Objective To analyze the clinical characteristics and changes of serum tumor markers in lung cancer patients with different smoking status in Hanzhong area. Methods A retrospective analysis was performed on 642 hospitalized lung cancer patients in Hanzhong area from March 2017 to March 2019. According to their smoking status, they were divided into observation group (smoking history, n=404) and control group (no smoking history, n=238). Age, sex, place of residence, basic information of the disease including pathological stage, pathological type, short-term efficacy, survival and serum tumor marker level were analyzed retrospectively. Results The proportion of male in observation group (67.08%) was significantly higher(57.56%) (χ²=5.855,P<0.05). Observed a group of 50 or more patients (80.94%) were significantly higher (73.53%) (χ²=4.824 , P<0.05); There was no significant difference between the two groups (χ²=2.110 , P<0.05). The proportion of adenocarcinoma in the control group (49.16%) was the highest, and that of small cell lung cancer in the observation group (41.34%) was the highest (χ²=15.291, P <0.05). Comparison of pathological stages between the two groups showed that stage IIIB (32.77%) was the highest in the control group, followed by stage IV (23.53%), Stage IIIA (20.59%), Stage II (13.03%) and stage I (10.08%). The observation group had the highest proportion in stage IIIA (35.40%), followed by Stage IIIB (25.00%), stage IV (16.09%), Stage IIIA (16.09%), stage II (15.10%) and stage I (8.42%). The difference between the two groups was statistically significant (χ²=10.817,P<0.05). Before treatment, serum CEA, CA125 and CA199 levels in observation group were significantly higher (P<0.05). After treatment, the levels of serum tumor markers in both groups were significantly decreased (P<0.05); The serum CEA, CA125 and CA199 levels in observation group were significantly higher (P<0.05). After treatment, THE ORR of the observation group (48.76%) was lower than that of the control group (53.78%), but the difference was not statistically significant (χ²=2.051, P>0.05). The 1-year survival rate of the observation group (64.85%) was significantly lower than that of the control group (73.95%) (χ²=5.255, P<0.05). Conclusion Middle-aged and elderly male smokers in Hanzhong area have a high incidence of lung cancer, multiple stage Ⅲ squamous cell carcinoma, and the level of tumor markers in serum is higher than that of non-smokers. The prognosis is not good, so we should encourage patients to quit smoking, which can improve the survival rate of patients.

Since December 2019, COVID-19 has been found in Wuhan, Hubei Province of China, which has spread in many countries and regions around the world. A large number of clinical trials have been launched in China aiming to find safe and effective drugs and treatments.The protection of subjects' legal rights, welfare and safety should be superior to the consideration of scientific and social benefits. Therefore, all parties involved in clinical trials should take corresponding measures to protect subjects' legal rights, welfare and safety. This paper discussed about the protection of subjects' legal rights, welfare and safety in clinical trials of COVID-19 from all aspects of the clinical trials, aiming to provide reference for all parties involved in clinical trials and basic ideas for the protection of subjects' legal rights, welfare and safety in clinical trials of emergencies.

Objective To investigate the effect of the Notch signaling pathway on the proliferation and invasion of human SW982 synovial sarcoma cells. Methods SW982 cells and normal human synovial cells were routinely cultured, and the expression of proteins related to the Notch pathway was compared. The Notch signaling pathway was manipulated by NICD1 overexpression, CFB1 shRNA lentivirus, and the γ-secretase inhibitor, DAPT. CCK-8 and wound healing assays were carried out to investigate the role of the Notch signaling pathway in SW982 cells. Results The Notch signaling pathway clearly showed higher activity in human SW982 synovial sarcoma cells than in normal human synovial cells (P ＜ 0.05). The proliferation and invasion of SW982 cells were significantly upregulated by overexpressing NICD1; however, were suppressed by downregulating the Notch signaling pathway using CFB1 shRNA or DAPT (P ＜ 0.05). Conclusion Our findings demonstrate that the proliferation and invasion of human SW982 synovial sarcoma cells are dependent on Notch signaling pathway activity.

