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ObjectiveThe objective is to investigate the possibility of isocenter dual-guided resetting of surface guided radiation therapy （SGRT） combined with image guided radiation therapy （IGRT） in postoperative radiotherapy for breast cancer. To assess the setup error accuracy between the new resetting mode and the traditional resetting mode. MethodsRetrospective analysis was performed on breast cancer patients who underwent ELEKTA infinity accelerator radiotherapy in sun yat-sen university cancer center from July 13， 2021 to October 15， 2022. According to different reset methods， the patients were divided into a simulation group （41 cases） and a dual-guided group （40 cases）. The simulation group was reset using a simulator， CBCT scans were performed and setup errors were recorded during the first treatment； The dual-guided group was guided by AlignRT and combined with CBCT for isocenter dual-guided resetting， and the setup error obtained by CBCT registration was recorded. The global setup errors of chest region of interest （CROI） ， the local residual errors of supraclavicular region of interest （SROI） and the resetting time of the two reset methods were calculated and compared respectively. The advantages of the CBCT error distribution in the dual-guided resetting of SGRT combined with IGRT were analyzed. ResultsThe median of the global setup errors （X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz°） of the simulation group and the median of the dual-guided group in the CROI were statistically significant （P<0.05） except the Rz and Ry directions. The local residual errors of the two groups of the SROI were calculated. The median of the errors of X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz° were statistically significant （P<0.05） except the X and Y axis. The resetting time of the simulation group was significantly longer than that of the dual-guided group （238.64±28.56） s， t=-24.555， P=0.000， and the difference was statistically significant （P<0.05）. The CBCT error distribution of the dual-guide group was analyzed， and it was found that the absolute values of translation errors of X， Y and Z axis were all within 0.4 cm， while the proportions of ≤ 0.3 cm were 95%， 93% and 93%， respectively. The proportions of rotation errors of Rx， Ry and Rz ≤ 1.5 ° were 90%， 93% and 90%， respectively. ConclusionIn postoperative radiotherapy of breast cancer， SGRT combined with IGRT for isocenter dual-guided resetting can effectively correct the rotational setup errors and residual errors， and improve the accuracy of radiotherapy with less resetting time and high feasibility， which compared with the traditional simulator resetting mode. This precise， unmarked resetting method can be widely used in clinical practice.
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OBJECTIVE To compare the efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy， and to provide evidence-based reference. METHODS The databases including CNKI， VIP， China Biomedical Literature Database， Wanfang data， PubMed， Embase and Cochrane Library were searched for the RCTs about levetiracetam （trial group） and valproic acid （control group） were collected from the inception to October 1st， 2021. After literature screening and data extraction， the quality of included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0 and RevMan 5.3 software were used for meta-analysis， sensitivity analysis and bias risk analysis. RESULTS A total of 33 RCTs were included， involving 3 116 patients in total. The results of the meta-analysis showed that the effective rate of trial group was significantly higher than control group [RR＝1.06， 95%CI （1.02， 1.11）， P＝0.003]. The subgroup analysis according to different courses of treatment showed that there was no statistical significance in the effective rate between 2 groups after 1 and 3 months of treatment （P＞0.05）； after 6 months of treatment， the effective rate of trial group was significantly higher than that of control group （P＜0.05）. The incidence of adverse drug reaction in trial group was significantly lower than control group [RR＝0.50， 95%CI （0.41， 0.61）， P＜0.000 01]； among specific adverse drug reactions， the incidence of nausea and vomiting in trial group was significantly lower than control group （P＜0.05）； but there was no statistical significance in the incidence of rash， drowsiness， abnormal mood， loss of appetite， dizziness or headache （P＞0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS The short-term efficacy （1， 3 months） of LEV is similar to that of VPA in the treatment of pediatric epilepsy， but long-term efficacy （6 months） of LEV is better than that of VPA； moreover， LEV shows better safety in digestive system.
