Multiple myeloma (MM) is a common malignant hematological tumor in adults, which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins (M protein), leading to bone destruction, hypercalcemia, anemia, and renal insufficiency (Alexandrakis et al., 2015; Yang et al., 2018). Since a large number of new drugs, represented by proteasome inhibitors and immunomodulators, have been successfully used to treat MM, treatment efficacy and survival of patients have been significantly improved. However, due to the high heterogeneity of this disease, patients have responded differently to treatments with these new drugs (Palumbo and Anderson, 2011; Wang et al., 2016; Huang et al., 2020). Growth and survival of MM cells depend on the bone marrow microenvironment, especially numerous inflammatory cytokines secreted by myeloma cells and bone marrow stromal cells, such as vascular endothelial growth factor (VEGF), interleukin (IL)‍-6, transforming growth factor-‍β (TGF‍‍-‍‍β), and IL-10. These cytokines can promote the growth of myeloma cells, induce angiogenesis, and inhibit antitumor immunity, and are often linked to patient prognosis (Kumar et al., 2017). In this era of new drugs, the prognostic values of the serum levels of these cytokines in MM need further evaluation.
Adult ; Humans ; Cytokines ; Disease Progression ; Interleukin-10 ; Interleukin-6/metabolism* ; Multiple Myeloma/drug therapy* ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A

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:This study aims to evaluate the prognostic effect of peripheral blood cells in multiple myeloma (MM) patients treated with bortezomib.Methods:The clinical data of 155 newly diagnosed MM patients in two blood disease treatment centers from January 2014 to December 2016 were retrospectively studied. All patients received bortezomib as the first-line treatment. The results of the peripheral blood cell counts, including absolute neutrophil count, absolute monocyte count (AMC) , hemoglobin level, mean corpuscular volume (MCV) , and platelet count, and other clinical features were analyzed.Results:AMC (>0.6×10 9/L) , MCV (>99.1 fl) , and platelet count (<150×10 9/L) significantly affected patients’ PFS and OS. The above three factors were assigned 1 point, respectively, to form the blood cell score. The analysis showed that 64 cases (41.3% ) had a score of 0, 57 cases (36.8% ) had 1, 32 cases (20.6% ) had 2, and 2 cases (1.3% ) had 3. The median PFS of the four groups were 42.8 m, 26.5 m, 15.8 m, and 6.4 m, respectively ( P<0.001) . The median OS were NR, 48.2 m, 31.1 m, and 31.4 m, respectively ( P=0.001) . Multivariate analysis suggested that the blood cell score (2-3 vs 0-1) and the proportion of marrow plasma cells (>30% ) were independent prognostic factors for PFS ( HR=1.95 and 1.76, respectively) , while age (>65y vs ≤65y) , R-ISS stage (3 vs 1-2) , and blood cell score (2-3 vs 0-1) were independent prognostic factors for OS ( HR=2.08, 2.13 and 2.12, respectively) . Conclusion:As an easy-to-access biomarker, the blood cell score can be used to evaluate the prognosis of newly diagnosed MM patients in the era of new drugs, but it is still necessary to expand the cases and make further confirmation in the prospective study.

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Bortezomib ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; Humans ; Multiple Myeloma ; drug therapy ; metabolism ; pathology ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Structure-Activity Relationship ; Ubiquitin-Protein Ligases ; genetics ; metabolism

Objective To investigate the effect of estrogen on the fibrosis process of intrauterine adhesions and the expression of forkhead box F2 (FoxF2).Methods Primary human endometrial stromal cells (HESCs) were obtained by separation with 0.2％ collagenase Ⅰ digestion-mesh filtration-differential adherence,and identified by immunocytochemistry.HESCs affected with 10ng/ml transforming growth factor β1 (TGF-β1) for 48 hours.HESCs in model group were affected with 0,10-6,10-8,10-10 and 10-12mol/L estrogen,the expressions of smooth muscle actin alpha (α-SMA),Collagen I (COL Ⅰ) and FoxF2 were detected by quantitative PCR (qPCR) and Western blotting.Results HESCs with high purity and good activity were obtained by using 0.2％ collagenase Ⅰ digestion-mesh filtration-differential adherence separation method.Immunocytochemistry showed positive vimentin and negative cytokeratin 18 in HESCs.The results of qPCR and Western blotting showed that the mRNA and protein expression levels of α-SMA,COL Ⅰ and FoxF2 were higher in model group than in control group (P＜0.05),the model was built successfully.qPCR revealed that the mRNA expression levels ofα-SMA,COL Ⅰ and FoxF2 were significantly lower in 10-6,10-8 and 10-10mol/L estrogen groups than in model group (P＞0.05 in 10-10mol/L estrogen group,P＜0.05 in other groups),while in 10-12mol/L estradiol group,the expression levels of FoxF2 mRNA significantly decreased (P＜0.05),and of α-SMA and COL Ⅰ mRNA increased,but no significant difference were found (P＞0.05).Compared with the model group,the protein expression levels of α-SMA,COL Ⅰ and FoxF2 in 10-6,10-8 and 10 10mol/L estrogen groups decreased,but no significant difference was found (P＜0.05),while in 10-12mol/L estradiol group,the expression levels ofα-SMA protein increased (P＞0.05),and of COL Ⅰ and FoxF2 proteins decreased (P＜0.05).Conclusions The expression of FoxF2 in intrauterine adhesions is increased.Estrogen can reverse the fibrosis process of intrauterine adhesions in a certain range and inhibit the expression of FoxF2.