Objective:To explore the incidence, clinical characteristics, imaging features, clinical outcome and prognosis of indeterminate pulmonary nodules (IPN) in patients with osteosarcoma.Methods:A total of 69 patients of osteosarcoma with IPN in lung treated in the Bone tumor Center of Eastern Theater General Hospital from January 2011 to January 2021 were collected retrospectively, there were 47 males and 22 females, with a median age of 19 years old (range 7-60 years old). The clinical characteristics including disease-free interval, the chemotherapy response, with recurrence/non-pulmonary, IPN presence before / during / after chemotherapy and imaging features of IPN including number of IPN, location of IPN, density of IPN, boundary clarity of IPN and outcome. The patients were divided into the metastasis pulmonary nodules group and the benign nodules group according to the final outcome of IPN. Further, χ 2 test was performed for comparison of the clinical and imaging characteristics between the two groups. The survival of patients was counted and the correlation between single factor and survival was compared by Kaplan-Meier test, and multivariate survival analyses were performed using Cox proportional hazards regression models. Results:Sixty-nine cases occurred IPN in 211 patients with osteosarcoma, with an incidence of 32.7%. Of the 69 patients, 45 patients (65.2%) with IPN were diagnosed as metastases, and 24 patients (34.8%) with IPN were diagnosed as benign nodules. Follow-up length ranged from 1 to 124 months, with the median follow up time 43 months. To the end of follow-up, 41 patients (59.4%) remained alive and 28 patients (40.6%) had died. The median survival time was 41.0 (20.0, 65.0) months and the median survival time after diagnosis of IPN was 25.0 (10.0, 43.0) months. There were significant differences in lung nodule density ( P<0.001), boundary ( P=0.002), history of recurrence/extra-pulmonary metastasis ( P=0.023) and chemotherapeutic effect ( P<0.001) between the metastasis pulmonary nodules group and the benign nodules group. Multivariate survival analysis showed that chemotherapeutic effect was an independent factor affecting the overall survival of patients [ HR=0.048, 95% CI (0.01, 0.26)]. Boundary definition [ HR=0.12, 95% CI (0.02, 0.93)] and chemotherapeutic effect [ HR=0.06, 95% CI (0.01, 0.29)] were independent factors influencing survival after diagnosis of IPN. Conclusion:Osteosarcoma patients with IPN have a poor prognosis. The poor effect of chemotherapy is an independent risk factor for the overall survival time of those patients and the survival time after diagnosis of IPN. The boundary definition of IPN is an independent risk factor for the survival time after diagnosis of IPN.

Objective:To compare outcomes between standardized and misdiagnosis and mistreatment of osteosarcoma.Methods:A retrospective analysis of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (299 cases, control group) and those who were misdiagnosed (benign or infective) and received mistreatment (23 cases, study group) between January 2009 and December 2021. Gender, age, first operation mode, recurrence time, recurrence interval, metastasis time, metastasis interval, total survival time (months), survival status in the two group and tumor site reoperation mode in the study group were statistically analyzed. Further, chi-square test was performed for comparison of the clinical between two groups. The survival analysis was performed using Kaplan-Meier test and Log-rank test.Results:All the 322 patients were followed up. In the control group, the average follow-up time was 42 months (1-137 months), the average age was 24 years (3-80 years), male 184 cases, female 115 cases, and limb salvage rate was 85.3% (255/299). Seven patients underwent amputation, and the amputation rate was 17.7% (44/299). The recurrence rate was 8.4% (25/299), the average recurrence interval was 22.8 months (7-36 months), and the metastasis rate was 28.1% (85/299), the average metastasis time was 32.7 months (0-58 months). In the study group, the average of follow-up time was 30 months (9-117 months), the average age was 36 years (5-67 years), 17 males and 6 females. Among them, eleven patients were treated with limb salvage in the second stage, and the limb salvage rate was 47.8% (11/23). Seven patients underwent amputation, and the amputation rate was 30.4% (7/23). The recurrence rate was 26.1% (6/23), the average recurrence interval was 11 months (1-42 months), and the metastasis rate was 43.4% (10/23), the average metastasis time was 20.3 months (1-44 months). The 5-year survival rate was 50.7% in the study group and 56.1% in the control group. There was no significant difference between the two groups (χ 2=0.09, P=0.760). Conclusion:The overall prognosis of patients with high-grade osteosarcoma who receive active treatment after mistreatment is similar to that of patients with standardized treatment, but the recurrence and metastasis rate is higher, the recurrence time is earlier, and the amputation rate is higher.

p53 (encoded by TP53) is undoubtedly one of the most extensively studied genes and proteins. It is a highly potent transcription factor which, under normal circumstances, is maintained at low level. Both genotoxic and non-genotoxic stresses can induce p53 stabilized leading to changes in the expression of p53-responsive genes. The biological outcome inducing this pathway can be either growth arrest and apoptosis or senescence to maintain the integrity of the genome or to delete the damaged cells. The biochemical activity of p53 itself and the cellular environment govern the choice between these outcomes in a cell type- and stress-specific manner. So, p53 is a pivotal tumour suppressor and a mainstay of our body's natural anticancer defence. This review could provide some useful information for further study on the mechanisms of tumorigenesis and its progression, and also could contribute to the discovery of antitumor agents.