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Objective:To investigate the influencing factors of delayed methotrexate (MTX) elimination after high-dose methotrexate (HD-MTX) treatment in children with acute lymphoblastic leukemia (ALL) and the effects of delayed MTX elimination and HD-MTX reduction on the prognosis of children with ALL.Methods:The clinical data of 242 children with ALL diagnosed and treated in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to June 2020 in accordance with the Chinese Children's Cancer Group study ALL 2015 (CCCG-ALL 2015) were retrospectively analyzed. Low risk and intermediate/high risk children respectively received 3 g/m 2 and 5 g/m 2 HD-MTX for 4 times, and the serum MTX concentration was monitored. The serum MTX concentration > 1 μmol/L at 44 h of administration was considered as the delayed elimination, which was divided into mild (> 1 μmol/L and ≤ 5 μmol/L), moderate (> 5 μmol/L and ≤ 10 μmol/L) and severe (> 10 μmol/L) delayed elimination. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of delayed MTX elimination, and univariate Cox proportional hazards model was used to analyze the related factors of ALL relapse. Results:The 242 children with ALL completed 962 times of HD-MTX chemotherapy. The median serum MTX concentration [ M ( Q1, Q3)] at 44 h of administration was 0.45 μmol/L (0.33 μmol/L, 0.72 μmol/L). The total incidence of delayed MTX elimination was 17.7% (170/962). The incidence of mild, moderate and severe delayed elimination was 13.8% (133/962), 2.6% (25/962) and 1.2% (12/962), respectively. Logistic regression analysis showed that age ≥ 7 years old ( OR = 1.68, 95% CI 1.17-2.41, P = 0.005), MTX dose >3 g/m 2 at each course ( OR = 2.14, 95% CI 1.52-3.03, P < 0.001) and the first course of HD-MTX chemotherapy ( OR = 2.05, 95% CI 1.43-2.93, P < 0.001) were independent risk factors for delayed MTX elimination. The median follow-up time was 50 months (34 months, 68 months), 12.8% (31/242) of the children relapsed, and the median relapse time was 30 months (30 months, 39 months). Univariate Cox regression analysis showed that there were no significant differences in the relapse rates among children with different gender, immunophenotype, risk, the number of delayed MTX elimination, and the completion of HD-MTX chemotherapy (the ratio of MTX average dose to initial planned dose) (all P > 0.05). Conclusions:The independent risk factors of delayed elimination of MTX in children with ALL are age ≥ 7 years old, MTX dose > 3 g/m 2 at each course and the first course of HD-MTX chemotherapy. Delayed elimination of MTX and reduction of HD-MTX have no significant effect on ALL relapse.
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Objective:To investigate whether the real-world marital status is a factor affecting the survival of patients with early stage breast cancer.Methods:According to the data of 62 845 patients with early stage (T 1-2N 0M 0) breast cancer who received treatment from January 2012 to December 2015 in the Surveillance, Epidemiology and End Results (SEER) database, univariate survival analysis for 7 factors including age, race, surgery, T stage, tumor differentiation, molecular type and marital status was performed by Kaplan-Meier method. The 5-year cancer specific survival (5-CSS) rate was calculated. Multivariate Cox proportional hazards model was used to analyze the death risk of patients with different marital status (married, unmarried and bad marriage). Results:Univariate analysis showed that 7 factors were correlated with the survival of patients with early stage breast cancer (all P < 0.001). Multivariate analysis showed that marital status was an independent factor affecting the survival of patients, and the death risk of unmarried patients and patients with bad marriage was 2.014 times (95% CI 1.714-2.367, P < 0.001) and 2.559 times (95% CI 2.254-2.905, P < 0.001) higher than that of married patients, respectively. In tumor differentiation, molecular type, T stage and race subgroups, univariate analysis showed that the rates of 5-CSS in married patients were higher than those in unmarried patients and patients with bad marriage (all P < 0.001); multivariate analysis showed that the risk of death in patients with bad marriage (except undifferentiated type) was higher than that in married patients (all P < 0.001), and the risk of death in unmarried patients (except undifferentiation, Luminal B type, black and other races) was also higher than that in married patients (all P < 0.01). Conclusions:Marital status is one of the factors influencing the survival of patients with early stage breast cancer.
