BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Objective To establish a biotin-avidin system time-resolved fluorescence immunoassay(BAS-TRFIA)for detecting serum soluble fms-like tyrosine kinase-1(sFlt-1)and evaluate its performance.Methods A BAS-TRFIA was established to quantitatively determine the concentration of sFlt-1 in the serum of pregnant women,which based on the microplate was coated with streptavidin.The monoclonal antibody to capture sFlt-1 was labeled by biotin,and the detection of sFlt-1 monoclonal antibody was labeled by europium.The performance indicators such as lower limit of detection,biological limit of detection,functional sensitivity,precision,linearity,interference test,cross-reaction test,and high dose hook effect of the method were evaluated.A total of 106 remaining serum samples from pregnant women with no hemolysis,jaundice and lipemia at more than 9 weeks were detected by BAS-TRFIA and electrochemiluminescence for methodological comparison study,and the correlation of the comparison test results was analyzed by linear regression.Results The optimal reaction time of the sample was 90 min.The lower limit of detection was 1.00pg/ml.The biological limit of detection was 10.00pg/ml,and the functional sensitivity was 10.00pg/ml.The intra-assay CV and inter-assay CV were both within 5%,and the linear range was 20.00 to 40 000.00pg/ml.The relative bias of the detection results of the 17 interfering samples with interfering substances added to the low-concentration and high-concentration quality controls and the basic samples was within-4.94%～4.24%.The high dose hook effect was not found in sFlt-1 samples up to 150 000pg/ml.When the concentration of sFlt-1 in the sample was 105.40～40 972.00pg/ml,the linear regression equation of BAS-TRFIA and electrochemiluminescence(ECL)detection results was Y=1.086 7X+17.946(r=0.994 4,t=96.26,P＜0.05).Conclusion The quantitative detection of sFlt-1 by BAS-TRFIA has high sensitivity,good precision,wide linear range,strong anti-interference ability,and good correlation with the detection results of reference methods,which is valuable for clinical application.

Objective To develop a reagent for detecting of 17α-hydroxyprogesterone(17α-OHP)in dried blood spots on filter paper fixed on vascular stent by Auto TRFIA-4 automatic fluorescence immunoanalyzer and evaluate its performance.Methods The microwell plate was coated with the sheep anti-rabbit IgG antibody as microwell reaction plate,the rabbit anti-human 17α-OHP antibody was diluted as intermediate antibody,and the 17α-OHP-bovine serum albumin conjugate was labeled by europium as europium marker.The concentration of 17α-OHP in dried blood spots on filter paper fixed on blood spots stent was quantitatively detected by Auto TRFIA-4 automatic fluorescence immunoanalyzer.The analysis sensitivity,accuracy,linearity,precision,specificity and stability were evaluated,and whether they met the requirements of the formulated industry standards were evaluated.A total of 227 neonatal heel blood filter paper samples from newborns who were born 72 hours after birth and within 7 days and fully breastfeeding were selected for reagent comparison test.The consistency was analyzed by χ2 test,Kappa test,t test,linear correlation analysis,regression analysis,Bland-Altman method analysis and predictive bias analysis of medical decision level,P<0.05 indicated statistically significant difference.Results The optimal coating concentration of sheep anti-rabbit IgG antibody was 3 μg/ml.The optimal dilution ratio of rabbit anti-human 17α-OHP antibody was 1∶1 500.The optimal dilution ratio of 17α-OHP europium marker mother liquor was 1∶2 500.The limit of blank,limit of detection,limit of quantification was 0.75,1.08 and 1.99 nmol/L,respectively.The relative deviations of the standard check test were within±15.00%,and the average recovery rate was 92.36%.The linear correlation coefficient was 0.997 1 in the range of 2.00 to 300.00nmo/L.The intra-assay and inter-assay coefficients of variation were all within 10.00%.The cross-reactivity rates of 100.00 ng/ml progesterone,17α-hydroxypreg nenolone and 11-deoxycortisol were within 0.089%to 0.64%.The performance of stability test met the requirements.The total coincidence rate was 100%compared with the results of contrast reagent.The quantitative results were highly correlated with the contrast reagent(r=0.999 4,tr=452.02,P<0.05).Conclusion The self-developed reagent has the advantages of high sensitivity,good accuracy,wide linear range,good precision,high specificity and good stability,which meets the requirements of the formulated industry standards,and has high correlation and consistency with the result of contrast reagent,which meets the needs of clinical detection.

