death pathway and is highly associated with mitochondrial metabolism. However, the relationship between the expression level of cuproptosis-related genes (CRGs) and the prognosis of HCC is still unclear.MethodsCombining the HCC transcriptomic data from The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed cuproptosis-related genes (DECRGs) and obtained the prognosis-related DECRGs through univariate regression analysis.LASSO and multivariate COX regression analyses of these DECRGs yielded four genes that were used to construct the signature. Next, we use ROC curves to evaluate the performance of signatures. The tumor microenvironment, immune infiltration, tumor mutation load, half-maximum suppression concentration, and immunotherapy effects were also compared between the low-risk and high-risk groups. Finally, we analyzed the expression level, prognosis, and immune infiltration correlation on the four genes that constructed the model.ResultsFour DECRGs s were used to construct the signature. The ROC curves indicated that signature can better assess the prognosis of HCC patients. Patients were grouped according to the signature risk score. Patients in the low-risk group had a significantly longer survival time than those in the high-risk group. Furthermore, the tumor mutation burden (TMB) values were associated with the risk score and the higher-risk group had a higher proportion of TP53 mutations than the low-risk group.ESTIMATE analysis showed significant differences in stromal scores between the two groups.N6-methyladenosine (m6A) and multiple immune checkpoints were expressed at higher levels in the high-risk group. Then, we found that signature score correlated with chemotherapeutic drug sensitivity and immunotherapy efficacy in HCC patients. Finally, we further confirmed that the four DECRGs genes were associated with the prognosis of HCC through external validation.ConclusionsWe studied from the cuproptosis perspective and developed a new prognostic feature to predict the prognosis of HCC patients. This signature with good performance will help physicians to evaluate the overall prognosis of patients and may provide new ideas for clinical decision-making and treatment strategies.

Background This study aimed to identify the most valuable predictors of prognosis in glioblastoma (GBM) patients and develop and validate a nomogram to estimate individualized survival probability. Methods We conducted a real-world retrospective cohort study of 987 GBM patients diagnosed between September 2010 and December 2018. Computer generated random numbers were used to assign patients into a training cohort (694 patients) and internal validation cohort (293 patients). A least absolute shrinkage and selection operator (LASSO)-Cox model was used to select candidate variables for the prediction model. Cox proportional hazards regression was used to estimate overall survival. Models were internally validated using the bootstrap method and generated individualized predicted survival probabilities at 6, 12, and 24 months, which were compared with actual survival. Results The final nomogram was developed using the Cox proportional hazards model, which was the model with best fit and calibration. Gender, age at surgery, extent of tumor resection, radiotherapy, chemotherapy, and IDH1 mutation status were used as variables. The concordance indices for 6-, 12-, 18-, and 24-month survival probabilities were 0.776, 0.677, 0.643, and 0.629 in the training set, and 0.725, 0.695, 0.652, and 0.634 in the validation set, respectively. Conclusions Our nomogram that assesses individualized survival probabilities (6-, 12-, and 24-month) in newly diagnosed GBM patients can assist healthcare providers in optimizing treatment and counseling patients. Trial registration: retrospectively registered.

Multi-material decomposition (MMD) decomposes CT images into basis material images, and is a promising technique in clinical diagnostic CT to identify material compositions within the human body. MMD could be implemented on measurements obtained from spectral CT protocol, although spectral CT data acquisition is not readily available in most clinical environments. MMD methods using single energy CT (SECT), broadly applied in radiological departments of most hospitals, have been proposed in the literature while challenged by the inferior decomposition accuracy and the limited number of material bases due to the constrained material information in the SECT measurement. In this paper, we propose an image-domain SECT MMD method using material sparsity as an assistance under the condition that each voxel of the CT image contains at most two different elemental materials. L0 norm represents the material sparsity constraint (MSC) and is integrated into the decomposition objective function with a least-square data fidelity term, total variation term, and a sum-to-one constraint of material volume fractions. An accelerated primal-dual (APD) algorithm with line-search scheme is applied to solve the problem. The pixelwise direct inversion method with the two-material assumption (TMA) is applied to estimate the initials. We validate the proposed method on phantom and patient data. Compared with the TMA method, the proposed MSC method increases the volume fraction accuracy (VFA) from 92.0% to 98.5% in the phantom study. In the patient study, the calcification area can be clearly visualized in the virtual non-contrast image generated by the proposed method, and has a similar shape to that in the ground-truth contrast-free CT image. The high decomposition image quality from the proposed method substantially facilitates the SECT-based MMD clinical applications.

Background While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. Objective To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. Methods IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. Results A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). Conclusion Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

Acute pancreatitis (AP) is a common disorder with significant hospital admission and mortality. Due to the unclarified pathological mechanism, there is still no effective and specific treatment for AP. Recently, autophagy has been found to be closely related with occurrence and development of AP, which is crucial in determining its severity and outcomes. Emerging evidence indicates that autophagy can be regulated and influenced by microRNAs and organelles, including mitochondria, endoplasmic reticulum and lysosome, through various ways in AP. Of note, the complex interplays and close relationships among autophagy, microRNA and organelles in AP are vital for figuring out pathogenesis but not clear yet. Thus, this review summarizes the role of autophagy in the pathological mechanism of AP, especially the relationship between impaired autophagy and organelles, and discusses the regulatory mechanism of microRNA on autophagy, which could offer new insights into understanding the pathogenesis of AP and developing new potential therapeutic targets against AP.

