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To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL).Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T.The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis.CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.嵌合抗原受体T细胞治疗儿童难治/复发急性B淋巴细胞白血病的疗效.观察嵌合抗原受体（CAR）T细胞治疗儿童难治/复发急性B淋巴细胞白血病（r/r B-ALL）的疗效及不良反应.回顾性分析32例r/r B-ALL患儿行CAR-T细胞治疗的临床资料，分别以复发、死亡为终点事件，评估CAR-T细胞治疗r/r B-ALL的疗效及安全性.2017年7月至2020年1月，共32例r/r B-ALL患儿接受CAR-T细胞治疗，中位年龄7.5（2-17.5）岁。32例患儿共回输CAR-T细胞40次，回输中位CAR-T细胞总量0.9×107/kg（患儿体重）。结果显示，2例患儿在评估前死亡，其余30例患儿3、6、9个月RFS分别为（96.3±3.6）%、（81.4±8.6）%和（65.3±12.5）%；3、6、9个月OS均为100%，12个月OS（94.7±5.1）%，24个月OS（76±12.8）%。回输前骨髓肿瘤负荷≥36%、CAR-T细胞回输2周内铁蛋白峰值≥2 500 ng/ml与复发相关。不良反应主要为细胞因子释放综合征（CRS）和CAR-T治疗相关脑病综合征（CRES），26例在CAR-T细胞回输1周内出现CRS反应，12例出现CRES反应。18例给予托珠单抗静滴，其中12例联合糖皮质激素，CRS反应及CRES反应经治疗后大多1周内缓解。激素使用剂量与患儿持续缓解时间相关，甲泼尼龙累积剂量≥8 mg/kg预后不佳.CAR-T细胞治疗儿童r/r B-ALL有效且安全，CRS及CRES反应经治疗后均可缓解；回输前骨髓肿瘤负荷≥36%、回输后甲泼尼龙累积剂量≥8 mg/kg预后不佳；回输后两周内铁蛋白峰值≥2 500 ng/ml与疾病复发相关，且为独立预后危险因素.

Knowledge gaps in the exposure parameters for recreational water activities make quantitative risk assessment related to water recreation difficult. Therefore, the annual exposure frequency and single exposure duration for the recreational water activities of residents from ten cities in the North and South of China were investigated. Questionnaire interviews were carried on recreational water activities comprising swimming (SW), boating (BA), playing in interactive fountains (PF), and watching fountains (WF). Quantitative microbial risk assessment for the exposure of urban residents to Cryptosporidium and Giardia was also performed. For the four recreational water activities, the participation rates of urban residents in SW and WF were higher than the others. For SW and BA, the mean annual exposure frequency and single exposure duration for males were significantly higher than those for females. PF and WF showed the opposite. The annual exposure frequency for above 35-year-old residents was higher than that for young residents (18-35 years). However, the single exposure duration for young residents was highest in SW, BA, and PF. The mean annual exposure frequency and single exposure duration for North China residents were higher than those for South China residents in all recreational water activities, except for SW. Overall, the annual exposure frequency and single exposure duration in recreational water activities for all urban residents followed a lognormal distribution. In the four recreational water activities, the total annual infection risk of male exposure to Cryptosporidium was 1.0 × 10

Neuroblastoma is the most common extracranial solid childhood tumor. Despite the availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the present study, we demonstrated that PAK4 was overexpressed in neuroblastoma tissues and was correlated with tumor malignance and prognosis. To investigate the function of PAK4 in neuroblastoma, we used a small-molecule inhibitor that targets PAK4, that is, PF-3758309. Our results showed that PF-3758309 significantly induced cell cycle arrest at the G1 phase and apoptosis in neuroblastoma cell lines. Meanwhile, the inhibition of PAK4 by PF-3758309 increased the expression of CDKN1A, BAD and BAK1 and decreased the expression of Bcl-2 and Bax. In addition, we screened the target genes of PAK4 by PCR array and found that 23 genes were upregulated (including TP53I3, TBX3, EEF1A2, CDKN1A, IFNB1 and MAPK8IP2) and 20 genes were downregulated (including TNFSF8, Bcl2-A1, Bcl2L1, SOCS3, BIRC3 and NFKB1) after PAK4 inhibition by PF-3758309. Moreover, PAK4 was found to regulate the cell cycle and apoptosis via the ERK signaling pathway. In conclusion, the present study demonstrated, for the first time, the expression and function of PAK4 in neuroblastomas and the inhibitory effect of PF-3758309, which deserves further investigation as an alternative strategy for neuroblastoma treatment.

