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Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.
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OBJECTIVE To investigate the effects of total glucosides of paeony （TGP） on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside （TWP） in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2，4-dinitrofluorobenzene-acetone olive oil solution （volume ratio was 4∶1） on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group， loratadine group （0.9 mg/kg）， TWP group （9.45 mg/kg）， TGP group （162 mg/kg） and compatibility group （TWP 9.45 mg/kg+TGP 162 mg/kg）， with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization， administration groups were given relevant medicine intragastrically， and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically， once a day， for consecutive 21 d. Twenty-four hours later after the final administration， the general condition of rats in each group was observed， and the eczema area and severity index （EASI） were scored； ear swelling degree of rats was measured， and the skinhistomorphology observation and pathological score were performed； protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase （p38 MAPK）， phosphorylated p38 MAPK （p- MAPK） and phosphorylation level of p38 MAPK in rat skin tissue were detected； the levels of inflammatory indexes （interleukin-4， interferon- γ）， liver and kidney function indexes [glutamic-pyruvic transaminase （GPT）， glutamic-oxaloacetic transaminase （GOT）， serum creatinine （SCr） and blood urea nitrogen （BUN）] and oxidant stress indexes [total superoxide dismutase （T-SOD） and malondialdehyde （MDA）] were measured. RESULTS Compared with normal group， EASI score， ear swelling degree， pathological score， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation level of p38 MAPK， the levels of inflammatory indexes and BUN were all increased significantly in model group （P＜0.05）. Compared with model group， EASI scores， ear swelling degree， pathological scores， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups （P＜0.05）. The levels of GPT， GOT， SCr and BUN were increased significantly in TWP group， while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly （P＜0.05）. The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group， while the levels of MDA were increased significantly （P＜0.05）. The compatibility group showed more obvious effect in improving the ear swelling degree， pathological score， p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes， and could reverse the abnormality of liver and kidney indexes caused by TWP （P＜0.05）. CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory， synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.
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Objective:To investigate the efficacy of fixation with cannulated screws alone via the Kocher approach in the treatment of adult humeral capitulum fractures.Methods:From August 2016 to August 2020, 16 patients with humeral capitulum fracture were treated at Department of Upper Limb Orthopedics, Zhengzhou Orthopaedic Hospital. They were 10 males and 6 females, aged from 36 to 62 years (average, 45 years). The left side was affected in 10 cases and the right side in 6. According to the Ring classification, 3 cases were type Ⅰ, 3 cases type Ⅱ, 6 cases type Ⅲ, and 4 cases type Ⅳ. All patients were treated with the Kocher approach on the lateral side of the elbow. After reduction under direct vision, the fractures were fixated temporarily with Kirschner wires and finally with cannulated screws. On the second postoperative day, the patients started active flexion and extension of the elbow joint and took indomethacin orally to prevent heterotopic ossification. At the last follow-up, the curative efficacy was evaluated according to the Mayo elbow performance score (MEPS). The flexion and extension of the elbow joint and the rotation of the forearm were also recorded.Results:All patients were followed up for 10 to 19 months (mean, 14.3 months) after surgery. Bony union was achieved after 7 to 12 monthes (average, 11.3 monthes) in all the 16 patients, 2 of whom developed heterotopic ossification. By the MEPS evaluation at the last follow-up, 8 cases were excellent, 6 good and 2 fair, scoring an average of 89.5 points (from 73 to 95 points). At the last follow-up, the elbow flexion ranged from 80° to 130° (averaging 113°), extension from 5° to 30° (averaging 15°), forearm pronation from 62° to 75° (averaging 67°), and forearm supination from 50° to 90° (averaging 75°).Conclusion:When the fracture ends are exposed through the lateral Kocher approach, the fracture fragments fixated with cannulated screws only, and the patients encouraged to start elbow joint exercises in the early stage, the treatment of adult humeral capitulum fractures can result in satisfactory curative effects.