Objective To establish a biotin-avidin system time-resolved fluorescence immunoassay(BAS-TRFIA)for detecting serum soluble fms-like tyrosine kinase-1(sFlt-1)and evaluate its performance.Methods A BAS-TRFIA was established to quantitatively determine the concentration of sFlt-1 in the serum of pregnant women,which based on the microplate was coated with streptavidin.The monoclonal antibody to capture sFlt-1 was labeled by biotin,and the detection of sFlt-1 monoclonal antibody was labeled by europium.The performance indicators such as lower limit of detection,biological limit of detection,functional sensitivity,precision,linearity,interference test,cross-reaction test,and high dose hook effect of the method were evaluated.A total of 106 remaining serum samples from pregnant women with no hemolysis,jaundice and lipemia at more than 9 weeks were detected by BAS-TRFIA and electrochemiluminescence for methodological comparison study,and the correlation of the comparison test results was analyzed by linear regression.Results The optimal reaction time of the sample was 90 min.The lower limit of detection was 1.00pg/ml.The biological limit of detection was 10.00pg/ml,and the functional sensitivity was 10.00pg/ml.The intra-assay CV and inter-assay CV were both within 5%,and the linear range was 20.00 to 40 000.00pg/ml.The relative bias of the detection results of the 17 interfering samples with interfering substances added to the low-concentration and high-concentration quality controls and the basic samples was within-4.94%～4.24%.The high dose hook effect was not found in sFlt-1 samples up to 150 000pg/ml.When the concentration of sFlt-1 in the sample was 105.40～40 972.00pg/ml,the linear regression equation of BAS-TRFIA and electrochemiluminescence(ECL)detection results was Y=1.086 7X+17.946(r=0.994 4,t=96.26,P＜0.05).Conclusion The quantitative detection of sFlt-1 by BAS-TRFIA has high sensitivity,good precision,wide linear range,strong anti-interference ability,and good correlation with the detection results of reference methods,which is valuable for clinical application.

Objective To develop a reagent for detecting of 17α-hydroxyprogesterone(17α-OHP)in dried blood spots on filter paper fixed on vascular stent by Auto TRFIA-4 automatic fluorescence immunoanalyzer and evaluate its performance.Methods The microwell plate was coated with the sheep anti-rabbit IgG antibody as microwell reaction plate,the rabbit anti-human 17α-OHP antibody was diluted as intermediate antibody,and the 17α-OHP-bovine serum albumin conjugate was labeled by europium as europium marker.The concentration of 17α-OHP in dried blood spots on filter paper fixed on blood spots stent was quantitatively detected by Auto TRFIA-4 automatic fluorescence immunoanalyzer.The analysis sensitivity,accuracy,linearity,precision,specificity and stability were evaluated,and whether they met the requirements of the formulated industry standards were evaluated.A total of 227 neonatal heel blood filter paper samples from newborns who were born 72 hours after birth and within 7 days and fully breastfeeding were selected for reagent comparison test.The consistency was analyzed by χ2 test,Kappa test,t test,linear correlation analysis,regression analysis,Bland-Altman method analysis and predictive bias analysis of medical decision level,P<0.05 indicated statistically significant difference.Results The optimal coating concentration of sheep anti-rabbit IgG antibody was 3 μg/ml.The optimal dilution ratio of rabbit anti-human 17α-OHP antibody was 1∶1 500.The optimal dilution ratio of 17α-OHP europium marker mother liquor was 1∶2 500.The limit of blank,limit of detection,limit of quantification was 0.75,1.08 and 1.99 nmol/L,respectively.The relative deviations of the standard check test were within±15.00%,and the average recovery rate was 92.36%.The linear correlation coefficient was 0.997 1 in the range of 2.00 to 300.00nmo/L.The intra-assay and inter-assay coefficients of variation were all within 10.00%.The cross-reactivity rates of 100.00 ng/ml progesterone,17α-hydroxypreg nenolone and 11-deoxycortisol were within 0.089%to 0.64%.The performance of stability test met the requirements.The total coincidence rate was 100%compared with the results of contrast reagent.The quantitative results were highly correlated with the contrast reagent(r=0.999 4,tr=452.02,P<0.05).Conclusion The self-developed reagent has the advantages of high sensitivity,good accuracy,wide linear range,good precision,high specificity and good stability,which meets the requirements of the formulated industry standards,and has high correlation and consistency with the result of contrast reagent,which meets the needs of clinical detection.

