Chimeric antigen receptor T (CAR-T) lymphocytes are at the forefront of adoptive immunotherapy research, and this technology has significantly advanced the prospects of tumor immunotherapy. CAR-T therapy has demonstrated remarkable efficacy in haematological tumours of lymphoid origin and provided therapeutic possibility for solid tumours. Currently, CAR-T cell preparation predominantly involves transfection of T cells with viral vectors. However, the production of viral vectors is time-consuming, expensive, and the vectors have low loading capacity, along with insertion instability. Consequently, there is a pressing need to develop more convenient and precise non-viral gene delivery methods. This paper reviews the most promising non-viral gene delivery technologies, including CRISPR/Cas9 gene editing, transposon systems such as Sleeping Beauty (SB) and PiggyBac (PB), and mRNA, and anticipates the future development of non-viral vector-based CAR-T therapies.
Humans ; Immunotherapy, Adoptive/methods* ; Receptors, Chimeric Antigen/immunology* ; Animals ; Gene Transfer Techniques ; Genetic Vectors/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Transposable Elements/genetics* ; T-Lymphocytes/immunology* ; Neoplasms/immunology*

Objective:To investigate the clinical and pathological characteristics and prognosis of children with lupus nephritis(LN)and thrombotic microangiopathy (TMA).Methods:In this retrospective case-control study, clinical and pathological data of LN children confirmed by renal biopsy from January 2008 to January 2023 in Xuzhou Children′s Hospital, Xuzhou Medical University were analyzed.There were 46 LN children complicated with TMA (LN-TMA group). With matched age, sex and pathology, 92 LN children (1∶2) without TMA were selected as the control group (LN group). The Kaplan-Meier method was used to evaluate the overall and renal survival rates of children with LN, and the Cox regression model was used to analyze the risk factors for the progression to end-stage renal disease (ESRD).Results:TMA was moderately associated with serum creatinine, serum C3, anti-C1q antibody (a-C1q), estimated glomerular filtration rate (eGFR), endocapillary proliferation, fibrinoid necrosis, and renal C1q deposition (all r>0.5). Serum a-C1q≥20 U/mL ( HR=8.724, 95% CI: 0.976-16.114, P=0.026) and eGFR≤60 mL/(min·1.73 m 2) ( HR=12.213, 95% CI: 1.147-25.048, P=0.038) were independent risk factors for TMA in children with LN.Glomerular sclerosis ( HR=7.228, 95% CI: 0.186-22.358, P=0.016), TMA ( HR=11.387, 95% CI: 3.426-42.554, P=0.009) and eGFR≤60 mL/(min·1.73 m 2) ( HR=3.116, 95% CI: 0.592-10.064, P=0.030) were independent risk factors for developing ESRD in LN children.The 5-year and 10-year renal survival rates in the LN-TMA group were lower than those in the LN group (97.44% vs.98.28%, 80.90% vs.87.27%, χ2=4.918, P=0.027). Conclusions:Children with LN-TMA present with severe symptoms and poor prognosis.TMA is an independent risk factor for progression to ESRD in children with LN, and the mechanism may be related to complement activation.

Objective To evaluate the quality of infectious disease surveillance data and provide scientific basis for improving data quality and health decision-making. Methods The comprehensive index of infectious disease monitoring system evaluation and the integrity, accuracy and reliability of infectious disease report data were used to evaluate the quality of infectious disease monitoring data in multiple dimensions. Results In 2021, The comprehensive evaluation index of infectious disease surveillance system was 98.40%. In terms of data integrity, 1 105 data were missing, and the incomplete rate was 1.46%; In terms of data accuracy, 1978 cases were not accurately, rate of accuracy was 26.72%; In terms of data reliability, the card reporting rate of tertiary medical institutions accounted for 67.05%, the diagnosis rate of confirmed cases was 27.74%, and the correction rate of report card was 28.48%. Conclusion The accuracy and reliability of infectious disease data are insufficient, and new methods for infectious disease monitoring data quality are expanded to make up for the lack of data quality evaluation of the current national epidemic system.

