Empathy in undergraduate medical students: a multi-center cross-sectional study in China.

BACKGROUND: Fostering empathy has been continuously emphasized in the global medical education. Empathy is crucial to enhance patient-physician relationships, and is associated with medical students' academic and clinical performance. However, empathy level of medical students in China and related influencing factors are not clear. METHODS: This was a cross-sectional study among medical students in 11 universities. We used the Jefferson Scale of Empathy Student-version of Chinese version to measure empathy level of medical students. Factors associated with empathy were identified by the univariate and multivariate logistic regression analyses. Based on the variables identified above, the nomogram was established to predict high empathy probability of medical students. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate the discrimination, calibration and educational utility of the model. RESULTS: We received 10,901 samples, but a total of 10,576 samples could be used for further analysis (effective response rate of 97.02%). The mean empathy score of undergraduate medical students was 67.38 (standard deviation = 9.39). Six variables including gender, university category, only child or not, self-perception doctor-patient relationship in hospitals, interest of medicine, Kolb learning style showed statistical significance with empathy of medical students (P < 0.05). Then, the nomogram was established based on six variables. The validation suggested the nomogram model was well calibrated and had good utility in education, as well as area under the curve of model prediction was 0.65. CONCLUSIONS: We identify factors influencing empathy of undergraduate medical students. Moreover, increasing manifest and hidden curriculums on cultivating empathy of medical students may be needed among medical universities or schools in China.

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP and dual luciferase reporter assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

Effect of tobacco usage on surgical site wound problems after primary total hip and total knee arthroplasty: A meta-analysis.

The meta-analysis aims to assess and compare the effect of tobacco usage on surgical site wound problems (SSWPs) after primary total hip and total knee arthroplasty (PTH&TKA). Using dichotomous random- or fixed-effects models, the outcomes of this meta-analysis were examined, and the odds ratio (OR) with 95% confidence intervals (CIs) was computed. Fifteen studies from 2001 to 2023 were enrolled for the present meta-analysis including 560 819 personals with PTH&TKA. Smokers had significantly higher SSWPs (OR, 1.53; 95% CI, 1.21-1.94, p < 0.001) compared with non-smokers in personals with PTH&TKA. Current smokers had significantly higher SSWPs (OR, 1.59; 95% CI, 1.40-1.80, p < 0.001) compared with non-smokers in personals with PTH&TKA. Current smokers had significantly higher SSWPs (OR, 1.42; 95% CI, 1.19-1.70, p < 0.001) compared with former smokers in personals with PTH&TKA. However, former smokers and non-smokers had no significant difference in SSWPs (OR, 1.11; 95% CI, 0.95-1.30, p = 19) in personals with PTH&TKA. The examined data revealed that in personals with PTH&TKA smokers had significantly higher SSWPs compared with non-smokers, and current smokers had significantly higher SSWPs compared with non-smokers and former smokers; however, former smokers and non-smokers had no significant difference in SSWPs. Yet, attention should be implemented while relating to its values since some of the comparisons were made using a low number of selected studies.

Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.

Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the oncogenesis and progression of tumors, pyroptosis is crucial, and complex withal. Currently, pyroptosis is the focus topic in the research field of oncology, but there is no single bibliometric analysis systematically studying 'pyroptosis and cancer'. Our study aimed to visualize the research status of pyroptosis in oncology and excavate the hotspots and prospects in this field. Furthermore, in consideration of the professional direction of researchers, we particularly emphasized articles on pyroptosis in gynecology and formed a mini systematic review. This bibliometric work integrated and analyzed all articles from ISI Web of Science: Science Citation Index Expanded (SCI-Expanded) (dated April 25th, 2022), based on quantitative and visual mapping approaches. Systematically reviewing articles on pyroptosis in gynecology helped us complement our analysis of research advancements in this field. Including 634 articles, our study found that the number of articles on pyroptosis in cancer increased exponentially in recent years. These publications came from 45 countries and regions headed by China and the US mainly aiming at the mechanism of pyroptosis in cell biology and biochemistry molecular biology, as well as the role of pyroptosis in the development and therapeutic application of various cancers. The top 20 most cited studies on this topic mostly came from the US, followed by China and England, and half of the articles cited more than 100 times in total were published in Nature. Moreover, as for gynecologic cancer, in vitro and bioinformatics analysis were the main methodology conducting to explore roles of pyroptosis-related genes (PRGs) and formation of inflammasomes in cancer progression and prognosis. Pyroptosis has evolved into a burgeoning research field in oncology. The cellular and molecular pathway mechanism of pyroptosis, as well as the effect of pyroptosis in oncogenesis, progression, and treatment have been the hot topic of the current study and provided us the future direction as the potential opportunities and challenges. We advocate more active cooperation to improve therapeutic strategies for cancer.