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Objective:To detect the expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen in chronic lymphocytic leukemia (CLL) and evaluate its diagnostic value and explore its correlation with the abnormalities of genetics and molecular biology.Methods:All of 209 newly diagnosed B-cell chronic lymphoproliferative disorders (B-CLPD) patients who were admitted to the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital) from November 2020 to November 2021 were collected retrospectively, including 70 cases of CLL with typical phenotype, 16 cases of CLL with atypical phenotype, 14 cases of MCL, and 109 cases of other types of B-CLPD. Multi-parameter flow cytometry (FCM) was used to detect the expression levels of ROR1 in tumor cells of 209 patients. And then the diagnostic value of ROR1 in CLL patients and its correlation with the genetic and molecular biological abnormalities were analyzed by c2 test and fourfold table assessment.Results:The positive expression rate of ROR1 in CLL patients was significantly higher than that in non-CLL patients (78%>11%, P<0.001); there was no significant difference of ROR1 expression between typical phenotype CLL and atypical phenotype CLL (81%>63%, P>0.05). The positive expression rate of ROR1 in atypical phenotype CLL was significantly higher than that in MCL (63%>21%, P<0.05). Additionally, there was significant difference in detection rate of chromosomal abnormalities between ROR1 +CLL group and ROR1 -CLL group. The detection rate of complex karyotype in ROR1 +CLL group was higher than that in ROR1 -CLL group (34%>14%, P<0.05). The CLL patients over 60 years old had higher ROR1 positive rate ( P<0.05). Conclusions:ROR1 can be helpful in the diagnosis of CLL, especially in the differential diagnosis of atypical phenotype CLL, MCL and other types of B-CLPD. Patients with ROR1 positive expression were older and more likely to detect complex chromosomal karyotypes.
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Objective:To observe any therapeutic effect of repeated transcranial direct current stimulation (tDCS) on rats modeling neuropathic pain and explore possible mechanisms.Methods:Forty adult male Sprague-Dawley rats were randomly divided into a normal group ( n=10), a sham operation group ( n=10), a treatment group ( n=10) and a sham treatment group ( n=10). A model of chronic constriction injury of the sciatic nerve was established in the latter two groups. Fourteen days after the modeling, the treatment group was given tDCS for 8 consecutive days, while the sham treatment group received sham stimulation, and the other 2 groups did not receive any intervention. Von Frey and hotplate tests were used to test the rats′ pain thresholds 1 day before, as well as 14 and 22 days after the surgery (i.e., 8 days after the end of the treatment). Spinal cord tissue samples were taken to detect the protein expressions of N-methyl-D-aspartic acid receptor 2B, gamma-aminobutyric acid receptor types A (GABA a-R) and B (GABA b-R) using western blotting. Results:On the 14th day after the operation the average 50% MWT and WTL values of the sham treatment and treatment groups had decreased significantly compared with the sham operation group. By the 22nd day the average 50% MWT and WTL values of the treatment group were significantly higher than those of the sham treatment group, but there was no significant change in the treatment group′s average WTL between the 21st and 22nd days. On the 22nd day after the operation the average NR2B-NMDA-R level of the sham treatment group were significantly higher than that of the sham operation group, while the average GABA a-R and GABA b-R levels were significantly lower. At the same time point the treatment group′s average NR2B-NMDA-R level had decreased significantly compared to the sham treatment group, while the average GABA a-R level had increased significantly. There was no significant difference in average GABA b-R level between the treatment group and the sham treatment group at that point. On the 22nd day there was also no significant difference in the average NR2B-NMDA-R level between the treatment group and the sham operation group. Conclusions:Repeated tDCS can effectively relieve neuropathic pain. The relief of hyperalgesia is more significant than that of mechanical allodynia. A possible mechanism may be the down-regulation of spinal NR2B-NMDA-R to normal levels and modest up-regulation of GABA a-R.
