Acute B-lymphoblastic leukemia (B-ALL) is the most common type of acute lymphoblastic leukemia. Chemotherapy is the main treatment for most patients, but there are serious side effects. CD19 is generally highly expressed in B-lineage malignancies and plays a key role in B cell signal transduction, activation and development. Therefore, it has become one of the effective targets for treatment of B-cell malignancies. At present, a variety of therapies targeting CD19 have been developed, including antibody drug conjugates, monoclonal antibodies, bispecific antibodies and chimeric antigen receptors cell therapies. This paper reviews the clinical trial progress of CD19-targeted therapy for B-ALL.

ObjectiveIn order to explore the utilization value of the seeds dropped in the harvesting， processing， storage and transportation of Prunellae Spica， the character， turgidity and chemical composition of the seeds were analyzed and compared with those of the commercially available varieties， such as chia seeds and basil seeds. MethodCharacter was observed directly. The turgidity was determined according to the method of general rule 2101 of Chinese Pharmacopoeia （part Ⅳ， the 2020 edition）. The contents of six phenolic acids （danshensu， protocatechuic acid， protocatechuic aldehyde， caffeic acid， salviaflaside and rosmarinic acid） were determined by ultra performance liquid chromatography （UPLC）， acetonitrile （A）-0.1% formic acid aqueous solution （B） was used as mobile phase for gradient elution （0-7 min， 2%-8%A； 7-13 min， 8%A； 13-14 min， 8%-17%A； 14-30 min， 17%A）， the detection wavelength was at 280 nm. The liposoluble components were extracted by n-hexane and identified by gas chromatography-mass spectrometry （GC-MS）， and the contents of five fatty acids， namely palmitic acid， oleic acid， stearic acid， linolic acid and α-linolenic acid， were determined on a DB-35MS capillary column （0.25 mm×60.0 m， 0.25 µm）， the injection temperature was 250 ℃， the carrier gas was high-purity helium with a flow rate of 1.0 mL·min^-1 and the splitting ratio of 50∶1. The volatile oil was extracted by steam distillation method and its components were identified by GC-MS on a WM-5MS capillary column （0.25 mm×30.0 m， 0.25 µm） with the injection temperature of 250 ℃， the flow rate of 1.0 mL·min^-1 and the splitting ratio of 10∶1. ResultPrunellae Spica seeds were slightly smaller than chia seeds and basil seeds， and their color of seed coat was obviously different. Prunellae Spica seeds had strong water absorption and swelling characteristics， and the turgidity was 17.4 mL·g^-1， which was lower than that of chia seeds （25.2 mL·g^-1） and basil seeds （35.6 mL·g^-1）. Prunellae Spica seeds were rich in phenolic and fatty acids， while the content of volatile oil was very low. The main phenolic acids were salviaflaside and rosmarinic acid， with the contents of 0.579% and 0.392%， respectively. The total content of five fatty acids in n-hexane extract was 90.1%， and total content of unsaturated fatty acids was 80.6%， among which content of α-linolenic acid was 50.0%， which was slightly lower than 57.2% of chia seeds and similar to 50.0% of basil seeds. ConclusionPrunellae Spica seeds have good turgidity， rich in phenolic acids and unsaturated fatty acids， and especially with high amount of α-linolenic acid. It is worthy of being developed as functional food to realize comprehensive utilization of the waste resources of Prunellae Spica.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