Objective: To investigate the efficacy and safety of anlotinib hydrochloride capsules for the treatment of advanced soft tissue sarcoma based on the data from Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital&Institute. Methods: Patients were randomized allocated at 2:1 ratio for the anlotinib treatment and placebo group. The treatment group received 12 mg/day of anlotinib for 14 consecutive days in a 21-day cycle. The primary end-point was progression-free survival (PFS), and the secondary end-points were disease control rate (DCR), overall survival (OS), and adverse event rate. Results: A total of 46 patients were enrolled in this study; 7 of them were excluded from per protocol set (PPS). Among the remaining 39 patients, 28 were included in the anlotinib group and 11 in the placebo group. In the anlotinib group, 4 patients had partial remission and 13 had stable disease (SD), whereas in the placebo group, 3 patients had SD. The difference in DCR between the 2 groups was statistically significant (60.7% vs . 27.3%, P=0.082). The DCR of the advanced soft tissue sarcoma in the anlotinib group was 78.6% (11/14). The median PFS in the anlotinib group was 12.4 (95% confidence interval [CI]: 7.6 to 17.2) months, which was significantly longer than 4 months in the placebo group (95% CI: 1.7 to 6.3 months, P=0.043); however, the difference in OS between the 2 groups was not significant (19.4 vs . 17.6 months, P=0.961). Regarding the safety, 2 patients had severe adverse events (7.14%) possibly related with treatment in the anlotinib group; one of them had pneumothorax. The other adverse events were grade 1 to 2. Conclusions: Soft tissue sarcoma is highly responsive to anlotinib, with prolonged PFS. Anlotinib is well tolerated and can be used as a treatment option for advanced soft tissue sarcoma.

Objective To investigate the role of Notch signaling pathway to maintain the stem cell-like characteristics of osteosarcoma and its underlying mechanism.Methods Lentiviral NICD1 or Numb-shRNA was transduced into MG63 osteosarcoma cells to activate Notch activity in vitro.The impact of Notch on osteosarcoma stem cells were assessed by the tumor sphere formation assay and flow cytometry analysis of cell surface markers STRO-1/CD117.The expression of stem cell related genes (Sox2,Oct4) were evaluated by Western blot and qPCR.The nude mice were randomly divided into 3 groups:the NICD1 overexpression (NICD-OE) group,the DAPT group and the control (CON) group.The tumor growth was monitored for 8 weeks and the tumor volume and weight were recorded weekly.To investigate whether Notch regulates Eph pathway,Eph pathway related protein EphB,pEphB was measured by Western blot.The impact of ephrinB 1 on NICD overexpression cell were assessed by tumor sphere formation assay.The expression of Sox2 and Oct4 was evaluated by Western blot.Results NICD1 overexpression or Numb-shRNA increased the activity of Notch pathway.The Notch-activated osteosarcoma showed enhanced in vitro tumor spheroid formation capacity,increased Stro-1/CD117double positive ratio,and upregulated expression of Sox2 and Oct4 in vitro.In animal experiments,it was found that activation of Notch pathway promoted tumor formation in vivo and Notch inhibition decreased it.The primary osteosarcoma cells were obtained from mice xenograft treated with DAPT and its tumor sphere formation capacity was significantly reduced.Finally,The Notch pathway inhibits the phosphorylation of EphB,as well as the downstream signal pathway of EphB,but there is no significant change in total EphB.The activation of Eph pathway inhibited Notch induced up-regulation of tumor sphere formation and Sox2 and Oct4 expression.Conclusion Notch signaling pathway maintains the stem cell-like characteristics of osteosarcoma probably by inhibiting the Eph pathway.

Objective:To explore the outcome of soft tissue sarcoma (STS) on patients with soft tissue metastasis. Methods:We ana-lyzed 25 STS patients with soft tissue metastasis primarily localized on extremity and trunk. The study was conducted from June 2010 to June 2016 by retrospective analysis of the clinical and pathological characteristics of the patients. The assessed endpoints were overall survival. Results:Six patients (24%) had synchronous soft tissue metastasis, and 19 patients (76%) had metachronous metasta-sis. The average time for primary tumor recession of metastatic lesions was 45.3 months. Metastases were most common in parts of the trunk in 18 patients (72%), followed by the head and neck in 5 patients (20%). Eleven patients (44%) with lung metastasis had poor prognosis. Conclusion:STS occurred more rarely in soft tissue metastasis than in pulmonary metastasis. Neoadjuvant chemotherapy and surgical treatment were the major therapies employed. Targeted therapy as a new treatment rendered good results.

Objective To establish the reference range of thyroid function from the normal pregnant women in different pregnant period in Hanzhong region.Methods According to the NACB inclusion criteria,collected local resident pregnant women 4 031 cases,from July 2012 to December 2015.With the combination of random sampling,stratified sampling and cluster sampling,thyroid hormone levels were measured by a fully automated chemiluminescence analyzer and its accompanying reagents.All patients were divided into three groups:998 cases in early pregnancy (T1),1 543 cases in mid-pregnancy (T2),1 490 cases in late pregnancy (T3),and 105 cases of non-pregnant women in childbearing age (T0) were selected as control group.Results The levels of thyroid hormones were different among three periods of pregnant women.TSH were 0.25～5.32,0.42～6.26 and 0.61～7.68 mIU/L respectively in the early,middle and late stages.FT3 were 3.54～6.04,3.57～5.94 and 2.93～5.40 pmol/L,respectively.FT4 was 7.11～16.88,6.78～16.94 and 6.03～16.87 pmol/L.Thyroid hormone levels in pregnant women compared with non-pregnant women,there were significant differences (TSH:x2=233.183,P＜0.05,FT4:x2 =388.12,P＜0.05 and FT3:x2 =558.795,P＜0.05).TSH were lower in early pregnant women comparing to non-pregnancy women,and higher in middle-late pregnant women.The change of FT3 and FT4 were consistent,and reduced with the extension of pregnancy comparing to non-pregnancy women.Conclusion The level of thyroid function in pregnant women were different from non-pregnant women.and the normal reference range of local pregnant specific thyroid hormone should be established.

