Objective To evaluate the characteristics, related therapeutic regimens, risk factors of cardiovascular adverse events (CVAEs) and prognosis in the current therapy of newly diagnosed multiple myeloma (NDMM) patients in China. Methods A retrospective observational study was performed on patients with NDMM treated at Zhongshan Hospital, Fudan University, from January 2013 to October 2021. The propensity score matching at a ratio of 1∶1 was employed to balance baseline confounders between the therapeutic group and the control group, and CVAEs incidences were compared between the corresponding groups. Independent risk factors for CVAEs were identified through Fine-Gray competing risk regression model. Kaplan-Meier survival curves and log-rank tests were used to assess overall survival and progression-free survival of patients. Results A total of 829 patients with NDMM were analyzed, with a median of 33.1 months of follow-up for survivors. CVAEs occurred in 65 patients (7.8%) during first-line treatment, and a total of 74 events were recorded, with 52.7% grade 3 or greater in severity. Arrhythmia (particularly atrial fibrillation), thrombotic event (TE), and heart failure were the most common types. The median time from treatment to the first occurrence of CVAEs was 26 days, while the medium occurrence time of TE was later than the other events (76 d vs 19 d, P＝0.003). The exposure to immunomodulatory drugs was related to a higher incidence of TEs, whereas other therapeutic regimens, including bortezomib, didn’t show the effect of cardiovascular toxicity. Results of multivariate analysis showed that Eastern Cooperative Oncology Group performance status ＞2, symptomatic heart diseases within three months before treatment, and estimated glomerular filtration rate≤50 mL·min⁻¹·(1.73 m²)⁻¹ were independent risk factors for CVAEs. Compared with patients without CVAE, patients who experienced CVAEs had significantly inferior progression-free survival and overall survival, and higher cardiovascular mortality (P＜0.001). Conclusions The incidence of CVAE is relatively high during first-line treatment in NDMM patients, and the prognosis of CVAE patients is poor. The risk of CVAE is significantly increased in patients with underlying cardiovascular diseases.

Objective:To investigate the effects and possible mechanisms of targeted inhibition of Polo-like kinase 1 (PLK1) on the proliferation, mitosis and apoptosis of cervical cancer cells.Methods:Logarithmically growing human cervical cancer cell lines HeLa and C-33A were selected, and cells treated with 10 and 20 nmol/L PLK1 inhibitor GSK461364 were used as different concentrations of GSK461364 groups, while cells not treated with GSK461364 were used as the control group. CCK-8 method was used to detect cell proliferation ability (represented by absorbance values at wavelength 450 nm), flow cytometry was used to detect chromosome ploidy (propidium iodide staining), mitochondrial membrane potential detected by flow cytometry was used to evaluate cell apoptosis status (JC-1 fluorescent probe, the cells where the JC-1 monomers emitting green fluorescence were located were apoptotic cells), and Western blotting was used to detect the expression levels of cell cycle and apoptosis-related proteins.Results:The results of CCK-8 method showed that the proliferation ability of HeLa cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 24, 48 and 72 hours without GSK461364. The proliferation ability of C-33A cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 48 and 72 hours without GSK461364, and the differences were statistically significant (all P < 0.05). The results of flow cytometry analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of polyploid cell subpopulations in HeLa cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (13.89±3.73)%, (12.30±5.49)% and (9.86±1.15)%, respectively, with no statistically significant difference ( F = 0.82, P > 0.05); the proportions of polyploid cell subpopulations in C-33A cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (8.45±2.20)%, (11.06±2.53)% and (5.42±1.36)%, respectively, with statistically significant difference ( F = 5.46, P = 0.045). Among them, the proportion of polyploid cell subpopulations in the 20 nmol/L GSK461364 group was higher than that in the control group, with statistically significant differences ( t = 3.40, P = 0.027). The results of flow cytometry detection of mitochondrial membrane potential showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of apoptotic cells in HeLa cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (3.96±2.28)%, (24.38±4.89)%, and (46.24±4.38)%, respectively, and the difference was statistically significant ( F = 83.18, P < 0.000 1), the proportion of apoptotic cells in the 10 and 20 nmol/L GSK461364 groups was higher than that in the control group, and the difference was statistically significant (both P < 0.01), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group ( t = 5.76, P = 0.005); the proportions of apoptotic cells in C-33A cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (1.81±1.59)%, (5.22±1.57)% and (15.87±5.81)%, respectively, with statistically significant differences ( F = 12.49, P = 0.007), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group and the control group (both P < 0.05). The results of Western blotting analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the relative expression levels of cleaved Caspase-9 and cleaved polyadenosine diphosphate-ribose polymerase in HeLa and C-33A cells treated with 10 and 20 nmol/L GSK461364 were higher than those in the control group, and the relative expression levels of cdc25c and phosphorylated cdc25c (Ser216) were lower than those in the control group, and the differences were statistically significant (all P < 0.05). Conclusions:Targeted inhibition of PLK1 can inhibit the proliferation activity of cervical cancer cells in vitro, induce cell mitotic cycle arrest, and promote cell apoptosis; these may be achieved by regulating cell cycle and apoptosis-related proteins.