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Objective:To survey the knowledge levels of sudden cardiac death (SCD) prevention among general practitioners (GPs) in Henan province.Methods:From October to November 2019, a questionnaire survey on the knowledge of SCD prevention and treatment was conducted among GP residents participating in the standardized training and assistant GPs taking final examination after training in Henan province. The questionnaire included three dimensions of SCD knowledge: prevention, early diagnosis and first aid. The factors influencing the knowledge levels on SCD prevention were analyzed.Results:A total of 546 questionnaires were distributed and 519 responders (95.1%) completed the questionnaire, including 176 GP residencies and 343 assistant GPs. The age of the respondents was 22-44 (27.91±2.84) years, 234 (45.1%) were males and 285 were females. The overall correct rate of SCD prevention and treatment was (61.46±12.39) %, and the correct rates of prevention, early diagnosis and first aid knowledge were (65.22±17.88)%, (56.58±20.20)% and (62.57±14.60)%, respectively. The overall correct rate and the correct rates of SCD prevention and treatment knowledge among GP residents were higher than those among assistant GPs ( t=10.55, 9.20, 8.62, 3.42, P<0.001); the overall correct rates and the correct rates of SCD first aid knowledge of female GPs were higher than those of males ( t=2.26, 2.13, P=0.025, 0.033); the overall correct rate and the correct rates of each dimensions in age group ≥28 years were higher than those in age group <28 years ( t=4.21, 3.37, 3.20, 2.00, P<0.05). The multivariate logistic regression analysis showed that compared to GP residents,the assistant GPs was the factor influencing the lower levels of the overall knowledge ( OR=0.24, 95 %CI:0.16-0.38, P<0.001), knowledge of prevention ( OR=0.19, 95 %CI:0.10-0.32, P<0.001) and knowledge of early diagnosis ( OR=0.35, 95 %CI: 0.23-0.52, P<0.001);compared to male responders,the females had significantly higher pass rate in SCD first aid knowledge ( OR=1.56, 95 %CI:1.07-2.28, P=0.020). Conclusions:The SCD knowledge levels of the prevention, early diagnosis, and emergency treatment are less satisfactory among GPs in Henan province; it is necessity for targeted training on the weak points of SCD knowledge for GPs.
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ObjectiveTo analyze and predict the potential quality markers （Q-Marker） in the Genuine medicinal materials Jiangxi Aurantii Fructus based on fingerprints and network pharmacology. MethodUltra-high performance liquid chromatography （UPLC） and gas chromatography-mass spectrometry （GC-MS） fingerprints were established for 18 batches of Jiangxi Aurantii Fructus ，combined with chemometric methods to screen out candidate Q-Marker components.Use network pharmacology to construct a "core component-target-pathway" network to predict the Q-Marker and core targets of Jiangxi Aurantii Fructus，and then verify the biological activity of Jiangxi Aurantii Fructus Q-Marker by molecular docking method. ResultThe 18 batches of Jiangxi Aurantii Fructus use UPLC，GC-MS fingerprints combined with chemometric analysis，a total of 9 Q-Marker candidate components were screened out.Through network pharmacological analysis，it is predicted that nobiletin，neohesperidin，meranzin，naringin and D-limonene are the Q-Marker of Jiangxi Aurantii Fructus，acting on the core targets transforming protein p21/H-Ras-1（HRAS），cellular tumor antigen p53 （TP53），mitogen-activated protein kinase 8 （MAPK8），transcription factor AP-1（JUN），glycogen synthase kinase-3 beta（GSK3B），tumor necrosis factor（TNF），cyclin-dependent kinase inhibitor 1（CDKN1A），cAMP-dependent protein kinase catalytic subunit alpha（PRKACA），cysteine aspartate-specific protease-9（Caspase-9），cyclic AMP-responsive element-binding protein 1（CREB1），exerting gastrointestinal motility and antidepressant，anti-inflammatory，anti-tumor，etc.； molecular docking shows that nobiletin，neohesperidin，meranzin，naringin and D-limonene and the selected 10 core targets have good binding ability，reflecting the better biological activity of the Q-Marker of Jiangxi Aurantii Fructus. ConclusionThe Q-Marker of Jiangxi Aurantii Fructus can be comprehensively predicted from the two aspects of volatile and non-volatile components，providing a reference for the quality control of Jiangxi Aurantii Fructus and the further study of its pharmacodynamic mechanism.
