Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.

Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.

OBJECTIVE: To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis. OBJECTIVE: Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI. OBJECTIVE AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.
Acute Kidney Injury/epidemiology* ; Aged ; COVID-19 ; China/epidemiology* ; Humans ; Male ; Retrospective Studies ; SARS-CoV-2

Objective To evaluate the effects of the quality-improving program on reducing the bloodstream infection of preterm infants in NICU.The program included emphasizing hand hygiene,strictly controlling the use of antibiotics and following the extubation indications of peripherally inserted central catheter (PICC).Method From October 2016 to March 2017,preterm infants admitted to NICU after the implementation of quality improvement program were assigned into the intervention group,and the infants admitted from April 2016 to September 2016 without the program were in the control group.The x2 test and t test were used to analyse the effects of the program,the rate of bloodstream infection and related complications.Result A total of 432 cases were enrolled in this study.Among them,221 cases were in the intervention group and 211 cases the control group.The rate of hand hygiene in the intervention group was significantly higher and the duration of antibiotic use per 1 000 hospitalization days and the average days of retaining the PICC were significantly shorter than the control group (P ＜ 0.001).The incidence of bloodstream infection in the intervention group was lower than the control group (5.9％ vs.11.4％,P =0.047),and the duration of non-invasive ventilation,parenteral nutrition,average hospitalization days,and the incidence of stage 11 and above necrotizing enterocolitis were lower than the control group (P ＜ 0.05).Conclusion The evidence-based quality improvement program has positive effects on reducing the bloodstream infections and related complications of preterm infants in NICU.

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Objective To explore the efficacy and safety of high-dose second-generation fat emulsion usage on the very low birth weight premature infants.Methods A total of 88 premature infants with very low birth weight (VLBW) in Neonatal Intensive Care Unit (NICU)of Fujian Provincial Maternity and Children Hospital,Affiliated Hospital of Fujian Medical University from December 2013 to December 2014 were randomly divided into experimental group and control group,with 44 cases in each group according to the table of random number.The experimental group received intravenous nutrition with 200 g/L second-generation fat emulsion within 24 hours after birth,the initial dose was 2.0 g/(kg · d) with an increase of (0.5-1.0) g/(kg · d) daily,the maximum dose was 3.5 g/(kg · d);the control group received intravenous nutrition with 200 g/L second-generation fat emulsion 24 hours later after birth,the initial dose was 0.5 g/(kg · d) with an increase of 0.5 g/(kg · d) daily,the maximum dose was 3.5 g/(kg · d).The other intravenous nutrition methods were same.The general conditions at birth,blood biochemical parameters,growth parameters and complications were compared between the 2 groups.Results The mean value of intravenous nutrition duration,length of stay,the glucose infusion rates of postnatal days 6 and 7,the serum triglyceride levels of postnatal days 7,chest circumference of the fourth weeks,the incidence of the low triiodothyronine(T3) syndrome and parenteral nutrition associated cholestasis(PNAC) were (22.27 ± 7.17) d,(37.75 ± 12.28) d,(8.10 ± 0.92) mg/(kg · min),(8.49 ± 1.06) mg/(kg · min),0.18(0.03-0.59) mmol/L and (27.21 ± 1.62) cm in the experimental group respectively,but (27.36 ± 11.37) d,(44.36 ± 16.45) d,(7.98 ±0.79) mg/(kg · min),(8.22 ±0.76) mg/(kg · min),0.28 (0.07-0.99) mmol/L and (26.56 ± 0.96) cm in the control group,respectively,and the differences were statistically significant between the 2 groups (t =2.512,5.403,4.314,9.705,696.500,6.668,all P ＜ 0.05).The incidence of the T3 syndrome and parenteral nutrition associated cholestasis (PNAC) in the experimental group was 25.0％ (11/44 cases) and 0(0/44 cases),respectively,which were significantly lower than those in the control group[81.8％ (36/44 cases)and 9.1％ (4/44 cases)],and the differences were statistically significant between the 2 groups (x2 =28.542,5.736,all P ＜ 0.05).The 2 groups had no significant difference in the incidence rates of other complications such as necrotizing enterocolitis,infection,retinopathy of prematurity,bronchopulmonary dysplasia,and the duration of oxygen therapy and mechanical ventilation(all P ＞ 0.05).Conclusions The high-dose second-generation fat emulsion usage [the initial dose 2.0 g/(kg · d)] in VLBW infants is safe and well tolerated.Advisable parenteral nutrition support strategy can promote growth of VLBW infants,shorten the intravenous nutrition duration and length of stay,reduce the incidence of the low T3 syndrome and PNAC,which has no influence on the incidence rates of other complications.