Objective:To explore the effect of intraoperative blood salvage (IBS) in the operation of infective endocarditis (IE) and the risk factors of death within half a year after operation.Methods:Used retrospective research methods, a total of 61 patients who were diagnosed as IE and received surgical treatment in Department of Cardiovascular and Large Vascular Surgery, Huizhou Central People′s Hospital from April 2017 to November 2020 were selected as subjects. The patients were divided into autologous group ( n=30) and allogeneic group ( n=31) according to different blood transfusion methods. Patients in the autogenous group received IBS, and patients in the allogeneic group received allogeneic blood transfusion. The indexes of coagulation function [activated partial thromboplastin time(APTT), thrombin tim(TT), prothrombin time(PT), D-dimmer(D-D), fibrinogen degradation product(FDP)], immune reaction (CD3 + CD4 + T cells, CD3 + CD8 + T cells, CD16 + CD56 + NK cells, TLR2 + cells, TLR4 + cells) and inflammatory reaction [soluble CD40 ligand(sCD40L), neutrophil chemokine -1(CINC-1), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)] were compared between the autologous group and the allogeneic group, as well as the incidence of postoperative adverse reactions. The end event was death half a year after operation, and the subjects were divided into death group ( n=15) and survival group ( n=46). The clinical data of the death group and the survival group were compared. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups, and the IBS variables were included and excluded to establish the prediction models of death half a year after operation, respectively. The model was evaluated by the receiver operating characteristic curve (ROC), and the model was internally verified by the method of Bootstrap repeated sampling. IBS was included and removed to establish the prediction model of death within half a year after surgery, and ROC was used to evaluate the model. Bootstrap repeated sampling was used to verify the model internally. Results:Cardiac insufficiency, hypotension, IBS, multivalvular disease and age were independent risk factors for postoperative death ( P<0.05). The model with IBS variables has higher predictive value. 5 days after operation, there were significant differences in the indexes of immune reaction [CD3 + CD4 + T cells: (37.49±5.74)% vs (31.68±4.46)%, CD3 + CD8 + T cells: (23.07±3.24)% vs (17.82±2.29)%, CD16 + CD56 + NK cells: (1.61±0.18)% vs (1.02±0.15)%, TLR2 + cells: (9.24±1.15)% vs (18.40±2.21)%, TLR4 + cells: (7.79±0.82)% vs (12.33±1.57)%] and inflammatory reaction [sCD40L: (59.21±7.80) pg/mL vs (84.33±9.35) pg/mL, CINC-1: (40.27±5.83) pg/mL vs (72.86±9.35) pg/mL, TNF-α: (10.86±1.26) ng/mL vs (17.03±2.20) ng/mL and IL-6: (6.32±0.77) ng/mL vs (11.35±1.74) ng/mL] between autologous group and allogeneic group ( P<0.01). Intra-group comparison of patients in autologous group, before and 5 days after operation, there were significant differences in the indexes of immune response [CD3 + CD4 + T cells: (48.55±6.67)% vs (37.49±5.74)%, CD3 + CD8 + T cells: (30.38±4.69)% vs (23.07±3.24)%, CD16 + CD56 + NK cells: (2.53±0.44)% vs (1.61±0.18)%, TLR2 + cells: (6.50±0.61)% vs (9.24±1.15)%, TLR4 + cells: (4.02±0.63)% vs (7.79±0.82)%] and inflammatory response [sCD40L: (38.64±6.75) pg/mL vs (59.21±7.80) pg/mL, CINC-1: (31.65±5.68) pg/mL vs (40.27±5.83) pg/mL, TNF-α: (7.59±0.85) ng/mL vs (10.86±1.26) ng/mL and IL-6 (5.10±0.63) ng/mL vs (6.32±0.77) ng/mL] ( P<0.01). Intra-group comparison of patients in allogeneic group, before and 5 days after operation, there were significant differences in the indexes of immune reaction [CD3 + CD4 + T cells: (49.13±6.82)% vs (31.68±4.46)%, CD3 + CD8 + T cells: (30.65±4.91)% vs (17.82±2.29)%, CD16 + CD56 + NK cells: (2.51±0.26)% vs (1.02±0.15)%, TLR2 + cells: (6.36±0.66)% vs (18.40±2.21)%, TLR4 + cells (4.08±0.56)% vs (12.33±1.57)%] and inflammatory response [sCD40L: (39.14±6.03) pg/mL vs (84.33±9.35) pg/mL, CINC-1: (31.24±5.77) pg/mL vs (72.86±9.35) pg/mL, TNF-α: (7.64±0.76) ng/mL vs (17.03±2.20) ng/mL and IL-6: (5.04±0.82) ng/mL vs (11.3±1.74) ng/mL] ( P<0.01). There were 3 cases of hypoproteinemia, 2 cases of incision infection and 1 case of cardiac adverse event in the autologous group; 4 cases of hypoproteinemia, 3 cases of incision infection and 1 case of cardiac adverse event in the allogeneic group. There was no significant difference in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:The predictive model included in IBS can better predict the mortality of within half a year after IE. The use of IBS in IE surgery will not significantly affect the blood coagulation function and the incidence of postoperative adverse reactions, but can improve immune function and inhibit inflammatory reaction.