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ObjectiveTo explore the regulatory effect of Gouqi chewable tablets on innate and adaptive immunity in normal mice and its antioxidant activity in vitro and in vivo. MethodThe effects of low-， medium-， and high-dose groups （0.25， 0.5， 1.5 g·kg-1） on the immune function of normal mice were observed by carbon clearance test， immune organ index test， serum hemolysin test， ConA-induced splenic lymphocyte proliferation test， and natural killer cell （NK cell） activity test. The effects of Gouqi chewable tablets on the antioxidant capacity in vivo were determined by detecting the content of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） in mice serum. The in vitro antioxidant activity of Gouqi chewable tablets was detected by 2，2'-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid） diammonium salt （ABTS）， 2，2-diphenyl-1-picrylhydrazyl （DPPH）， and hydroxyl radical scavenging tests. ResultCompared with the blank control group， the low-， medium-， and high-dose groups of Gouqi chewable tablets improved the viability of NK cells， the proliferation of splenic lymphocytes， and the level of serum hemolysin antibody in mice （P<0.05）. The high-dose group increased the thymus index， spleen index， and phagocytic function of macrophages （P<0.05， P<0.01）. As compared with the blank control group， the activity of GSH-Px in mice serum in the medium-dose group was increased （P<0.05）， and the content of MDA in mice serum in the high-dose group was decreased （P<0.05）. In in vitro antioxidant tests， the median inhibitory concentration （IC50） values of Gouqi chewable tablets were 1.64±0.20， 2.04±0.03， and 10.27±0.03 g·L-1 by the DPPH， ABTS， and OH- free radical method， respectively. Those results indicated that Gouqi chewable tablets have good antioxidant effects in vitro. ConclusionGouqi chewable tablets can enhance the immune function of mice with good antioxidant effects.
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The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.
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Chromatin/genetics , Chromatin Assembly and Disassembly , Gene Regulatory Networks , Humans , Psoriasis/genetics , T-Lymphocytes, RegulatoryABSTRACT
Objective:To compare the dosimetric difference between intensity-modulated photon radiaotherapy (IMRT) planning and intensity-modulated proton radiotherapy (IMPT) planning for glioma.Methods:The clinical data of 15 glioma patients who underwent IMRT in ion medical center of the First Affiliated Hospital of USTC from November 2020 to April 2022 were retrospectively analyzed. IMRT planning and IMPT planning were designed for the image of each patient in the therapy planning system. Main dosimetric parameters were compared including plan target volume (PTV), coverage index (CI), dose homogeneity index (HI), and maximal dose (D max) and mean dose (D mean) of organs at risk between both plans. Results:There were no significant differences between IMRT planning and IMPT planning in terms of D max and D mean of PTV1 and PTV2, CI and HI (all P > 0.05). Compared with IMRT planning, brainstem D mean [6.92 GyE (0.09 GyE, 12.58 GyE) vs. 24.41 GyE (2.59 GyE, 34.18 GyE)], left optic nerve D max [0.78 GyE (0.04 GyE, 25.18 GyE) vs. 20.42 GyE (6.38 GyE, 37.17 GyE)], left optic nerve D mean [0.10 GyE (0.01 GyE, 11.63 GyE) vs. 9.74 GyE (2.99 GyE, 20.87 GyE)], right optic nerve D mean [1.57 GyE (0.13 GyE, 14.90 GyE) vs. 14.08 GyE (2.66 GyE, 23.67 GyE)], left len D max [0 GyE (0 GyE, 2.91 GyE) vs. 