Identification of Bone Metastatic and Prognostic Alternative Splicing Signatures in Prostate Adenocarcinoma.

As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Distant metastasis often occurs in advanced PRAD and most patients are dying from it. However, the mechanism of PRAD progression and metastasis is still unclear. It's widely reported that more than 94% of genes are selectively splicing in humans and many isoforms are particularly related with cancer progression and metastasis. Spliceosome mutations occur in a mutually exclusive manner in breast cancer, and different components of spliceosomes are targets of somatic mutations in different types of breast cancer. Existing evidence strongly supports the key role of alternative splicing in breast cancer biology, and innovative tools are being developed to use splicing events for diagnostic and therapeutic purposes. In order to identify if the PRAD metastasis is associated with alternative splicing events (ASEs), the RNA sequencing data and ASEs data of 500 PRAD patients were retrieved from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. By Lasso regression, five genes were screened to construct the prediction model, with a good reliability by ROC curve. Additionally, results in both univariate and multivariate Cox regression analysis confirmed the well prognosis efficacy of the prediction model (both P < 0.001). Moreover, a potential splicing regulatory network was established and after multiple-database validation, we supposed that the signaling axis of HSPB1 up-regulating the PIP5K1C - 46,721 - AT (P < 0.001) might mediate the tumorigenesis, progression and metastasis of PRAD via the key members of Alzheimer's disease pathway (SRC, EGFR, MAPT, APP and PRKCA) (P < 0.001).

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP, dual luciferase reporter, and mRNA stability assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

A multi-center cross-sectional study on identification of influencing factors of medical students' emotional engagement in China.

BACKGROUND: Studies exploring influencing factors of emotional engagement among medical students are scarce. Thus, we aimed to identify influencing factors of medical students' emotional engagement. METHODS: We carried out a multi-center cross-sectional study among 10,901 medical students from 11 universities in China. The Chinese version of Utrecht Work Engagement Scale-Student version (UWES-S) was used to evaluate emotional engagement level of medical students. The predictors related to engagement level were determined by the logistic regression analysis. Furthermore, we constructed a nomogram to predict emotional engagement level of medical students. RESULTS: A total of 10,576 sample were included in this study. The mean emotional engagement score was 74.61(± 16.21). In the multivariate logistic regression model, we found that males showed higher engagement level compared with females [odds ratio (OR) (95% confidence interval (CI)): 1.263 (1.147, 1.392), P < 0.001]. Medical students from the second batches of medical universities had higher engagement level and from "Project 985" universities had lower engagement level compared with 211 project universities [OR (95%CI): 1.376 (1.093, 1.733), P = 0.007; OR (95%CI): 0.682 (0.535, 0.868), P = 0.002]. Medical students in grade 4 and grade 2 presented lower engagement level compared with in grade 1 [OR (95%CI): 0.860 (0.752, 0.983), P = 0.027; OR (95%CI): 0.861 (0.757, 0.980), P = 0.023]. Medical students lived in provincial capital cities had higher engagement level compared with in country [OR (95%CI): 1.176 (1.022, 1.354), P = 0.024]. Compared with eight-year emotional duration, medical students in other emotional duration (three-year and four-year) had lower engagement level [OR (95%CI): 0.762 (0.628, 0.924), P = 0.006]. Medical students' engagement level increased with increases of grade point average and interest in studying medicine. Medical students learned by converging style showed lower engagement level [OR (95%CI): 0.827 (0.722, 0.946), P = 0.006] compared with accommodating style. The model showed good discriminative ability (area under curve = 0.778), calibrating ability and clinical utility. CONCLUSIONS: We identified influencing factors of medical students' emotional engagement and developed a nomogram to predict medical students' emotional engagement level, providing reference and convenience for educators to assess and improve emotional engagement level of medical students. It is crucial for educators to pay more attention to emotional engagement of medical students and adopt effective strategies to improve their engagement level.