Decreased autophagy is accompanied by the development of a myeloproliferative state or acute myeloid leukemia (AML). AML cells are often sensitive to autophagy‑inducing stimuli, prompting the idea that targeting autophagy can be useful in AML cytotoxic therapy. AML NB4 cells overexpressing microtubule-associated protein 1 light chain 3-green fluorescent protein were screened with 69 inhibitors to analyze autophagy activity. AML cells were treated with the polo-like kinase 1 (PLK1) inhibitors RO3280 and BI2536 before autophagy analysis. Cleaved LC3 (LC3-II) and the phosphorylation of mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase, and Unc-51-like kinase 1 during autophagy was detected with western blotting. Autophagosomes were detected using transmission electron microscopy. Several inhibitors had promising autophagy inducer effects: BI2536, MLN0905, SK1-I, SBE13 HCL and RO3280. Moreover, these inhibitors all targeted PLK1. Autophagy activity was increased in the NB4 cells treated with RO3280 and BI2536. Inhibition of PLK1 expression in NB4, K562 and HL-60 leukemia cells with RNA interference increased LC3-II and autophagy activity. The phosphorylation of mTOR was reduced significantly in NB4 cells treated with RO3280 and BI2536, and was also reduced significantly when PLK1 expression was downregulated in the NB4, K562 and HL-60 cells. We demonstrate that PLK1 inhibition induces AML cell autophagy and that it results in mTOR dephosphorylation. These results may provide new insights into the molecular mechanism of PLK1 in regulating autophagy.

To evaluate the reliability and validity of musculoskeletal questionnaire.A self-administered modified musculoskeletal questionnaire was used to investigate 12 098 workers from eight occupations, i.e. coal mining, petroleum, metallurgical, mechanical manufacturing, chemical, garment and railroad transportation industries and education. The Cronbach's α coefficient, analysis of covariance and multiple logistic regression were used to assess the reliability and validity of musculoskeletal questionnaire.The consistent test between total items of Musculoskeletal Questionnaire and each factor showed that the range of Cronbach's α was 0.52 ∼ 0.92, except from vibration factor, other Cronbach's α was more than 0.7. All 55 items of Musculoskeletal Questionnaire were subjected to factor analysis, and ten latent factors were identified, which explained 55.17% of the total variance. The potentially hazardous working conditions could be categorized into seven dimensions (force, dynamic load, static load, repetitive load, climate factors, vibration exposure and environmental ergonomic factor), which consisted with the theory model. The results of covariance analysis indicated that there were significant difference among 7 dimension indices in different jobs (P0.01).The modified Musculoskeletal Questionnaire is a valid and reliable tool for measuring musculoskeletal workload.

To investigate and analyze the occupational hazards of ultraviolet radiation, protective measures and related factors for typical symptoms among workers in electric welding, and to provide basic information for revision of the occupational standards of UV.Questionnaires and physical examinations were used in this investigation. A total of 828 workers from four vehicle manufacturers in Beijing and Guangdong Province were selected. Corresponding analyses were conducted with SPSS 16.0 statistic software.The top three injuries of faces and hands were burning tingling (48.7%41.3%), itch of skin (39%34.9%) and pigmentation (31.9%24.5%).The major injuries of eyes were ophthalmodynia (61.5%) , photophobia and tearing (61.4%), and blurred vision (50.2%). The incidences of facial and hands burning tingling, hands flushing, hands macula and papula were significantly different between the welders and auxiliary workers (P0.05). The differences of facial and hands burning tingling, flushing, facial disesthesia and anaesthesia, symptoms and signs of eyes were significant in different working years groups (P0.05). The top three usages of protective measures were welding masks (87.2%), gloves (84.3%) and glasses (65.9%). Except for UV cut cream, the usages of other protective equipments in the auxiliary workers were significantly lower than those in the welders (P0.05). The logistic regression analysis showed that prolonged exposure to arc welding, using argon arc welding and CO(2) gas shielded arc welding, not wearing welding masks, and not using UV cut cream was significantly associated with the increased risk of face burning tingling, and the ORs were 3.894 (6 h to 8 h), 2.665 (4 h to 6 h), 2.052, 1.765, 1.759, 1.833, respectively; working years might be a protective factor, and the OR was 0.440, respectively.The study suggested that the UV radiation produced during welding operations not only caused harm to welders, but also to the auxiliary workers. Protection should be strengthened,for example, wearing welding masks, glasses, etc. Meanwhile automatic welding machines should be adopted by the factories to reduce the exposure time for workers.