Many major neurodegenerative diseases are associated with proteins misfolding and aggregation, which are also called "neurodegenerative conformational disease". The interaction of gene mutation and environmental factors are probably primary events resulting in oligomer and aggregate formations of proteins. Moreover, the dysfunctions of protein control systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal system, also contribute to the neurodegenerative process. The present review mainly summarizes protein misfolding and aggregation in the development of neurodegenerative conformational disease and the underling mechanisms, as well as upregulation of heatshock proteins as a promising treatment method for this kind of disease.

syuclein is regarded as a presynaptic protein, which may play an important role in neuronal plasticity. However, abnormal accumulation of fibrillar ?-synuclein and mutation of ?-synuclein gene can affect the survival of neurons. Its aggregation and interaction with other proteins are the most critical factors. ?-synuclein is a precursor of non-amyloid component of senile plaques in Alzheimers disease. It is likely that ?-synuclein is associated with Alzheimers pathology. In this paper, we summarize the progress in the normal physical function of ?-synuclein and the mechanism in Alzheimers disease.

Gap junctional intercellular communication (GJIC) has been specu la ted to be a necessary biological function of metazoan cells for the regulation o f growth control, differentiation and apoptosis of normal progenitor cells. Rese arches show that most transformed cells and tumor cells have reduced or abolished GJIC. The prevention of the down regulation of GJIC by the tumor promoters or the restoration of GJIC in neoplastic cells may have potential in prevention and therapy of cancer.

Adenosine A_ 2A receptors are selectively localized in basal ganglia and can affect the locomotor activity. Epidemiological and laboratory data have suggested that A_ 2A blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. A_ 2A receptor antagonist may ameliorate the symptom of Parkinsons disease (PD) and block the disease progress. Thus, the data suggested that A_ 2A receptor antagonist might be effective as a novel therapy for the management of PD.

Aim Inflammation is a common characteristic of liver injury induced by hepatitis virus or other factors.The purpose of this paper was to study the modulating effect of bicyclol,a novel anti-hepatitis drug,on related inflammatory molecules.Methods Various non-cytotoxic concentrations of bicyclol were cultured with macrophage RAW264.7 line or mouse peritoneal macrophages for 1 h,and then added adequate lipopolysaccharide(LPS)to activate macrophages.NO and TNF-? levels in the supernatant of the culture medium were determined with Griess reagent and L929 cell bioassay,respectively.The iNOS expression and NF-?B activation were detected by Western blot method.Results Pretreatment of 0.1～0.5 mmol?L-1 bicyclol significantly inhibited NO release and TNF-? secretion from RAW264.7 cell line and mouse peritoneal macrophages induced by 1 mg?L-1 LPS in concentration dependent manners and 0.5 mmol?L-1 bicyclol also down-regulated LPS(1 mg?L-1)-induced iNOS expression and NF-?B activation in the cells.Conclusion Bicyclol has suppressive effect on related inflammatory molecules iNOS expression and NF-?B activation,indicating that bicyclol possesses anti-inflammatory property.

Glycogen synthase kinase-3(GSK3)is a fascinating serine/threonine protein kinase which exists in cells generally.GSK3 activity is regulated by phosphorylation,protein complex formation,and its intracellular localization.GSK3 regulates many functions including cell survival and apoptosis,structure and motility,intracellular signaling pathways and so on.It is very important to keep the activity of GSK3.GSK3 has been linked to all of the primary abnomalities associated with AD.It is very important to study the inhibition of GSK3 as a therapeutic approach to treat AD.All the studies suggest that GSK3 is a promising therapeutic target for AD.

MDR(multidrug-resistance)is a major obstacle in the chemotherapy of cancer.Numerous mechanisms are known to contribute to MDR,alterations at the level of apoptosis control are one of those mechanisms except overexpression of drug efflux pumps.This review focuses on the research progression of alterations at the level of apoptosis inducing MDR,and some of the strategies that have been used in an attempt to chemosensitize resistant tumors by manipulating dysregulated apoptosis pathways.