ObjectiveTo investigate the change in the activity of glucosylceramide synthase, the key enzyme in glycosphingolipid metabolism and synthesis, in Huh7 cells infected by hepatitis B virus (HBV) in vitro. MethodsBlood samples were collected from nine previously untreated patients with acute hepatitis B who attended Department of Infectious Diseases, The First Hospital of Lanzhou University, from June to August, 2019, and the blood samples collected from seven healthy individuals who underwent physical examination were established as control. Huh7 cells were inoculated with the high-copy HBV particles (＞9.9×107 IU/ml) in the serum of patients with HBV infection (infection group), and Huh7 cells co-cultured with the serum of healthy individuals were established as control group. The expression levels of HBsAg and HBV DNA in the cytoplasm of HBV-infected Huh7 cells were measured, and the correlation between GCS activity and virus was analyzed. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups, and a Pearson correlation analysis was performed. ResultsCompared with the control group, the infection group had a significant reduction in the number of cells, an increase in cell volume, and cell membrane fragmentation. The infection group had a significant increase in the expression of HBsAg in cytoplasm at 4 hours, 8 hours, 2 days, and 5 days after infection (P＜0.05); the expression level of HBV DNA tended to increase significantly from 4 hours after infection to 8 hours, 2 days, and 5 days after infection (16.67±11.55 IU/ml vs 112.01±25.94 IU/ml/328.01±10350 IU/ml/101.60±49.84 IU/ml, P＜0.001), with the highest level at 2 days after infection. During HBV infection, the activity of GCS gradually increased with the increase in viral replication from 4 hours after infection (126.21±9.59 IU/ml) and reached a peak at 2 days after infection (226.53±36.27 IU/ml), with a significant difference between the infection group and the control group at 2 days after infection (226.53±36.27 IU/ml vs 136.50±1544 IU/ml, t=3.956, P=0.016 7). The activity of GCS was positively correlated with HBV DNA level (r=0.576 8, P=0047 1). ConclusionHuh7 cells are successfully infected with the high-copy HBV particles in the serum of patients with HBV infection, which mimics the characteristics of HBV infection in vitro to a certain degree. The activity of GCS may be associated with HBV infection, suggesting that glycosphingolipid synthesis and metabolism may be closely associated with HBV.

目的：探讨成纤维细胞生长因子 13（fibroblast growth factor 13，FGF13）对非小细胞肺癌 A549 细胞活性氧（reactive oxygen species，ROS）的生成和凋亡的影响及其调控机制。方法：WB 法检测 FGF13 在人正常肺上皮细胞 BEAS-2B 和肺癌 A549、H460 细胞中的本底表达量。采用 FGF13 过表达载体转染 BEAS-2B 和 A549 细胞；设计两组靶向 FGF13 的 shRNA 序 列，构建慢病毒干扰载体，包装病毒后侵染 A549 细胞，采用 qPCR 和 WB 法检测干扰效果，DCFH-DA 探针结合荧光酶标仪分 析敲减 FGF13 对 A549 细胞内 ROS 水平的影响，MitoSOX 与 WB 法检测对线粒体 ROS 水平及烟酰胺腺嘌呤二核苷酸磷酸氧 化酶 4（nicotinamide adenine dinucleotide phosphate oxidase 4，NOX4）蛋白表达量的影响，Annexin V-FITC-PI 双染法检测对细胞 凋亡和 Caspase-3 及 Cleaved Caspase-3 蛋白表达的影响。结果：与 BEAS-2B 细胞相比，FGF13 蛋白在两种肺癌细胞中均高表 达（均 P<0.05）。成功构建 FGF13 过表达、低表达的 A549 细胞系。过表达 FGF13 后，BEAS-2B 和 A549 细胞内 ROS 水平显著 降低（P<0.05）；敲减 FGF13 表达后，A549 细胞内 ROS 水平显著升高（P<0.05）；然而过表达及干扰 FGF13 对 A549 细胞内线粒 体 ROS 水平无显著影响，但 NOX4 蛋白表达量显著下调（P<0.05）及显著上调（P<0.05）。FGF13 干扰后 A549 细胞凋亡率显著 升高（P<0.01），Caspase-3 及 Cleaved Caspase-3 蛋白表达量显著上调（P<0.05）。结论：FGF13 可能通过 NOX 家族途径调控 ROS 的生成，并通过 ROS/Caspase-3 通路调控 A549 细胞凋亡。

Objective:Based on the data of Global Burden of Disease 2019 data, to analyze the past, current, and future burden of disability-adjusted life years (DALYs) in China and compare with the international status.Methods:The total number of DALYs, age-standardized DALY rate, and the composition of different subgroups were extracted and described to analyze the time trend in 2000-2019 and the current situation in 2019 for Chinese female breast cancer. The burden of DALYs in 2050 was predicted by Joinpoint using average annual percent change (AAPC).Results:In 2000-2019, the ranking of DALYs caused by female breast cancer in China rose from the fourth to the second in all female cancers. The total DALYs increased by 48.4%, of which the years lived with disability increased from 4.8% to 8.8%. The age-standardized DALY rate only slightly decreased (AAPC=-0.3%; which increased during 2016-2019, AAPC=1.6%). In 2019, the age-standardized DALY rate for breast cancer in China was 278.0/100 000. The DALYs were 2.88 million (accounting for 14.2% of the global burden and 12.1% of all female cancers burden in China), 26.5% of which attributed known risk factors (overweight and obesity were the largest: 0.34 million DALYs, but some common breast cancer risk factors were not available on the platform, such as menstruation and fertility). In 2050, the prediction suggests that the total DALYs caused by female breast cancer in China will reach 3.80 million person-years-5.16 million person-years, increasing 32.1%-79.4% over 2019. From 2000 to 2019, the peak age of DALYs and DALY rate became older, and the DALYs among females aged 65 years and above increased faster than those younger than 65 years (AAPC were 4.8% and 1.3%, respectively). In 2019, females aged 45-74 (the starting age recommended by local guidelines for breast cancer screening) contributed 74.3% of the total DALYs.Conclusions:Over the past 20 years, the age-standardized DALY rate for breast cancer in female populations in China has not changed obviously. Without the continuous expansion of effective intervention and population aging, the burden of DALYs for female breast cancer in China will increase. DALYs for breast cancer attributed leading risk factors were still limited.