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Objective:To evaluate the clinical efficacy of the axillary approach in the treatment of scapular glenoid fracture.Methods:A retrospective analysis was performed of the 12 patients who had been treated for scapular glenoid fracture from November 2019 to April 2021 at Department of Upper Limb Orthopaedics, Zhengzhou Orthopaedic Hospital. They were 4 males and 8 females, aged from 30 to 75 years (mean, 53.5 years). According to the Ideberg classification, there were 2 cases of type Ⅰa, 9 cases of type Ⅱ and one case of type Ⅴa. All cases were treated through the axillary approach. Two patients complicated with anterior shoulder dislocation were treated with manual reduction under anesthesia before operation and the other 10 cases with special plate fixation through the axillary approach. The 3 patients complicated with fracture of greater tuberosity were fixated with a special plate through the lateral shoulder split deltoid approach. Constant-Murley score, visual analogue scale (VAS) and Hawkins grading were used at the last follow-up to evaluate shoulder function, pain and stability after operation.Results:All patients were followed up for 9 to 20 months (mean, 14.4 months). The operation time ranged from 55 to 110 min (mean, 76.3 min), intraoperative bleeding from 60 to 160 mL (mean, 103.8 mL), and hospital stay from 8 to 14 d (mean, 11.1 d). All incisions healed primarily and all scapular glenoid fractures got united 6 months after operation. The last follow-up showed no shoulder instability, neurovascular injury or internal fixation failure. At the last follow-up, the range of motion of the shoulder was 159.2°±26.1° in forward bending, 156.7°±29.6° in abduction, 48.3°± 15.3° in external rotation (neutral position), and 73.3°±12.3° in internal rotation (neutral position), and the Constant-Murley score was (94.0±5.3) points. The range of motion of the shoulder and Constant-Murley score were significantly improved compared with those before operation (10.8°±11.6°, 7.5°±11.4°, 5.8°±10.0°, 42.5°±16.0° and 4.9±4.0, respectively) (all P<0.05). The VAS score was 0 in 11 patients and 2 in one patient at the last follow-up. Conclusion:The axillary approach is feasible for the treatment of scapular glenoid fracture, because it is hidden and less invasive, leading to good clinical outcomes.
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Objective:To analyze the relationship between self-disclosure, self-efficacy and medical coping modes in adolescent depression, and explore the mediating effect of self-efficacy between self-disclosure and medical coping modes.Methods:Using the convenience sampling method, a total of 403 adolescents with depression in a tertiary psychiatric hospital in Beijing were recruited from March 2020 to March 2021. The data of general information questionnaire, distress disclosure index scale, medical coping modes questionnaire and general self-efficacy scale were collected.SPSS 26.0 software was used to analyze the correlation between self-disclosure, self-efficacy and medical coping modes of adolescent patients with depression, and Stata 13.1 software was used to analyze the mediating effect of self-efficacy between self-disclosure and medical coping modes.Results:The scores of dimension of the medical coping modes of adolescent depression patients were(16.90±3.84) for facing, (16.34±2.88) for yielding, (12.48±4.31) for avoiding, (30.47±9.91) for self-disclosure and (19.63±6.54) for self-efficacy, respectively. Self-disclosure and self-efficacy were positively correlated with facing of medical coping modes ( r=0.301, 0.327, both P<0.01), and negatively correlated with yielding of medical coping modes ( r=-0.465, -0.487, both P<0.01). Self-disclosure was negatively correlated with avoidance of medical coping modes ( r=-0.118, P=0.018). The direct effect of self-efficacy on medical coping modes was 0.103, and the total effect was 0.365, and the mediating effect accounted for 28.22%. Conclusion:Self-efficacy partially mediates between self-disclosure and medical coping modes in adolescents with depression.