Glioma is the most common primary brain tumor. Clear classification is crucial for accurate diagnosis and individualized treatment. Histopathological characteristics and genetic alterations have shown to be related to prognosis and treatment response. Germline variants are important components of genetic alterations. However, the distribution of germline variations in glioma patients and their association with survival remain unknown. We carried out whole-exome sequencing on 99 cases to explore germline variants in glioma. We also analyzed the association of germline variants with clinicopathological features and other prognostic indicators. All the glioma cases harbored rare germline variants. Germline ALK variants (gALK-Mut) were identified in 12/99 (12.12%) patients. The gALK-Mut patients had significantly shorter overall survival than germline ALK wildtype (gALK-WT) patients in the all glioma group (99 cases) and the subset of patients with IDH-wildtype glioblastoma (IDH-WT-GBM, 39 cases) (P = 0.013 and 0.027, respectively). The gALK-Mut patients also had higher frequency of BIRC5, PIK3CA and RPN1 somatic mutations than the gALK-WT patients in IDH-WT-GBM. Other confounding factors appeared to contribute to patient survival. The subgroup of patients in IDH-WT-GBM with gALK-Mut/TP53-Mut had worse prognosis than the gALK-WT/TP53-Mut subgroup (P = 0.031); The gALK-Mut/TERT-WT and gALK-Mut/TERT-Mut subgroups both had a worse prognosis than the gALK-WT/TERT-Mut subgroup (P = 0.031 and 0.018, respectively). Our study revealed ALK variation was an independent indicator of poor prognosis in glioma and IDH-WT-GBM. It could be a promising biomarker and tractable therapeutic target for this deadly disease.

Complement component 1 Q subcomponent-binding protein (C1QBP) has been shown to interact with the porcine circovirus type 2 (PCV2) Cap protein. Here, using yeast two-hybrid (Y2H) and co-immunoprecipitation assays, as well as laser confocal microscopy, the interaction between C1QBP and Cap was confirmed. Furthermore, overexpression of C1QBP in cells altered the intracellular location of Cap, which was observed using confocal microscopy and verified by detection of Cap in nuclear protein extracts in a Western blot assay. By inhibiting nuclear transport of Cap, overexpression of C1QBP downregulated PCV2 proliferation in PK-15 cells, as determined by quantitative polymerase chain reaction (qPCR). As C1QBP plays a similar role in a fusion of green fluorescent protein (GFP) with the Cap nuclear localisation signal (NLS) sequence, (CapNLS-GFP), we propose that the target site for C1QBP in Cap is possibly located in the NLS region. Considering all the results together, this study demonstrated that C1QBP interacts with the Cap NLS region, resulting in changes in the intracellular localisation of the Cap protein. We confirmed that overexpression of C1QBP inhibits the proliferation of PCV2, and this is possibly related to the function of C1QBP in controlling nuclear transport of Cap.

Pancreatic cancer (PC) is one of the deadliest malignant tumors, and its resistance to gemcitabine chemotherapy is the primary reason for poor prognosis in patients. Ubiquitin-like protein FAT10 has recently been reported to promote tumor chemotherapy resistance. In this study, the expression of FAT10 in PC was significantly higher than that in adjacent noncancerous tissues. Increased expression of FAT10 in PC was related to a late TNM stage and decreased overall survival. Functional experiments revealed that downregulating the expression of FAT10 inhibits the proliferation and epithelial-mesenchymal transition (EMT) of PC cells, promotes the apoptosis of PC cells, and enhances sensitivity to gemcitabine chemotherapy. In addition, upregulation of FAT10 increased the expression of FOXM1 protein. The effect of downregulating FAT10 was reversed by FOXM1 overexpression, and FOXM1 knockdown inhibited EMT driven by FAT10 overexpression. Mechanistically, FAT10 stabilized the expression of FOXM1 by competing with ubiquitin to bind FOXM1 and inhibiting the ubiquitination-mediated degradation of FOXM1. In conclusion, the FAT10-FOXM1 axis is a pivotal driver of PC proliferation and gemcitabine resistance, and the results provide novel insights into chemotherapy resistance in PC.

Background Meningioma is the most common type of primary intracranial tumor with 0.1–1% of all primary meningiomas have been reported to develop into metastases. However, there is no proven therapeutic strategy for multiple metastases of meningiomas. Case presentation A 60-year-old female accepted total tumor resection of a right frontal lobe meningioma in September 2018, In October 2021, the patient was admitted to hospital because of cough and shortness of breath and diagnosed with metastatic meningiomas. The computed tomography (CT) scan revealed the presence of large masses in the right thoracic and abdominal cavity. After two cycles of anti-PD-1 and anti-VEGF treatment, the symptoms were relieved and the tumor was necrotic. Follow up to June 21, 2022, the patient has been given eleven cycles of the treatment every 3 weeks without tumor progression. Conclusions This case showed combined anti-PD-1 and anti-VEGF treatment stimulates peripheral blood immune cells to kill metastatic meningioma cells. Whether combined immunotherapy is more effective for metastatic meningioma needs further exploration.

The novel HLA-B*48:54 allele was identified in an individual from the Sichuan province of China.

The novel HLA-C*08:242 allele was identified in an individual from the Sichuan province of China.

The demand for health care has increased with the development of global technology and the rise of public health awareness, and smart service systems have also been introduced to medical care to relieve the pressure on hospital staff. However, the survey found that patients’ willingness to use smart services at the time of consultation has not improved. The main research purpose of this study was to understand the willingness of patients from various groups to use smart medical service systems and to explore the influencing factors on patients’ use of smart service systems in hospitals through the technology acceptance model. This study distributed questionnaires in the outpatient area of National Taiwan University Hospital Yunlin Branch, and a total of 202 valid questionnaires were obtained. After related research and regression analysis, it was found that patients paid more attention to the benefits and convenience brought by smart services. If patients believed that smart services were trustworthy and beneficial to themselves, their usage intention and attitude would be positive. The results of this study are summarized by the following four points: (1) Designed according to the cultural conditions of different regions; (2) think about design from the patient’s perspective; (3) strengthen the explanation and promotion of smart services; and (4) add humanized care and design. This study could be used as a reference for hospitals to improve their service quality and systems in the future.

