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.

Chronic kidney disease (CKD) affects 8%-15% of the population globally and can cause renal failure, partly due to lack of effective treatments and drug targets. Three novel cembrane diterpenoids papyifurans A‒C (1-3), in particular of 1 with an unprecedented trioxatetracyclo[10.2.1.1^2,5.1^6,9]heptadecane polyether scaffold, derived from Boswellia papyrifera resin, were found to effectively protect against renal fibrosis in vitro and in vivo. Their structures were fully characterized using a combination of spectroscopic, computational, modified Mosher's, and X-ray crystallographic analysis. In particular, we performed chemical proteomic analyses and found that Elongation factor 2 (EEF2) is the key target of compound 1 for anti-renal fibrosis in vitro. Moreover, previous studies have linked EEF2 with lung fibrosis, while compound 1 was found to inhibit the hallmarks of organ fibrosis in vitro. Such effects were observed to decrease with the knock down of EEF2 in vitro, suggesting that EEF2 might be a universal drug target of organ fibrosis. Collectively, the present study demonstrated an example of identifying drug targets by using structurally novel natural products, which will be beneficial for developing therapeutic agents against organ fibrosis.

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

OBJECTIVETo screen for KIT gene mutations in two Han Chinese pedigrees affected with Piebaldism.

METHODSClinical data of the pedigrees was collected. Genomic DNA was extracted from blood samples collected from the pedigrees and 120 unrelated healthy controls. All coding exons of the KIT gene were subjected to PCR amplification and direct sequencing.

RESULTSTwo missense mutations, c.1861G>A(p.Ala621Thr) and c.1872G>A(p.Met624Ile), were identified respectively in the two pedigrees. Neither mutation was found among healthy members from the respective pedigree and the 120 unrelated healthy controls. c.1872G>A is a novel mutation.

CONCLUSIONMutations of the KIT gene may affect the structure and function of the transmembrane receptor KIT, which lead to the disease.

Objective: To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis. Methods: The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents. Results: The probands were 11 years and 3 moths, 9 years and 1 month,10 years and 1 month old. All were normal at birth, and from 5-6 years old they began to develop "regression of cognition and motion, impaired vision". Physical examination at the first consultation: clear minded butignorant, unable to speak and understand instructions, unable to stand up and sit alone, unable to maintain postureupright. The brain magnetic resonance imaging(MRI) indicated diffuse cerebral and cerebellar atrophy, white matter damage. Blood biochemistry, lactic acid, acid-base balancewere normal. Electron microscopic examination of peripheral blood lymphocytes showed swelling of the nucleus, autophagy, intracellular massive deposits and abnormal vacuoles. Two compound heterozygous c.334C> T (p.Arg112Cys) and c.595C> T (p.Arg199Ter) mutations of CLN5 gene were identified in the two siblings, and the proband 3 was c.335G> A (p.Arg199His) homozyousmutation, which were inherited from their unaffected parents. Conclusions The 3 cases with Finnish variant late infantileneuronal ceroid lipofuscinosises were normal at birth, cognitive and motor function was regressed at preschool age.Brain MRI showed whole brain atrophy, white matter lesions, there were no bovious difference from other neurodegenerative diseases. Blood biochemistry and pathological examination of lymphocytes had no specific changes. The pathogenic genes were CLN5,most are inherited in autosomal recessive way.

Objective To evaluate our results of external quality assessment (EQA) program of the newborn screening laboratory for 6 years, summarize the problems in the screening measurement and improve the quality of measurement.Methods The phenylalanine (Phe) and thyrotropin (TSH) values in dried blood spot specimens on filter paper distributed by national center were measured by fluorometric method and time -resolved fluorescence im-munoassay ( DELFIA ) respectively.The results sent by national center were analyzed .Results In the 90 specimens of 18 batches, the bias range of Phe and TSH measurement was wide (-62.50%~66.67%and-66.67%~54.31%respectively) and their average values were 8.62%and 10.18% respectively;85 quantitative results of Phe and 84 quantitative results of TSH measurement were in the quality control , accounting for 94.44%and 93.33%respective-ly.The qualitative analysis of 90 Phe and TSH specimens all conformed to the expected results , accounting for 100%.The result of every batch was up to 80%.Conclusion Our neonatal screening laboratory is in control and it is useful to evaluate the measurement competence , find out the problems in the Phe and TSH measurement and re-solve them in time through participated in the national EQA in neonatal screening laboratory , so as to improve the quality of measurement and ensure the accuracy and reliability of results .

Object To study the chemical constituents of our folk herb, Cucubalus baccifer L Methods The components were separated on Diaion HP 20 and silica gel column chromatography and the structures were identified by spectral evidence Results Six compounds from ethyl acetate extracts were elucidated as 6? methoxy piperidin 2 one (Ⅰ), pterolactam (Ⅱ), 5, 7, 4′ trihydroxyflavone (Ⅲ), 4 hydroxy 3 methoxybenzopropanyl acid (Ⅳ), 4 hydroxybenzoaldehyde (Ⅴ), and 4 hydroxybenzoic acid (Ⅵ) Conclusion Compound Ⅰ was a new naturally occurring compound and others were first isolated from this plant