Programmed cell death(PCD)of human leukemic HL-60 cell and human poorly differentiated gastric adenocarcinoma cell BGS-180 induced by efoposid(VP-16) was preliminarily observed comparatively in the same experimental condition through rate of cell death, DNA agarose gels electrophoresis and terminal deoxynucleotidyl transferase(TdT) mediated biotin-11-dUTP nickend labeling(TUNEL).It was found that apoptosis is the main pattern of HL-60 cell death induced by low does VP-16 in a short time, and it can be suppressed when protein kinase C(PKC) is activated. The main pattern of BGS-180 cell death induced by VP-16 is necrosis, and PCK activation does not affect its necrosis rate. Extracellular Ca2+ reduction do not affect BGS-180 and HL-60 cell death rate. The mechanism of VP-16 action on BGS-180 and HL-60 cell is different, apoptosis is not the main pattern of cell BGS-180 death induced by VP-16.

Programmed cell death(PCD)of human leukemic HL 60 cell and human poorly differentiated gastric adenocarcinoma cell BGS 180 induced by efoposid(VP 16) was preliminarily observed comparatively in the same experimental condition through rate of cell death, DNA agarose gels electrophoresis and terminal deoxynucleotidyl transferase(TdT) mediated biotin 11 dUTP nickend labeling(TUNEL).It was found that apoptosis is the main pattern of HL 60 cell death induced by low does VP 16 in a short time, and it can be suppressed when protein kinase C(PKC) is activated. The main pattern of BGS 180 cell death induced by VP 16 is necrosis, and PCK activation does not affect its necrosis rate. Extracellular Ca 2+ reduction do not affect BGS 180 and HL 60 cell death rate. The mechanism of VP 16 action on BGS 180 and HL 60 cell is different, apoptosis is not the main pattern of cell BGS 180 death induced by VP 16.

Objective To compare the oil yield of celery seeds and the contents of 3-n-butylphthalide and the total phthalocyanine lactones of celery seed oil extracted by different methods. Methods Three routine extraction methods involving organic solvent extraction, Soxhlet extraction, steam distillation extraction, as well as subcritical extraction method and supercritical fluid extraction method were used to extract the celery seed oil. The contents of 3-n-butylphthalide and total phthalocyanine lactones were respectively detected by high performance liquid chromatography(HPLC) and ultraviolet visible spectrophotometry. Results The ranges of oil yield and the contents of 3-n-butylphthalide and total phthalocyanine lactones of celery seed oil extracted by different methods were 0.30%-20.02%, 1.40%-10.13%, 4.74%-17.65%, respectively, indicating obvious differences. Conclusion With R134a and butane as the solvents, the subcritical extraction method is better than other extraction methods for the extraction of 3-n-butylphthalide. With dimethyl ether as the solvent, the subcritical extraction method is the best for the extraction of total phthalocyanine lactones.

Objective:To explore the clinical significance of standardized screening for diagnosis and treatment of early gastric cancer in Qinghai Province.Methods:Opportunistic early gastric cancer screening was conducted in outpatients of Digestive Department, Physical Examination Center and inpatients of Qinghai Provincial People′s Hospital from January 2016 to December 2020, according to the optimal cut-off values of serum pepsinogen (PG)Ⅰ, PGⅠ/PGⅡ ratio (PGR) and serum gastrin 17 (G17) obtained from the previous screening study of gastric cancer and precancerous diseases in different areas of Qinghai Province. At the same time, the standardized early gastric cancer screening program was applied in 10 municipal (county-level) hospitals in Qinghai Province. The detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital and the above 10 hospitals in the past five years were analyzed respectively.Results:In the five years, the total detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital were 0.214% (407/190 178), 17.54% (407/2 321) and 81.82% (333/407), respectively. The above indices in 10 other hospitals were 0.085% (264/309 217), 12.94% (264/2 040) and 37.12% (98/264), respectively. The overall detection rate of early gastric cancer was higher than 0.024% reported previously.Conclusion:The standardized early gastric cancer screening program can not only improve the diagnosis rate of early gastric cancer in Qinghai Province, but also save medical resources. It is an economical, efficient and feasible program, suitable for the highin-cidence area of gastric cancer in Qinghai Province.