Introduction Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. Current specific diagnosis regarding CRC remains complicated and costly, and specific diagnostic biomarkers are lacking. Methods To find potential diagnostic and prognostic biomarkers for CRC, we screened and analyzed many CRC sequencing data by The Cancer Genome Atlas Program and Gene Expression Omnibus, and validated that CEP55 may be a potential diagnostic biomarker for CRC by molecular cytological experiments and immunohistochemistry, among others. Results We found that CEP55 is upregulated in CRC tissues and tumor cells and can promote CRC proliferation and metastasis by activating the p53/p21 axis and that CEP55 mutations in tumor patients result in worse overall survival and disease‐free survival time. Besides, we also found that genes, such as CDK1, CCNB1, NEK2, KIF14, CDCA5, and RFC3 were upregulated in tumors, and their mutations would affect the prognosis of CRC patients, but these results await for more experimental evidence. Conclusion Our study validates CEP55 as a potential diagnostic and prognostic biomarker for CRC, and we also provide multiple genes and potential molecular mechanisms that may serve as diagnostic and prognostic markers for CRC., CEP55 is upregulated in CRC tissues and tumor cells and can promote CRC proliferation and metastasis by activating the p53/p21 axis.

Increasing evidence suggests long non-coding RNAs (lncRNAs) are distinctively expressed in several cancers. However, the functions of these lncRNAs in cancer development remain unknown. In the current study, we report high expression of a novel lncRNA, RP11-59H7.3, and its association with prognosis in colorectal cancer (CRC) patients. Functional analyses of this lncRNA revealed its role in promoting proliferation and progression of the cell cycle, as well as enhancement of cell migration and invasion. Furthermore, our results revealed that knockdown of RP11-59H7.3 promoted cell apoptosis, with luciferase reporter assays showing that it directly binds to miR-139-5p. Knockdown of this lncRNA significantly reduced expression of NOTCH1, a direct target of miR-139-5p. Additionally, we show that suppression NOTCH1 by miR-139-5p could be partially rescued by overexpressing RP11-59H7.3. Analysis of the relationship between RP11-59H7.3 and miR-139-5p, in CRC tissues, showed a negative correlation while a positive association was observed between the RP11-59H7.3 expression and levels of NOTCH1. Taken together, these results demonstrated that the RP11-59H7.3/miR-139-5p/NOTCH1 axis functions as a key regulator in CRC metastasis. RP11-59H7.3 represents a potential biomarker for CRC diagnosis and could be an important target for development of novel therapies to manage the disease.

Emerging evidence indicates that DJ-1 is highly expressed in different cancers. It modulates cancer progression, including cell proliferation, cell apoptosis, invasion, and metastasis. However, its role in colorectal cancer (CRC) remains poorly defined. The current study noted increased DJ-1 expression in CRC tumor tissue and found that its expression was closely related to clinical-pathological features. Similarly, DJ-1 increased in CRC cells (SW480, HT-29, Caco-2, LoVo, HCT116, and SW620), and especially in SW480 and HCT116 cells. Functional analyses indicated that overexpression of DJ-1 promoted CRC cell invasion, migration, and proliferation in vitro and in vivo. Mechanistic studies indicated that DJ-1 increased in CRC cell lines, activated specific protein cyclin-D1, and modulated the MDM2/p53 signaling pathway by regulating the levels of the downstream factors Bax, Caspase-3, and Bcl-2, which are related to the cell cycle and apoptosis. Conversely, knockdown of DJ-1 upregulated p53 expression by disrupting the interaction between p53 and MDM2 and inhibiting CRC cell proliferation, revealing the pro-oncogenic mechanism of DJ-1 in CRC. In conclusion, the current findings provide compelling evidence that DJ-1 might be a promoter of CRC cell invasion, proliferation, and migration via the cyclin-D1/MDM2-p53 signaling pathway. Findings also suggest its potential role as a postoperative adjuvant therapy for patients with CRC.

Purpose To explore the challenges of parents caring for early-stage schizophrenia (ESS) children/adolescents in China. Design and methods Thirteen parents of ESS subjects completed semi-structured interviews. Thematic analysis was used to analyze data. Findings Seven themes emerged from the data: psychological shock and emotional burden; lack of disease knowledge and care skill; poor treatment compliance of the patient; difficulty getting along with the patient; conflict within the family or in the workplace; financial burden; and need sufficient social support. Each challenge was produced and influenced under the Chinese special social context. Practice implications Professional support was needed to help patients with schizophrenia to cope with their situation promptly. Education initiatives should focus on mental health to prevent discrimination from society and enable people to recognize the early symptoms of schizophrenia in children. Telemedicine should be explored for application in the treatment of mental illness. Also, a broader nationwide healthcare policy would be needed to help to reduce the individual and societal financial burdens associated with schizophrenia.

Extracts of Siraitia grosvenorii (Swingle), in Chinese known as Luo Han Guo (LHG), is authorized for use as a natural sweetener. LHG is rich in mogroside V that contains five glucoses, but also contains mogroside IIIE and analogues with fewer than three glucose units that cause an unpleasant aftertaste, limiting the use of the extract. Snailase was applied here to convert mogroside V in LHG extract in favor of siamenoside I formation, the sweetest mogroside with a taste similar to sucrose. For application, snailase was immobilized by adsorption to NKA (a macroporous resin), resulting in 10.9 U per g of adsorbed protein. Reuse of the NKA-adsorbed snailase was demonstrated for four cycles, and a continuous production of improved LHG extract at a 0.5 L scale had a productivity of 68.4 g/(L⋅day). The resulting product containing over 50% siamenoside I displayed an improved taste profile with satisfying safety toward HEK293T cells.

