Differentiating treatment necrosis from tumor recurrence poses a diagnostic conundrum for many clinicians in neuro-oncology. To investigate the potential role of circulating tumor cells (CTCs) detection in differentiating tumor recurrence and treatment necrosis in brain gliomas, we retrospectively analyzed the data of 22 consecutive patients with tumor totally removed and new enhancing mass lesion(s) showed on MRI after initial radiotherapy. The 22 patients were finally classified into tumor recurrence group (n = 10) and treatment necrosis group (n = 12), according to evidence from the clinical course (n = 11) and histological confirmation (n = 11). All 22 patients received CTCs detection, and DSC-MRP and 11C-MET-PET were performed on 20 patients (90.9%) and 17patients (77.3%) respectively. The data of the diagnosis efficacy to differentiate the two lesions by CTC detection, MPR and PET were analyzed by ROC analysis. The mean CTCs counts were significantly higher in the tumor recurrence group (6.10 ± 3.28) compared to the treatment necrosis group (1.08 ± 2.54, p < 0.001). The ROC curve showed that an optimized cell count threshold of 2 had 100% sensitivity and 91.2% specificity with AUC = 0.933 to declare tumor recurrence. The diagnostic efficacy of CTC detection was superior to rCBV of DSC-MRP and rSUVmax in MET-PET. Furthermore, we observed that CTCs detection could have a potential role in predicting tumor recurrence in one patient. Our research results preliminarily showed the potential value of CTC detection in differentiating treatment necrosis from tumor recurrence in brain gliomas, and is worthy of further confirmation with large samples involved.
The development and progression of rheumatoid arthritis (RA) are complex and the pathogenesis of this disease is not fully understood. E2F transcription factor 2 (E2F2) affects the development and progression of many diseases. To identify the mechanisms underlying the role of E2F2 in RA, chromatin immunoprecipitation was performed followed by sequencing (ChIP-seq) using the E2F2 antibody. Gene Ontology (GO) analysis of differentially expressed genes (DEGs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of captured downstream target genes and Metascape analysis of 22 protein molecules partly elucidated the mechanism by which E2F2 affects the progression of RA. Results indicated that E2F2 affects the metabolism of RASFs and the development of ribosome synthesis as well as the stress response. Results indicated that E2F2 can affect multiple biological processes involving RASFs and indicate a unique possibility of targeting E2F2 in the treatment of RA.
E2F transcription factor 2 (E2F2) is a member of the E2F family of transcription factors. The classical view is that some E2Fs act as "activators" and others "inhibitors" of cell cycle gene expression. However, the so-called "activator" E2F2 is particularly enigmatic, with seemingly contradictory roles in the cell cycle, proliferation, apoptosis, inflammation, and cell migration and invasion. How can we rationalize the apparently opposing functions of E2F2 in different situations? This is difficult because different methods of studying E2F2 have yielded conflicting results, so extrapolating mechanisms from an observed endpoint is challenging. This review will attempt to summarize and clarify these issues. This review focuses on genetic studies that have helped elucidate the biological functions of E2F2 and that have enhanced our understanding of how E2F2 is integrated into pathways controlling the cell cycle, proliferation, apoptosis, inflammation, and cell migration and invasion. This review will also discuss the function of E2F2 in cancer and other diseases. This review provides a strong basis for further research on the biological function and clinical potential of E2F2.
Severe acute pancreatitis (SAP) is a common critical disease with a high mortality rate that involves a complex, rapid change in condition and multiple organ systems. Therefore, a multidisciplinary team (MDT), including staff from the emergency department, intensive care unit, pancreatic surgery, gastroenterology , and imaging, is necessary for the early diagnosis, evaluation, and treatment of patients with SAP. This involves managing the systemic inflammatory response and maintaining organ function in the early stage and managing systemic infection and treatment of peripancreatic complications in the middle-to-late stages. The MDT should be led by departments corresponding to the clinical characteristics of each stage, and those departments should be responsible for the coordination and implementation of treatment by other relevant departments. In the late stage, pancreatic surgery and gastroenterology are the main departments that should manage peripancreatic complications. In line with the principle of minimally invasive treatment, the timely and reasonable selection of endoscopic or minimally invasive surgical debridement can achieve good therapeutic outcomes. Open surgery is also an effective method for treating an intractable massive hemorrhage in the abdominal cavity or necrotic cavity, intractable abdominal compartment syndrome, visceral perforation, and fistulae.
