Objective To explore the potential mechanism of proguanil on the proliferation and apoptosis of bladder cancer cells.Methods 253J cells were randomly divided into control group(normal treatment),proguanil group(42.06 μmol·L-1 proguanil),pcDNA group(transfected with pcDNA+42.06 μmol·L-1 proguanil),FADS2 group[transfected fatty acid desaturase gene 2(FADS2)+42.06 μmol·L-1 proguanil],si-NC(transfection si-NC),si-FADS2(transfection si-FADS2),Ferrostatin-1 group(transfected with si-FADS2+10 μmol·L-1 ferrostatin-1).Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)assay was used to detect mRNA expression of related genes;Western blot assay was used to detect the expression of each protein;apoptosis was detected by TdT mediated dUDP nick end labeling(Tunel)assay;5-ethynyl-2'-deoxyuridine(EdU)assay to detect cell proliferation;the Transwell assay measures the ability of cells to migrate;Fe2+levels were determined by kit method;DCFH-DA probe was used to detect ROS levels.Results The mRNA levels of FADS2 in control group,proguanil group,pcDNA group and FADS2 group were 1.00±0.11,0.47±0.09,0.49±0.06 and 2.09±0.21,respectively;cell proliferation rate were(100.00±3.50)％,(54.31±4.90)％,(56.46±5.17)％and(78.76±6.50)％,respectively;the apoptosis rate were(3.92±0.53)％,(28.79±3.30)％,(27.20±2.90)％and(7.34±0.68)％,respectively;the migration number were 132.70±9.81,70.10±5.05,68.70±537 and 101.80±11.25,respectively;Fe2+level were(100.00±8.14)％,(201.33±17.84)％,(192.38±21.34)％and(116.70±10.90)％,respectively;GPX4 protein relative expression level were 0.77±0.05,0.31±0.05,0.34±0.05 and 0.68±0.06,respectively.The above indexes in proguanil group were compared with those in control group,the above indexes in FADS2 group were compared with those in pcDNA group,all the differences were statistically significant(all P＜0.05).The ROS levels of si-NC,si-FADS2 and Ferrostatin-1 groups were 9.72±1.18,40.94±5.63 and 13.77±1.40,respectively.Compared the si-FADS2 group with the si-NC group,Ferrostatin-1 group compared with si-FADS2 group,ROS level were significantly different(all P＜0.05).Conclusion Proguanil can induce the apoptosis of bladder cancer cells by inhibiting FADS2 expression mediated by oxidation-reduction driven ferroptosis pathway.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:Duanteng Yimutang(DTYMT) has a significant effect in treating rheumatoid arthritis, but its composition is complex and its mechanism is not clear. It is worthwhile to use network pharmacology approach to find active components, therapeutic targets and signal pathways of DTYMT. Method:The drug composition was selected according to the pharmacokinetic parameters in the pharmacology database, the analysis platform (TCMSP) and the TCM integrated database (TCMID) of the Traditional Chinese Medicine System. The drug and disease targets were excavated in the Drugbank database and the Therapeutic Target Database (TTD), and the drug-target-pathway network was constructed by network pharmacology tool Cytoscap, in order to explore the mechanism of the action of the components in the DTYMT. Result:It was found that 11 effective components of DTYMT could target 42 proteins in rheumatoid arthritis, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), cyclooxygenase-2 (COX2), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3), and inducible nitric oxide synthase (NOS2). Various pathways, including tumor necrosis factor (TNF) signaling pathway, interleukin-17 (IL-17) pathway, helper T cell 17 (Th17) differentiation pathway, rheumatic arthritis pathway, nuclear factor κB (NF-κB) pathway, osteoclast differentiation pathway, and ovarian steroid production pathway, were involved. Conclusion:DTYMT may be used to regulate inflammatory cytokines mainly through multiple inflammatory-related signal pathways, so as to play anti-inflammatory and immunoregulatory roles in the treatment of rheumatoid arthritis.

Spinal cord injury is a serious trauma of the spinal and nervous system, local tissue destruction and microcirculation disturbance can lead to a more serious spinal cord injury and extensive necrosis of neurons. Spinal cord injury often accompany with Inflammation reaction producing a variety of cytokines and bioactive substances, result in macrophage polarization. M1 macrophages polarization are induced by IFN-γ, LPS, TNF-α and so on, it show the damage and proinflammatory effect. M2 macrophages polarization are caused by IL-4, IL-10, IL-13 and show the recovery and anti-inflammatory effect. However, clinical treatment after spinal cord injury is very limited, inhibition of proinflammatory and promotion of anti-inflammatory by regulating the M1 macrophages and M2 macrophages is a new direction for the treatment of spinal cord injury. The article will review different phenotype and function of macrophages after spinal cord injury.

