Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.

The successful application of tyrosine kinase inhibitor (TKI) has kicked off the targeted therapy of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) since the discovery of EGFR gene mutations. Patients harboring the two most classic representative mutations of EGFR gene including exon 19 in-frame deletion or exon 21 L858R mutation could get significant clinical benefits from EGFR-TKIs compared to traditional chemotherapy. Among other approximately 10% of EGFR gene mutation type, exon 20 insertion occupies the first place. Available research had demonstrated that EGFR exon 20 insertion in NSCLC was highly malignant and most insertion variants showed de novo drug resistance towards current approved 1^st to 3^rd generation EGFR-TKIs, with much poorer clinical prognosis. Currently, there is a lack of comprehensive research and clinical guideline on the treatment of this specific mutation. In this article, we review the pathogenesis, amino acid sequence variants and current management of EGFR exon 20 insertion mutant NSCLC. Moreover, we come up with the emphasis on the treatment challenges and further development of this rigid mutation in NSCLC.

BACKGROUND: With the rapid spread of novel coronavirus pneumonia (NCP) worldwide and the escalation of prevention and control efforts, the routine medical needs of patients have been restricted. The aims were to investigate medical needs of lung cancer patients and their mental health status during the epidemic periods, so as to provide rational recommendations for subsequent diagnosis and treatment. METHODS: The questionnaire was sent in the form of an electronic questionnaire at 7am on 4th, March, 2020, until 7am 6th, March, 2020, 368 questionnaires were recollected from 25 provinces (autonomous regions/municipalities) in 48 h. RESULTS: Of the 368 patients, 18 patients were excluded as they didn't receive anti-tumor treatment, and 350 patients were included in the final analysis. 229 cases were treated with oral targeted drugs, and 121 cases were treated with chemotherapy or immunotherapy. 41.3% of patients treated with intravenous chemotherapy or immunotherapy experienced treatment discontinuation, and the proportion of treatment discontinuation in chemotherapy or immunotherapy was higher than those treated with oral targeted drugs (21.0%). Whether oral targeted drugs or intravenous chemotherapy or immunotherapy, more than 60% of patients experienced delays in imaging examinations. Nearly one third of patients developed new symptoms or exacerbation of existing symptoms. 26.6%-28.9% of patients have changed their treatment plans through online consultation. During novel coronavirus pneumonia, 40%-75% of lung cancer patients have mental health problems, and more than 95% of patients support government's prevention and control measures. CONCLUSIONS During the emergence of NCP, the medical needs of patients with lung cancer have not been enough, especially those who discontinued chemotherapy or immunotherapy. When medical institution resumes work, priority should be given to them. At the same time, mental health problems of patients should be valued and resolved timely.
Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Betacoronavirus ; physiology ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; virology ; Female ; Humans ; Lung Neoplasms ; drug therapy ; psychology ; Male ; Middle Aged ; Pandemics ; Pneumonia ; epidemiology ; virology ; Pneumonia, Viral ; epidemiology ; virology ; Retrospective Studies

Objective: To explore the correlation and consistency between thromboelastography (TEG) and traditional coagulation tests (CCTs) in ischemic cerebral vascular disease (ICVD). Methods: Totally 108 ICVD patients admitted to Nanyang Central Hospital from May 1 to October 31 2018 were enrolled. Patients’ TEG parameters (R value, K value, Angle value, MA value, CI value and G value) and CCTs parameters (PT, APTT, TT, and FIB) were collected and analyzed retrospectively. The Spearman correlation coefficient was used to explore the correlation between TEG and CCTs parameters, and Kappa (κ) to explore the consistency in determining the coagulation status of the patients. The ROC curve was used to analyze the predictive value of TEG parameters for abnormal results of CCTs, and the results of TEG and CCTs were comprehensively analyzed to evaluate the ability to predict the coagulation status of patients. Results: (1) PLT was positively correlated with MA value and G value; PT and APTT were positively correlated with K value; TT was positively correlated with R value and K value; FIB was positively correlated with Angle value, MA value and G value. TT was negatively correlated with Angle value and CI value; FIB was negatively correlated with K value. (2) PT and MA values, PT and G values, FIB and MA values, FIB and G values were accordant in valuing the hypoxic state of ICVD patients. (3) PLT and Angle values, PLT and MA values, PLT and CI values, PLT and G values were accordant in assessing hypercoagulable status of ICVD patients; FIB and Angle values, FIB and MA values, FIB and CI value, and FIB and G value were consistent in evaluating the hypercoagulable state of ICVD patients. (4) For detecting TT>20 s, the AUC of K value and Angle value were 0.648, 0.651, respectively; For detecting FIB>4 g/L, the AUC of Angle value and MA value were 0.717 and 0.747, respectively; For detecting PLT>300×10⁹/L, the AUC of MA value was 0.808 (all P<0.05). Conclusions There is weak correlation and consistency between TEG and CCTs parameters in ICVD patients. The TEG parameters have good predictive value in evaluating the abnormal results of CCTs, but cannot replace the CCTs. Combination of these two methods can better reflect the coagulation status of patients, so as to afford assistance.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC stem-like cells (GCSCs), with unlimited self-renewal, differentiation, and tumor-regenerating capacities, contribute significantly to the refractory features of GC and have gained increasing attention for their role in GC drug resistance, relapse, and metastasis. Therapies targeting GCSCs seem to be one of the most promising methods to improve the outcomes of GC patients. Extensive investigations have attempted to outline the regulatory mechanisms in GCSCs and to develop GCSCs-targeting therapies with which to diminish GC drug resistance, metastasis and relapse. To the best of our knowledge, there is a lack of reviews summarizing these studies. In this review, we systematically recapitulated findings regarding the regulatory mechanisms of GCSCs, as well as therapies that target GCSCs, hoping to support the development of prognostic biomarkers and GCSCs-targeting anticancer therapies in GC.
Biomarkers ; Drug Resistance ; Hope ; Humans ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Recurrence ; Stem Cells* ; Stomach Neoplasms*