Objective To systematically evaluate and sequentially analyze the clinical efficacy and safety of Baogong Zhixue Granules for the treatment of abnormal uterine bleeding due to ovulation disorder.Methods The randomized controlled trials(RCTs)of Baogong Zhixue Granules for the treatment of abnormal uterine bleeding due to ovulation disorder were retrieved from the databases of CNKI,Wanfang Data,VIP,China Biology Medicine,PubMed,Embase,and Cochrane Library from the establishment of the databases to January 5th,2023.Literature screening and data extraction were conducted according to Cochrane Handbook for Systematic Reviews of Interventions,and Meta-analysis was performed by RevMan 5.4.Results Totally 15 articles were included,involving 1 425 patients.Meta-analysis results showed that Baogong Zhixue Granules could effectively improve the clinical efficacy of abnormal uterine bleeding due to ovulatory disorder(RR=1.17,95%CI[1.13,1.23],P<0.000 01),shorten hemostasis time[bleeding control time(MD=-6.35,95%CI[-8.89,-3.81],P<0.000 01),complete hemostasis time(MD=-12.56,95%CI[-16.22,-8.89],P<0.000 01)],reduce endometrial thickness(MD=-1.26,95%CI[-1.71,-0.80],P<0.000 01),reduce hemoglobin loss(MD=13.35,95%CI[11.41,15.29],P<0.000 01),improve the score of uterine bleeding(MD=-2.22,95%CI[-2.43,-2.01],P<0.000 01),and reduce the recurrence of disease(RR=0.37,95%CI[0.19,0.72],P=0.004).There was no statistical significance between the test group and the control group in terms of adverse reactions(P=0.82).The trial sequential analysis of the total efficiency was carried out,and the cumulative included research passed the traditional threshold and trail sequential analysis threshold.Conclusion Baogong Zhixue Granules have a certain clinical efficacy in the treatment of abnormal uterine bleeding due to ovulation disorder,but there may be publication bias in the study,and higher quality clinical RCTs need to be carried out.

Objective:To establish a HPLC characteristic spectrum method of Centipeda minima based on standard decoction; To evaluate the correlation of materia medica, decoction pieces, standard decoction, intermediates and formula granule; To provide a reference for the quality standard research of Centipeda minima formula granules.Methods:The materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima were analyzed by a HPLC characteristic spectrum method, and the software "Similarity Evaluation System for Chromatographic Fingerprint of TCM" was employed to conform the common peaks. The clustering analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were adopted to find out the correlation of materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima. The Iconic components which can make differences was screened at the same time.Results:The characteristic chromatogram of materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima shared high similarity with the respective control chromatogram. Fourteen common peaks were confirmed, and eleven chromatographic peaks were identified. The results of CA and PCA were consistent, and the standard decoction, intermediates and formula granules of Centipeda minima were closer. Six differential components with VIP values greater than 1 were screened by OPLS-DA.Conclusions:The method is stable, accurate and characteristic. The study can provide a reference for the quality standard research of Centipeda minima Formula Granules by analyzing the correlation of characteristic spectrum of materia medica, decoction pieces, standard decoction, intermediates and formula granules.