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Objective:To observe and analyze the clinical characteristics of children who died of intraocular retinoblastoma (RB).Methods:A retrospective clinical study. Fourteen children (23 eyes) with intraocular RB who died after receiving treatment in Beijing Children's Hospital from 2009 to 2017 were included in the study. Among the children, there were 7 males (10 eyes) and 7 females (13 eyes); 5 had unilateral and 9 had bilateral tumor. Age were 17.2±15.5 months. All children underwent RetCam examination. RB was staged according to the international intraocular RB classify. Among the 23 eyes, 1 eye was in stage B, 2 eyes were in stage C, 12 eyes in stage D, and 8 eyes in stage E. Treatment methods included a systemic (vincristine, etoposide and carboplatin) chemotherapy (VEC chemotherapy), enucleation surgery, and vitrectomy. The basic conditions including age, time of diagnosis, pathological diagnosis, treatment and main causes of death were retrospectively analyzed.Results:Among the 14 cases, the first symptom was leukemia in 12 cases, red eye in 1 case, and squintin in 1 case. Systemic VEC chemotherapy was used for 1-6 courses of treatment; 5 cases were enucleated, 3 cases underwent histopathological examination; 3 cases were treated with vitrectomy. Among the 3 cases who underwent histopathological examination, the sclera and optic nerve, optic nerve and optic disc were invasted respectively. Seven patients died of tumor metastasis and/or intracranial lesions (50.0%, 7/14); the median survival time was 19 months. Four patients died of treatment (28.6%, 4/14), including 3 patients died of chemotherapy-related side effects, and 1 died of organ failure after enucleation surgery (7.1%); the median survival time was 3.5 months. Early abandonment of treatment died in 3 cases (21.4%, 3/14); the median survival time was 15 months.Conclusion:Intracranial metastasis is the main cause of death in children with intraocular RB.
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ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.
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ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.
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OBJECTIVE@#Sort out and analyze the current status and existing problems of the pilot work of the medical device marketing authorization holder system to provide reference opinions for the full implementation of the medical device marketing authorization holder system.@*METHODS@#Use literature analysis, comparative analysis and field research to comprehensively analyze the status, advantages and risks of commissioned production under the medical device marketing authorization holder system.@*RESULTS@#The commissioned production under the medical device marketing authorization holder system brings dividends and also brings risks.@*CONCLUSIONS@#We should consider improving the medical device marketing authorization holder system from marketing authorization holder, the entrusted manufacturer, and the regulatory authority, and strengthen the quality supervision of the entrusted production of products.
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China , MarketingABSTRACT
Objective:To evaluate the clinical efficacy of Yiqi-Tongmai Decoction on isolated coronary muscle bridge angina patients with qi deficiency and blood stasis syndrome. Methods:A total of 64 patients with isolated coronary artery muscular bridge angina pectoris with qi deficiency and blood stasis syndrome in Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University from April 2016 to January 2020 who met the inclusion criteria were divided into 2 groups by random number table method, with 32 patients in each group. The control group took diltiazem hydrochloride tablets orally, and the treatment group took Yiqi-Tongmai Decoction on the basis of the control group. Both groups were treated for 8 weeks. The TCM syndrome scores were observed before and after treatment, and Seattle Angina Questionnaire was assessed for patient's quality of life and functional status. The exercise ECG test was observed before and after treatment, and the cause of angina pectoris need to be recorded, including the movement time and plate movement caused by time of ST segment in electrocardiogram (ecg) and dynamic evolution. Results:The total effective rate of angina pectoris was 84.38% (27/32) in the treatment group, and 53.13% (17/32) in the control group, and the difference between the two groups was statistically significant ( χ2=8.09, P<0.05). After treatment, the degree of physical activity limitation (69.24 ± 14.21 vs. 59.42 ± 11.71, Z=-2.61), stable state of angina (82.25 ± 21.24 vs. 69.11 ± 19.52, Z=2.64), angina (80.24 ± 18.31 vs. 69.11 ± 15.54, Z=2.63), treatment satisfaction (86.16 ± 19.23 vs. 61.19 ± 17.35, Z=2.22), degree of disease cognition (74.41 ± 21.13 vs. 60.43 ± 19.42, Z=2.40) scores in the treatment group were significantly higher than those in the control group ( P<0.05). In the treatment group, the time of exercise-induced angina pectoris [(476.15 ± 62.15)s vs. (399.38 ± 78.42)s, Z=-2.08], the time of ST segment descending 1 mm after exercise [(394.54 ± 75.61)s vs. (309.64 ± 81.62)s, Z=-2.40] in the treatment group were significantly longer than those in the control group ( P<0.05). The total effective rate of TCM syndrome was 93.8% (30/32) in the treatment group and 65.6% (21/32) in the control group, and the difference was statistically significant ( χ2=7.96, P<0.05). The TCM syndrome scores of the treatment group (25.15 ± 6.15 vs. 36.38 ± 10.42, Z=-2.56) in the treatment group were significantly lower than that of the control group ( P<0.05). There were no obvious adverse reactions in both groups during treatment. Conclusion:Yiqi-Tongmai Decoction can improve the clinical symptoms of isolated coronary artery muscle bridge angina pectoris with qi deficiency and blood stasis syndrome, reduce the onset of angina pectoris, delay the time of exercise induced angina pectoris, and improve the clinical efficacy.