Objective:To investigate the effects and possible mechanisms of targeted inhibition of Polo-like kinase 1 (PLK1) on the proliferation, mitosis and apoptosis of cervical cancer cells.Methods:Logarithmically growing human cervical cancer cell lines HeLa and C-33A were selected, and cells treated with 10 and 20 nmol/L PLK1 inhibitor GSK461364 were used as different concentrations of GSK461364 groups, while cells not treated with GSK461364 were used as the control group. CCK-8 method was used to detect cell proliferation ability (represented by absorbance values at wavelength 450 nm), flow cytometry was used to detect chromosome ploidy (propidium iodide staining), mitochondrial membrane potential detected by flow cytometry was used to evaluate cell apoptosis status (JC-1 fluorescent probe, the cells where the JC-1 monomers emitting green fluorescence were located were apoptotic cells), and Western blotting was used to detect the expression levels of cell cycle and apoptosis-related proteins.Results:The results of CCK-8 method showed that the proliferation ability of HeLa cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 24, 48 and 72 hours without GSK461364. The proliferation ability of C-33A cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 48 and 72 hours without GSK461364, and the differences were statistically significant (all P < 0.05). The results of flow cytometry analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of polyploid cell subpopulations in HeLa cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (13.89±3.73)%, (12.30±5.49)% and (9.86±1.15)%, respectively, with no statistically significant difference ( F = 0.82, P > 0.05); the proportions of polyploid cell subpopulations in C-33A cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (8.45±2.20)%, (11.06±2.53)% and (5.42±1.36)%, respectively, with statistically significant difference ( F = 5.46, P = 0.045). Among them, the proportion of polyploid cell subpopulations in the 20 nmol/L GSK461364 group was higher than that in the control group, with statistically significant differences ( t = 3.40, P = 0.027). The results of flow cytometry detection of mitochondrial membrane potential showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of apoptotic cells in HeLa cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (3.96±2.28)%, (24.38±4.89)%, and (46.24±4.38)%, respectively, and the difference was statistically significant ( F = 83.18, P < 0.000 1), the proportion of apoptotic cells in the 10 and 20 nmol/L GSK461364 groups was higher than that in the control group, and the difference was statistically significant (both P < 0.01), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group ( t = 5.76, P = 0.005); the proportions of apoptotic cells in C-33A cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (1.81±1.59)%, (5.22±1.57)% and (15.87±5.81)%, respectively, with statistically significant differences ( F = 12.49, P = 0.007), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group and the control group (both P < 0.05). The results of Western blotting analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the relative expression levels of cleaved Caspase-9 and cleaved polyadenosine diphosphate-ribose polymerase in HeLa and C-33A cells treated with 10 and 20 nmol/L GSK461364 were higher than those in the control group, and the relative expression levels of cdc25c and phosphorylated cdc25c (Ser216) were lower than those in the control group, and the differences were statistically significant (all P < 0.05). Conclusions:Targeted inhibition of PLK1 can inhibit the proliferation activity of cervical cancer cells in vitro, induce cell mitotic cycle arrest, and promote cell apoptosis; these may be achieved by regulating cell cycle and apoptosis-related proteins.