4.84 GyE (1.42 GyE, 5.48 GyE)], left len D mean [0 GyE (0 GyE, 1.73 GyE) vs. 3.84 GyE (1.25 GyE, 4.30 GyE)], right len D max [0.25 GyE (0.04 GyE, 4.55 GyE) vs. 4.28 GyE (1.58 GyE, 5.84 GyE)], right len D mean [0.16 GyE (0.01 GyE, 1.95 GyE) vs. 3.73 GyE (1.04 GyE, 4.86 GyE)], pituitary D max [6.97 GyE (0.18 GyE, 39.70 GyE) vs. 36.60 GyE (2.74 GyE, 45.19 GyE)], pituitary D mean [1.36 GyE (0.06 GyE, 13.85 GyE) vs. 24.74 GyE (2.42 GyE, 32.80 GyE)], hippocampus D max [5.10 GyE (0.24 GyE, 26.52 GyE) vs. 35.83 GyE (5.03 GyE, 46.11 GyE)], hippocampus D mean [0.36 GyE (0.04 GyE, 25.65 GyE) vs. 18.79 GyE (2.37 GyE, 28.10 GyE)] in IMPT planning were lower, and the differences were statistically significant (all P < 0.05). There were no statistical differences in brainstem D max [51.98 GyE (0.66 GyE, 53.43 GyE) vs. 53.29 GyE (3.87 GyE, 53.48 GyE)], right optic nerve D max [9.60 GyE (0.01 GyE, 43.32 GyE) vs. 25.37 GyE (3.45 GyE, 41.25 GyE)] of both plans (all P > 0.05). Conclusion:In the radiotherapy for glioma, IMRT and IMPT can meet the dose demand in clinic. Furthermore, IMPT planning can protect organs at risk and reduce radiation dose in hippocampus, brainstem, optic nerve, lens and pituitary.
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Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.
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Objective:To investigate factors related to non-variceal upper gastrointestinal bleeding(NVUGIB)in hospitalized elderly patients.Methods:A retrospective study was conducted to collect the medical records of 1 085 elderly patients at the Affiliated Hospital of Qingdao University from January 1, 2018 to January 1, 2019.According to whether NVUGIB occurred during hospitalization, they were divided into the bleeding group(173 cases)and the control group(912 cases). General information(age, sex, smoking and drinking), diseases, medications and laboratory test results for the two groups were compared and analyzed, and factors related to NVUGIB were analyzed via binary Logistic regression.Results:There were significant differences in age, smoking, drinking, peptic ulcer, tumor, coronary heart disease, atrial fibrillation, stroke, helicobacter pylori(HP)infection, acute respiratory failure, use of anti-coagulant, anti-platelet drugs, nonsteroidal anti-inflammatory drugs and glucocorticoids, leukocyte counts, hemoglobin, C-reactive protein, procalcitonin, prothrombin time and international normalized ratio(INR), D-dimer, triglycerides, albumin and glycosylated hemoglobin(all P<0.05). Multivariate Logistic regression analysis showed that history of tumor( OR=1.552, 95% CI: 1.028-2.344), peptic ulcer( OR=4.797, 95% CI: 2.263-10.165), HP infection( OR=7.199, 95% CI: 1.825-28.571), acute respiratory failure( OR=2.977, 95% CI: 1.314-6.757), use of anti-coagulant and anti-platelet drugs( OR=2.715, 95% CI: 1.769-4.167), prolonged INR( OR=21.314, 95% CI: 2.321-195.727), increased leukocyte count( OR=10.370, 95% CI: 6.521-16.493)and hypoproteinemia( OR=1.970, 95% CI: 1.304-2.976)were independent risk factors for NVUGIB in hospitalized elderly patients. Conclusions:For hospitalized elderly patients, attention should be paid to their history of tumor, peptic ulcer, HP infection, acute respiratory failure, prolonged INR, elevated leukocyte counts, hypoalbuminemia and the use of anti-coagulant and anti-platelet drugs.The occurrence of NVUGIB, early evaluation and intervention should be carefully monitored or carried out to reduce its incidence in hospitalized elderly patients.