Objective:To establish a prediction model of postoperative 1-year mortality risk in elderly patients undergoing hip fracture surgery and verify its efficacy.Methods:Patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅳ, who underwent an operation for traumatic hip fracture in the Second Affiliated Hospital of Wenzhou Medical University from January 2017 to December 2018, were enrolled and randomly assigned to model group and verification group in a ratio of 3∶1.The demographic characteristics, clinical data and results such as laboratory examinations were collected.In model group, the logistic regression analysis was used to recognize the independent risk factors for 1-year mortality after procedure, and the prediction model was established.In verification group, the prediction efficacy was analyzed using the receiver operating characteristic curve, and the degree of fitting was evaluated by Hosmer-Lemeshow goodness-of-fit test.Results:Multivariate logistic analysis indicated that age ≥84 yr, Charlson comorbidity index ≥2 points, Braden score on admission to hospital ≤16 points, preoperative urea nitrogen ≥8.8 mmol/L and postoperative albumin ≤ 29.6 g/L were the independent risk factors for 1-year mortality after hip fracture surgery in elderly patients ( P<0.05). The prediction model was established based on the risk factors mentioned above.The area under receiver operating characteristic curve was 0.870, and the sensitivity and specificity were 82.8% and 80.0%, respectively.The prediction model showed good fitting ( χ2=4.672, P=0.700). Conclusion:Age ≥84 yr, Charlson comorbidity index ≥2 points, Braden score on admission to hospital≤16 points, preoperative urea nitrogen ≥8.8 mmol/L and postoperative albumin ≤ 29.6 g/L are the independent risk factors for 1-year mortality after hip fracture surgery in elderly patients, and the prediction model established based on the above indicators has good efficacy.

Objective:To observe the effect of parecoxib on neutrophil-to-lymphocyte ratio (NLR)after the modified radical mastectomy,and to explore its potential mechanisms for inhibition ofperioperative inflammation.Methods:A total of 40 breast cancer patients undergone the modified radical mastectomy were randomly divided into a parecoxib group (n=20) and a control group (n=20).The parecoxib group received intravenous parecoxib (40 mg,5 mL) during general anesthesia induction,post-operative day 1 and day 2;the control group received intravenous normal saline (5 mL) at the corresponding time points.Their peripheral bloods were collected for routine test in the morning of the surgery day (T1),and Day 1 (T2),Day 3 (T3) and Day7 (T4) after the surgery, and NLRwas calculated.Results:Compared with T1,NLR in the control group at T2 and T3 was significantly increased (P＜0.05),but not at T4 (P＞0.05);NLR in the parecoxib group was sharply increased at T2 (P＜0.01),and returned to preoperative levels at T3 and T4 (P＞0.05).NLR in the parecoxib group was significantly lower than that in the control group at T2 (P＜0.05),but there were no significant difference between the two groups at other time points (P＞0.05).Conclusion:Parecoxib can restrain the inflammatory responses and improve immune function of the breast cancer patients by suppressing the elevation of NLR after the modified radical mastectomy,which is expected to improve the prognosis of the breast cancer patients.

Objective: To observe the expression level of microRNA-181 (miR-181) and importin-α3 in oxidized low density lipoprotein (ox-LDL) induced vascular endothelial cell injury models, and explore the effect and mechanism of miR-181 on endothelial cell injury. Methods: Human vein endothelial cell line CRL-1730 were cultured and vascular endothelial cell injury model was established by intervention with ox-LDL. The cells were divided into control group (intervened by double distilled water), low-dose group (intervened by 10 μg/ml ox-LDL) and high-dose group (intervened by 20 μg/ml ox-LDL). In addition, cells of low-dose group were divided into miR-181 mimic group (miR-181 mimic was transfected) and mimic control group (miR-181 mimic control was transfected). Cell viabilities, mRNA and protein expression level of interleukin-6 (IL-6), miR-181, importin-α3, and nuclear transcription factor-κB (NF-κB) were measured by methyl thiazolyl tetrazolium (MTT), real-time PCR and Western blot, respectively. Results: (1) The cell viabilities in low-dose group and high-dose group were lower than control group (0.207±0.012 and 0.204±0.007 vs. 0.323±0.018, all P<0.01). The relative IL-6 mRNA expression in low-dose group and high-dose group were higher than control group (1.24±0.16 and 1.36±0.23 vs. 0.22±0.03, all P<0.01). The relative miR-181 mRNA expression in low-dose group and high-dose group were lower than control group (0.91±0.11 and 0.88±0.07 vs. 2.20±0.13, all P<0.01). The relative importin-α3 mRNA expression in low-dose group and high-dose group were higher than control group (1.23±0.22 and 0.55±0.03 vs. 0.44±0.06, all P<0.01). The relative NF-κB mRNA expression in low-dose group and high-dose group were higher than control group (1.67±0.34 and 0.41±0.11 vs. 0.11±0.04, all P<0.01). The relative importin-α3 protein expression in low-dose group and high-dose group were higher than control group (1.44±0.23 and 1.31±0.22 vs. 0.29±0.08, all P<0.01). The relative NF-κB protein expression in low-dose group and high-dose group were higher than control group (0.43±0.05 and 0.37±0.04 vs. 0.16±0.03, all P<0.01). (2)The cell viabilities in miR-181 mimic group was higher than in mimic control group (0.262±0.008 vs. 0.211±0.021, P<0.01). The relative miR-181 mRNA expression level in miR-181 mimic group was higher than in mimic control group (4.23±0.34 vs. 0.88±0.16, P<0.01). The relative importin-α3 mRNA expression level in miR-181 mimic group was lower than in mimic control group (0.24±0.03 vs. 1.08±0.13, P<0.01). The relative NF-κB mRNA expression level was lower in miR-181 mimic group than in mimic control group (0.13±0.03 vs. 0.51±0.06, P<0.01). The relative importin-α3 protein expression level was lower in miR-181 mimic group than in mimic control group (0.34±0.06 vs. 1.67±0.26, P<0.01). The relative NF-κB protein expression level was lower in miR-181 mimic group than in mimic control group (0.43±0.02 vs. 1.53±0.36, P<0.01). Conclusions Lower miR-181 expression but higher importin-α3 and its downstream NF-κB signaling are associated with ox-LDL induced vascular endothelial cell injury and up-regulation of miR-181 could alleviate ox-LDL induced vascular endothelial cell injury possibly via importin-α3/NF-κB pathway.