Risk factors for postoperative surgical site wound problems after metastatic and primary spine tumour surgery: A meta-analysis.

A meta-analysis study was conducted to assess the risk factors (RFs) for postoperative surgical site wound problems (POSSWPs) after metastatic and primary spine tumour surgery (STS). A comprehensive literature examination until February 2023 was implemented, and 1786 linked studies were appraised. The 18 picked studies contained 18 580 subjects with surgery in the studies' baseline with and without different RFs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of RFs for POSSWPs after metastatic and primary STS using the dichotomous and continuous styles and a fixed or random model. Subjects with surgical instrumentation in their surgery had a significantly higher rate of POSSWPs in STS (OR, 2.28; 95% CI, 1.49-3.49, P < 0.001) compared with those without surgical instrumentation. Subjects with preoperative chemotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.81; 95% CI, 1.09-3.00, P = 0.02) compared with those without preoperative chemotherapy. Subjects with preoperative radiotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.93; 95% CI, 1.12-3.34, P = 0.02) compared with those without preoperative radiotherapy. Subjects with corticosteroid intake had a significantly higher rate of POSSWPs in STS (OR, 2.89; 95% CI, 1.73-4.82, P < 0.001) compared with those without corticosteroid intake. No significant difference was found between males and females in the rate of POSSWPs in STS (OR, 0.95; 95% CI, 0.66-1.37, P = 0.78). Surgical instrumentation, preoperative chemotherapy, preoperative radiotherapy and corticosteroid are RFs for the higher rate of POSSWPs in STS; however, gender was not shown to be a risk factor. Though precautions should be taken when commerce with the consequences since some of the studies picked for this meta-analysis had low sample sizes.

The Identification of Prognostic and Metastatic Alternative Splicing in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is a type of highly invasive cancer originated from melanocytes. It is reported that aberrant alternative splicing (AS) plays an important role in the neoplasia and metastasis of many types of cancer. Therefore, we investigated whether ASEs of pre-RNA have such an influence on the prognosis of SKCM and the related mechanism of ASEs in SKCM. The RNA-seq data and ASEs data for SKCM patients were obtained from the TCGA and TCGASpliceSeq database. The univariate Cox regression revealed 1265 overall survival-related splicing events (OS-SEs). Screened by Lasso regression, 4 OS-SEs were identified and used to construct an effective prediction model (AUC: .904), whose risk score was proved to be an independent prognostic factor. Furthermore, Kruskal-Wallis test and Mann-Whitney-Wilcoxon test showed that an aberrant splicing type of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) regulated by CDC-like kinase 1 (CLK1) was associated with the metastasis and stage of SKCM. Besides, the overlapped signal pathway for AIMP2 was galactose metabolism identified by the co-expression analysis. External database validation also confirmed that AIMP2, CLK1, and the galactose metabolism were associated with the metastasis and stage of SKCM patients. ChIP-seq and ATAC-seq methods further confirmed the transcription regulation of CLK1, AIMP2, and other key genes, whose cellular expression was detected by Single Cell Sequencing. In conclusion, we proposed that CLK1-regulated AIMP2-78704-ES might play a critical role in the tumorigenesis and metastasis of SKCM via galactose metabolism. Besides, we established an effective model with MTMR14-63114-ES, URI1-48867-ES, BATF2-16724-AP, and MED22-88025-AP to predict the metastasis and prognosis of SKCM patients.

Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.

BACKGROUND: Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells. METHODS: RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data. RESULTS: A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P < 0.001, R = 0.829) and hematopoietic cell lineage pathway (P < 0.001, R = 0.375). The transcriptional regulatory pattern between PAX5 and LTB was validated by ChIP sequencing data. CONCLUSIONS: We hypothesized that down-regulated LTB (immune gene) modulated by PAX5 (TF) in STSs may have the capability of inducing cancer cell metastasis in patients with STS.

Downregulation of long non-coding RNA UCA1 represses tumorigenesis and metastasis of osteosarcoma via miR-513b-5p/E2F5 axis.