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BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors. OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients. METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.
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OBJEC TIVE To provide reference for clinical comprehensive evaluation of pediatric drugs in China. METHODS Taking pediatric anti-allergic drugs as an example ，the clinical comprehensive evaluation methods of pediatric drugs in medical institutions were explored from the aspects of theme selection ，evaluation content and dimension ，evaluation index ，evaluation method and evaluation result report. RESULTS & CONCLUSIONS During the clinical comprehensive evaluation of pediatric drugs，under the guidance of relevant national guidelines for clinical comprehensive evaluation ，the evaluation topics could be selected according to the three principles of importance ，relevance and evaluability ，and then an appropriate evaluation index system could be developed around the six dimensions of safety ， effectiveness， economy， suitability，accessibility and innovativeness；qualitative and quantitative data integration analysis of the drugs to be evaluated were performed. In the evaluation ， it is necessary to focus on children ’s clinical basic drug use practice and decision-making needs ，normatively，scientifically and reasonably define the core index set and standard data set required by different dimensions of evidence ，standardize the collection and use of real-world data ，and effectively combine other types of evidence to truly play its advantageous role in the clinical comprehensive evaluation of pediatric drugs in China.
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Objective:To investigate effect and underlying lipid-lowering mechanisms of catalpol in non-alcoholic fatty liver disease(NAFLD).Methods:In vivo model of NAFLD was established with high-fat diet-fed ICR mice for 8 weeks. Low(50 mg/kg), medium(150 mg/kg), and high(300 mg/kg) doses of catalpol were administered, and the body weight, liver weight, hepatic index, and biochemical parameters of the mice were analyzed. Free fatty acid-induced LO2 in human hepatocytes to establish NAFLD cell model. Quantitative realtime PCR reaction to detect fatty acid synthesis-related gene levels. Western blotting assay was adopted to analyze proteins in the endoplasmic reticulum stress(ERS)-mediated protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α) signaling pathway. Results:Compared with model mice, body weight [(39.43±1.84)g, (34.01±1.83)g, (32.28±1.11)g vs(42.17±1.37)g, all P<0.001], liver weight [(1.03±0.06)g, (0.79±0.05)g, (0.64±0.04)g vs(1.30±0.13)g, P<0.01 or P<0.001], and liver index [(2.60±0.09)%, (2.32±0.09)%, (1.99±0.11)% vs(3.07±0.30)%, P<0.05 or P<0.001] were reduced in low, medium, and high doses of catapol model. Medium and high doses of catalpol diminished total cholesterol, triglyceride, low density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase( P<0.01 or P<0.001), increased high density lipoprotein-cholesterol( P<0.01 or P<0.001). In the cell model, elevated levels of both fatty acid synthesis genes and PERK-eIF2α pathway proteins were attenuated by catalase, and this attenuation was reversed by signaling pathway agonists. Conclusion:The Chinese herb catalpol may play a role in improving NALFD by regulating the ERS-mediated PERK-eIF2α signaling pathway.