ObjectiveTo investigate the incidence and gene mutation spectrum of childhood thalassemia in Sanya city. MethodsThere were 938 children in our hospital screened by routine blood test, C-reactive protein test and hemoglobinelectro-phoresis. Based on the screening results in children with thalassemia and its subtypes, the alpha thalassaemia children were diag-nosed by gap - polymerase chain reaction, while the beta thalassaemia ones were diagnosed by polymerase chain reaction-reverse dot blot, and all the results were retrospectively analyzed.ResultsScreening positive rate of thalassemia anemia was 13.65% (128/938), genetic diagnosis positive rate was 11.41% (107/938). In 107 cases diagnosed with thalassemia by genetic test, 59 were alpha thalassaemia, and 46 were beta thalassaemia, and 2 cases were alpha thalassaemia combined with beta thalassaemia. In 59 cases of alpha thalassaemia, 31 had genotype of - SEA/alpha alpha , 13 cases with genotype alpha 4.2 / alpha alpha, and 6 were of HbH disease. In the 46 cases of beta thalassaemia children, six gene locus mutations were found : CD41-42 (CTTT) in 21 cases, TATAbox - 28 (A - G) in 13 cases, CDs14/15 (G) in 5 cases, IVS - Int 654 (C - > T) in 4 cases, CD17 (A - > T) in 2 cases, and 27-28 (C) in 1 case.ConclusionHigh prevalence of thalassemia in children from Sanya city warrants genetic counseling, premarital check-up and prenatal diagnosis.

Objective To explore the effects of different ventilation modes of tracheobronchial foreign body in children with fiberoptic operation under general anesthesia.Methods Sixty children (1ys≤ age≤3ys) undergoing fiberoptic bronchoscopy tracheal foreign body removal according to the combinations of different ventilation modes during and after fiberoptic bronchoscopy (FOB) procedures were divided into group A [volume control ventilation (VCV) + VCV,n =20],group B [pressure control ventilation (PCV) + VCV,n =20] and group C (PCV + PCV,n =20) randomly.The P mean,Pmax,and PetCO2 during and after fiberoptic bronchoscopy procedures were monitored.The SpO2,PaO2,and PaCO2 after mechanical ventilation 1.5 hours were recorded.Results Compared to group A,groups B and C had lower P max and P mean (P ＜ 0.05) during the FOB procedures.Compared to groups A and B,group C had a lower P max and P mean (P ＜0.01) after the FOB procedures.At the 1.5 hours after the procedure,all the children showed significant increase in SpO2 and PaO2 (P ＜ 0.05) and decrease in PaCO2 (P ＜ 0.05) in groups A,B,and C.Conclusions When fiberoptic bronchoscopy in tracheobronchial foreign body operation is applied in children undergoing general anesthesia,the pressure control ventilation (VCV) mode can decrease the pressure of airway (Paw) and PaCO2 than volume control mode during procedure.