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Objective:To summarize the clinical characteristics of single-center children with low and intermediate-risk neuroblastoma (NB), report the long-term follow-up results of the growth and survival quality, and provide a basis for further clinical research.Methods:Clinical characteristics, including the sex, age, stage, risk of disease, and metastatic site of 370 newly treated children with low and intermediate-risk NB admitted to Hematology Oncology Center, Beijing Children′s Hospital from March 2007 to June 2019 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.WHO Anthro Plus was used for calculating Z score.Results:A total of 370 eligible children with low and intermediate-risk NB were included, with the mean age at onset of 16.8 months (1-191 months). Among them, 148 cases (40%) were younger than 12 months old.Mediastinal region was the most common primary site of NB (47.8%, 177 cases), followed by retroperitoneum/adrenal gland (41.4%, 153 cases). The median follow-up time of 370 patients was 31 months (0.3-157.0 months), the 5-years event free survival (EFS) and 5-year overall survival (OS) were 86.2% and 96.9%, respectively.Thirty-seven cases had growth and deve-lopment problems, of which 22 cases had stunted growth, 6 cases had low body mass, 9 cases had wasting, and 7.3%(27/370 cases) had scoliosis.5.5% of them had heart damage and 5.0%(18/357 cases) had kidney damage, involving 12 cases related to the primary tumor and 6 cases were surgically related.30.2%(95/315 cases) of them had hair changed after chemotherapy, and curly hair was the most common change.Compared with before treatment, 14.9% of the children had a personality change, with an impatient being the most common.Conclusions:The 5-year overall survival rate of the single-center large sample of low and intermediate-risk NB was high, mediastinal was the most common primary site of tumor, and the long-term quality of life is good, but there were still treatment-related side effects, and further clinical monitoring and long-term follow-up were needed.
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Objective:To summarize the causes of death and severe complication in the early diagnosis of children with neuroblastoma (NB), and to analyze the relative factors of early death of children with NB, so as to raise awareness and reduce early mortality by early detection and early intervention.Methods:Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively, and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients, immediate causes of death, complications, time elapsed between death and diagnosis, whether to receive chemotherapy and other information were collected.Results:A total of 654 cases were included for diagnosis, treatment and follow-up, 31 cases of which died in early stage, accounting for 4.7% of the total.The major complication were pulmonary infection in 18 cases (58.1%) and bone marrow suppression after chemotherapy in 17 cases (54.8%), tumor rupture hemorrhage in 16 cases (51.6%), multiple organ failure in 8 cases (25.8%). Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis: there were statistical differences between early death group and non-early death group in risk grouping ( P=0.006 6), bone marrow invasion ( P=0.020 7), site of primary tumor ( P=0.016 7), age ( P=0.003 3), lactate dehydrogenase (LDH) level ( P<0.000 1), neuron-specific enolase (NSE) level ( P<0.000 1), serum ferritin level ( P=0.016 0), D dimer level ( P<0.000 1), fibrinogen level ( P=0.002 7), diameter of tumor ( P<0.000 1), hemoglobin ( P<0.000 1), platelet level ( P<0.000 1), serum albumin level ( P<0.000 1). Multiple-factor analysis: age younger than 30 months, OR=2.824 (95% CI: 1.084-7.359), LDH level greater than 1 004 IU/L, OR=6.991 (95% CI: 2.135-22.887), albumin level less than 36 g/L, OR= 65.237 (95% CI: 2.024-13.545), hemoglobin level less than 92 g/L, OR=5.358 (95% CI: 2.024-13.545), platelet level less than 192×10 9/L, OR=3.554 (95% CI: 1.267-9.965). Conclusions:Strengthening vital signs detection after admission, identifying severe life-threatening complications such as rupture of tumors as early as possible, implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation, and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.