Lake Victoria, a lifeline for millions of people in East Africa, is affected by anthropogenic activities resulting in eutrophication and impacting the aquatic life and water quality. Therefore, understanding the ongoing changes in the catchment is critical for its restoration. In this context, catchment and lake sediments are important archives in tracing nutrient inputs and their dominant sources to establish causality with human activities and productivity shifts. In this study, we determine the 1) changes in concentrations of total organic carbon (TOC), black carbon (BC), total nitrogen (TN), C/N ratio, and phosphorous (P) fractions in catchment sediments and the open lake, 2) distribution of diatom population in the lake, and 3) land use and land cover changes in the catchment. The distribution of TOC, BC, TN, C/N, and P correlate while showing spatial and temporal variations. In particular, the steady increase in BC confirms atmospheric inputs from anthropogenic activities in the catchment. However, lake sediments show more variations than catchment-derived sediments in geochemical trends. Notably, the catchment has undergone dramatic land use changes since the 1960s (post-independence). This change is most evident in satellite records from 1985 to 2014, which indicate accelerated human activities. For example, urban growth (666-1022%) and agricultural expansion (23-48%) increased sharply at the expense of a decline in forest cover, grassland, and woodlands in the catchment. Cities like Kisumu and Homa Bay expanded, coinciding with rapid population growth and urbanization. Consequently, nutrient inputs have increased since the 1960s, and this change corresponds with the divergence of diatom communities in the lake. In addition, the transition to Nitzschia and cyanobacteria mark increasing cultural eutrophication in the lake. The geochemical trends and statistical data support our inference(s) and provide insights into urban development and agriculture practices, which propelled increased nutrients from the catchment and productivity shifts in the lake.

Objective. The quantitative and routine imaging capabilities of cone-beam CT (CBCT) are hindered from clinical applications due to the severe shading artifacts of scatter contamination. The scatter correction methods proposed in the literature only consider the anatomy of the scanned objects while disregarding the impact of incident x-ray energy spectra. The multiple-spectral model is in urgent need for CBCT scatter estimation. Approach. In this work, we incorporate the multiple spectral diagnostic multidetector CT labels into the pixel-to-pixel (Pix2pix) GAN to estimate accurate scatter distributions from CBCT projections acquired at various imaging volume sizes and x-ray energy spectra. The Pix2pix GAN combines the residual network as the generator and the PatchGAN as the discriminator to construct the correspondence between the scatter-contaminated projection and scatter distribution. The network architectures and loss function of Pix2pix GAN are optimized to achieve the best performance on projection-to-scatter transition. Results. The CBCT data of a head phantom and abdominal patients are applied to test the performance of the proposed method. The error of the corrected CBCT image using the proposed method is reduced from over 200 HU to be around 20 HU in both phantom and patient studies. The mean structural similarity index of the CT image is improved from 0.2 to around 0.9 after scatter correction using the proposed method compared with the MC-simulation method, which indicates a high similarity of the anatomy in the images before and after the proposed correction. The proposed method achieves higher accuracy of scatter estimation than using the Pix2pix GAN with the U-net generator. Significance. The proposed scheme is an effective solution to the multiple spectral CBCT scatter correction. The scatter-correction software using the proposed model will be available at: https://github.com/YangkangJiang/Cone-beam-CT-scatter-correction-tool.

Background An increasing number of studies have shown that immune-related long noncoding RNAs (lncRNAs) do not require a unique expression level. This finding may help predict the survival and drug sensitivity of patients with colon cancer. Methods We retrieved original transcriptome and clinical data from The Cancer Genome Atlas (TCGA), sorted the data, differentiated mRNAs and lncRNAs, and then downloaded immune-related genes. Coexpression analysis predicted immune-related lncRNAs (irlncRNAs) and univariate analysis identified differentially expressed irlncRNAs (DEirlncRNAs). We have also amended the lasso pending region. Next, we compared the areas under the curve (AUCs), counted the Akaike information standard (AIC) value of the 3-year receiver operating characteristic (ROC) curve, and determined the cutoff point to establish the best model to differentiate the high or low disease risk group of colon cancer patients. Results We reevaluated the patients regarding the survival rate, clinicopathological features, tumor-infiltrating immune cells, immunosuppressive biomarkers, and chemosensitivity. A total of 155 irlncRNA pairs were confirmed, 31 of which were involved in the Cox regression model. After the colon cancer patients were regrouped according to the cutoff point, we could better distinguish the patients based on adverse survival outcomes, invasive clinicopathological features, the specific tumor immune cell infiltration status, high expression of immunosuppressive biomarkers, and low chemosensitivity. Conclusions In this study, we established a characteristic model by pairing irlncRNAs to better predict the survival rate, chemotherapy efficacy, and prognostic value of patients with colon cancer.

BackgroundRestoration with locking-taper implants is a widely used methodology. However, conical connection systems such as locking-taper implant systems have rarely been examined. This study provides a retrospective investigation of locking-taper fixed restorations, mainly focusing on prosthetic complications.MethodsPatients undergo treatment with conical connected implants from 2008 to 2010 were examined. Preparation of the implant sites was performed according to the standard procedures for the Bicon system. Bone healing took over 6 months, and the prosthetic procedure was initiated thereafter. Integrated abutment crowns or gold porcelain crowns were used, and the prosthesis type was a single crown or a fixed dental prosthesis. Once the crown was in place, its occlusion was thoroughly checked and adjusted, and then the crown was glazed or finely polished. The Kaplan–Meier method was used to calculate the cumulative complication-free rates for 5 and 10 years. Additionally, a Cox regression model was used to identify the factors that independently influenced the results. Implant survival and marginal bone loss were also investigated.ResultsA total of 392 patients who underwent 541 implants and 434 locking taper implant-based restorations from 2008 to 2010 were examined. The overall 5-year cumulative complication-free rate was 83.34%. The most common prosthetic complication was veneer chipping, with a frequency of 67.53%. According to the Cox regression model, the complication-free rate of integrated abutment crowns was significantly higher than that of gold porcelain crowns, that of molar regions was significantly higher than that of premolar regions, and that of females was significantly higher than that of males. Only three implant failures happened, and the mean marginal bone loss values at 1- year, 5-years and 10- years were 0.25 mm (95% CI ± 0.12), 0.40 mm (95% CI ± 0.03) and 0.51 mm (95% CI ± 0.05), respectively.ConclusionVeneer chipping was the most common complication with locking-taper implant-supported fixed restorations. The incidence of complications for IACs is significantly higher than that for GPCs. Age, location, and prosthesis type are not determinants of prosthetic complications. Besides, the long-term clinical effect of locking-taper implant can meet the clinical needs. The bone tissue level around the implant can maintain long-term stability.