Objective To investigate the effect of the third party evaluation on improving the quality of medical service as well as the degree of patient trust in hospital.Methods Discharge patients from a two-level hospital in Minhang District was enrolled to evaluate their trust for medical service.Telephone follow-up were implemented in group A by the third party evaluation team.Group B was evaluated by the in-patient department when they left the hospital.These two evaluation methods were compared for the effects.Results During the first evaluation,1 073 people in group A,the equipartition satisfaction was 3.83 ± 0.57,the satisfaction rate was 54.99％.While in group B of 1 480 people,the equalization satisfaction was 3.83 ± 0.49,the satisfaction rate was 57.03％ (P＞0.05).At the fourth evaluation,1 233 people in group A and 1 512 people in group B were evaluated.Regarding group A,the patient satisfaction scores was 4.18 ± 0.33,patients satisfaction rate was 84.43％,the equipartition of patients referral was 3.44 ± 0.83,the equipartition of patients recommends the physician was 3.52 ±0.88,the equipartition of the doctor and patient had a quarrel was 4.33 ± 0.60,the equipartition of patients will find another doctor for diagnosis was 3.31 ± 0.72,the equipartition of patients expressed fully in accordance with the doctor's order of medication was 3.45 ± 0.72,group A were better than groupB (P＜0.05).Of the28 entries in the level of trust related to medical services,15 entries of group A were higher than group B (P＜0.05).In group A,the equipartition of moderate intensity activity was 3.62 ± 0.81,the equipartition of emotional coordination refers to 3.71 ± 0.76,the equipartition of family coordination was 3.69 ± 0.58,the equipartition of friends coordination was 3.73 ± 0.74,the equipartition of overall health was 3.31 ± 0.77,all were superior to group B (P＜0.05).Conclusions The third party evaluation is a supplementation for hospital management,which has positive effects on improving medical service quality of medical institutions,the hospital performance appraisal system,patients' experiences and trust degree.

OBJECTIVETo investigate the relationship of serum omentin-1 and chemerin with gestational diabetes mellitus (GDM).

METHODSSerum levels of omentin-1 chemerin, glycolipids biochemical index, inflammation index, fasting insulin (FINS), and insulin resistance indexes (HOMA-IR) were determined in 85 women with GDM and 85 pregnant women with normal glucose tolerance (NGT).

RESULTSBMI, FPG, hs-CRP, blood lipids, blood glucose, FINS, HOMA-IR and serum chemerin level were all significantly higher while serum omentin-1 significantly lower in GDM group than in NGT group (P<0.05). In both groups, serum omentin-1 level was significantly lower and serum chemerin was significantly higher in obese subjects than in the non-obese subjects (P<0.05). Obesity before delivery and/or HOMA-IR ≥2 was associated with a significantly decreased serum omentin-1 level; serum chemerin increased significantly in obese women before delivery but was not associated with HOMA-IR. Serum omentin-1 level was positively correlated with HDL but inversely with BMI (at pregnancy and before delivery), FPG, FINS and HOMA-IR; Chemerin was positively correlated with TC, TG, hs-CRP and FPG; serum omentin-1 and chemerin levels were not significant correlated (P=0.301). In women with GDM, BMI at pregnancy, TG, FPG, and FINS were all independent factors affecting serum omentin-1; TG, LDL, and hs-CRP were independent factors affecting serum chemerin.

CONCLUSIONAn decreased serum omentin-1 can be indicative of glucose and lipid metabolism disorder and insulin resistance, and an increased serum chemerin level indicates hyperlipidemia and chronic inflammation in pregnant women. Both of the adipokines are closed associated with GDM and probably participate in the occurrence and development of GDM.

Objective To investigate the relationship between plasma homocysteine on admission and the outcome at discharge of acute ischemic stroke.Methods A non-concurrent cohort study was performed and a total of 1 3 1 9 patients with acute is-chemic stroke were continuously included in this study.According to tertile range of plasma homocysteine,patients were di-vided into three group.Logistic regression analysis was used to assess the independent association between plasma homocys-teine on admission and poor outcome at discharge of acute ischemic stroke.Results The difference of plasma homocysteine on admission between the poor outcome and those with good outcome had statistical significance (P<0.000 1).Without the adj ustment of multiple factors,when comparing to the first group,the second and third tertile seemed to have a tendency of increasing the risk of poor outcome at discharge,the OR (95%CI)was 2.111 (1.297~3.437,P<0.05),2.113 (1.361~3.279,P<0.05).After adjustment for multivariate,the second and third tertile also seemed to have a tendency of increasing the risk of poor outcome at discharge,the OR (95%CI)was 1.876 (1.160~3.036,P<0.05),2.396 (1.414~4.062,P<0.05).Conclusion The current study indicated that higher plasma homocysteine level was an independent risk factor for poor outcome at discharge in ischemic stroke patients.It would increase the risk of the outcome at discharge in patients with acute ischemic stroke,and suggests that there is a dose-response relationship between plasma homocysteine level on admis-sion and the poor outcome at discharge.

