Prognostic factors for squamous cervical carcinoma identified by competing-risks analysis: A study based on the SEER database

Cervical cancer has a high incidence of malignant tumors and a high mortality rate, with squamous cervical carcinoma (SCC) accounting for 80% of cases. A competing-risks model is recommended as being more feasible for evaluating the prognosis and guiding clinical practice in the future compared to Cox regression. Data originating from the Surveillance, epidemiology, and end results (SEER) database during 2004 to 2013 were analyzed. Univariate analysis with the cumulative incidence function was performed to assess the potential risk of each covariate. Significant covariates (P < .05) were extracted for inclusion in a Cox regression analysis and a competing-risks model that included a cause-specific (CS) hazard function model and a sub-distribution (SD) hazard function model. A total of 5591 SCC patients met the inclusion criteria. The three methods (Cox regression analysis, CS analysis, and SD analysis) showed that age, metastasis, American Joint Committee on Cancer stage, surgery, chemotherapy, radiation sequence with surgery, lymph node dissection, tumor size, and tumor grade were prognostic factors affecting survival in patients with SCC. In contrast, race and radiation status were prognostic factors affecting survival in the Cox regression and CS analysis, but the results were different in the SD analysis. Being separated, divorced, or widowed was an independent prognostic factor in the Cox regression analysis, but the results were different in the CS and SD analyses. A competing-risks model was used as a new statistical method to more accurately identify prognostic factors than conventional Cox regression analysis leading to bias in the results. This study found that the SD model may be better suited to estimate the clinical prognosis of a patient, and that the results of an SD model analysis were close to those of a CS analysis.     

Silybin suppresses ovarian cancer cell proliferation by inhibiting isocitrate dehydrogenase 1 activity

Metabolic reprogramming is a sign of malignant tumors, and targeting the metabolism of tumor cells has become a promising therapeutic approach. Here, we report that Silybin (a nontoxic flavonoid commonly used for liver protection) exhibits prominent anti‐tumor effects on human ovarian cancer cells. Treatment of an ovarian cancer cell line with Silybin interfered with glutamine metabolism and the tricarboxylic acid cycle. We applied the drug affinity responsive target stability approach to show that Silybin binds to isocitrate dehydrogenase 1 (IDH1). This combination leads to reduced phosphorylation of IDH1 and inhibits enzyme activity. IDH1 dysfunction significantly increases the ratio of NADP/NADPH in the cell, causing an increase in reactive oxygen species generation. Immunohistochemistry demonstrated that IDH1 was increased in ovarian cancer samples compared with normal para‐tumoral tissues. Xenograft murine experiments indicated that Silybin administered orally suppressed the growth of the tumor formed by ovarian cancer cells. In combination, our data strongly suggest that Silybin targets IDH1 in ovarian cancer cells and may be a novel treatment candidate.     

Fusobacterium nucleatum induces excess methyltransferase‐like 3‐mediated microRNA‐4717‐3p maturation to promote colorectal cancer cell proliferation

Fusobacterium nucleatum infection plays vital roles in colorectal cancer (CRC) progression. Overexpression of microRNA‐4717‐3p (miR‐4717) was reported to be upregulated in F. nucleatum positive CRC tissues, however, the underlying mechanism is unknown. In this study, we found that miR‐4717 promoted CRC cell proliferation in vitro and growth of CRC in vivo following F. nucleatum infection. MicroRNA‐4717 suppressed the expression of mitogen‐activated protein kinase kinase 4 (MAP2K4), a tumor suppressor, by directly targeting its 3′‐UTR. Furthermore, we confirmed that methyltransferase‐like 3 (METTL3)‐dependent m⁶A methylation could methylate primary (pri)‐miR‐4717, which further promoted the maturation of pri‐miR‐4717, and METTL3 positively regulated CRC cell proliferation through miR‐4717/MAP2K4 pathways. In conclusion, F. nucleatum‐induced miR‐4717 excessive maturation through METTL3‐dependent m⁶A modification promotes CRC cell proliferation, which provides a potential therapeutic target and diagnostic biomarker for CRC.     

