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Objective To investigate the correlation between the concentration of air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases in a general hospital in Shanghai. Methods Data including pediatric respiratory disease outpatient and emergency visits in a hospital in Pudong New Area of Shanghai from May 1, 2013 to March 20, 2022 were collected. Daily concentration of air pollutants including PM10, SO2 and NO2 and meteorological data in Pudong New Area during the same period were collected. A case-crossover study with distributed lag non-linear model was conducted to explore the correlation between air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases. Results The concentrations of PM10, SO2 and NO2 were positively with the number of outpatient and emergency visits for pediatric respiratory diseases. The strongest cumulative effect was observed on six days lag (Lag0-5) for PM10. For a 10 μg/m3 increase of the concentrations of PM10, the corresponding increase of cumulative pediatric respiratory disease outpatients was 1.10% (95%CI:0.97%, 1.23%) in Lag0-5. The strongest cumulative effect was observed on eight days lag (Lag0-7) for SO2 and NO2. For a 10 μg /m3 increase of the concentrations of SO2 and NO2, the corresponding increase of cumulative pediatric respiratory disease outpatients was 5.64% (95%CI:5.16%, 6.13%) and 5.41% (95%CI:5.15%, 5.66%) in Lag 0-7, respectively. The association of PM10 and SO2 with the number of pediatric respiratory disease visits in males was significantly stronger than that in females. The impact of PM10 on the number of pediatric respiratory disease visits in children aged 0-6 was higher than that in children aged 7-14, while the impact of SO2 and NO2 on the number of pediatric respiratory disease visits in children aged 7-14 was higher than that in children aged 0-6. Conclusion The concentration of ambient PM10, SO2, and NO2 is positively correlated with outpatient and emergency visits for pediatric respiratory diseases, with obvious lag and cumulative effect. Boys and children aged 0-6 are more susceptible to the hazard of air pollution.
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Objective:To analyze the distribution of different SF3B1 genotypes in patients with myelodysplastic syndromes (MDS) and its prognostic value.Methods:Totally, 377MDS patients who were initially diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to January 2022 were included in the retrospective analysis.The patients were divided into three different groups according to mutation stcote of SF3B1, including 317 patients with SF3B1 wild type (SF3B1 WT) (214 males and 103 females, 63(49, 71) years old),39 patients with SF3B1 K700E mutation(SF3B1 K700E(17 males and 22 females, 65(52, 73)years old)) and 21 patients with SF3B1 non-K700E mutation(SF3B1 non-K700E)(13 males and 8 females, 67(63, 73) years old). MDS-related 20 gene mutations were detected using targeted sequencing technology; Survival curves were constructed by the Kaplan-Meier method; Cox proportional hazards model was established to evaluate different factors at diagnosis on survival by univariate and multivariate analyses.. Results:Compared with SF3B1 non-K700E patients, SF3B1 K700E patients had a higher median absolute neutrophil count ( P=0.002) and were likely to be in the low/int-1 International Prognostic Scoring System (IPSS) categories ( P=0.023). A 20-gene targeted sequencing analysis showed that, compared with SF3B1 WT patients, SF3B1 K700E patients were associated with lower frequency of ASXL1 and U2AF1 mutations ( P=0.018 and P=0.003); while compared with SF3B1 non-K700E patients, the frequency of ASXL1 mutation was significantly lower in SF3B1 K700E cases ( P=0.029). Patients with SF3B1 K700E had better overall survival (OS) in comparison with SF3B1 WT and SF3B1 non-K700E in MDS patients ( P<0.001 and P=0.045, respectively). In comparison with SF3B1 WT patients, SF3B1 MUT patients had more favorable OS and progression-free survival (PFS) in MDS without excess blasts ( P<0.001 and P<0.001, respectively), but no significant difference was found in MDS with excess blasts ( P>0.05). Compared with SF3B1 WT patients, SF3B1 K700E patients had superior OS and PFS in the int-1 IPSS category ( P=0.010 and P=0.013, respectively). By multivariable analysis, the presence of SF3B1 K700Ewas an independent predictor of superior OS ( HR=0.461,95% CI 0.262-0.811, P=0.007). Conclusion:SF3B1 K700E and SF3B1 non-K700E patients had significantly improved OS in comparison with SF3B1 WT MDS patients. Furthermore, SF3B1 K700E patients were associated with a better OS compared with SF3B1 non-K700E MDS patients. SF3B1 mutation could not overcome the poor prognostic effect of excess blasts, which highlights the importance of the SF3B1 mutation subtype in risk assessment of MDS without excess blasts.
