In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

OBJECTIVE: To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection. METHODS: DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 β-thalassemia point mutations which were common gene mutions in China. RESULTS: There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of β-thalassemia and 29 cases (7.07%) carried gene mutations of complex αβ-thalassemia syndrome. The mutations of α-thalassemia were involved with -- CONCLUSION The most common genetic mutations are --
China ; Humans ; Mutation ; Oligonucleotide Array Sequence Analysis ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

Objective:To investigate the changes of CTCs and the correlation between the changes of CTCs and the clinical efficacy of neoadjuvant immunotherapy for non-small cell lung cancer (NSCLC).Methods:A retrospective case-control study was conducted to collect the data of 23 patients with NSCLC who received neoadjuvant immunotherapy in the Third Xiangya Hospital from June 2018 to December 2019. They were 35-76 years old with a median age of 52 years old, including 13 male patients and 10 female patients. The CTCs value, evaluation results from response evaluation criteria in solid tumor (RECIST) and major pathological response were evaluated before treatment, after neoadjuvant immunotherapy and after operation. Mann Whitney U test was used for the comparison between the two groups, Wilcoxon test was used for the comparison of association samples, and Kruskal Wallis test was used for the comparison between multiple samples.Results:The CTCs value was positively correlated with tumor progression, that the CTCs value of ⅡB group, ⅢA group and ⅢB group was 10.69 (3.87) FU/3 ml, 12.90 (2.24) FU/3 ml and 16.04 (3.43) FU/3 ml, and the difference was statistically significant (χ 2=7.829, P=0.020). Then CTCs decreased to 7.60(4.79) FU/3 ml significantly ( Z=4.197, P=0.000), and decreased to 6.22(2.80) FU/3 ml significantly again after surgery( Z=-2.950, P=0.005). In RECIST results, the CTCs value of CR group, PR group and SD group was 12.90(3.79)FU/3 ml, 12.52(3.96) FU/3 ml and 13.58(5.11) FU/3 ml,and no significant difference before treatment (χ2=1.806, P=0.405). After neoadjuvant immunotherapy, the CTCs of CR group decreased to 6.22(3.87) FU/3 ml significantly ( Z=-4.950, P= 0.000), and also PR group to7.32(4.31) FU/3 ml ( Z=-3.180, P=0.001) or SD group to ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-0.838, P=0.402), but significant difference between SD group and CR/PR group ( Z=-1.922, P=0.050). After operation, the CTCs of CR, PR and SD group decreased to 6.09(3.43) FU/3 ml, 6.40(1.82) FU/3 ml and 9.20(5.16) FU/3 ml,and there was no significant difference to preparation in CR group and PR group, but significant difference in SD group ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-1.134, P=0.257), but significant difference between SD group and CR/PR group ( Z=-1.624, P=0.014). Before treatment,CTCs of MPR group and non-MPR group were 11.98(4.14) FU/3 ml and 13.54(4.76) FU/3 ml,and there was no significant difference between them ( Z=-1.354, P=0.176). After neoadjuvant immunotherapy, the CTCs of MPR group decreased to 6.36(2.65) FU/3 ml significantly ( Z=-2.934, P=0.001) and also in non-MPR group to 10.88(2.80) FU/3 ml ( Z=-2.840, P=0.003); but there was significant difference between MPR group and non-MPR group ( Z=-3.693, P=0.000), and also the change of CTCs between two groups ( Z=-2.770, P=0.006). After operation, the CTCs of MPR group decreased to 5.40(1.33) FU/3 ml insignificantly ( Z=-0.533, P=0.594) but significantly to 7.05(3.80) FU/3 ml in non-MPR group ( Z=-2.734, P=0.030), and significant difference between them ( Z=-1.900, P=0.011). Conclusion:The value of CTCs is negatively correlated with the efficacy (RECIST and MPR) of neoadjuvant immunotherapy for NSCLC, which can be used for clinical efficacy evaluation of neoadjuvant immunotherapy.