Objective:To summary the mixed infection as well as clinical characteristics and analyze the risk factors for mixed infection of severe adenovirus pneumonia(SAP) in children.Methods:The clinical data of 114 children with SAP were retrospectively analyzed.Multivariate Logistic regression analysis was performed to assess the risk factors for mixed infection.Results:The incidence age was from 6 months to 2 years(62.5%). High fever(94.7%), cough(98.2%), dyspnea(86.8%) and lethargy(95.6%) were the main symptoms.Laboratory examination showed that children with SAP were prone to increased white blood cell count, C-reactive protein, procalcitonin, aspartate aminotransferase, alanine aminotransferase and CK-MB, as well as decreased proportion of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and NK cells.The main complications intrapulmonary organ were respiratory failure(80.7%). The main complications extrapulmonary organ were circulatory complications (55.3%). SAP was easily combined with other pathogenic infections.Streptococcus pneumoniae(22.9%)was the most common bacterial pathogen.Respiratory syncytial virus(10.0%)were the most common virus, in addition, mycoplasma pneumoniae(17.1%) was also common.Multivariable Logistic regression analysis showed that the decreasing ratio of CD4 + /CD8 + and NK cells, congenital heart disease and congenital airway dysplasia were the independent risk factors for mixed infection of SAP in children( P<0.05). Conclusion:The SAP patients could easily suffer from mixed infection and high fatality rate.Immune dysregulation is the important risk factors for mixed infection of SAP in children.So immunoregulatory treatment is very important.

Objective:To discuss the role of continuous blood purification (CBP) therapy in children with severe adenovirus pneumonia.Methods:A total of 114 children with severe adenovirus pneumonia admitted to the Department of PICU at Children′s Hospital of Hunan Province from June 2018 to July 2019 were selected as the research objects.According to whether treated with CBP, they were divided into CBP group and control group.The following indicators during the process of treatment were compared between two groups, including respiratory mechanics indicators[respiratory index(PaO 2/FiO 2), dynamic lung compliance(Cdyn)]; hemodynamic indicators(heart rate and mean arterial pressure); changes in levels of inflammatory factors interleukin(IL)-6, IL-10, tumor necrosis factor(TNF)-α and the prognosis 28 days after admission. Results:The respiratory mechanics index, serum IL-6 and TNF-α levels of two groups after treatment were significantly lower than those before treatment, and the serum IL-10 level was significantly higher than that of this group before treatment.There were statistical differences in the CBP group before and after treatment, while there was no statistical difference in control group.In the CBP group, the serum IL-6 and TNF-α levels after treatment were significantly lower than those of the control group( P<0.05), and the serum IL-10 level was significantly higher than that of the control group( P<0.05). The 28-day mortality rate of patients in CBP group was 8.6%(3/35), which was significantly lower than 13.9%(11/79) of control group ( P<0.05). Conclusion:CBP could improve the main respiratory mechanical indexes of adenovirus pneumonia and decrease the level of inflammatory cytokines.

Objective: To observe the effect of curcumin on myocardial mitochondrial related gene (mtATP6), high mobility group box 1(HMGB1) mRNA expression and plasma HMGB1 level in rats with sepsis, and to explore a new strategy for protection of myocardial injury in sepsis. Methods: A rat sepsis model was established by cecal ligation and puncture (CLP). Thirty male Sprague-Dawley rats were randomly (random number) divided into the sham operation group (sham group), sepsis group (CLP group), and curcumin intervention group (Cur group), with 10 rats in each group. Rats in the Cur group were treated with curcumin by intraperitoneal injection at 100 mg/kg, and normal saline was injected into rats in the sham and CLP groups. Five rats were randomly (random number) sacrificed at 6 h and 24 h after modeling. The pathological changes of myocardial tissue were observed under light microscope. The levels of CK and CK-MB in serum were detected. The HMGB1 level in plasma was detected by ELISA. Real-time PCR was used to detect the expression of HMGB1 mRNA and mtATP6 in myocardial tissue. One-way ANOVA were performed in multigroup mean comparison, LSD-t test was used to compare the mean values of two samples, and P<0.05 was considered statistically significant. Results: The pathological score of myocardial tissue in the Cur group was lower than those in the CLP group at 6 h and 24 h (P<0.05). The CK and CK-MB in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The levels of HMGB1 in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the CLP group were lower than those in the sham group at 6 h (P<0.05), while the expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the Cur group were higher than those in the CLP group at 6 h, but the difference was not statistically significant (P>0.05). Conclusion Curcumin protects acute myocardial injury by affecting HMGB1 release and translocation down-regulation of extracellular levels and regulation of mtATP6 expression in CLP model rats.