Prediction of tumor recurrence by distinct immunoprofiles in liver transplant patients based on mass cytometry

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a marker of poor prognosis. However, the reliable biomarkers of post-LT HCC recurrence remain to be identified. In this study, serial peripheral blood samples from the LT recipients with and without HCC recurrence were collected at five time points. Single-cell mass cytomertry (CyTOF) was utilized for the in-depth analysis of peripheral blood monocellular cells (PBMCs). CyTOF analysis showed that at 3 weeks post-LT, the activated immune cell population was increased, while the fraction of immune cells with suppressive functions (myeloid-derived suppressive cells) was reduced. The post-LT immune composition in patients with LT for HCC was enormously different from that in patients with LT for causes other than HCC. Furthermore, at 3 weeks after LT, compared with patients without recurrence, the patients with HCC recurrences were high in two subsets of T cells: CD57⁺ HLA-DR⁺ CD8⁺ and CD28⁺γδ. The CD57⁺ HLA-DR⁺ CD8⁺ T cells presented high levels of perforin, granzyme B, and Ki-67 and displayed a highly cytotoxic and proliferative phenotype, while the CD28⁺γδ T cells had reduced levels of IFN-γ and, hence, were less activated compared to CD28^- cells. Based on these findings, we concluded that analyzing the PBMCs of LT recipients by CyTOF can predict the post-LT HCC recurrence. The distinct immune features can stratify patients with the risk of HCC recurrence at 3 weeks after LT, which will help clinician in further management plan and improve the prognosis of patients.     

Association between Branched-Chain Amino Acid Intake and Physical Function among Chinese Community-Dwelling Elderly Residents

This study aimed to evaluate the potential associations of dietary BCAAs (isoleucine, leucine, and valine) with physical function in the elderly Chinese population. A validated semiquantitative food frequency questionnaire and anthropometric and physical function measurements were used to collect data. We modeled trends in physical function indicators for BCAA quartiles using multivariate linear regression models. Among 4336 (43.97% men) participants aged 72.73 ± 5.48 years, a higher dietary intake of BCAAs was positively associated with increased handgrip strength (all p trends < 0.001), shorter times for 4-m fast walking (all p trends < 0.001) and repeated chair rises (all p trends < 0.001). No linear association was found between subtypes of amino acids and any physical functions (all p trends > 0.05). Individuals in the highest quartiles of BCAA intake had a reduced risk of developing low muscle strength, and the multiadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for women and men were 0.50 (0.38–0.65) and 0.67 (0.50–0.91), respectively. Similarly, higher BCAA consumption was associated with a lower risk of developing low physical performance (4-m walking speed: OR = 0.68 [0.50–0.93]; repeated chair rises: OR = 0.66 [0.54–0.81]). Higher dietary BCAA intake might be beneficial for physical function in the elderly population.     

The Combined Use of Medium- and Short-Chain Fatty Acids Improves the Pregnancy Outcomes of Sows by Enhancing Ovarian Steroidogenesis and Endometrial Receptivity

Fatty acids play important roles in maintaining ovarian steroidogenesis and endometrial receptivity. Porcine primary ovarian granulosa cells (PGCs) and endometrial epithelial cells (PEECs) were treated with or without medium- and short-chain fatty acids (MSFAs) for 24 h. The mRNA abundance of genes was detected by fluorescence quantitative PCR. The hormone levels in the PGCs supernatant and the rate of adhesion of porcine trophoblast cells (pTrs) to PEECs were measured. Sows were fed diets with or without MSFAs supplementation during early gestation. The fecal and vaginal microbiomes were identified using 16S sequencing. Reproductive performance was recorded at parturition. MSFAs increased the mRNA abundance of genes involved in steroidogenesis, luteinization in PGCs and endometrial receptivity in PEECs (p < 0.05). The estrogen level in the PGC supernatant and the rate of adhesion increased (p < 0.05). Dietary supplementation with MSFAs increased serum estrogen levels and the total number of live piglets per litter (p < 0.01). Moreover, MSFAs reduced the fecal Trueperella abundance and vaginal Escherichia-Shigella and Clostridium_sensu_stricto_1 abundance. These data revealed that MSFAs improved pregnancy outcomes in sows by enhancing ovarian steroidogenesis and endometrial receptivity while limiting the abundance of several intestinal and vaginal pathogens at early stages of pregnancy.     