Objective:To explore the teaching reform effect of the integrated "theory virtual reality" course in Fundamentals of Nursing in vocational colleges, providing reference for related research in other courses. Methods:From January to June 2023, a convenience sampling method was used to select vocational nursing students from 11 classes of the Nursing College of Guangxi Health Vocational and Technical College in 2022 as the research objects. Through class experimental research methods, a smart simulation virtual classroom was used to carry out the integrated teaching of Fundamentals of Nursing (referred to as "theory virtual reality") in theory virtual practice. The teaching resources and pre class, in class, and post class tasks were published on the Chaoxing Learning Platform. Theory practical teaching was conducted in the simulated virtual smart classroom, and virtual training scenes were constructed using virtual simulation software. Operations evaluation, planning, implementation, and evaluation were completed by forming groups and using training related molds. In class, live broadcasting was used to display the details of student operations, and Chaoxing Learning Platform was used for teaching. The platform conducts interactive activities such as group discussions, answering questions, and testing to achieve integrated teaching of "theory virtual reality". Before and after intervention, the Chinese version of the Critical Thinking Ability Scale and Nurse Competency Scale were selected to evaluate the critical thinking ability and nursing competency of nursing students. The Simulated Teaching Design Scale (SDS) was used to evaluate student satisfaction with teaching. Results:A total of 650 nursing students were included in this study, including 89 males and 561 females, aged (18.00 ± 1.20) years old. The total score of critical thinking before intervention was (247.17 ± 33.63) points, and compared with the score after intervention (294.16 ± 33.63) points, the difference was statistically significant ( t=-10 182.33, P<0.05). The total score of nursing competence before intervention was (485.09 ± 147.68) points, and compared with the score after intervention (507.09 ± 147.68) points, the difference was statistically significant ( t=-7 154.72, P<0.05) points. The approval rate of SDS was over 87%, and the total approval rate of the five dimensions was over 95%. Conclusions:The teaching reform of the Fundamentals of Nursing course in vocational colleges based on the integration of "theory virtual reality" can help improve students′ experience and interactivity, enhance their critical thinking and nursing competence, and achieve high satisfaction. It is worth promoting.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Objective:To explore a fast method to identify and confirm suspected clonorchis sinensis infection.Methods:For suspected clonorchis sinensis infection, the clonorchiasis serum antibody was detected first with ELISA. If the antibody was positive, the fecal examination for eggs was performed. If the fecal examination was negative, duodenal drainage under gastroscopy was recommended to detect eggs from the drainage fluid.Results:A total of 126 patients met the requirements and aged 54.14±13.33 (24- 87). There were 83 cases (65.87%, 83/126) with eggs positive in the drainage fluid, of which 53 cases were male, aged 55.91±11.47 (30-86), and 30 cases female, aged 55.87± 13.85(30-87). There was no significant difference in age between males and females( P>0.05). The time of catheterization (T1) of 126 cases was 3.79 ±1.45 min. The time of drainage (T2) of 126 cases was 31.39 ±14.29 min. There was no significant difference in T1 or T2 between the positive group and the negative group( P>0.05). The detection rates of eggs were 91.57% (76 cases) in intrahepatic bile duct drainage, 81.93% (68 cases) in the bile-cyst juice and 75.90% (63 cases) in the common bile duct fluid. No serious adverse reactions occurred during or after the operation. Conclusion:The detection rate of clonorchiosis sinensis can be effectively improved by the combination of clonorchiasis serum antibody test and gastroscopy-guided duodenal drainage.