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Objective To investigate the efficacy and safety of anlotinib combined with PD-1 blockades for patients with advanced epithelial ovarian cancer (EOC). Methods A retrospective study was performed, enrolling 33 patients with advanced EOC who failed standard systematic therapy. All patients were administered with anlotinib combined with PD-1 blockades. The efficacy and safety profile were determined during treatment. Results The objective response rate of the 33 patients was 36.4% (95%CI: 20.4%-54.9%) and the disease control rate of the patients was 81.8% (95%CI: 64.5%-90.0%). The median PFS and OS of the 33-patient cohort were 7.6 months (95%CI: 3.1-12.1) and 19.6 months (95%CI: 15.1-24.1), respectively. The most common treatment-related adverse reactions were fatigue (66.7%), nausea and vomiting (54.5%), hypertension (48.5%), and diarrhea (39.4%). Furthermore, multivariate Cox regression analysis indicated that ECOG performance status and FIGO stage were independent factors for predicting the PFS of the combination regimen for patients with advanced EOC. Conclusion Anlotinib combined with PD-1 blockades preliminarily exhibit satisfactory efficacy and tolerable safety profile for patients with advanced EOC.
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Objective:To investigate the significance of 12 inflammatory cytokines in early detection and treatment guidance of hematologic malignant patients with Cytokine release syndrome (CRS) after Chimeric antigen receptor (CAR)-T cell immunotherapy.Methods:A total of 12 patients, including 6 males and 6 females, aged 53.0 (49.8, 62.5) years old, were treated with CAR-T cell immunotherapy in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020. Cytometric bead array was used to detect the serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IFN-α, IFN-γ, and TNF-α at different time points after cell infusion in all patients receiving CAR-T cell immunotherapy. C-reactive protein (CRP), D-dimer (D-D), serum ferritin (SF), and lactate dehydrogenase (LDH) were measured at the corresponding period. CRS was classified into four grades according to the diagnostic criteria, from 0 to 3. The differences of the above mentioned parameters between the four groups were compared. The Speedman correlation coefficient was used to analyze the correlation between inflammatory cytokine expression levels and CRS grades. Plot the subject′s receiver operating characterist (ROC) curve to determine the sensitivity and specificity of inflammatory cytokines to predict CRS.Results:CRS grading was performed on day 1, 4, 7, and 11 after CAR-T cell infusion in 12 patients. There are 48 cases in total, including 25 cases of CRS grade 0, 6 cases of CRS grade 1, 9 cases of CRS grade 2, and 8 cases of CRS grade 3. The correlation analysis of 48 cases showed that the expression levels of IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-1β, and IL-8 were positively correlated with CRS grade ( P<0.05). The correlation coefficients were 0.384, 0.730, 0.632, 0.341, 0.681, 0.319, and 0.622, respectively. 7 inflammatory cytokines (IL-6, IL-10, IFN-γ, IL-8, IL-2, TNF-α, and IFN-α) were elevated in 12 patients, and the average time to start the rise was 3.4, 5.3, 6.1, 2.9, 4.3, 6.0 and 5.8 days, respectively. The time for CRP, D-D, SF, and LDH to begin to rise were 6.6, 7.6, 8.3 and 7.6 days, which were higher than that of the 7 inflammatory cytokines. After effective treatment, except for IL-6, the remaining 6 inflammatory cytokines (IL-10, IFN-γ, IL-8, IL-2, TNF-α and IFN-α) had their recovery times as 7.8, 3.9, 5.1, 8.0, 6.0, and 2.5 day,respectively, which were lower than that of CRP, D-D, SF, and LDH(9.7, 9.2, 13.7, and 13.8 days, respectively). The ROC showed that IL-6, IL-10, IFN-γ, and IL-8 can serve as biomarkers for diagnosis of CRS with high sensitivity and specificity. Conclusion:The monitoring of 12 inflammatory cytokines play an important role in CRS grading after CAR-T cell immunotherapy, which contributes to the early diagnosis of CRS and the prediction of clinical outcome.