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Objective:To summarize the clinical characteristics, treatment response and long-term postoperative complications in children with neuroblastoma (NB) in the pelvic and sacral regions as the primary site.Methods:The clinical characteristics of 16 NB children (8 males and 8 females) with primary pelvic and sacral admitted to the Department of Hematology Oncology Center in Beijing Children′s Hospital, Capital Medical University from March 2007 to June 2019 were analyzed retrospectively with respect to the age at first diagnosis, primary tumor site, tumor size, clinical stage, risk grouping, and other clinical characteristics.The clinical characteristics of the patients who were followed up for regular treatment were analyzed, and the postoperative complications of the patients were summarized, and the Kaplan-Meier method was used for survival analysis.Results:The median age at diagnosis of these 16 children was 23.0 months (5.7-102.0 months), of which 6 cases (37.5%) were younger than 12 months old.All these children received chemotherapy, with a median of 6 (1-8) courses of chemotherapy.Fifteen children received surgical resection of the pelvic tumor, with complete resection in 12 cases (80%). The surgical approach was mainly transabdominal (86.7%, 13/16 cases). The median follow-up time of these children was 33.5 (8-136) months.The patella was absent in 3 patients (18.8%) after the operation, and no permanent neurological damage occurred in all patients.Five-year overall survival (OS) rate was 100%.Conclusions:A single-center summary showed a high survival rate for NB patients in the pelvic and sacral regions.Complete tumor resections combined with chemotherapy could be effective measures and rare cases occurred permanent postoperative neurological complications.
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Vitamins are organic substances that are essential for the maintenance of life activities. Generally, vitamins need to be obtained from the diet or from some synthetic source as the body cannot synthesize vitamins, or the amounts of the synthesized vitamins are insufficient. At present, vitamins are widely used in medicine, food additives, feed additives, cosmetics and other fields, and the global demand for vitamins is constantly growing. Vitamins can be produced from chemical or microbial synthesis. Chemical synthesis usually requires harsh reaction conditions, produces serious wastes, and creates great potential safety hazard. In contrast, microbial synthesis of vitamins is greener, safer, and requires much less energy input. This review summarizes the advances in metabolic engineering for vitamins production in the past 30 years, with a focus on production of water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, B12 and vitamin C precursors) and lipid-soluble vitamins (vitamin A, precursors of vitamin D, vitamin E and vitamin K). Moreover, the bottlenecks for fermentative production of vitamins are discussed, and future perspectives for developing next generation vitamins producing strains using synthetic biotechnology are prospected.
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Biotechnology , Metabolic Engineering , Vitamin A , Vitamin K , Vitamins/analysisABSTRACT
Bacillus subtilis is a model strain for studying the physiological and biochemical mechanisms of microorganism, and is also a good chassis cell for industrial application to produce biological agents such as small molecule compounds, bulk chemicals, industrial enzymes, precursors of drugs and health product. In recent years, studies on metabolic engineering methods and strategies of B. subtilis have been increasingly reported, providing good tools and theoretical references for using it as chassis cells to produce biological agents. This review provides information on systematically optimizing the Bacillus subtilis chassis cell by regulating global regulatory factors, simplifying and optimizing the genome, multi-site and multi-dimensional regulating, dynamic regulating through biosensors, membrane protein engineering. For producing the protein reagent, the strain is optimized by optimizing the promoters, signal peptides, secretion components and building the expression system without chemical inducers. In addition, this review also prospects the important issues and directions that need to be focused on in the further optimization of B. subtilis in industrial production.