Acute pancreatitis (AP) is an inflammatory disorder initiated by activation of pancreatic zymogens, leading to pancreatic injury and systemic inflammatory response. MicroRNAs (miRNAs) have emerged as important regulators of gene expression and key players in human physiological and pathological processes. Discoveries over the past decade have confirmed that altered expression of miRNAs is implicated in the pathogenesis of AP. Indeed, a number of miRNAs have been found to be dysregulated in various cell types involved in AP such as acinar cells, macrophages, and lymphocytes. These aberrant miRNAs can regulate acinar cell necrosis and apoptosis, local and systemic inflammatory response, thereby contributing to the initiation and progression of AP. Moreover, patients with AP possess unique miRNA signatures when compared with healthy individuals or those with other diseases. In view of their stability and easy detection, therefore, miRNAs have the potential to act as biomarkers for the diagnosis and assessment of patients with AP. In this review, we provide an overview of the novel cellular and molecular mechanisms underlying the roles of miRNAs during the disease processes of AP, as well as the potential diagnosis and therapeutic biomarkers of miRNAs in patients with AP.

Purpose: Accurate lymph node (LN) status evaluation for intrahepatic cholangiocarcinoma (ICC) patients is essential for surgical planning. This study aimed to develop and validate a prediction model for preoperative LN status evaluation in ICC patients. Methods and Materials: A group of 106 ICC patients, who were diagnosed between April 2011 and February 2016, was used for prediction model training. Image features were extracted from T1-weighted contrast-enhanced MR images. A support vector machine (SVM) model was built by using the most LN status-related features, which were selected using the maximum relevance minimum redundancy (mRMR) algorithm. The mRMR method ranked each feature according to its relevance to the LN status and redundancy with other features. An SVM score was calculated for each patient to reflect the LN metastasis (LNM) probability from the SVM model. Finally, a combination nomogram was constructed by incorporating the SVM score and clinical features. An independent group of 42 patients who were diagnosed from March 2016 to November 2017 was used to validate the prediction models. The model performances were evaluated on discrimination, calibration, and clinical utility. Results: The SVM model was constructed based on five selected image features. Significant differences were found between patients with LNM and non-LNM in SVM scores in both groups (the training group: 0.5466 (interquartile range (IQR), 0.4059-0.6985) vs. 0.3226 (IQR, 0.0527-0.4659), P

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

Brominated flame retardant 2,2′,4,4′‑tetrabromodiphenyl ether (PBDE-47) is known to induce developmental neurotoxicity by disturbing thyroid hormones (THs). Evidence shows that maternal THs are crucial for brain development and growth of fetuses and infants. However, little is known about the effects of PBDE-47 on maternal thyroid status and its mode of action. Here, using female Sprague-Dawley rats orally exposed to low doses of PBDE-47 (0.1, 1.0, 10 mg/kg/day) from pre-pregnancy until weaning of offspring to mimic human exposure, we show that perigestational exposure to PBDE-47 elevated serum triiodothyronine and thyroxine levels in mother rats. This is accompanied by disrupted thyroid follicle structure including expanded follicles, hyperplastic epithelial cells and shed cell remnants filled in the exhausted follicular lumen. Mechanistically, PBDE-47 enhanced apoptosis in thyroid tissue, as demonstrated by Caspase-3 activation, PARP cleavage and DNA fragmentation. Further study identified that PBDE-47 upregulated the levels of GRP78, ATF4, active Caspase-12 and CHOP, suggesting endoplasmic reticulum (ER) stress and unfolded protein response activation. Moreover, PBDE-47 reduced the levels of LC3-II, an autophagy marker protein essential for the autophagosomes formation, while increased the autophagy substrate p62 accumulation, indicating autophagy defect. Importantly, the colocalization of apoptotic cells with CHOP, a key mediator of ER stress-induced apoptosis, or p62, uncovered the contribution of excessive ER stress and defective autophagy to apoptosis. Collectively, our results suggest that excessive ER stress, defective autophagy and the resultant apoptosis are implicated in maternal thyroid injury following perigestational PBDE-47 exposure, which offers insight into a better understanding of PBDE-47-induced maternal thyroid toxicity.

Background COVID-19 is still rampant all over the world. Until now, the COVID-19 vaccine is the most promising measure to subdue contagion and achieve herd immunity. However, public vaccination intention is suboptimal. A clear division lies between medical professionals and laypeople. While most professionals eagerly promote the vaccination campaign, some laypeople exude suspicion, hesitancy, and even opposition toward COVID-19 vaccines. Objective This study aims to employ a text mining approach to examine expression differences and thematic disparities between the professionals and laypeople within the COVID-19 vaccine context. Methods We collected 3196 answers under 65 filtered questions concerning the COVID-19 vaccine from the China-based question and answer forum Zhihu. The questions were classified into 5 categories depending on their contents and description: adverse reactions, vaccination, vaccine effectiveness, social implications of vaccine, and vaccine development. Respondents were also manually coded into two groups: professional and laypeople. Automated text analysis was performed to calculate fundamental expression characteristics of the 2 groups, including answer length, attitude distribution, and high-frequency words. Furthermore, structural topic modeling (STM), as a cutting-edge branch in the topic modeling family, was used to extract topics under each question category, and thematic disparities were evaluated between the 2 groups. Results Laypeople are more prevailing in the COVID-19 vaccine–related discussion. Regarding differences in expression characteristics, the professionals posted longer answers and showed a conservative stance toward vaccine effectiveness than did laypeople. Laypeople mentioned countries more frequently, while professionals were inclined to raise medical jargon. STM discloses prominent topics under each question category. Statistical analysis revealed that laypeople preferred the “safety of Chinese-made vaccine” topic and other vaccine-related issues in other countries. However, the professionals paid more attention to medical principles and professional standards underlying the COVID-19 vaccine. With respect to topics associated with the social implications of vaccines, the 2 groups showed no significant difference. Conclusions Our findings indicate that laypeople and professionals share some common grounds but also hold divergent focuses toward the COVID-19 vaccine issue. These incongruities can be summarized as “qualitatively different” in perspective rather than “quantitatively different” in scientific knowledge. Among those questions closely associated with medical expertise, the “qualitatively different” characteristic is quite conspicuous. This study boosts the current understanding of how the public perceives the COVID-19 vaccine, in a more nuanced way. Web-based question and answer forums are a bonanza for examining perception discrepancies among various identities. STM further exhibits unique strengths over the traditional topic modeling method in statistically testing the topic preference of diverse groups. Public health practitioners should be keenly aware of the cognitive differences between professionals and laypeople, and pay special attention to the topics with significant inconsistency across groups to build consensus and promote vaccination effectively.