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Objective:To investigate the expression pattern of TCR variable region subfamily (Vβ and Vδ) in patients with mature T-cell lymphoma (TCL), and to compare the diagnostic value of TCRVβ and TCRVδ analysis in TCL.Methods:The TCRVβ flow cytometry kit was used to detect the expression of Vβ subtypes of αβT cell in 199 patients with αβ TCL and 398 patients with non-TCL, who hospitalized in Jiangsu Provincial People Hospital from 2011 to 2020. Among them, 185 cases of αβ TCL and 355 cases of non-TCL also underwent TCRβ and TCRγ gene rearrangement detection. The TCRVδ based 10-color protocol was used to detect the expression of Vδ subtypes in 24 cases of γδTCL, 10 cases of normal controls, and 15 cases with reactively higher CD4 and CD8 double-negative ratio from 2017 to 2020, and 24 cases of γδTCL and 15 cases with reactively higher CD4 and CD8 double-negative ratio underwent TCRβ, TCRγ and TCRδ gene rearrangement detection. The diagnostic performance and degree of coincidence for detecting malignant clonality were compared between TCRVβ and TCRVδ analysis and the TCR gene scanning method.Results:In the 199 cases of αβ TCL, 182 cases (91.5%) showed restricted expression or the sum of the positive percentages of the subgroups was less than 30% for the 24 TCRVβ subtypes. Among them, the subfamily members with the highest incidence of clonal T lymphocytes were TCRVβ13.2 (12.6%, 23/182) and TCRVβ3 (8.2%,15/182); the TCRVβ subtypes showed nonclonal results in 99.0% (394/398) of non-TCL. All 24 cases of γδTCL (100%) showed abnormal distribution patterns of Vδ1 and Vδ2, of which 19 cases showed restricted expression of Vδ1, and the remaining 5 cases had negative expression of either Vδ1 or Vδ2, and the positive rate of Vδ1 cells was significantly higher than that of Vδ2 cells (79.9%±10.8% vs 0.7%±0.3%, P<0.001). Among the normal control and cases with reactively higher CD4 and CD8 double-negative ratio, the positive rate of Vδ2 cells was significantly higher than that of Vδ1 cells (73.7%±6.7% vs 15.6%±4.2%, P<0.001), and all cases (25/25) showed a normal distribution pattern. In terms of the diagnostic performance of TCL, there was no significant difference of sensitivity and specificity between TCR variable region subfamily detection by flow cytometry and TCR gene scanning technology (the sensitivity was 92.4% and 91.4% respectively; the specificity was 99.0% and 95.9% respectively, P=0.065), and the coincidence rate of the two diagnostic methods is high (Kappa=0.809, P<0.001). Conclusion:Detection of TCR variable region subfamily by flow cytometry could quickly and effectively diagnose mature TCL.
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Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.
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Cervix carcinoma is one of the most common malignant tumors in women.Bone metastases are uncommon,and mandibular metastases are particularly rare.Cervical cancer patients with bone metastases have very poor prognosis.Treatments reduce clinical symptoms and improve quality of life as the goal.