As the COVID-19 epidemic is still ongoing, a more rapid detection of SARS-CoV-2 infection such as viral antigen-detection needs to be evaluated for early diagnosis of COVID-19 disease. Here, we report the dynamic changes of SARS-CoV-2 viral antigens in nasopharyngeal swabs of COVID-19 patients and its association with the viral nucleic acid clearance and clinical outcomes. Eighty-five COVID-19 patients were enrolled for detection of SARS-CoV-2 viral antigens, including 57 anti-SARS-CoV-2 antibody negative cases and 28 antibody positive cases. The viral antigen could be detected in 52.63% (30/57) patients with SARS-CoV-2 antibody negative at the early stage of SARS-CoV-2 infection, especially in the first 5 days after disease onset (p = 0.0018) and disappeared in about 8 days after disease onset. Viral antigens were highly detectable in patients with low Ct value (less than 30) of SARS-CoV-2 nucleic acid RT-PCT assay, suggesting the expression of viral antigen was associated with high viral load. Furthermore, positive antigen detection indicated disease progression, nine cases with positive antigen (9/30, 30.0%), in contrast to two cases (2/27, 7.40%) (p = 0.0444) with negative antigen, which progressed into severe disease. Thus, the viral antigens were persistent in early stages of infection when virus was in highly replicating status, and viral antigen detection promises to rapidly screen positive patients in the early stage of SARS-CoV-2 infection.
During the COVID-19 pandemic, frontline nurses have faced extraordinary personal and professional challenges. These challenges have had mental health consequences, and concerning reports of burnout have emerged globally. We conducted a cross-sectional survey at a designated COVID-19 hospital in Shanghai at the peak of the pandemic, i.e. about 2 months after the onset of the outbreak from February to April 2020. Findings revealed burnout in 6.85% of nurses. Of 336 respondents, 87 (25.89%) had a high level of emotional exhaustion, 61 (18.15%) had a high level of depersonalization, and 100 (29.76%) had a low level of personal accomplishment. Burnout can be prevented by offering more support from families and supervisors, paying attention to health monitoring and personal protection, and creating a rational human resource allocation and shift management system. Specific training on infection control and self-protection, mental health guidance, and stress coping techniques must be implemented. As the current health crisis ultimately abates, moving the focus from mental health issues to public health issues, more attention and support at the national and organizational levels are needed to reduce occupational discrimination, nurse autonomy and status need to be promoted, and public health emergency teams need to be created. A positive and fair working environment is essential to effective healthcare delivery.
Pancreatic cancer is known to have the poorest prognosis among digestive cancers. With the development of new chemotherapeutic agents and introduction of multidisciplinary therapy, however, the treatment outcomes for pancreatic cancer have dramatically improved over the past two decades. The keys to successful treatment will be accurate assessment of resectability [resectable (R), borderline resectable (BR) or unresectable (UR)] at the time of diagnosis and prompt adoption of an appropriate multidisciplinary treatment strategy. Prep-02/JSAP-05 trial which is an RCT of upfront surgery versus neoadjuvant chemotherapy using GEM and S-1 (GS) and subsequent surgery for R-PDAC in Japan indicated neoadjuvant chemotherapy had a longer overall survival (OS) than those undergoing upfront surgery (36.7M vs. 26.6M, p = 0.015). In a retrospective multicenter study in Japan reported that in BR-PDAC, median survival time (MST) in the pretreatment group was significantly better than that in the upfront surgery group (25.7 months vs. 19.0 months, p = 0.015) according to a propensity score matching analysis. Another retrospective multicenter study with UR-LA PDAC in Japan reported that conversion surgery was more beneficial for patients with more than 8 months of preoperative therapy than those with less than 8 months of that therapy. Various clinical trials on pancreatic cancer are ongoing, and the results of trials on chemotherapeutic regimens and multidisciplinary treatments will be of further interest.
Vasa previa (VP) is a rare and life-threatening condition for the fetus. It is associated with increased perinatal mortality rates. The current study sought to retrospectively analyze the perinatal outcomes of VP in singleton and multiple pregnancies between January 1, 2013 and December 31, 2019 at a tertiary hospital in west China. One hundred and fifty-seven cases of VP were identified, including 131 singletons, 23 twins and 3 triplets. VP in 20 cases was diagnosed at delivery. There were 183 live births. Neonatal mortality was significantly higher in cases with no prenatal diagnosis (9.7% vs. 1.3%, p = 0.035). There was a significantly higher rate of NICU admission, premature infant and neonatal pneumonia in cases with prenatal diagnosis (p < 0.05). Among twin pregnancies with VP as a prenatal diagnosis, there were significantly earlier gestational age at admission (31.1 vs. 34.1 weeks, p = 0.000) and delivery age (33.4 vs. 35.3 weeks, p = 0.000) than those among singleton pregnancies. The neonatal mortality in twins with prenatal diagnosis was significantly higher than that in singletons (0% vs. 6.9%, p = 0.037). Early hospitalization of VP in the third trimester may be reasonable. The data suggest that the timing of elective delivery at 34-36 weeks in singletons and 32-34 weeks in twins may be suitable. It should be emphasized to make corresponding optimal delivery time according to individual differences for the women, especially in twin pregnancy.
Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has affected tens of millions of people globally since it was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. There is an urgent need for safe and effective preventive vaccines to curb this pandemic. A growing amount of related research has been published. This study aimed to provide the current status of COVID-19 vaccine using bibliometric analysis. We searched Embase.com and MEDLINE comprehensively and included articles, articles in press, reviews, short surveys, conference abstracts and conference papers about COVID-19 vaccine. VOSviewer1.6.11 (Leiden University, Leiden, Netherlands) was applied to perform the bibliometric analysis of these papers. A total of 1,312 papers were finally included. The BMJ has been the most popular journal in this field. The United States maintained a top position worldwide and has provided a pivotal influence, followed by China, India and United Kingdom. Among all the institutions, Harvard University was regarded as a leader for research collaboration. We analyzed the keywords and identified seven COVID-19 vaccine research hotspot clusters. COVID-19 vaccine research hotspots focus on clinical trials on vaccine safety and efficacy, research on vaccine immunology and immunoinformatics, and vaccine hesitancy. Our analysis results demonstrated that cooperation between countries, institutions, and authors were insufficient. The results suggested that clinical trials on vaccine safety, efficacy, immunology, immunoinformatics, production and delivery are research hotspots. Furthermore, we can predict that there will be a lot of research focusing on vaccine adverse reactions.
Despite strict control measures implemented worldwide, the COVID-19 pandemic continues to rage. Several drugs, including lopinavir/ritonavir, hydroxychloroquine, dexamethasone, and remdesivir, have been evaluated for the treatment of COVID-19 during the past year. While most of the drugs failed to display efficacy in treating COVID-19, scientists have encouraged herd immunity to control the pandemic. Immunity generated after natural infection with SARS-CoV-2 is precarious, as indicated by real-world evidence in the form of epidemiological data from Manaus, Brazil. Vaccines using different platforms are therefore the most promising approach to help us return to normality. Although several vaccines have been authorized for emergency use, there are still many concerns regarding their accessibility, the vaccination rate, and most importantly, their efficacy in preventing infection with emerging virus variants. Continued virus surveillance and rapid redesign of new vaccines to counter new variants are crucial to fighting COVID-19. Rapid production and extensive vaccination are also essential to preventing the emergence of new variants. Nevertheless, antivirals including monoclonal antibodies and oral medicines need to be developed in light of uncertainties with regard to vaccination. In the battle between humans and SARS-CoV-2, the speed with which we fight the virus, and especially its emerging variants, is the key to winning.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and cirrhosis is a risk factor for HCC. Resection is indicated for those unilobar tumors without vascular invasion and metastases in the liver and preserved liver function. Small HCC (< 2 cm) without microvascular invasion is associated with a 5-year recurrence rate as high as 50% to 60%, whereas liver transplantation is indicated for those within the Milan criteria (solitary tumor ≤ 5 cm or two or three nodules ≤ 3 cm) who have decompensated cirrhosis. The 1-, 3-, and 5-year survival rates of living donor liver transplantation for HCC are 85%, 75%, and 70%, respectively. This review summarizes the scientific evidence supporting the clinical practice recommendations for patients with HCC, and it discusses surgical treatment of HCC.
Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.
Hepatocellular carcinoma (HCC) remains a major public health problem. MCM4, a constitutive member of the minichromosomal maintenance protein family, has been reported to play a vital role in cancer malignancy behavior. However, the function of MCM4 in HCC remains largely unknown. The present study explored the specific role of MCM4 in HCC. The data from public datasets including TCGA and GTEx showed that MCM4 was overexpressed in HCC and significantly associated with poor prognosis. Immunohistochemistry results from 102 HCC patients suggested that high-level expression of MCM4 was correlated with tumor size. Then a series of in vivo and in vitro experiments were performed to investigate the function of MCM4 in HCC tumor cells. MCM4 silencing suppressed the cell proliferation and sphere formation of hepatoma cells. Moreover, silencing MCM4 significantly decreased the growth of tumors in a xenograft tumor model. In conclusion, the results of the present study indicated that MCM4 was a potential prognostic predictor associated with poor outcomes of HCC patients and even a therapeutic target for HCC.
Alcoholism is a global socially significant problem and still remains one of the leading causes of disability and premature death. One of the main signs of the disease is the loss of cognitive control over the amount of alcohol consumed. Among the mechanisms of the development of this pathology, changes in neuroimmune mechanisms occurring in the brain during prolonged alcohol consumption and its withdrawal have recently become the focus of numerous studies. Ethanol consumption leads to the activation of neuroimmune signaling in the central nervous system through many subtypes of Toll-like receptors (TLRs), as well as release of their endogenous agonists (high-mobility group protein B1 (HMGB1), S100 protein, heat shock proteins (HSPs), and extracellular matrix degradation proteins). TLR activation triggers intracellular molecular cascades of reactions leading to increased expression of genes of the innate immune system, particularly, proinflammatory cytokines, causing further development of a persistent neuroinflammatory process in the central nervous system. This leads to death of neurons and neuroglial cells in various brain structures, primarily in those associated with the development of a pathological craving for alcohol. In addition, there is evidence that some subtypes of TLRs (TLR3, TLR4) are able to form heterodimers with neuropeptide receptors, thereby possibly playing other roles in the central nervous system, in addition to participating in the activation of the innate immune system.