Objective:To investigate the role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells.Methods:Human cervical cancer HeLa cell lines were selected and HeLa cells were radiated under 7 Gy of 6 MV X-ray. The morphological changes of the cells were observed with an inverted microscope on day 5 after radiation induction. All cells were divided into the 7 Gy group (7 Gy X-ray radiation but not transfected polyploidy HeLa cells) and the control group (the non-radiation-induced and not transfected HeLa cells). In addition, the plasmid carrying pcDNA3 negative control sequence and the plasmid carrying pcDNA3-TT-AKT sequence were transfected into HeLa cells, respectively, which were induced by 7 Gy X-ray radiation after 48 h of transfection, and then they were recorded as the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group. Cell proliferation ability was detected by using CCK-8 assay, cell cycle was detected by using flow cytometry, cell apoptosis was detected by using mitochondrial membrane potential assay, the relative expression levels of cell proliferation, cell cycle, apoptosis and autophagy related proteins were tested by using Western blot.Results:Most of the normal HeLa cells in the 7 Gy group died on day 5 after radiation induction, and only a few surviving cells increased in size with multiple nuclei. The results of Western blot showed that the relative expression levels of p-AKT, p-mTOR and p-P70S6K in HeLa cells of the 7 Gy group were lower than those of the control group (all P < 0.05). CCK-8 assay showed that the absorbance ( A) values were 0.45±0.06, 0.65±0.06 after 48 h of culture and 0.75±0.05, 1.05±0.02 after 72 h of culture, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant (all P < 0.05), and the A values in the pcDNA3-TT-AKT + 7 Gy group were all higher than those in the pcDNA3 +7 Gy group. Flow cytometry results showed that the proportion of cells was (29.2±3.6)%, (26.7±1.7)% in G 0/G 1 phase and (29.6±1.6)%, (30.3±0.6)% in G 2/M phase, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were not statistically significant (all P > 0.05); the proportion of cells in S phase was (10.2±0.9)% and (14.6±1.5)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant ( t = 2.86, P = 0.043). Mitochondrial membrane potential assay showed that the green fluorescence proportion was (23.1±2.5)% and (14.3±1.9)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the different was statistically significant ( t = 4.82, P = 0.009). Western blot results showed that the relative expression level of p-cdc25c (Ser216) in the pcDNA3-TT-AKT+7 Gy group was higher than that in the pcDNA3+7 Gy group ( P < 0.001); and the relative expression levels of Bak and LC3-Ⅱ/Ⅰ in the pcDNA3-TT-AKT+7Gy group were lower than those in the pcDNA3 +7 Gy group, respectively (all P < 0.05). Conclusions:The p-AKT-mTOR-P70S6K signaling pathway may be involved in the regulation of radiation-induced polyploidy HeLa cell proliferation, cell cycle and cell apoptosis.