Advanced and recurrent ovarian cancer has a poor prognosis and is frequently resistant to numerous therapeutics; thus, safe and effective drugs are needed to combat this disease. Previous studies have demonstrated that triptolide (TPL) exhibits anticancer and sensitization effects against cisplatin (DDP)-resistant ovarian cancer both in vitro and in vivo by inducing apoptosis; however, the involvement of autophagy induced by TPL in resistant ovarian carcinoma remains unclear. In the present study, the results revealed that TPL induced autophagy to facilitate SKOV3/DDP ovarian cancer cell death. The xenograft experiment revealed that the autophagy inhibitor CQ significantly reduced TPL-mediated chemosensitization and tumor growth inhibition. Mechanically, TPL-induced autophagy in SKOV3/DDP cells was associated with the induction of ROS generation and inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) pathway. The inhibitory effect of TPL on the JAK2/STAT3 pathway could be restored in the presence of the antioxidant NAC. Furthermore, it was further determined that TPL disrupted the interaction between Mcl-1 and Beclin1, which was prevented by the JAK2/STAT3 signaling activator IL-6. Overall, the present results revealed a novel molecular mechanism whereby TPL induced lethal autophagy through the ROS-JAK2/STAT3 signaling cascade in SKOV3/DDP cells. The present study has provided the groundwork for future application of TPL in the treatment of ovarian cancer.

Long non-coding RNAs (lncRNAs) have been characterized by playing a crucial role in tumorigenesis. However, the detail biological function and clinical importance of lncRNAs in colorectal cancer (CRC) are unclear and have attracted different levels of in-depth research. In this context, we explored the differentially expressed profiles of lncRNAs in six CRC tissues and three adjacent non-tumor tissues from RNA-sequencing (RNA-seq) study and noted a lncRNA, RP11-51O6.1, which is markedly overexpressed in CRC tissues, particularly in aggressive cases. Impressively, an elevated RP11-51O6.1 level was highly correlated with poor prognosis in clinical patients. Functional analyses revealed that RP11-51O6.1 could promote cell proliferation in vitro and in vivo. Furthermore, we reported that RP11-51O6.1 enhances cell migration and invasion in vitro. Mechanistic studies (Bioinformatics binding site analyses, the Luciferase reporter, Ago2 immunoprecipitation, the RNA pull-down, immunofluorescence colocalization, rescued assays and western blotting) implicated that RP11-51O6.1 could regulate YAP1 expression by competitively sponging miR-206 and blocking its activity in promoting CRC progression. Conclusively, our findings identify a novel RP11-51O6.1/miR-206/YAP1 regulatory axis that participates in CRC progression and development, suggesting RP11-51O6.1 is an exploitable biomarker and appealing therapeutic target in treating CRC.

Liver cancer most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, dietary carcinogens, and so forth. The current treatment modalities, including surgical resection and liver transplantation, have been found far from effective. Hence, there is an obvious critical need to develop alternative strategies for the treatment of it. In this review, we discuss the formation process and therapeutic targets of liver cancer. Currently, targeted therapy is limited to sorafenib, lenvatinib, regorafenib, ramucirumab and cabozantinib which leads to a survival benefit in patients, but on the other hand is hampered by the occurrence of drug resistance. Pleasingly and importantly, there are multiple natural products undergoing clinical evaluation in liver cancer, such as polyphenols like icaritin, resveratrol, and silybin, saponins including ginsenoside Rg3 and glycyrrhizinate, alkaloid containing irinotecan and berberine and inorganic compound arsenic trioxide at present. Preclinical and clinical studies have shown that these compounds inhibit liver cancer formation owing to the influence on the anti-viral, anti-inflammation, anti-oxidant, anti-angiogenesis and anti-metastasis activity. Furthermore, a series of small molecule derivatives inspired by the aforementioned compounds are designed and synthesized according to structure-activity relationship studies. Drug combination and novel type of drug-targeted delivery system thereof have been well developed. This article is ended by a perspective remark of futuristic development of natural product-based therapeutic regimen for liver cancer treatment. We expect that this review is an account for current status of natural products as promising anti-liver cancer treatments and should contribute to its understanding.

A new compound, α-siamenoside I (α-SI), with a glucose unit selectively bound to the 6-hydroxyl group of the 24-O-β-glucosyl moiety of mogroside IIIE by α-1,6-glucosidic bond, was bio-created by two screened cyclodextrin glycosyltransferases with a maximum yield of 59.3%. Compared to mogroside IIIE, α-SI showed a significantly increased sweetness intensity (508 times sweeter than 5% sucrose), which is superior to siamenoside I (SI), the sweetest triterpenoid saponin isolated from Siraitia grosvenorii to date. Sensory evaluation showed that the taste quality of α-SI also was obviously better than mogroside IIIE. In addition to α-SI possessing a good stability similar to that of SI, it also did not cause a significant decrease in cell viability at a concentration of 200 μg/mL and had a negative influence on islets function at 1 μM. All of these preliminarily results pave the way for promoting α-SI as a potential low-calorie sweetener.