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Objective:To evaluate the clinic efficacy of channel bone grafting [preservation of the sclerotic bone at the broken nonunion ends and fixation with limited contact dynamic compression plate (LC-DCP)] in the treatment of postoperative atrophic nonunion of middle clavicular fracture.Methods:The 41 patients were retrospectively analyzed who had been treated at Department of Orthopaedics and Traumatology, Xi'an Hong-Hui Hospital for atrophic nonunion after internal fixation of middle clavicular fracture from June 2015 to December 2019. They were 23 males and 18 females, with a mean age of 47.6 years (from 28 to 63 years). The left side was affected in 25 cases and the right side in 16 cases. The time interval between initial fracture surgery and nonunion surgery averaged 18.5 months (from 9 to 40 months). Thirty-six cases had undergone one operation and 5 cases 2 operations before admission. The length of bone defect was measured during operation. All nonunions were treated with construction of a graft channel, iliac bone graft and LC-DCP internal fixation above the clavicle. The upper limb function of the affected side was evaluated by the Disabilities of Arm, Shoulder and Hand (DASH) 12 months after operation.Results:The 41 patients were followed up for an average of 13.6 months (from 12 to 15 months). A bone defect ≤2.0 cm was found in 25 cases and that >2.0 cm in 16 ones. Nonunion healed in all patients after an average time of 14 weeks (from 12 to 16 weeks). One patient reported continuous pain in the donor area after operation and the other developed deep venous thrombosis at the right lower limb. The DASH upper limb scores at 12 months after operation averaged 14.7.Conclusion:Channel bone grafting is a feasible clinical treatment of postoperative atrophic nonunion of middle clavicular fracture, because it preserves the sclerotic bone at the broken nonunion ends, reduces the amount of iliac bone graft and leads to fine clinic efficacy.
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Community-acquired pneumonia (CAP) is the leading cause of death among children under 5 years of age globally.Due to the lack of medical resources, the incidence of severe pneumonia and even death is higher in less-developed areas.The early diagnosis and accurate treatment of CAP contribute to improve the prognosis.In recent years, the integration of artificial intelligence (AI) technology and medicine is becoming a research hotspot, which also provides a new idea for the diagnosis of CAP.This study aims to review the application and research progress of AI in the diagnosis of CAP based on clinical symptoms, physical examination and imaging examination, and analyzes the advantages and limitations of various auxiliary AI diagnostic algorithms.In the future, innovative methods will be provided for the diagnosis and treatment of CAP with the further advance in the application of AI, which will improve the diagnostic efficiency of CAP and reduce the death rate of pneumonia.
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Objective:To explore the parenting characteristics of children with attention deficit hyperactivity disorder (ADHD) and conduct problems.Methods:This was a cross-sectional study involving 84 ADHD children with conduct problems and 75 ADHD children without conduct problems treated in the Outpatient Department of Children′s Health and Mental Health Center, Shenzhen Children′s Hospital from September 2017 to December 2019, and 54 healthy control children (healthy children in ordinary primary and secondary schools in Shenzhen) were included.The Egna Minnen av Barndoms Uppfostran (EMBU) scale was used to access the parenting styles of participants. ANCOVA was used to compare the different score of all factors in EMBU among these 3 groups and Tukey′s post-hoc comparisons were also performed.All comparisons were corrected for age and sex. Results:Among the factor scores of EMBU scale, ADHD children with conduct problems scored significantly higher on parental and maternal harsh/punishment [Parental (22.10±4.92) scores vs.(19.40±4.01) scores vs.(17.40±2.51) scores; Maternal (15.10±3.54) scores vs.(13.70±2.78) scores vs.(12.40±1.97) scores] and the reject/deny factors [Parental(10.60±2.49)scores vs.(9.40±2.06)scores vs.(8.90±1.61)scores, Maternal(13.90±3.28)scores vs.(12.40±2.64)scores vs.(11.60±2.19)scores] than ADHD children without conduct problems and the healthy control group (all P<0.001). On parental overprotection factors, both ADHD groups scored higher than the healthy control group [(10.30±2.03) scores vs.(9.80±2.13) scores vs.(8.70±1.92) scores, P<0.001], while on maternal over-interference factor, ADHD children with conduct problem scored significantly higher than ADHD children without conduct problems and the healthy controls [(36.00±4.64) scores vs.(34.60±4.38) scores vs.(33.30±4.92) scores, P=0.009]. Conclusions:Parents of ADHD children with conduct problems tend to use more negative parenting skills like punishment, over-interference, rejection and denial.This kind of negative parenting style, to some extent, causes the conduct problems in children with ADHD.
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OBJECTIVE@#To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).@*METHODS@#PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.@*RESULTS@#Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.@*CONCLUSIONS@#The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).