Subject(s)
Bacillus subtilis/genetics , Bacterial Proteins/genetics , Biotechnology , Metabolic Engineering , Promoter Regions, Genetic , Protein Sorting Signals/geneticsABSTRACT
Objective:To explore the changes and clinical significance of inflammatory indices of urogenic sepsis with different severity.Methods:A retrospective case-control study was used to analyze the clinical data of 71 patients with urogenic sepsis admitted to 940th Hospital of PLA Joint Logistics Support Force from January 2010 to April 2018, including 34 males and 37 females, aged 39-96 years [(63.1±18.3)years]. The patients were divided into three groups according to the clinical diagnostic criteria for septic shock and sepsis according to the 2014 edition of the Chinese Urology Surgical Guidelines for Diagnosis and Treatment: 21 cases in sepsis group [sequential organ failure assessment (SOFA) score of 3.0 (2.0, 3.0)points], 21 cases in severe sepsis group [SOFA score of 9.0 (6.0, 11.0)points], and 29 cases in septic shock group [SOFA score of 15.0 (14.0, 16.0)points]. Spearman correlation analysis was used to analyze the correlation of inflammatory indicators with SOFA, including white blood cell count, percentage of neutrophils, C-reactive protein, interleukin-6, procalcitonin, fibrinogen, D-dimer, and platelet. Multiple linear regression analysis and stepwise regression weighted analysis were performed to analyze the relation between inflammatory indicators and sepsis severity. Levels of each inflammatory indicator was detected and compared among the groups.Results:① Spearman correlation analysis: percentage of neutrophils, D-dimer, interleukin-6, procalcitonin and SOFA scores were significantly positively correlated, with the r s value of 0.738, 0.712, 0.31, 0.795, respectively ( P<0.01); platelet and SOFA scores were significantly negatively correlated, with the r s value of -0.661 ( P<0.01). ② Multiple linear regression analysis: percentage of neutrophils, platelet, D-dimer, procalcitonin and SOFA score were significantly correlated ( P<0.01); Stepwise regression weighted analysis suggested that the model linear relationship and fit was good. ③ Inflammatory index comparison: percentage of neutrophils in sepsis group, severe sepsis group and septic shock group was 82.30 (76.25, 88.45), 90.50 (86.55, 93.85), 95.10 (92.05, 97.95), respectively; level of platelet was 183.01 (144.50, 246.50)×10 9/L, 149.11 (81.04, 207.00)×10 9/L, 81.26 (50.01, 93.50)×10 9/L, respectively; level of D-dimer was 0.98 (0.71, 1.74)mg/L, 3.45 (1.79, 5.56)mg/L, 7.19 (4.26, 11.63)mg/L, respectively; level of procalcitonin was 0.55 (0.21, 1.09)ng/ml, 5.45 (3.74, 11.80)ng/ml, 17.68 (13.97, 26.75)ng/ml, respectively. There were significant differences in above indicators among the groups ( P<0.05). Conclusions:The serum levels of procalcitonin, percentage of neutrophils, D-dimer and platelet are positively correlated with the severity of urogenic sepsis. While combined detection of those indicators can better predict the severity of the sepsis.
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Objective:To investigate and analyze the epidemiological and clinical characteristics of 46 patients with corona virus disease 2019 (COVID-19) in Beijing City.Methods:A retrospective study was conducted to analyze the data of 46 patients with COVID-19 in Beijing from 20th January 2020 to 8th February 2020 at the Fifth Medical Center of the PLA General Hospital in Beijing City. Twelve, 23 and 11 patients were assigned to the mild group, common group and severe group, respectively. The epidemiological history, clinical characteristics, laboratory tests and imaging inspections were analyzed. Statistical analysis used Fisher exact test. If P<0.05, post- hoc test was used for pairwise comparison, and the statistics were corrected by Bonferroni test. Results:Among the 46 patients included in this study, 27 were male and 19 were female. The age range was between 3-79 years old, and the age was (41.8±16.3) years old. The average incubation period was (4.85±3.00) days. A total of 26 cases (56.5%) were clustered patients, and 26 cases had a history of staying in Wuhan, 10 cases had contact with Wuhan personnel. Fever (39 cases, 84.8%), cough (27 cases, 58.7%), and fatigue (25 cases, 54.3%) were the main clinical symptoms for these patients. The decrease in white blood cell counts occurred in 12 patients, four had the decrease in T lymphocyte percentage, 17 had the decrease in CD4 + T lymphocyte counts, seven had the decrease in CD8 + T lymphocyte counts, 21 had the increase level of C reactive protein (45.7%), and interleukin-6 (IL-6) level increased in 32 cases (69.6%), erythrocyte sedimentation rate (ESR) increased in 23 cases (50.0%), serum ferritin level increased in 26 cases (56.5%), and blood lactic acid level increased in nine cases. There were statistically significant differences in the proportion of cases with decreased absolute value of CD8 + T lymphocytes and T lymphocytes counts among the mild, common and severe groups (all P<0.05). Comparing the proportion of cases in the three groups with elevated C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels, the differences were statistically significant (all P<0.05). The proportion of cases with elevated C reactive protein levels in severe group was higher than those in mild and common groups. The proportion of cases with elevated IL-6, ESR, and serum ferritin levels in severe and common group were higher than those in mild group. The proportion of cases with elevated blood lactic acid levels in severe group was higher than those in mild group. The differences between the above groups were statistically significant (all adjusted P<0.017). Analysis of chest X-rays results showed that 34 patients (73.9%) had inflammation in the lungs. Conclusions:The epidemiological characteristics of patients with COVID-19 in Beijing City are mainly imported cases and clustered cases. The clinical manifestations are mainly fever, fatigue and cough. C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels are higher in severe patients.