BACKGROUND:Our previous studies confirmed that NGF-PEG-PLGA-NPs has good sustained release effect and biological activity in vitro, and can induce the differentiation of PC12 cel s into neuron-like cel s.
OBJECTIVE:To investigate the feasibility of neuronal differentiation of neural stem cel s from septal area of fetal brain induced by NGF-PEG-PLGA-NPs and its influence on PI3K/Akt signaling pathway.
METHODS:According to optimization prescription, NGF-PEG-PLGA-NPs were prepared by multiple emulsion solvent diffusion method. Neural stem cel s were induced to neuronal differentiation in six groups, including control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group. Neurons were identified by immunofluorescence, while phosphorylation levels of Akt in PI3K/Akt signaling pathway were detected by western blotting.
RESULTS AND CONCLUSION:The proportions ofβ-Tubulin III-positive neurons in control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group were (22.80±2.58)%, (35.80±3.98)%, (35.40±5.77)%, (26.60±3.87)%, (21.20±2.59)%and (25.80±7.22)%, respectively. There were no statistical differences in neuronal differentiation between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the ratios of neural differentiation in the two groups were both higher than that in the other four groups (P<0.05). Western blotting results revealed that there were no statistical differences in Akt phosphorylation levels between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the phosphorylation levels of Akt were both higher than other four groups (P<0.05). There were also no significant differences between LY294002+NGF and LY294002+NGF-PEG-PLGA-NPs groups and control group (P>0.05), but the phosphorylation levels of Akt were higher than LY294002 group (P<0.05). Results suggest that NGF-PEG-PLGA-NPs promoted neural differentiation of neural stem cel s. The role might be related to increasing phosphorylation levels of Akt in PI3K/Akt signaling pathway.

OBJECTIVETo estimate the size of female sex workers and clients in Taizhou city.

METHODSA household survey using network scale-up method (NSUM) was conducted among the 3000 community residents in Taizhou city from August to October in 2011, which aimed to estimate the social network size (c value) of Taizhou residents, and the c value was adjusted by demographic characteristics, back estimation and outlier elimination. Using the adjusted c value, the number of acquaintance of female sex workers or clients and the respect level toward female sex workers or clients were used to estimate the size of female sex workers and clients.

RESULTSA total of 2783 valid questionnaires were collected, among which 1380 (49.6%) were collected from Taixing city, 1403 (50.4%) were collected from Jingjiang city. 1334 respondents were male (47.9%) and 1449 (47.9%) respondents were female. The mean age was (39.4 ± 10.7) years. The average personal social network size using original data for Taizhou residents was 525, which differed from place, sex, age, educational level and marriage status. Using the remaining known populations through back estimation, the social network size was 419 and became 424 after the elimination of outliers. The estimated population size for female sex worker was 6370 (95%CI: 5886 - 6853), which accounted for 0.52% (6370/1 229 980) of the total number of female aged from 15 to 49. The estimated population size for clients was 15 202 (95%CI: 14 560 - 15 847), which accounted for 1.28% (15 202/1 190 340) of the total number of males aged from 15 to 49 and the ration of clients to female sex worker was 2.39:1.

CONCLUSIONNSUM is an easy and quick way to estimate the size of female sex workers or clients, but the estimated sizes are subject to bias and error due to estimate effect and sample representativeness.

Adolescent ; Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Sex Work ; statistics & numerical data ; Sex Workers ; statistics & numerical data ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in Sprague-Dawley (SD) rats.

METHODSThirty-two male SD rats were randomly and equally divided into 4 groups: control group and high-, middle-, and low-dose exposure groups. The rats in high-, middle-, and low-dose exposure groups were fed with the feed mixed with AlCl(3) (120.0, 12.0, and 1.2 mg/kg, respectively), while the rats in control group were fed conventionally. After 6 months of feeding, brain aluminum levels were determined by inductively coupled plasma mass spectrometry; Morris water maze was employed to test the learning and memory abilities; the expression and content of BDNF in brain tissue were measured by Western blot and enzyme-linked immuno sorbent assay (ELISA).

RESULTSThe high- and middle-dose exposure groups had significantly higher brain aluminum levels than the control group (P<0.05). The Morris water maze test showed that the high- and middle-dose exposure groups had significantly prolonged escape latency (P<0.05), significantly prolonged time taken to first reach the target quadrant (P<0.01), and significantly decreased number of platform crossings and time spent in the target quadrant (P<0.05), as compared with the control group. The Western blot and ELISA showed that the expression and content of BDNF in brain tissue decreased as the dose of AlCl(3) increased, and they were significantly lower in the high- and middle-dose exposure groups than in the control group (P<0.05).

CONCLUSIONChronic aluminum exposure (12.0 and 120.0 mg/kg) can lead to cognitive dysfunction in rats, and the decreased expression of BDNF may be one of the mechanisms of learning and memory deficits induced by aluminum.

Aluminum ; toxicity ; Animals ; Brain ; metabolism ; Brain-Derived Neurotrophic Factor ; metabolism ; Male ; Maze Learning ; drug effects ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Chronic