Heat-Treated Meat Origin Tracing and Authenticity through a Practical Multiplex Polymerase Chain Reaction Approach

Meat adulteration have become a global issue, which has increasingly raised concerns due to not only economic losses and religious issues, but also public safety and its negative effects on human health. Using optimal primers for seven target species, a multiplex PCR method was developed for the molecular authentication of camel, cattle, dog, pig, chicken, sheep and duck in one tube reaction. Species-specific amplification from the premixed total DNA of seven species was corroborated by DNA sequencing. The limit of detection (LOD) is as low as 0.025 ng DNA for the simultaneous identification of seven species in both raw and heat-processed meat or target meat: as little as 0.1% (w/w) of the total meat weight. This method is strongly reproducible even while exposed to intensively heat-processed meat and meat mixtures, which renders it able to trace meat origins in real-world foodstuffs based on the authenticity assessment of commercial meat samples. Therefore, this method is a powerful tool for the inspection of meat adulterants and has broad application prospects.     

Research Status and Hotspots of Chronic Osteomyelitis: A Bibliometric and Visualized Analysis

ObjectiveThe treatment of chronic osteomyelitis (COM) is extremely challenging for physicians and patients. It is of great significance to explore the research status, development trend and future research hotspots in the field of COM to promote the development of this field. This study is aimed to explore the global research status of COM and predict its future research hotspots based on bibliometric and visualized analysis.MethodsWeb of Science core collection database was used to search the related literature of COM from 1994 to 2020. All data were imported into Microsoft Excel 2019 for collation. Additionally, the literature quality of countries, authors, journals, and institutions is evaluated. The VOS viewer software was used for conducting co‐analysis, co‐citation analysis, and keyword co‐occurrence analysis of literature to analyze the global status and predict the future hotspots of the COM field.ResultsA total of 726 articles were retrieved in this study. The number of global publications shows a trend of wave growth, but the increase is not significant. It is expected that the number of COM articles will remain at more than 50 per year in the next decade. The COM literature published in the United States (Publications = 160, H index = 37, average citations per item = 28.63) is of the highest quality. Girschick HJ (Publications = 16, H index = 14, average citations per item = 52.25) is the most contributed scholar in the field of COM. UNIV IOWA (Publications = 15, H index = 11, average citations per item = 57.27) and UNIV WURZBURG (Publications = 18, H index = 15, average citations per item = 47.5) are influential institutions in the field of COM. The results of co‐occurrence analysis show that the field of COM can be roughly divided into the following five modules: COM surgical research, COM basic research, COM diagnosis‐related research, chronic recurrent multifocal osteomyelitis (CRMO)‐related research, risk factors of COM. Risk factors of COM are the module with the highest concentration of hot words.ConclusionCOM‐related research will continue to develop further in the next decade. The diagnosis research and risk factors of COM are the most popular research modules in recent years. Some controversial or troubled issues including the efficacy of perforator flap and fascia flap covering soft tissue, searching exclusive detection methods for the diagnosis of COM and bisphosphonates and biological agents in the treatment of CRMO may lead to the development of the COM field.     

A retrospective assessment of the clinical efficacy of different internal fixation methods in the treatment of distal fibula fractures in the elderly

An ankle fracture is a fracture of the distal tibia or fibula that forms the ankle joint, usually associated with ligament and soft tissue injury, and is a common type of lower limb fracture and one of the most common types of fracture in the elderly. Although ankle fractures are one of the most common injuries seen by orthopedic trauma surgeons, there is no uniform protocol for the diagnosis and treatment of ankle fractures in the elderly, and there are many controversial indications for surgery. The aim of this study is to assess the clinical efficacy of different internal fixation methods in the treatment of distal fibular fractures in the elderly, in an effort to improve the rational selection and application of clinical acts. A retrospective analysis was performed on 68 cases of patients who suffered an ankle fracture and were treated with different internal fixation methods according to the fracture types and individual differences in distal fibula fractures. The postoperative therapeutic effect assessment was performed in terms of clinical examination, imaging evaluation, and AOFAS ankle-hind foot function scoring. There was no unhealed bone, ankle instability and loose/fractured internal fixation. Fracture healing time was 2.7 to 4.0 months (average 3.2 months). AOFAS score was 88.3 ± 6.2, of which, 34 excellent cases, 30 good cases, and 4 fair cases. Ankle activity dorsiflexion 6º~18º, average 15º; plantar flexion 26º~47º, average 37º. A good clinical efficacy could be achieved from the most appropriate individualized internal fixation for distal fibula fractures of elderly patients.