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BACKGROUND: Compared with the traditional organic fluorescent dyes, quantum dots present good biomarker characteristics. Especially, quantum dots for cell labeling and targeted bioimaging present unique optical properties.OBJECTIVE: To investigate the biocompatibility of CdSe/ZnS quantum dots with mononuclear macrophages.METHODS: The macrophages RAW264.7 were inoculated into 96-well plates containing 0, 50, 100 mg/L CdSe/ZnS quantum dots for 1 or 2 hours. Then, the fluorescent signal was detected by flow cytometry. After 0-24 hours of culture,the fluorescence signal intensity of the macrophages cultured with 50 mg/L CdSe/ZnS quantum dots was detected by flow cytometry. After 18 hours of culture, quantitative PCR was used to detect the levels of tumor necrosis factor α and interleukin 1β in macrophages, and macrophage proliferation cell apoptosis were detected by MTT and flow cytometry,respectively.RESULTS AND CONCLUSION: The fluorescence signal intensity was positively correlated with the mass concentration of CdSe/ZnS quantum dots, and the intensity of the fluorescent signal was increased with the labeling time. After labeling using 50 mg/L CdSe/ZnS quantum dots, the fluorescence signal of macrophages increased continuously with time, and reached the peak at 18 hours. Compared with 0 mg/L quantum dot group, 50, 100mg/L quantum dot groups could significantly promote the expression of tumor necrosis factor α and interleukin 1β in macrophages (P < 0.01 or P < 0.05).The level of tumor necrosis factor α in the 100 mg/L quantum dot group was higher than that in the 50 mg/L quantum dot group (P < 0.01). The expression of interleukin-1β showed no difference between 50 and 100 mg/L quantum dot groups.The cell proliferation in the 50 and 100 mg/L CdSe/ZnS quantum dot groups was significantly higher than that in the 0 mg/L quantum dot group (P < 0.05), but there was no difference between the former two groups. In addition, 50 and 100 mg/L CdSe/ZnS quantum dots had no significant effect on apoptosis of macrophages. To conclude, CdSe/ZnS quantum dots could activate macrophages and promote their proliferation and secretion of inflammatory factors, but did not affect their apoptosis.
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Objective:To investigate the effect of butyrate produced by bacterial metabolism on immune features of murine bone marrow-derived dendritic cells(BMDCs) and its potential mechanisms.Methods: BMDCs were prepared from bone marrow cells of C57BL/6 mice by being cultured with GM-CSF and IL-4.The expression of CD80,CD86,B7-DC and MHCⅡ on BMDCs and its pri-ming ability on the proliferation of OVA257-264 antigen specific CD8+T cell were analyzed by using Flow cytometry.The mRNA levels of IL-6 and IL-12 in BMDCs were detected by real-time fluorescence quantitative PCR(q-PCR).Simultaneously,Griess reaction and Western blot was used for analyzing the levels of NO2-in BMDCs culture supernatant and the ERK phosphortylation in BMDCs respectivly.Results:Butyrate could decrease the levels of CD80,CD86,MHCⅡand B7-DC,and downregulate the capability of BMDCs in priming the proliferation of CD8+T cells.Furthermore,the secretions of IL-6,IL-12,NO2-and the phosphorylation of ERK were sup-pressed.Conclusion:Butyrate down-regulats the immune functions of BMDCs via inhibition of ERK phosphorylation in TLR 4 signaling pathway.
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Objective To investigate the effects of different dialysates on expression of protein kinase C-δ (PKCδ) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKCδ specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKCδ mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group , normal control group and fluid A+powder B+rottlerin group (P<0.05). Compared with normal control group, blank control group and fluid A+powder B+rottlerin group, the expression of PKCδ mRNA and protein of U937 cells in fluid A+powder B group were significantly increased (P<0.05). There was no significant difference in cell apoptosis rates and expression of PKCδ mRNA and protein between fluid A+fluid B group and blank control group, normal control group and fluid A+fluid B+rottlerin group (P＞0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKCδ. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.
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Specialist training is an important part of specialist system,which is pilot stage in our country.Quite a few key issues should be discussed deeply,including the leading role of the government,the management degree of the government,bases development,teachers training,assessment criteria,training generally or directed,training expenditure,and so on.
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Objective:To explore the effect elements of teaching quality in a constitution,to learn the attitudes from different level of people towards effect elements of teaching quality and to examine the ways to guarantee the improvement of teaching quality and the complement of cultivating talents.Methods:The index of appraisal system of teaching quality originates from the transformation achievements of the study in our school "To apply the ISO9000 standard to construction assurance system of medical education quality".The investigation subjects are all the teaching and administration staff and students of the school.The investigation involves index of 4 levels,6 aspects and 84 observation points.The statistical analysis is carried on in 3 levels:the entire school,the teachers and the students.Results:The sequence of the index of 4 levels of influencing teaching quality is made clear and analyzed,and the improvement proposals are also given.
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The authors have analyzed the present situation of teaching experiment in higher vocational education of china. And then the process of researching and practicing the basic medical experimental technique curriculum reform has been discussed from the aspects such as the teaching aims,curriculum setup,teaching content selection,teaching methods and education evaluation system for the purpose of exploring the experimental teaching mode to fulfill the requirements of the comprehensive career competence of higher vocational education.