Long non-coding RNAs have the regulatory roles in different kinds of human cancers. The key point of this study was to research the functional mechanisms of urothelial carcinoma associated 1 (UCA1) in the development of osteosarcoma. Quantitative real-time PCR was adopted for the expression detection of UCA1, microRNA-513b-5p (miR-513b-5p) and E2F transcription factor 5 (E2F5). The target relation was verified via dual-luciferase reporter assay and RNA pull-down assay. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Transwell assay was applied to assess cell migration and invasion. Western blot was performed for protein examination. Xenograft experiment was used to explore the effect of UCA1 on osteosarcoma in vivo. UCA1 expression was enhanced while miR-513b-5p was refrained in osteosarcoma tissues and cells. MiR-513b-5p was a target of UCA1. Inhibition of UCA1 or overexpression of miR-513b-5p suppressed osteosarcoma cell proliferation, migration and invasion. E2F5 was identified as a downstream gene of miR-513b-5p. MiR-513b-5p inhibitor or E2F5 overexpression rescued the progression inhibition of osteosarcoma by UCA1 knockdown, and UCA1 regulated E2F5 and Cyclin E expression by targeting miR-513b-5p. Downregulation of UCA1 restrained the tumorigenesis of osteosarcoma in vivo through the miR-513b-5p/E2F5 axis. Collectively, knockdown of UCA1 inhibited tumorigenesis and metastasis of osteosarcoma via regulating the miR-513b-5p/E2F5 axis. UCA1 might be a biological indicator in the progression and treatment of osteosarcoma.

Prognostic Factors for Survival in Patients with Malignant Giant Cell Tumor of Bone: A Risk Nomogram Analysis Based on the Population.

BACKGROUND Malignant giant cell tumor of bone (MGCTB) is a rare histological type of malignant tumor that has a high tendency for local relapse and distant metastasis and ultimately leads to a poor prognosis. The purpose of this study was to describe the epidemiological features, identify the prognostic factors, and construct nomograms for patients with MGCTB. MATERIAL AND METHODS Patients with MGCTB that was histologically diagnosed between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. Survival analysis, Lasso regression, and random forests were used to identify the prognostic variables and establish the nomograms for patients with MGCTB, while an external cohort of 37 patients from our own institution and an external cohort of 163 patients from the SEER database in 2016 were used to validate the generalization performance of the nomograms. RESULTS In total, univariate and multivariable analysis indicated that age, International Classification of Diseases for Oncology, historical stage, primary site, surgery information, radiotherapy, and chemotherapy were independent prognostic variables for overall survival or cause-specific survival. Nomograms based on the multivariable models were built to predict survival, and we achieved a higher C-index in subsequent multidimensional validation. CONCLUSIONS Age, historical stage, and chemotherapy were independent prognostic variables for overall survival and cause-specific survival of MGCTB patients, and radiotherapy and primary site were independent prognostic variables for overall survival. Nomograms based on significant clinicopathological features and clinical experience can be effective in predicting the probability of survival for MGCTB patients.

Collagen Type III Alpha 1 chain regulated by GATA-Binding Protein 6 affects Type II IFN response and propanoate metabolism in the recurrence of lower grade glioma.

Some studies suggested the prognosis value of immune gene in lower grade glioma (LGG). Recurrence in LGG is a tough clinical problem for many LGG patients. Therefore, prognosis biomarker is required. Multivariate prognosis Cox model was constructed and then calculated the risk score. And differential expressed transcription factors (TFs) and differential expressed immune genes (DEIGs) were co-analysed. Besides, significant immune cells/pathways were identified by single sample gene set enrichment analysis (ssGSEA). Moreover, gene set variation analysis (GSVA) and univariate Cox regression were applied to filter prognostic signalling pathways. Additionally, significant DEIG and immune cells/pathways, and significant DEIG and pathways were co-analysed. Further, differential enriched pathways were identified by GSEA. In sum, a scientific hypothesis for recurrence LGG including TF, immune gene and immune cell/pathway was established. In our study, a total of 536 primary LGG samples, 2,498 immune genes and 318 TFs were acquired. Based on edgeR method, 2,164 DEGs, 2,498 DEIGs and 31 differentials expressed TFs were identified. A total of 106 DEIGs were integrated into multivariate prognostic model. Additionally, the AUC of the ROC curve was 0.860, and P value of Kaplan-Meier curve < 0.001. GATA6 (TF) and COL3A1 (DEIG) were selected (R = 0.900, P < 0.001, positive) as significant TF-immune gene links. Type II IFN response (P < 0.001) was the significant immune pathway. Propanoate metabolism (P < 0.001) was the significant KEGG pathway. We proposed that COL3A1 was positively regulated by GATA6, and by effecting type II IFN response and propanoate metabolism, COL3A1 involved in LGG recurrence.