Objective:To investigate the changes of CTCs and the correlation between the changes of CTCs and the clinical efficacy of neoadjuvant immunotherapy for non-small cell lung cancer (NSCLC).Methods:A retrospective case-control study was conducted to collect the data of 23 patients with NSCLC who received neoadjuvant immunotherapy in the Third Xiangya Hospital from June 2018 to December 2019. They were 35-76 years old with a median age of 52 years old, including 13 male patients and 10 female patients. The CTCs value, evaluation results from response evaluation criteria in solid tumor (RECIST) and major pathological response were evaluated before treatment, after neoadjuvant immunotherapy and after operation. Mann Whitney U test was used for the comparison between the two groups, Wilcoxon test was used for the comparison of association samples, and Kruskal Wallis test was used for the comparison between multiple samples.Results:The CTCs value was positively correlated with tumor progression, that the CTCs value of ⅡB group, ⅢA group and ⅢB group was 10.69 (3.87) FU/3 ml, 12.90 (2.24) FU/3 ml and 16.04 (3.43) FU/3 ml, and the difference was statistically significant (χ 2=7.829, P=0.020). Then CTCs decreased to 7.60(4.79) FU/3 ml significantly ( Z=4.197, P=0.000), and decreased to 6.22(2.80) FU/3 ml significantly again after surgery( Z=-2.950, P=0.005). In RECIST results, the CTCs value of CR group, PR group and SD group was 12.90(3.79)FU/3 ml, 12.52(3.96) FU/3 ml and 13.58(5.11) FU/3 ml,and no significant difference before treatment (χ2=1.806, P=0.405). After neoadjuvant immunotherapy, the CTCs of CR group decreased to 6.22(3.87) FU/3 ml significantly ( Z=-4.950, P= 0.000), and also PR group to7.32(4.31) FU/3 ml ( Z=-3.180, P=0.001) or SD group to ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-0.838, P=0.402), but significant difference between SD group and CR/PR group ( Z=-1.922, P=0.050). After operation, the CTCs of CR, PR and SD group decreased to 6.09(3.43) FU/3 ml, 6.40(1.82) FU/3 ml and 9.20(5.16) FU/3 ml,and there was no significant difference to preparation in CR group and PR group, but significant difference in SD group ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-1.134, P=0.257), but significant difference between SD group and CR/PR group ( Z=-1.624, P=0.014). Before treatment,CTCs of MPR group and non-MPR group were 11.98(4.14) FU/3 ml and 13.54(4.76) FU/3 ml,and there was no significant difference between them ( Z=-1.354, P=0.176). After neoadjuvant immunotherapy, the CTCs of MPR group decreased to 6.36(2.65) FU/3 ml significantly ( Z=-2.934, P=0.001) and also in non-MPR group to 10.88(2.80) FU/3 ml ( Z=-2.840, P=0.003); but there was significant difference between MPR group and non-MPR group ( Z=-3.693, P=0.000), and also the change of CTCs between two groups ( Z=-2.770, P=0.006). After operation, the CTCs of MPR group decreased to 5.40(1.33) FU/3 ml insignificantly ( Z=-0.533, P=0.594) but significantly to 7.05(3.80) FU/3 ml in non-MPR group ( Z=-2.734, P=0.030), and significant difference between them ( Z=-1.900, P=0.011). Conclusion:The value of CTCs is negatively correlated with the efficacy (RECIST and MPR) of neoadjuvant immunotherapy for NSCLC, which can be used for clinical efficacy evaluation of neoadjuvant immunotherapy.

Objective:To construct HIV-1 pseudovirus containing enhanced green fluorescent protein ( EGFP ) gene. To understand the interaction between the virus and the cells. Methods: HIV-1 pseudovirus containing EGFP gene was constructed by lentiviral packaging systems, and its EGFP gene was amplified using RT-PCR. The level of genomic integration and transcription of HIV-1 pseudovirus containing EGFP gene were detected on iDCs infected with HIV-1 pseudovirus. At the same time, research on expression of the EGFP gene in iDCs infected with HIV-1 pseudovirus was performed. Results:The EGFP gene of HIV-1 pseudovirus was detected through RT-PCR. The EGFP gene was identified in iDCs infected with HIV-1 pseudovirus through PCR and RT-PCR. The EGFP was observed in iDCs infected with HIV-1 pseudovirus under fluorescence microscopy. Conclusion: HIV-1 pseudovirus containing EGFP gene has been successfully produced. The HIV-1 pseudovirus that we constructed can infect iDCs,then its RNA can integrate into the genome of iDCs in the way of reverse transcription,and the EGFP gene could express in the iDCs after infected with HIV-1 pseudovirus.

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Adolescent ; Adult ; Anesthesia, General ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Septal Occluder Device ; Treatment Outcome ; Young Adult

We systematically reviewed the results of the studies on expression regulation, biological functions, and clinical prognostic significance of CASP8AP2 gene. At present, the studies showed that the expression of CASP8AP2 gene was regulated by Homeobox proteins and DNA methylation, and could be silenced by miRNA-210. This protein was involved in apoptosis mediated by FAS and TNFα, NF-κB activation mediated by TNFα, regulation of gene expression induced by glucocorticoid and mineralocorticoid receptor, comprising Cajal body and histone locus body, transcription of replication-dependent histone, 3' end processing of histone, regulation of S phase progression, in addition to functioning as coactivator of transcription factors c-Myb and p73 to activating many genes' expression. On the other hand, low expression of CASP8AP2 gene was associated with relapse in childhood ALL. The deletion of this gene was related to the poor prognosis of children with T-ALL and T lymphoblastic lymphoma. Furthermore, 3 SNPs in this gene were possibly correlated with genesis of diffuse large B cell lymphoma and childhood leukemia. In conclusions, CASP8AP2 was a multifunctional protein. It could function to regulate cell proliferation, apoptosis, and gene expression. In childhood hematological malignancies, CASP8AP2 was a promising molecular marker with prognostic significance. Some SNPs were possibly correlated with leukemo- and lymphomogenesis.
Apoptosis ; Apoptosis Regulatory Proteins ; Calcium-Binding Proteins ; DNA Methylation ; Gene Expression ; Gene Expression Regulation ; Histones ; Humans ; NF-kappa B ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

OBJECTIVETo study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.

METHODSA lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.

RESULTSNo lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.

CONCLUSIONThe expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.

Adenocarcinoma ; chemically induced ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Gene Expression Regulation ; physiology ; Humans ; Lung ; drug effects ; pathology ; Lung Neoplasms ; blood ; chemically induced ; metabolism ; Male ; MicroRNAs ; blood ; genetics ; metabolism ; Nitrosamines ; pharmacology ; Rats ; Rats, Inbred F344

BACKGROUND: Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS). METHODS: Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO2/FiO2), hepatic function, platelet count, and blood coagulation were determined. RESULTS: Signifi cant improvement was observed in HR, MAP, PaO2/FiO2, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1％ (18/31), viral survival rate 36.4％ (4/11), and non-viral survival rate 70％ (14/20). CONCLUSION: Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.