Objective: To establish a simple, reliable and reproducible animal model of neonatal hypoxic-ischemic encephalopathy (HIE) with similar clinical pathological process to neonates. Methods: Seven days after birth, 180 Sprague-Dawley (SD) rats were randomly divided into six groups: blank control group, experimental control group and four hypoxia groups (8, 10, 12 and 14 min hypoxia groups). Those in the experimental groups were locally anesthetized with 5% lidocaine to separate their tracheas through blunt dissection, followed by tracheal clamping with vascular clamp for 8, 10, 12 and 14 min, respectively. Rats in the experimental control group were only treated with blunt dissection of trachea. No intervention was given to the blank control group. Due to significant reduction in rat survival rate after 14 min of hypoxia, no further morphological or behavioral examination was performed in this group. Rat brain tissue sections were stained with hematoxylin-eosin (HE) 12 h after modeling. Three days after modeling, the rat brain was weighted and the apoptosis of neural cells was detected with terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL). Morris water maze was used to screen cognitive impairment in these rats at the age of two months. One-way analysis of variance was used for statistical analysis. SNK test and Dunnett 's T3 test were performed to compare homogeneous and non-homogeneous data between groups. Results: Systemic cyanosis, loss of consciousness, paled body, urinary and fecal incontinence, twitching of the limbs and tail and other abnormal behavior were induced by hypoxia. Ischemic necrosis, bleeding, nucleus shrinkage in a large number of neurons and hyperchromatic nuclei were observed in the 8, 10 and 12 min hypoxia groups. Three days after modeling, brain weights of rats in the 8, 10 and 12 min hypoxia groups were lower than those of the blank control group and experimental control group [(1.16±0.07), (1.04±0.06), (0.97±0.12), (1.31±0.06) and (1.28±0.09) g, F=36.437, P<0.001]. However, the numbers of apoptotic cortical [(22.83±4.52), (30.25±3.02), (39.18±5.04), (7.96±2.24) and (8.86±2.49)/400 scope field, F=164.532, P<0.001] and hippocampal CA3 neurons of that three hypoxia groups were higher than those of the two control groups [(14.63±2.26), (20.25±3.02), (24.81±1.98), (4.75±2.66) and (6.67±1.78)/400 scope field, F=141.026, P<0.001]. At the age of two months, rats in the 8, 10 and 12 min hypoxia groups had longer escape latency [(17.99±6.48), (23.07±9.90), (38.94±32.46), (14.37±6.06) and (12.78±7.21) s, F=26.912, P<0.001] and fewer times of platform crossings than those in the control group and experimental control group [(5.00±1.41), (4.90±1.29), (3.75±1.83), (7.57±1.16) and (7.14±1.15) times, F=14.336, P<0.001]. Conclusions Pathological changes in brain tissues and behaviors of rats after modeling are in line with the characteristics of classic animal model of HIE and similar to the clinical pathology and physiology of HIE, and this could be a new, simple, reliable and reproducible animal model of HIE, being capable of controlling the duration of hypoxia accurately.

Objective To discuss the correlation of P-glycoprotein(P-gp) and lymphocyte subgroup(CD4+,CD8+) in patients with immune thrombocytopenia.Methods A total of 20 patients with immune thrombocytopenia were selected from August 2015 to September 2016 in the Eighth Hospital Affiliated to Sun Yat-sen University.According to the platelet count,all patients were divided into mild group and severe group,20 cases of health persons were selected at the same period as the healthy group,flow cytometry technique was used to detect the plasma lymphocyte subsets(CD4+,CD8+) and P-gp level of all the objects.Pearson correlation analysis was used to analyze the relationship between plasma P-gp and plasma CD4+,CD8+,CD4+ / CD8+ level,analyzed all the objects plasma platelet count,P-gp and CD4+,CD8+,CD4+ / CD8+ levels.Results Plasma CD4+,CD8+,CD4+ / CD8+ and P-gp level of severe group were significant higher than those of mild group(t=3.587,2.957,2.315,2.646,P<0.05),plasma CD4+,CD8+,CD4+ / CD8+ and P-gp level of mild group patients were significant higher than those of healthy group(t=5.479,2.921,4.536,7.750,P<0.05).Pearson correlation analysis results showed that the plasma levels of P-gp and plasma CD4+,CD8+,CD4+ / CD8+ levels were positively correlated(r=0.683,0.617,0.548,P<0.05).Conclusion Plasma CD4+,CD8+,CD4+/CD8+and P-gp level is associated with immune thrombocytopenia patients condition,plasma levels of P-gp closely links with abnormal immune function in patients with hyperthyroidism,prompting detection the level of change could help doctors to assess patients medication curative effect.