Electroacupuncture improves neurogenic bladder dysfunction through activation of NGF/TrkA signaling in a rat model.

OBJECTIVE: To observe the effect of electroacupuncture on the morphological change of the bladder tissue and the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT in the bladder tissue of rats with neurogenic bladder after suprasacral spinal cord injury and to preliminarily explore its partial mechanism of action. METHODS: Eighty female Sprague-Dawley rats were randomly divided into blank group, model group, electroacupuncture group, model/siNGF group, and electroacupuncture/siNGF group according to random number table method with 16 rats in each group. Eighty Neurogenic bladder models after suprasacral spinal cord injury were established by adopting a modified spinal cord transection method. Electroacupuncture intervention was conducted on the 19th day after modeling. The bladder function was detected by bladder weight, urine output, serum BUN, and urine protein. After treatment for 7 consecutive days, the rats were killed and the bladder tissues were removed rapidly for microscopic observation of morphological change after hematoxylin and eosin stain and for determination of the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT via Western blot analysis. The transcription of NGF was measured by reverse-transcription polymerase chain reaction. RESULTS: After treatment, compared with the blank group, the bladder weight of model and electroacupuncture groups were significantly increased (P < 0.05). Compared with the model group, the bladder weight of the electroacupuncture group was decreased (P > 0.05). Compared with the blank group, the urine output of the model group was increased ( P < 0.05). Compared with the blank group, the urine output of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the serum BUN of the model group was increased ( P < 0.05). Compared with the blank group, the serum BUN of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the urine protein of the model group was increased ( P < 0.05). Compared with the blank group, the urine protein of the electroacupuncture group was increased ( P > 0.05). The expression of NGF, p-TrkA, and p-AKT in the model and electroacupuncture groups was obviously higher than that in the blank group ( P < 0.05). The expression of NGF, p-TrkA, and p-AKT in the electroacupuncture group was higher than that in the model group. The expression of TrkA and AKT were unchanged in blank, model, and electroacupuncture groups ( P > 0.05). After tail vein injection with siNGF lentivirus, the expression of NGF in the model/siNGF group and electroacupuncture/siNGF group was significantly decreased ( P < 0.05). And the protein level of p-AKT and p-TrkA was significantly lower than that of the model and electroacupuncture groups ( P < 0.05). CONCLUSION: Sacral electroacupuncture therapy can improve the expression of both NGF/TrkA signaling and AKT signaling in the local nerve of the damaged spinal cord, inhibit apoptosis of the damaged spinal cord, protect nerve cells, and promote the recovery of the damaged nerve. At the same time, electroacupuncture can promote the coordination of micturition reflex and improve neurogenic bladder function after the spinal cord injury.

Nomograms for predicting the overall and cause-specific survival in patients with malignant peripheral nerve sheath tumor: a population-based study.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is extremely rare in soft tissue sarcoma, with a high rate of recurrence and metastasis. Due to its rarity, the epidemiological features and prognostic factors are still uncertain. Moreover, nomograms for patients with MPNST have not been constructed and validated until now. PATIENTS AND METHODS: Patients diagnosed with MPNST between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning and Lasso regression were used to identify the prognostic factors for overall survival (OS) and cause-specific survival (CSS). Significant prognostic factors were integrated to construct nomograms and then the nomograms were validated externally with a separate cohort from our own institution. RESULTS: A total of 689 patients were included in the training set and 42 patients in the validation set. Multivariate analysis suggested that age, histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The nomograms based on multivariate models were developed and validated for predicting 3- and 5-year OS and CSS, with a C-index of 0.686 and 0.707, respectively. In the external validation set, the C-index was 0.700 for OS and 0.722 for CSS. CONCLUSION: ICD-O-3 histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The constructed nomograms could provide individual prediction for MPNST patients and assist oncologists in making accurate survival evaluation.