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.

Objective: To understand the consciousness of the cancer early treatment and its demographic and socioeconomic factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The questionnaire collected personal information, the consciousness of the cancer early treatment and relevant factors. The Chi square test was used to compare the difference between the consciousness of the cancer early treatment and relevant factors among the four groups. The logistic regression model was used to analyze the influencing factors related to the consciousness of the cancer early treatment. Results: With the assumption of being diagnosed as precancer or cancer, 89.97% of community residents, 91.84% of cancer risk assessment/screening population, 93.00% of cancer patients and 91.52% of occupational population would accept active treatments (P<0.001). If the immediate family members were diagnosed as precancer or cancer, people who would encourage their family members to receive early treatment in the four groups accounted for 91.96%, 91.94%, 92.44% and 91.55%, respectively (P<0.001). The company employees, annual household income with 40 000 yuan and more and other three groups had a relatively better consciousness of the cancer early treatment (P<0.05). Male, widowed, unemployed and from the central and western regions had a relatively worse consciousness of the cancer early treatment (P<0.05). Conclusion Residents in urban China participants had a good consciousness of the cancer early treatment. The marital status, occupation, annual household income and residential regions were major factors related to the consciousness of the cancer early treatment.

Objective: To understand the health literacy of the cancer prevention and treatment among urban residents of China, and explore the related factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The health literacy of the cancer prevention, early discovery, early diagnosis, early treatment and the demands of cancer prevention and treatment knowledge was analyzed. The level of health literacy among different groups were calculated and compared. The binary logistic regression model was used to analyze the influencing factors of the health literacy of the cancer prevention and treatment. Results: The level of health literacy of the cancer prevention and treatment was 56.97% among all study population; in each group it was 55.01% for community residents, 59.08% for cancer risk assessment/screening population, 61.99% for cancer patients and 57.31% for occupational population, respectively (P<0.001). The level of health literacy of the cancer prevention and treatment of residents aged 50 to 69 years old, other occupational groups, unmarried, the central and western region residents and the group with unclear self-assessment of cancer risk was significantly lower than that of residents younger than 40 years old, personnel of public institutions/civil servants, married, the eastern region residents and the group whose self-assessment without cancer risk (P<0.05) . The level of health literacy of cancer prevention and treatment of females, people who went to high school or over, cancer risk assessment/screening population, cancer patients and occupational population was significantly higher than that of males, people who had an education level of primary school or below and community residents (P<0.05) . Conclusion The health literacy of the cancer prevention and treatment of urban residents in China was relatively high, but there was still room for improvement. Gender, age, educational level, occupation, region, marital status, self-assessment of cancer risk, and type of respondents were the key influencing factors of the health literacy of the cancer prevention and treatment. Male, 50-69 years old, lower educational level, central and western regions, unclear cancer risk self-assessment, and without specific environmental exposure to cancer prevention and treatment knowledge or related risk factors were the characteristics of the key intervention group of the health literacy of the cancer prevention and treatment.

Objective: To investigate the demand and access to the cancer prevention and treatment knowledge and related factors among urban residents in China from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of general demographic characteristics, the demand and access to cancer prevention and treatment knowledge, and the influencing factors of the attitude. The Chi-square test was used to analyze the difference of the demand of the cancer prevention knowledge among different groups and the corresponding factors of the cancer prevention and treatment knowledge were analyzed by using the logistic regression model. Results: The proportion of residents who need the cancer prevention and treatment knowledge was 79.5%. The demand rate of the inducement, symptom and diagnosis methods of cancer in the occupational population was highest, about 66.8%, 71.0% and 20.8%, respectively. The demand rate of treatment methods and cost in current cancer patients was the highest, about the 45.9% and 21.9%, respectively. The top three sources to acquire the cancer prevention and treatment knowledge were "broadcast or television" (69.5%), "books, newspapers, posters or brochures" (44.7%) and "family and friends" (33.8%). The multivariate analysis showed that compared with public institution personnel/civil servants, unmarried/cohabiting/divorced/widowed and others, annual household income less than 20 000 CNY, from the eastern region, people without cancer diagnosis and people with self-assessment of cancer risk, the demand rate of cancer prevention and treatment knowledge was higher in enterprise personnel/workers, married, annual household income between 60 000 CNY and 150 000 CNY, from the central region, people with cancer and people with unclear cancer risk (all P values <0.05). Conclusion There was a high demand for the cancer prevention and treatment knowledge among urban residents in China from 2015 to 2017. The main access to the knowledge is from the radio or television. The occupation, marital status, annual household income, residential region, health status and risk of disease were the main factors of the demand of the cancer prevention and treatment knowledge.

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10⁷/kg on day 0) and (4.0-6.8) ×10⁷/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.