Objective:To investigate the characteristics related to proliferation, migration and invasion of radiation-induced polyploid colon cancer SW1116 cells and their progeny.Methods:Colon cancer SW1116 cells were conventionally cultured in Leibovitz's L-15 medium containing 10% fetal bovine serum. SW1116 cells at logarithmic growth stage were irradiated with 7 Gy X-ray, and the morphological changes of the cells were observed by inverted microscope on days 3, 5, 10 and 19 after radiation induction. According to the morphological changes of the cells, the cells at day 3 after radiation induction were labeled as polyploid giant cancer cell (PGCC) group, and the cells at day 19 were recorded as PGCC progeny group. SW1116 cells without radiation induction were used as control group. Flow cytometry was used to detect cell ploidy in the control, PGCC and PGCC progeny groups, CCK-8 assay was used to detect the proliferation ability of the three groups, cell migration and invasion abilities of the three groups were detected by cell scratch assay and Transwell assay, and Western blotting was used to detect the expressions of cell cycle and proliferation-related proteins and epithelial-mesenchymal transition (EMT) marker N-cadherin (N-cad) in the three groups.Results:The volume of SW1116 cells gradually became larger on days 3, 5 and 10 after radiation induction, and returned to normal on day 19. The proportions of polyploid (DNA content >4N) cell subsets in the control group, PGCC group and PGCC progeny group were (2.3±1.1)%, (23.1±8.1)% and (3.2±0.5)%, the difference was statistically significant ( F = 18.52, P < 0.05), and the proportion of polyploid cell subpopulations in the PGCC group was higher than that in the control group ( t = 5.38, P < 0.01), but the differences between the PGCC progeny group and the control group were not statistically significant ( t = 0.22, P > 0.05). After 72 h of culture, the cell proliferation rates of the control, PGCC and PGCC progeny groups were (100.0±4.1)%, (73.5±0.7)% and (123.9±3.5)%, and the difference was statistically significant ( F = 190.27, P < 0.001). After 48 h of cell scratching, the scratch healing rates in the control, PGCC and PGCC progeny groups were (38.0±2.7)%, (41.5±4.0)% and (63.7±4.2)%, and the difference was statistically significant ( F = 43.05, P < 0.001). After 24 h of culture, the number of invasive cells in the control, PGCC and PGCC progeny groups was 12.9±1.2, 3.4±0.6 and 23.7±1.5, and the difference was statistically significant ( F = 63.64, P < 0.001). The expression levels of cell cycle-related proteins P-cdc25c, cdc25c and cdc2 in the PGCC group were lower than those in the control group (all P < 0.05), and the expression levels of transcription factor-related proteins E2F-2, E2F-3 and EMT marker N-cad were downregulated compared with the control group (all P < 0.05); the expression levels of P-cdc25c, cdc25c, cdc2, E2F-2, E2F-3 and N-cad proteins in the PGCC progeny group were higher than those in the control group (all P < 0.05). Conclusions:Radiation can induce colon cancer SW1116 cells to produce polyploid, which may then generate daughter cells through asymmetric mitosis and gain new life, and then promote the recurrence and metastasis of colon cancer.

Objective To analyze the related factors of foot blisters caused by long-distance weight-bearing march and to explore the pathogenesis of foot blisters to provide a useful way for the prevention and treatment.Methods After the 300 km march,counted the number who had accomplished the march,and then recorded the number of foot blisters,location of blisters,and abrasion of sole.Collected the data of gender,age,body mass index (BMI),hand dominance,and whether had bliters before the march through questionnaire.And the data were coded for analysis with SPSS 13.0 statistical package.Results The 7 cases who complete the whole march and 17 cases who already had foot blisters before the march were ruled out of the final statistics.Among the remaining 590 cases,there were 554 cases (93.9%)suffered from foot blisters.And there were 1 282 blisters in total,among which the plantar blisters occupied 98% (1 257 cases).The analysis showed that the incidence of foot blisters had no significant correlation with gender,left/right foot,hand dominance,BMI and age.The predilection sites of blisters were the second and third metatarsals (28.2%),the hallux (21.3%),the fifth metatarsal (18.1%),and the calcaneus (15.8%)of the left foot.The predilection sites of blisters were the second and third metatarsals (33.3%),the hallux (22.4%),the fifth metatarsal (18.6%),and the calcaneus (14.5%)of the right foot.In terms of the abrasion of sole,the lateral heel was worn out the most (34.6% on the left and 34.2% on the right).Conclusion The study confirmed that the incidence of foot blisters had no significant correla-tion with gender,left/right foot,hand dominance,BMI and age,which may be affected by the particularity of this march.Most of the foot blisters occurred in the planta,and the predilection sites of blisters were in accord with sites of of the abrasion of sole and the distribution of plantar shear force,which demonstrated the shear force is the most critical factor on the pathogenesis of foot blisters.

Objective To investigate the level of professional commitment of nursing baccalaureate students,and explore the relationship between the professional commitment and communication ability.Methods Questionnaires were used to investigate 430 nursing baccalaureate students who were studying in the school.Results The professional commitment of nursing students was in the middle level.Correlation analysis revealed that the communication ability was correlated with the professional commitment.Conclusions We should take measures to improve the competency of professional commitment of nursing undergraduate students,strengthen their communication ability,promote the construction of nursing staff.