Objective: To understand the prevalence and development of pulmonary tuberculosis(PTB) in students and teachers in Liangyungang over the last ten years, and provide reference for PTB surveillance and control at schools and colleges. Methods: The epidemic information of PTB among students and teachers in Lianyungang during 2008-2017 was collected from Chinese Infectious Disease Report Information Management System and Chinese Tuberculosis Information Management System, and analyzed with quantitative description method. Results: From 2008 to 2017, 1 112 students and teathers with PTB were found in Lianyungang City, the average reported incidence was 14.03/100 000, pathogenic positive incidence was 4.52/100 000. The above two rates both showed a trend of decline year by year (Z=4.55,6.83, P<0.01). The incidence of registered PTB in schools in the second quarter was the highest, especially in April. Guanyun County has the highest incidence. The average age was (20.11±7.54) years old, and the obvious high-incidence age group was 16-21; the sex ratio between men and women was 1.87∶1. Most of the 1 112 patients were Han, accounting for 99.64%, the rest were Hui, Tujia and Uygur. Teachers’ reported incidence was positively correlated with students’ reported morbidity (rs=0.93, P<0.01); there were differences between school population and general population in gender, patient origin, etiological results, treatment classification and positive patients’ treatment outcome (χ2=49.54, 528.27, 63.55, 121.40, 9.80, P<0.05). Conclusion Overall, the reported incidence of PTB in schools in Lianyungang City has been decreasing year by year, however,it should not be taken lightly. Prevention and control of PTB in schools should be further strengthened.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

Objective To study the clinical distribution characteristics of psychiatric symptoms in patients with multiple system atrophy ( MSA ) and analyze the influence factors of neuropsychiatric symptoms.Methods Twelve psychiatric symptoms were evaluated in 47 patients with MSA by the Neuropsychiatric Inventory of the Chinese version ( CNPI ) .The occurrence rate and distribution were evaluated.The correlation between the neuropsychiatric symptoms and the clinical features including gender , age, education duration, disease course, cognitive level, Unified Multiple System Atrophy Rating Scale part 3 ( UMSARS-Ⅲ) score, Unified Parkinson's Disease Rating Scale part 3 ( UPDRS-Ⅲ) score, Hamilton Depression Rating Scale ( HAMD) score, Hamilton Anxiety Scale ( HAMA) score, MSA subtype and levodopa and benserazide usage dose was also analyzed .Results A total of 74.5%( 35/47 ) of the MSA patients presented at least one kind of psychiatric symptoms .The most common neuropsychiatric symptoms were depression (66.0%, 31/47) and sleep disorder (63.8%, 30/47), while the symptom of euphoria was not found.The highest mean score was found for depression ( mean score:5.23 ±1.67 ) .The CNPI scores of MSA patients were negatively correlated to the education duration and Simple Mental State Examination (MMSE) score (r=-0.238, -0.334 respectively, both P<0.01).The CNPI scores of MSA patients were positively correlated to the disease course and HAMD score ( r=0.308, 0.307 respectively, both P<0.01) .The CNPI scores of MSA patients had no relevance to the gender , age, UMSARS-Ⅲscore, UPDRS-Ⅲscore, MSA subtype and levodopa and benserazide dosage ( all P>0.05). Multiple liner regression analysis showed that HAMA and MMSE scores had the greatest impact on CNPI (r2 =0.196, 0.270, respectively, both P=0.000) .Conclusions The incidence of neuropsychiatric symptoms is high and varied in patients with MSA .The neuropsychiatric symptoms were more severe in MSA patients with lower cognitive levels and longer disease courses .