Objective To explore the irradiation-increased krebs yon den lungen-6 (KL-6) in predicting radiation pneumonitis (RP) after lung cancer radiotherapy.Methods A total of 87 hospitalized patients with Ⅰ-Ⅲ stages of lung cancer from June 2015 to December 2015 were followed up,and their clinicopathological data and serum KL-6,transforming growth factor-beta 1 (TGF-β1)and lactate dehydrogenase (LDH)before and 3 months after radiotherapy were analyzed to determine their role in predicting RP induction in lung cancer.Results Among the 87 lung cancer patients based on clinical symptoms and chest CT,13 patients were diagnosed with ≥2 grape RP.Before radiotherapy,the average levels of serum KL-6 were (247 ± 105.44) U/ml in 13 patients with ≥ 2 grape RP and (209 ± 71.09) U/ml in 74 cases 0/1 grape RP,respectively.Within 3 months after radiotherapy,the highest level of KL-6 approached to (456 ± 202.84) and (222 ± 80.42) U/ml with increase ratios of 2.01 ± 1.04 and 1.13 ± 0.60 in the ≥2 grape RP and 0/1 grape RP,respectively.The difference of KL-6 levels between these two groups was significant (t =2.901,P ＜ 0.005).While the levels of TGF-β1 and LDH did not change.ROC analysis showed that the sensitivity of the ratio of serum KL-6 increased after radiotherapy was 0.923％ and the specificity was 0.851％ at 1.435 as the critical value.Furthermore,the multi-variate logistic regression analysis showed that the ratio of KL-6 increased as an independent risk factor of ≥ 2 grade RP in lung cancer (OR =12.886,95％ CI =3.372-49.247,P =0.002).Conclusions The increased ratio (≥ 1.435) of KL-6 is closely correlated with the ≥2 grape RP in lung cancer,which could be used as a predictor of ≥2 grape RP in lung cancer.

OBJECTIVETo explore the value of serum neuron-specific enolase (NSE) before treatment in predicting brain metastases and prognosis of advanced non-small cell lung cancer (NSCLC).

METHODSA total of 128 hospitalized patients with advanced NSCLC from Jan 2012 to Mar 2012 were followed up, and their clinicopathological data, serum NSE, carcinoembryonic antigen, cytokeratin 21-1 (cyfra21-1) levels, albumin (ALB), white blood cell (WBC) before treatment were analyzed retrospectively to determine the factors affecting brain metastasis and prognosis of advanced NSCLC.

RESULTSAmong the 128 NSCLC patients, 90 cases were of adenocarcinoma, 30 cases were of squamous cell carcinoma, and 8 cases were of large cell carcinoma. The median levels of pre-treatment NSE, CEA and cyfra21-1 were 13.6 ng/ml, 7.8 ng/ml and 6.1 ng/ml, respectively. The average levels of ALB and WBC were (35.41 ± 5.60) g/L and (8.16 ± 2.53) × 10⁹/ml, respectively. Multi-variate logistic regression analysis showed that serum NSE before treatment was associated with brain metastasis of advanced NSCLC (P = 0.030). Pre-treatment NSE levels were (34.18 ± 28.48) ng/ml in 28 patients with brain metastasis and (13.87 ± 4.49) ng/ml in 98 patients without brain metastasis (P < 0.05). The median survival time were 3.5 months in patients with normal levels of NSE, and 10.7 months in patients with elevated levels of NSE pre-treatment (P < 0.05).

CONCLUSIONSA higher pre-treatment level of NSE is closely correlated with brain metastasis of advanced NSCLC, and can be used as a predictor of brain metastases in advanced NSCLC. High pre-treatment levels of NSE indicate a poor prognosis in advanced NSCLC patients.