Background As the birth policy has been adjusted from one-child-one-couple to universal two-child-one-couple in China, there is an increasing number of women undergoing a second pregnancy after a previous cesarean section (CS). Undertaking an elective repeat CS (ERCS) has been taken for granted and has thus become a major contributor to the increasing CS rate in China. Promoting trial of labor after CS (TOLAC) can reduce the CS rate without compromising delivery outcomes. This study aimed to investigate Chinese obstetricians’ perspectives regarding TOLAC, and the factors associated with their decision-making regarding recommending TOLAC to pregnant women with a history of CS under the two-child policy. Methods A cross-sectional survey was carried out between May and July 2018. Binary logistic regression was used to determine the factors associated with the obstetricians’ intention to recommend TOLAC to pregnant women with a history of CS. The independent variables included sociodemographic factors and perceptions regarding TOLAC (selection criteria for TOLAC, basis underlying the selection criteria for TOLAC, and perceived challenges regarding promoting TOLAC). Results A total of 426 obstetricians were surveyed, with a response rate of ≥83%. The results showed that 31.0% of the obstetricians had no intention to recommend TOLAC to pregnant women with a history of CS. Their decisions were associated with the perceived lack of confidence regarding undergoing TOLAC among pregnant women with a history of CS and their families (odds ratio [OR] = 2.31; 95% CI: 1.38–1.38); obstetricians’ uncertainty about the safety of TOLAC for pregnant women with a history of CS (OR = 0.49; 95% CI: 0.27–0.96), and worries about medical lawsuits due to adverse delivery outcomes (OR = 0.14; 95% CI: 0.07–0.31). The main reported challenges regarding performing TOLAC were lack of clear guidelines for predicting or avoiding the risks associated with TOLAC (83.4%), obstetricians’ uncertainty about the safety of TOLAC for women with a history of CS (81.2%), pregnant women’s unwillingness to accept the risks associated with TOLAC (81.0%) or demand for ERCS (80.7%), and the perceived lack of confidence (77.5%) or understanding (69.7%) regarding undergoing TOLAC among pregnant women and their families. Conclusion A proportion of Chinese obstetricians did not intend to recommend TOLAC to pregnant women with a history of CS. This phenomenon was closely associated with obstetricians’ concerns about TOLAC safety and perceived attitudes of the pregnant women and their families regarding TOLAC. Effective measures are needed to help obstetricians predict and reduce the risks associated with TOLAC, clearly specify the indications for TOLAC, improve labor management, and popularize TOLAC in China. Additionally, public health education on TOLAC is necessary to improve the understanding of TOLAC among pregnant women with a history of CS and their families, and to improve their interactions with their obstetricians regarding shared decision making.

Background COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. Methods Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. Results The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. Conclusions Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.

Background Colorectal cancer (CRC) accounts for the highest fatality rate among all malignant tumors. Immunotherapy has shown great promise in management of many malignant tumors, necessitating the need to explore its role in CRC. Results Our analysis revealed a total of 71 differentially expressed IRGs, that were associated with prognosis of CRC patients. Ten IRGs (FABP4, IGKV1-33, IGKV2D-40, IGLV6-57, NGF, RETNLB, UCN, VIP, NGFR, and OXTR) showed high prognostic performance in predicting CRC outcomes, and were further associated with tumor burden, metastasis, tumor TNM stage, gender, age, and pathological stage. Interestingly, the IRG-based prognostic index (IRGPI) reflected infiltration of multiple immune cell types. Conclusions This model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor prognosis of CRC. Methods We performed a comprehensive analysis of expression profiles for immune-related genes (IRGs) and overall survival time in 437 CRC patients from the TCGA database. We employed computational algorithms and Cox regression analysis to estimate the relationship between differentially expressed IRGs and survival rates in CRC patients. Furthermore, we investigated the mechanisms of action of the IRGs involved in CRC, and established a novel prognostic index based on multivariate Cox models.

Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

Background Quantitative radiomic features of medical images could provide clinical significance in assisting decision making, but the existing feature selection and modelling methods are usually parameter dependent. We aim to develop and validate a generalized radiomic method applicable to a variety of clinical outcomes. Methods and materials A generalized methodology for radiomic feature selection and modelling ("GRFM" for short), including a two-step feature selection and logistic regression, was performed for correlating with clinical outcomes. The two-step feature selection consists of Pearson correlation analysis followed by sequential forward floating selection algorithm to identify robust feature subset. We also applied an adaptive searching strategy to systematically determine globally optimal parameters, rather than relying on preset parameters. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of three outcomes: lymph node metastasis of gastric cancer (GC), the 5-year survival status of high-grade osteosarcoma (HOS), and pathological grade of pancreatic neuroendocrine tumors (pNETs). Results The optimal Pearson thresholds were 0.85, 0.80 and 0.75, and the optimal feature numbers were 11, 14 and 8 in GC, HOS and pNETs respectively. AUC values of three predictive models combined with the corresponding parameters were 0.9017 vs. 0.9026, 0.7652 vs. 0.7113, and 0.8438 vs. 0.8212 at the training and validation cohorts, showing higher generality than other methods and better performance than other classifiers. Conclusion The proposed method was helpful in predicting different clinical outcomes, which has potential as a general and noninvasive prediction tool to guide clinical decision-making of various patients.