Evaluating and Predicting the Probability of Death in Patients with Non-Metastatic Osteosarcoma: A Population-Based Study.

BACKGROUND Osteosarcoma is one of the most common bone tumors, with strong local aggressiveness and early metastasis. The aim of this study was to describe the epidemiological data and evaluate the prognostic factors for overall survival (OS) and cause-specific survival (CSS) in patients with non-metastatic osteosarcoma. MATERIAL AND METHODS Patients histologically diagnosed with non-metastatic osteosarcoma between 2005 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning, and Lasso regression were used to identify the prognostic factors for OS and CSS, and the accuracy of the nomograms was tested and compared with the American Joint Committee on Cancer (AJCC) staging systems. RESULTS The entire cohort comprised 1000 patients with non-metastatic osteosarcoma. The multivariable analysis suggested that age, tumor size, grade, and American Joint Committee on Cancer (AJCC) T staging were independent prognostic factors for OS and CSS. Additionally, the nomograms based on these results could better predict probability of OS (Internal validation C-index, 0.7095) and CSS (0.7100) compared with the sixth (OS: 0.613; CSS: 0.628) and seventh edition AJCC staging systems (0.602, 0.613). CONCLUSIONS Relatively young age and low histopathological grade were favorable factors for both OS and CSS. Nomograms based on multivariable models worked well in predicting the probability of death for patients with non-metastatic osteosarcoma.

MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis.

Background: Rheumatoid Diseases (RDs) are a group of systemic auto-immune diseases that are characterized by chronic synovitis, and fibroblast-like synoviocytes (FLSs) play an important role in the occurrence and progression of synovitis. Our study is the first to adopt bibliometric analysis to identify the global scientific production and visualize its current distribution in the 21st century, providing insights for future research through the analysis of themes and keywords. Methods: We obtained scientific publications from the core collection of the Web of Science (WoS) database, and the bibliometric analysis and visualization were conducted by Biblioshiny software based on R-bibliometrix. Results: From 2000 to 2022, a total of 3,391 publications were reviewed. China is the most prolific country (n = 2601), and the USA is the most cited country (cited 7225 times). The Center of Experimental Rheumatology at University Hospital Zürich supported the maximum number of articles (n = 40). Steffen Gay published 85 records with 6263 total citations, perhaps making him the most impactful researcher. Arthritis and Rheumatism, Annals of Rheumatic Diseases, and Rheumatology are the top three journals. Conclusion: The current study revealed that rheumatoid disease (RD)-related fibroblast studies are growing. Based on the bibliometric analysis, we summarized three important topics: activation of different subsets of fibroblasts; regulation of fibroblast function; and in vitro validation of existing discoveries. They are all valuable directions, which provide reference and guidance for researchers and clinicians engaged in the research of RDs and fibroblasts.

The Recurrent-Specific Regulation Network of Prognostic Stemness-Related Signatures in Low-Grade Glioma.

Gliomas including astrocytomas, oligodendrogliomas, mixed oligoastrocytic, and mixed glioneuronal tumors are an important group of brain tumors. Based on the 2016 WHO classification for tumors in the central nervous system, gliomas were classified into four grades, from I to IV, and brain lower grade glioma (LGG) consists of grade II and grade III. Patients with LGG may undergo recurrence, which makes clinical treatment tough. Stem cell-like features of cancer cells play a key role in tumor's biological behaviors, including tumorigenesis, development, and clinical prognosis. In this article, we quantified the stemness feature of cancer cells using the mRNA stemness index (mRNAsi) and identified stemness-related key genes based on correlation with mRNAsi. Besides, hallmark gene sets and translate factors (TFs) which were highly related to stemness-related key genes were identified. Therefore, a recurrency-specific network was constructed and a potential regulation pathway was identified. Several online databases, assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell sequencing analysis, and immunohistochemistry were utilized to validate the scientific hypothesis. Finally, we proposed that aurora kinase A (AURKA), positively regulated by Non-SMC Condensin I Complex Subunit G (NCAPG), promoted E2F target pathway in LGG, which played an important role in LGG recurrence.

Construction of Metastasis-Specific Regulation Network in Ovarian Cancer Based on Prognostic Stemness-Related Signatures.

WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.