Adenocarcinoma ; blood ; enzymology ; secondary ; Antigens, Neoplasm ; blood ; Brain Neoplasms ; secondary ; Carcinoembryonic Antigen ; blood ; Carcinoma, Large Cell ; blood ; enzymology ; secondary ; Carcinoma, Non-Small-Cell Lung ; blood ; enzymology ; secondary ; Carcinoma, Squamous Cell ; blood ; enzymology ; secondary ; Humans ; Keratin-19 ; blood ; Leukocyte Count ; Lung Neoplasms ; blood ; enzymology ; pathology ; Phosphopyruvate Hydratase ; blood ; Prognosis ; Retrospective Studies ; Serum Albumin ; analysis

Objective To explore the value of serum neuron?specific enolase ( NSE ) before treatment in predicting brain metastases and prognosis of advanced non?small cell lung cancer ( NSCLC ) . Methods A total of 128 hospitalized patients with advanced NSCLC from Jan 2012 to Mar 2012 were followed up, and their clinicopathological data, serum NSE, carcinoembryonic antigen, cytokeratin 21?1 ( cyfra21?1 ) levels, albumin ( ALB ) , white blood cell ( WBC ) before treatment were analyzed retrospectively to determine the factors affecting brain metastasis and prognosis of advanced NSCLC. Results Among the 128 NSCLC patients, 90 cases were of adenocarcinoma, 30 cases were of squamous cell carcinoma, and 8 cases were of large cell carcinoma. The median levels of pre?treatment NSE, CEA and cyfra21?1 were 13.6 ng/ml, 7.8 ng/ml and 6.1 ng/ml, respectively. The average levels of ALB and WBC were(35.41±5.60)g/L and (8.16±2.53)×109/ml, respectively. Multi?variate logistic regression analysis showed that serum NSE before treatment was associated with brain metastasis of advanced NSCLC ( P=0.030). Pre?treatment NSE levels were (34.18±28.48) ng/ml in 28 patients with brain metastasis and (13.87±4.49) ng/ml in 98 patients without brain metastasis (P<0.05). The median survival time were 3.5 months in patients with normal levels of NSE, and 10.7 months in patients with elevated levels of NSE pre?treatment(P<0.05). Conclusions A higher pre?treatment level of NSE is closely correlated with brain metastasis of advanced NSCLC, and can be used as a predictor of brain metastases in advanced NSCLC. High pre?treatment levels of NSE indicate a poor prognosis in advanced NSCLC patients.

Objective To explore the value of serum neuron?specific enolase ( NSE ) before treatment in predicting brain metastases and prognosis of advanced non?small cell lung cancer ( NSCLC ) . Methods A total of 128 hospitalized patients with advanced NSCLC from Jan 2012 to Mar 2012 were followed up, and their clinicopathological data, serum NSE, carcinoembryonic antigen, cytokeratin 21?1 ( cyfra21?1 ) levels, albumin ( ALB ) , white blood cell ( WBC ) before treatment were analyzed retrospectively to determine the factors affecting brain metastasis and prognosis of advanced NSCLC. Results Among the 128 NSCLC patients, 90 cases were of adenocarcinoma, 30 cases were of squamous cell carcinoma, and 8 cases were of large cell carcinoma. The median levels of pre?treatment NSE, CEA and cyfra21?1 were 13.6 ng/ml, 7.8 ng/ml and 6.1 ng/ml, respectively. The average levels of ALB and WBC were(35.41±5.60)g/L and (8.16±2.53)×109/ml, respectively. Multi?variate logistic regression analysis showed that serum NSE before treatment was associated with brain metastasis of advanced NSCLC ( P=0.030). Pre?treatment NSE levels were (34.18±28.48) ng/ml in 28 patients with brain metastasis and (13.87±4.49) ng/ml in 98 patients without brain metastasis (P<0.05). The median survival time were 3.5 months in patients with normal levels of NSE, and 10.7 months in patients with elevated levels of NSE pre?treatment(P<0.05). Conclusions A higher pre?treatment level of NSE is closely correlated with brain metastasis of advanced NSCLC, and can be used as a predictor of brain metastases in advanced NSCLC. High pre?treatment levels of NSE indicate a poor prognosis in advanced NSCLC patients.

BACKGROUND:Nowadays, growth factors are commonly used to induce bone marrow mesenchymal stem cells. However, this is a high-cost method with a great amount of growth factors. In addition, the chondrogenic potential of bone marrow mesenchymal stem cells wil decrease significantly with increasing times of culture. OBJECTIVE:To observe the directed differentiation of bone marrow mesenchymal stem cells co-cultured with human synovial fluid. METHODS:Human bone marrow mesenchymal stem cells were isolated and cultured by adherence screening method. The synovial fluid of the knee was aspirated from healthy volunteers by aseptic operation. Passage 3 human bone marrow mesenchymal stem cells were co-cultured with the fol owing media:synovial fluid+complete medium;synovial fluid+bone marrow mesenchymal stem cells+complete medium;bone marrow mesenchymal stem cells+complete medium. The morphology and growth of the cells were observed under an inverted microscope every day. At days 7, 14 and 21 of induction, toluidine blue staining and immunocytochemical staining were performed.
RESULTS AND CONCLUSION:After co-culture with human synovial fluid, human bone marrow mesenchymal stem cells proliferated slowly, and varied from fusiform to oval or polygonal;toluidine blue and col agen II staining were positive. These findings indicate that the synovial fluid has a positive role in the chondrogenic differentiation of bone marrow mesenchymal stem cells. The synovial fluid may contain substances that promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.