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Objective:To analyze the clinical features and prognosis of pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and further understand these tumors.Methods:Twenty-nine NRSTS children were admitted to the Hematological Oncology Ward of Beijing Children′s Hospital from June 2011 to May 2018.The clinical and pathological data of these children were collected, and the relationships of the prognosis with clinical characteristics Intergroup Rhabdomyosarcoma Study(IRS) stage, Children′s Oncology Group(COG) risk grouping were analyzed.All the patients were followed up until October 31, 2018.The survival analysis was performed by Kaplan-Meier method.Results:There were 14 boys and 15 girls in the enrolled 29 children, aging from 7 to 169 months, with a median age of 59.5 months.There were 10 pathological types, including synovial sarcoma, infantile fibrosarcoma and malignant rhabdomyoid tumors in 5 cases, and other pathological types in 14 cases.Tumors originated from the head and neck in 10 cases, limbs or trunk in 6 cases, visceral sites in 13 cases.Ten cases showed distant metastasis.There were 12 cases at IRS stage Ⅰand Ⅱ, and 17 cases of stage Ⅲ and Ⅳ.All the children were treated with surgery and chemotherapy with or without radiotherapy.Nine cases received preoperative chemotherapy, 17 cases received postoperative chemotherapy, 3 cases could not be resected surgically.The follow-up period ranged from 4 to 89 months, with a median follow-up of 16 months.Six of 29 children died, including 3 cases of malignant rhabdomyoid sarcoma.The 2-year overall survival(OS) rate of all the children was 77.4% and the 2-year event-free survival (EFS) rate of all the children was 53.2%.By analyzing the clinical factors, it was found that the IRS stage, COG risk group, primary sites were related to prognosis.The 2-year EFS rate of children with IRS Ⅰ-Ⅱ and Ⅲ-Ⅳ were 75.0% and 35.9%, respectively ( χ2=7.303, P=0.007), the 2-year OS rate was 100% and 61.8%, respectively( χ2=4.81, P=0.028); The 2-year EFS of children in COG low-risk group and median/high-risk group were 66.7% and 44.7%, respectively( χ2=4.155, P=0.042), the 2-year OS rate of children in COG low and median/high-risk was 100% and 66.3%, respectively( χ2=3.383, P=0.066); the 2-year OS rate of children in visceral and non-visceral sites were 59.3% and 92.9%, respectively ( χ2=4.202, P=0.04). Conclusions:NRSTS in children is heterogeneous, and surgery is the main treatment. Children with primary tumors located in visceral sites and at IRS Ⅲ-Ⅳ had poor outcomes.