Objective To study the clinical characteristics of inherited metabolic disease(IMD) in the neonatal intensive care unit and to improve the ability of early diagnosis of the disease.Methods A total of 5 590 newborns were hospitalized in the Neonatal Intensive Care Unit (NICU),Fujian Maternity and Children Hospital between January 2012 and April 2015,and 340 neonates who were suspected of IMD consecutively were recruited.Tandem mass spectrometry and gas chromatography-tandem mass spectrometry were used to diagnose IMD.A retrospective study of analyzing the clinical characteristics of the patients of IMD in the NICU was conducted.Results Fifteen neonates were diagnosed as IMD,among whom methylmalonic academia,maple syrup urine disease,hyperphenylalaninemia,citrin deficiency,propionic acidemia,glutaric academia,ornithine transcarbamylase deficiency and primary carnitine deficiency were 5,2,2,2,1,1,1 and 1,respectively.Sixty-six point seven percent (10/15 cases) of IMD onset in the first week after birth were severe.Clinical presentations include the nervous was severe,digestive system and respiratory system symptoms,such as poor response,coma,lethargy,dystonia,convulsion,shortness of breath,dyspnea,milk refusal,diarrhea,jaundice,and so on.The main early manifestations were anorexia,lethargy,seizures and shortness of breath,which were nonspecific.Conclusions Clinical manifestations of IMD are nonspecific.The earlier onset of the disease is more serious,and early tandem mass spectrometry and gas phase chromatography-mass spectrometry are useful for early diagnosis and may guide early clinical intervention.

Objective To investigate the clinical features of rheumatoid arthritis (RA) associated with thyroid function abnormalities.Methods Serum thyroid function,anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were detected in 186 RA patients.Clinical data were then analyzed.Comparison of continuous data between groups was made by t test,while comparison of categorical data was made by x2 test.The non-normal distribution of the data was analyzed by Mann-Whitney U rank sum test.Results Fifty-six RA cases (30％) had abnormal thyroid function,including 25 low T3 syndrome cases,16 subclinical hypothyroidism cases,10 hypothyroidism cases and 5 Graves' disease cases.Among them 23 cases were diagnosed as Hashimoto's thyroiditis.The positive rate in the hypothyroidism group with chills (45 cases,80.3％,x2=99.94),lazy words (14 cases,25.0％;x2=7.896),lethargy (24 cases,42.9％;x2=7.433) and abdominal distension (21 cases,37.5％;x2=7.15) was higher than that in the group with normal thyroid function (all P＜0.05).Level of serum high density lipoprotein was decreased in hypothyroid group [(1.0±0.5) mmol/L vs (1.4±0.6) mmol/L,t=4.087,P＜0.05].Patients with abnormal thyroid function had higher positive rate of ANA [(10 cases,7.7％) vs (25 cases,44.5％),x2=34.98],anti-SSA [(3 cases,2.3％) vs (23 cases,41.1％),x2=48.91],anti-SSB [(2 cases,1.5％) vs (12 cases,21.4％),x2=22.25],TGAb [(20 cases,15.4％) vs (43 cases,76.7％),x2=65.88] and TPOAb [(13 cases,10.0％) vs (27 cases,48.2％),x2=35.90] than those with normal thyroid function (all P＜O.05).Conclusion Rheumatoid arthritis is often accompanied by thyroid disease.The positive rate of auto-antibodies in RA with abnormal thyroid function is higher than those with normal thyroid function and has no relationship with the disease activity.