Objective:Cancer stem cells (CSCs) are resistant to chemotherapy. Our study aimed to investigate the stem cell-like proper-ties of doxorubicin-resistant osteosarcoma cell line 143B and its correlation with Notch signaling. Methods:We generated doxorubicin-resistant osteosarcoma cells by treating them with 2μm doxorubicin. Stem cell-like properties such as morphology change, Stro-1/CD117 double positive ratio, stem cell-related gene expression, sphere formation efficiency, and EMT character were assessed on day 5 after doxorubicin withdrawal. Notch receptor and its target genes were examined using qPCR and Western blot analysis. The stem cell-like properties of doxorubicin-resistant osteosarcoma cells were assessed when pretreated with Notch inhibitor or vehicle. The an-ti-tumor effect of Notch inhibitor was tested using a xenograft model. Results:Doxorubicin-resistant osteosarcoma cells were enriched in Stro-1+/CD117+cells, which showed obvious increased expression of stem cell-related genes, and exhibited enhanced spheroid for-mation and evident mesenchymal characteristics unlike doxorubicin-sensitive cells. qPCR and Western blot assays showed that Notch intracellular domain 1 (NICD1) and target genes Hes1 and Hey1 were upregulated in doxorubicin-resistant osteosarcoma stem cells compared with those in vehicle cells. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signaling en-hanced chemo-sensitivity and inhibited doxorubicin-enriched osteosarcoma stem cell activity in vitro. Finally, the Notch inhibitor pre-vented tumor growth in mice xenograft models. Conclusion: Doxorubicin induced the enrichment of osteosarcoma stem-like cells through Notch signaling, and inactivation of Notch could be useful for overcoming drug resistance and eliminating osteosarcoma.

OBJECTIVETo characterize the clinical features of desmoid tumor, assess the efficacy of conservative chemotherapy for inoperable desmoid tumor and analyze the prognostic factors.

METHODSFrom August 2009 to December 2013, 52 patients with inoperable desmoid tumor were treated in our department and received chemotherapy with vinorelbine combined with low-dose methotrexate. The clinical data of the patients were analyzed retrospectively.

RESULTSThe patients studied included 22 male and 30 female patients with the age of disease onset ranging from 2 to 46 years (mean 18.7 years). The lesions occurred most frequently in the lower limbs (36.5%, 19/52) and the tumor size ranged from 2.7 to 37 cm (mean 9.5 cm). The patients were followed up for a median of 29 months (7 to 64 months). The chemotherapy lasted for 4 to 30 months (median 12 months). After completion of the chemotherapy, 1 patient had a complete response (CR), 18 showed partial responses (PR), 27 cases had stable disease (SD), and 6 had progressive disease (PD), with an overall response rate (ORR) of 88.5%. The progression-free survival (PFS) time of the patients ranged from 4 to 63 months (median 26.5 months) with a 2-year PFS rate of 76.7% and 5-year PFS rate of 41.9%. A longer chemotherapy duration (over 12 months) was associated with a more favorable prognosis. No significant differences in PFS were found between the patients stratified by gender, age of disease onset, age when receiving chemotherapy, tumor site, or tumor size.

CONCLUSIONFor recurrent, inoperable and progressive desmoid tumor, long enough cycles of vinorelbine combined with low-dose methotrexate can be an effective and safe option for tumor control.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Fibromatosis, Aggressive ; drug therapy ; Humans ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Prognosis ; Retrospective Studies ; Vinblastine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Young Adult

Treatment resistant depression is a common and severe mental disorder associated with significant burden of disease .Most individuals receiving conventional pharmacotheraphy fail to achieve and sustain remission.So this is still one of the difficult challenges for the psychiatrist .Much of the research pro-vided indications that the efficacy of treatment for the disease was not optimistic, but the treatment was still made great progress .The common treatments for this disease included pharmacotherapy,psychotherapy,elec-troconvulsive therapy(ECT),transcranial magnetic stimulation (TMS),magnetic resonance guided focused ultrasound surgery( MRgFUS) ,deep brain stimulation ( DBS) ,aerobic exercise,light therapy and so on.Each therapeutic strategy has its own features, and could be suitable or unsuitable in some situations.The high rates of non-remission with first-line treatment strategies make the combination of antidepressant and non-drug treatments to be the new trend of the treatments for treatment resistant depression in the future.