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Objective:To summarize the clinical features, therapeutic effects and prognostic factors of children with extracranial malignant germ cell tumor (MGCT), and further to improve the recognition of this disease.Methods:The clinical information and therapeutic effects of children patients diagnosed with MGCT and treated in Hematology-Oncology Center in Beijing Children′s Hospital, Capital Medical University from January 2008 to December 2018 were analyzed retrospectively, and the risk factors affecting the prognosis were discussed.Results:A total of 35 patients were collected in this study, including 19 girls and 16 boys, with a median age of 71 months.Forty-two point four percent (14/33 cases) of them were <3 year-old, and 39.3% (13/33 cases) of them were >6 year-old.The primary tumors were located at the gonad in 9 cases (6 cases in the ovary and 3 cases in the testis), and extragonadal sites in 26 cases (8 cases in the pelvic cavity, 8 cases in the mediastinum, and 10 cases in the sacrococcygeal region). Five cases were in stage Ⅱ, 16 cases in stage Ⅲ, and 14 cases in stage Ⅳ.Eleven cases were at intermediate risk, and 24 cases were at high risk.All children were followed up for (25.43±4.82) months, and given standard treatment of surgery plus chemotherapy.The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 87.4% and 67.1%, respectively.The 2-year OS rate and EFS rate in patients at stage Ⅱ and Ⅲ (93.8% and 80.4%, respectively) were significantly higher than those at stage Ⅳ (66.7% and 45.1%, respectively) ( χ2=0.649, 0.739; P=0.021, 0.037). The 2-year EFS rate in patients with and without distant metastasis at the early stage of the disease was 43.8% and 86.9%, respectively, and the differences were significant ( χ2=0.694, P=0.028). The complete remission (CR) rates of intermediate-risk and high-risk children with tumor completely resected at the early stage of the disease were 100.0% (8/8 cases) and 71.4% (5/7 cases), respectively.The CR rate of patients who received 2-4 cycles of chemotherapy and had complete tumor resection after diagnosis by puncture was 72.7% (8/11 cases), and 40.0% (2/5 cases) of the children with incomplete resection got tumor progression.For eight patients with events, their alpha-fetoprotein (AFP) levels decreased slowly at the early stage of the disease and increased significantly as the disease progressed. Conclusions:The onset-age of MGCT is mainly <3 year-old and >6 year-old.The stan-dard treatment that combines surgery and chemotherapy can achieve a good overall prognosis.Incomplete surgical resection and a slow decline of AFP during treatment contribute to adverse prognosis.The outcomes of patients with tumor progression can be improved by increasing chemotherapy courses, secondary surgery and autologous stem cell transplantation.
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Objective:To summarize and analyze the results of chromosome karyotype in children with neuroblastoma (NB) with bone marrow metastasis at first diagnosis, and to discuss the clinical significance.Methods:G-banding was applied to the analysis of chromosome karyotype of patients who were regularly treated in the Hematological and Oncology Center in Beijing Children′s Hospital from January 2015 to December 2017, and all the patients were followed up until December 31, 2018.Their clinical features and prognosis were analyzed.Results:(1) There were 120 cases with bone marrow metastasis, including 74 boys and 46 girls, and 98 cases (81.7%) were ≥ 18 months.Among 60 cases with normal chromosome, 56 cases (93.3%) were in International Neuroblastoma Staging System(INSS)-Ⅳ phase, and 4 cases in INSS-Ⅳs phase; there were 2 low-risk (LR) cases, 9 intermediate-risk (MR) cases, and 49 high-risk (HR) cases (81.7%); 7 cases had MYCN gene amplifications.All 60 patients with chromosome abnormalities were in INSS-Ⅳ phase; there was 1 case in MR and 59 cases (98.3%) in HR; 14 cases had MYCN gene amplifications.(2) Among 60 children (50%) with chromosome abnormalities, 4 children had number abnormalities, 14 children had structural abnormalities, and 42 children had both number and structural chromosome abnormalities.Chromosome 21, 10, 11 deletions were the most common in number abnormalities; structural abnormalities involving 11q, 1p, 3p segments had a high incidence.(3) Seventeen cases of children with normal chromosome had tumor progression or recurrence during the 4 to 44-month follow-up period, and 31 cases of children with chromosome abnormalities had tumor progression or recurrence during the 2 to 42-month follow-up period.The 3-year overall survival rate and event-free survival rate of all children were 60.0% and 48.4%, respectively; children in the normal chromosome group had a 3-year overall survival rate of 74.2% and an event-free survival rate of 65.7%; the 3-year overall survival rate and event-free survival rate of children with chromosome abnormalities were 47.5% and 24.9%, respectively.Most children suffering from tumor progression or recurrence had chromosome 10 deletion, and abnormal structure of 11q, 1p, 2p segments. Conclusion:The chromosomal abnormality rate of Nb children's tumor cells is high, but the repetition rate is low, and the individual difference is obvious.The deletion of chromosome 10, abnormal regional structure of 11q, 1p and 2p segments may be poor prognostic factors for NB.Chromosome karyotype analysis of bone marrow samples is feasible, which can provide a basis for more accurate risk stratification and treatment.