To develop a draft questionnaire (China Musculoskeletal Questionnaire, CMQ) for evaluating of musculoskeletal workload and associated potential hazardous working conditions as well as musculoskeletal symptoms of workers in Sitting Posture.Multi-methods, which include the reviewing references, the summarizing results of preliminary studies, the reviewing ergonomic tools, the consulting experts and occupational health workers and the interviewing or discussing with individual workers in sitting posture, were used in developing item pool. The experts and epidemiologists of occupational health scored the importance of every single item in the item pool, and then the survey and sampling were carried out in 325 workers of sitting posture who completed the questionnaire. On the basis of these data, the methods including experts scoring, item analysis, Cronbach's α analysis and factor analysis were synthetically used to select the reliable items which consisted of the formal questionnaire.The standard of the CMQ, which consists of 34 items on musculoskeletal workload and associated potentially hazardous working conditions, can be divided into nine indices (dynamic loads, static loads, repetitive loads, forces-exertion, prolong time, climatic factors, vibration, position and ergonomic environmental factors).The CMQ possesses good content validity, and the items of CMQ are divergent, reliable and typical. However, the reliability and validity of CMQ should be validated.

To investigate and analyze present conditions of the assembling line illumination in our country, and to set the recommended values of illuminance standard.Questionnaires and field surveys were used in this investigation. A total of 752 workers from seven factories in textile, shoes and electronics industries were selected for the questionnaire survey and site measurement, and corresponding analyses made with SPSS 13.0 statistic software.Uniformity of illumination, definition in working face, general satisfactory degrees, asthenopia were significantly correlated with each other. Assembly line illuminances for five different visual characteristics were recommended in this paper. The illuminances were 500-1 000-1 500 lx, 300-500-1 000 lx, 200-300-750 lx, 100-300-500 lx, 50-100-200 lx, respectively.Present conditions of the assembling line illumination are less than satisfactory, uniformity of illumination is on the low side, and there is no assembling line illuminance standard for general satisfactory degrees and asthenopia of workers. The related work should be further improved.

To investigate the interactive effect of job task and psychosocial factors on the outcomes of musculoskeletal disorders.653 workers from different type of manufacturing industries and administration office recruited in a cross-sectional epidemiological survey. The Quick Exposure Check (QEC) was applied to assess the ergonomic load of job task, Job Content Questionnaire (JCQ) for identifying psychological characteristics, and Nordic Standardized Questionnaire for investigating outcomes of WMSDs.The prevalence of WMSD in shoulder, upper back, lower back and hand/wrist were significantly different under a variety of combined job task and psychosocial characteristics (P0.05 or P0.01). The more physical and psychological loads, the higher prevalence of WMSDs were revealed. By using multivariate analyses, a potential interactive effect was found in terms of the WMSDs symptoms in hand/wrist, shoulder, upper back and lower back after adjusted by work year, age, and gender.Higher physical load and greater psychosocial risk are more frequent self-reported symptoms of WMSDs than those of lower exposures. Ergonomic intervention strategies aimed at reducing the incidence of WMSDs should not only be focused on control of physical work factors but also psychosocial risks of relevance.

To investigate the morbidity and influence factors of work-related musculoskeletal disorders (WMSD) in oil drillers.The modified Nordic Standardized Questionnaire for WMSD was used to perform the epidemiological investigation in 860 oil drillers.The predominant sites of WMSD in the oil drillers were waist (50.6%), neck (29.8%) and shoulder (23.4%), respectively. There were significant differences of the WMSD morbidities in all body sites except for wrist and hip among groups with different working years (P0.05 of P0.01). The WMSD morbidities in the neck, shoulder, back and waist of oil drillers working for more than 40h a week were significantly higher than those of oil drillers working for less than 40 ha week (P0.05). The results of logistic regression analysis revealed that some occupational factors, i.e. keeping stoop and stand for long time, repeating trunk bend, keeping awkward lift posture and lifting the heave objects, were the risk factors for WMSD at waist (P0.05), also some management factors, i.e. overtime work and inadequate rest, were the risk factors for WMSD at waist (P0.05).The WMSD appears to be a serious ergonomic problem in oil drillers, it is necessary to correct working posture, reduce working load, improve organizational management, and encourage a workplace health program with regular work and rest.

To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy.Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine.Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement.The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.