Objective:To investigate the safety and effectiveness of endoscopic cold snare resection of small colorectal polyps and prophylactic hemostatic clip.Methods:A total of 260 patients diagnosed as having small colorectal polyps in Qinghai Provincial People's Hospital from January 2021 to March 2022 were randomly assigned to cold snare polypectomy (CSP) group (receiving CSP), CSP+hemostatic clip group (receiving CSP+prophylactic hemostatic clip), hot snare polypectomy (HSP) group, and HSP +hemostatic clip group (receiving HSP+prophylactic hemostatic clip). Each group had 65 cases. The treatment, incidence of bleeding, and other complications were compared.Results:There was no significant difference in the basic characteristics of patients or polyps among the four groups ( P>0.05). Immediate intraoperative bleeding occurred in 5 cases (7.69%), 4 cases (6.15%), 3 cases (4.62%), and 3 cases (4.62%) in the four groups respectively with no significant difference ( χ2=0.778, P=0.855), while only 1 delayed postoperative bleeding was observed in HSP group with no significant difference among the four groups ( χ2=3.012, P=0.390). The incidence of postoperative abdominal pain was the highest in the HSP group ( n=7, 10.77%) significantly different from those of the CSP group ( n=1, 1.54%) and the CSP+hemostatic clip group ( n=1, 1.54%) ( P<0.05). Polypectomy time of single polyp in CSP group was the shortest (2.18±1.07 min) , followed by HSP group (2.83±0.82 min), then CSP+hemostatic clip group (3.15±1.16 min), with HSP+hemostatic clip group (4.88±1.85 min) being the longest ( F=50.397, P<0.001). Conclusion:It is suggested to use CSP for small colorectal polyps. If there is no risk of bleeding or perforation during the operation, it is not necessary to use prophylactic hemostatic clips.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. Conclusion The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.

OBJECTIVE： To study the anti-tumor effect of ethanol extract of Smilax trinervula and its different polar extract parts， and to provide reference for the screening of anti-tumor active parts. METHODS： MTT method was used to detect the inhibitory rates of different concentrations of ethanol extract of S. trinervula， its petroleum ether， ethyl acetate， n-butanol and water layer extract parts to the proliferation of human hepatocellular carcinoma cell line HepG2， human lung cancer cell line A549， human breast cancer cell line MCF-7 and MDA-MB-231， human cervical cancer cell line HeLa and human ovarian cancer cell line HO-8910. Semi-inhibitory concentration （IC50） was calculated. A total of 80 KM mice were subcutaneously inoculated with S180 cell suspension in right forelimb axilla to induce tumor-bearing mice model. The mice were randomly divided into 8 groups： e.g. model group （normal saline， twice a day， i.g.）， cyclophosphamide （positive drug） group （0.025 g/kg， once a day， i.p.）， S. trinervula ethanol extract high-dose， medium-dose and low-dose groups， ethyl acetate part of ethanol extract high-dose， medium-dose and low-dose groups （0.1， 0.05， 0.025 g/kg by extract， twice a day， i.g.）， with 10 rats in each group. The mice in each group were given medicine for consecutive 14 days. The inhibition rate， spleen index and thymus index of mice in each group were measured after fasting for 12 hours after the last administration. RESULTS： In vitro experiments showed that S. trinervula and different polar extracts inhibited the proliferation of 6 kinds of tumor cells in significant dose-effect manner， especially ethyl acetate part of ethanol extract. IC50 of it to tumor cells was 40-210 μg/mL， that of it to MCF-7， MDA-MB-231 and HeLa cells were 70.56， 83.58， 44.67 μg/mL， respectively. In vivo experiments showed that the tumor mass of mice were decreased significantly in each administrations （P＜0.05 or P＜0.01）， the tumor mass of mice in S. trinervula ethanol extract high-dose group， ethyl acetate part of ethanol extract high-dose and medium dose groups were significantly lower than cyclophosphamide group （P＜0.01）. The spleen index of mice was decreased significantly in cyclophosphamide group， S. trinervula ethanol extract high-dose group， ethyl acetate part of ethanol extract high-dose and medium dose groups， compared with model group （P＜0.01）； thymus index of mice in cyclophosphamide group was increased significantly， compared with model group and other administration groups （P＜0.01）. CONCLUSIONS： The ethyl acetate part of ethanol extract of S. trinervula has the best anti-tumor effect and less immunosuppressive effect.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*