BackgroundThe COVID-19 pandemic has caused more than 462,417 deaths worldwide. A large number of patients with severe COVID-19 face death in hospital. Hospice care is truly a philosophy of care that delivers patient-centred care to the terminally ill and their families. Hospice care could provide many benefits for patients, families, and for hospice caregivers. The aim of this study is to investigate hospice care self-efficacy and identify its predictors among Chinese clinical medical staff in COVID-19 isolation wards of designated hospitals.MethodsA cross-sectional design was used. The Hospice Care Self-Efficacy, Self-Competence in Death Work Scale, Positive Aspects of Caregiving, and Simplified Coping Style Questionnaires were administered between February and April 2020. A total of 281 eligible medical staff responded to the questionnaires, with a response rate of ≥78.9%.ResultsThe mean score of hospice care self-efficacy was 47.04 (SD = 7.72). Self-efficacy was predicted by self-competence in death work (B = 0.433,P P = 0.027), positive coping (B = 0.219,P P = 0.023), occupational exposure while fighting against COVID-19 (B = -5.244,P = 0.004), holding respect for life and professional sentiment as motivation in fighting against COVID-19 (B = 2.372,P = 0.031), and grade of hospital employment (B = -1.426,P = 0.024). The variables co-explained 58.7% variation of hospice care self-efficacy.ConclusionClinical nurses and physicians fighting COVID-19 reported a moderate level of hospice care self-efficacy during this pandemic. Exploring the traditional Chinese philosophy of life to learn from its strengths and make up for its weaknesses and applying it to hospice care may provide a new framework for facing death and dying during the COVID-19 pandemic. Continuous hospice care education to improve self-competence in death work, taking effective measures to mobilize positive psychological resources, and providing safer practice environments to avoid occupational exposure are also essential for the improvement of the hospice care self-efficacy of clinical nurses and physicians. These measures help caregivers deal effectively with death and dying while fighting against the COVID-19 pandemic.

This work aims to study the variation, robustness, and feature redundancy of PET/MR radiomic features in the primary tumor of nasopharyngeal carcinoma (NPC). PET/MR scans of 21 NPC patients were used in this study. The primary tumor volumes were defined using PET, T2-weighted-MR (T2-MR), and diffusion-weighted MR (DW-MR) images. A random-dilation-erosion method was used to simulate 10 sets of tumor volumes for identifying features invariant with manual segmentation uncertainties. Feature robustness was evaluated against imaging modalities, pixel sizes, slice thickness, and grey-level bin sizes using intraclass correlation coefficient (ICC) and spearman correlation coefficient. Feature redundancy was analyzed using the hierarchical cluster analysis. Voxel size of 0.5 × 0.5 × 1.0 mm3 was found optimal for robust feature extraction from PET and MR. Normalized grey level of 64 and 128 was suggested for PET and MR, respectively. The features from wavelet-transformed images were less stable than those from the original images. The robustness analysis and volume correlation analysis identified 335 (62.04 %) PET features, 240 (44.44 %) T2-MR features, and 366 (67.78 %) DW-MR features. The cluster analysis grouped PET, T2-MR, and DW-MR features into 106, 83, and 133 representative features, respectively. The present study analyzed and identified robust features extracted from tumor volumes on PET/MR, which can provide guidance and promote standardization for PET/MR radiomic studies in NPC.

The past nine months witnessed COVID-19’s fast-spreading at the global level. Limited by medical resources shortage and uneven facilities distribution, online help-seeking becomes an essential approach to cope with public health emergencies for many ordinaries. This study explores the driving forces behind the retransmission of online help-seeking posts. We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion of help-seeking messages. A quantitative content analysis was conducted with a probability sample consisting of 727 posts. The results illustrate the importance of individual information completeness, high proximity, instrumental support seeking. This study also demonstrates slight inconformity with the severity principle but stresses the power of anger in help-seeking messages dissemination. As one of the first online help-seeking diffusion analyses in the COVID-19 period, our research provides a reference for constructing compelling and effective help-seeking posts during a particular period. It also reveals further possibilities for harnessing social media’s power to promote reciprocal and cooperative actions as a response to this deepening global concern.

Many factors are involved in the development of cancer pain, which is a serious complication of cancer and affects the quality of life of patients, Normally, drugs are used to relieve pain in clinic, but the effect is not satisfactory to patients. Therefore, it is necessary to explore the molecular basis of the pathogenesis of cancer pain and carry out targeted therapy. Fortunately, the important role of P2X purine receptors dependent on ATP ion channels in the development of cancer pain has been recognized. In the development of cancer, ATP concentration in the tumor microenvironment is high enough to activate P2X purine receptors, sensitive peripheral receptors, enhance sensory nerve fiber information transmission, sensitize the central nervous system, and induce or aggravate pain. Here, we outlined the role of P2X purine receptors in the development of cancer, and discussed the intrinsic correlation between P2X purine receptors and cancer pain. Moreover, we also explored the pharmacological properties of P2X antagonists or inhibitors to inhibit cancer pain, and hope to provide some value for the treatment of cancer pain in the future. In short, up-regulation of P2X expression can induce or aggravate cancer pain, while reducing P2X expression level can inhibit cancer pain. Therefore, P2X may be another potential pharmacological target for the treatment of cancer pain.

Background Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. Objective The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. Methods We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19–related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify “sick posts,” in which users report their own or other people’s symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. Results We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. Conclusions Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.

Interferon-induced transmembrane protein 3 (IFITM3) is associated with cancer development. Proto-oncogene c-myc can promote tumor proliferation. However, collections of IFITM3 and c-myc in hepatocellular carcinoma (HCC) and the potential role and mechanisms of IFITM3 in c-myc-mediated tumor proliferation remain unclear. In this study, we investigated a positive correlation between the expression of IFITM3 and c-myc in HCC. The down-regulation of IFITM3 significantly reduced c-myc expression and inhibited the proliferation of HCC in vitro and in vivo. In addition, upregulated c-myc expression restored the decrease in cell proliferation caused by the downregulation of IFITM3, while downregulation of c-myc reduced the proliferation of HCC enhanced by IFITM3. Mechanistically, IFITM3 regulates c-myc expression via the ERK1/2 signalling pathway. In conclusion, a novel path of IFITM3-ERK1/2-c-myc regulatory circuitry was identified, and its dysfunction may lead to HCC tumorigenesis.