Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

Cyclin-dependent kinase (CDK)4/6 inhibitors combined with traditional endocrine therapy can significantly improve the progression-free survival and overall survival of hormone receptor-positive and human epithelial growth factor receptor 2-negative breast cancer patients. But different drugs, dosage and medication cycle will also bring different efficacy and safety incidents to patients. At the same time, confirming whether CDK4/6 inhibitors are equally applicable to Chinese breast cancer patients is not only an academic hotspot concerned by domestic clinicians, but also a practical need in actual diagnosis and treatment. This article reviews the classic clinical trials of drugs and the latest research progress.

Recently, the cases of acute hepatitis of unknown etiology (AHUE) in children worldwide have been increasing continuously and rapidly, involving more than 396 cases in 26 countries, and global public health actions, including surveillance, health alerts, research, are being implemented. AHUE mainly affects immunocompetent children with typical acute hepatitis, which can be severe and require liver transplantation. There are few systematic studies at present; the risk factors are unknown, the etiology remains to be established, and the clinical features and pathogenesis remain elucidated. It is urgent to strengthen the monitoring and research of AHUE cases.
Acute Disease ; Child ; Hepatitis/etiology* ; Humans ; Risk Factors

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Objective:We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen (BCMA) , chimeric antigen receptor T cells (CAR-T) , and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma (RRMM) .Methods:Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected. Among them, 26 patients received anti-BCMA target, and 35 patients received anti-BCMA combined with anti-CD19 target. Using flow cytometry, we determined T cell subsets (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) , B cells (CD19 +) , and NK cells (CD16 + CD56 +) at different time points before and after CAR-T treatment, and detected immunoglobulin IgG, IgA and IgM levels by immunoturbidimetry. We compared the reconstruction rules of lymphocyte subsets and immunoglobulins in the two groups. Results:CD8 + T lymphocytes recovered most rapidly after the infusion of CAR-T cells, returning to pre-infusion levels at 3 months and 1 month after infusion, respectively[BCMA: 695 (357, 1264) /μl vs 424 (280, 646) /μl; BCMA+CD19: 546 (279, 1672) /μl vs 314 (214, 466) /μl]. NK cells returned to normal levels at 3 months after infusion in both groups[BCMA: 171 (120, 244) /μl, BCMA+CD19: 153 (101, 218) /μl (Normal reference range 150-1100/μl) ]; however, the NK cells were not maintained at stable levels in the BCMA CAR-T cells group. The recovery of CD4 + T lymphocytes in both groups was slow and remained persistently low within 12 months after infusion, and no recovery was observed in most patients. The reversal of the ratio of CD4 +/CD8 + lasted for more than a year. The levels of CD19 + B cells in both groups returned to baseline 3 months after infusion[BCMA: 62 (10, 72) /μl vs 57 (24, 78) /μl; BCMA+CD19: 40 (4, 94) /μl vs 29 (14, 46) /μl]. IgG returned to the pre-infusion level 12 months after infusion in the group with anti-BCMA cells alone, but not in the group with combined infusion of CD19 CAR T cells[7.82 (6.03, 9.64) g/L vs 6.92 (4.62, 12.76) g/L]. IgA returned to pre-infusion levels at 9 and 12 months after infusion, respectively[BCMA: 0.46 (0.07, 0.51) g/L vs 0.22 (0.12, 4.01) g/L; BCMA+CD19: 0.46 (0.22, 0.98) g/L vs 0.27 (0.10, 0.53) g/L]. IgM in both groups returned to pre-infusion levels 6 months after infusion[BCMA: 0.43 (0.06, 0.60) g/L vs 0.20 (0.13, 0.37) g/L; BCMA+CD19: 0.53 (0.10, 0.80) g/L vs 0.16 (0.11, 0.28) g/L]. There was no significant difference in the indexes of lymphocyte subpopulation reconstruction and immunoglobulin recovery between the two groups at each time point. Conclusion:This study showed that in patients with RRMM treated with CAR-T cells, the appropriate target antigen can be selected without considering the difference of immune reconstruction between anti-BCMA CAR-T and combined anti-CD19 CAR-T therapy.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

Objective To make a rapid dose estimation for a patient exposed locally to high dose radiation exposure in early stage of 5.7 192Ir source accident in Nanjing.Methods Based on source parameters,exposure pattern,and time duration,the doses were estimated using MCNP simulations with the aid of the proper East Asia adult male voxel phantom and main physiological parameters of the exposed patient.Result Absorbed doses to 16 organs or tissues were estimated to be in the range 0.03 to 9.16 Gy.Also,the iso-dose curves for the skin of legs showed clearly the dose difference between right and left legs.Absorbed doses to patient's testicles and prostrate,about 9.16 Gy,were higher than those to other organs or tissues.The skin of both legs was exposed locally to high dose radiation exposure,for which the estimated doses were in agreement with the results obtained from infrared thermal imaging.Conclusions Monte Carlo simulation technique and common software can be used for dose estimation in early stage of radiation accidents effectively with integrating proper models.

Objective To use three different methods in attempt to estimate the biological dose of the patient partially exposed to 192Ir source at5.7 accident in Nanjing,so as to provide dosimetric information for clinical remedy of exposed patients in the emergency of a nuclear accident.Methods Peripheral blood samples were collected on days 5 after exposure.The biological dose was estimated by the yields of dicentrics plus rings ( dic + r),cytokinesis-block micronuclei (CBMN) assay and nucleoplasmic bridge plus FHC (NPB + FHC).The homogeneity of radiation exposure was examined by Poisson distribution of dicentrics.Results By using three different methods,the whole body equivalent dose was dic + r estimated to be 1.51 Gy (95％ CI 1.40-1.61),1.47 Gy (95％ CI 1.36-1.60) by CBMN and 1.30 Gy (95％ CI 1.00-1.60) by NPB + FHC,respectively.A non-poisson distribution was also detected,suggesting partial body radiation exposure.Conclusions The estimated whole body equivalent dose ot a non-uniform radiation exposure was consistent with clinical diagnosis,suggesting that the yields ofdic + r,CBMN,as well as NPB + FHC,are efficient approaches to the estimation of biological doses.

Objective To explore the natural attenuation pattern of three biological dose estimation indexes in vivo by investigating the effect on biological dosimetry of peripheral blood sampling at different time points from the victim partially exposed to 192Ir radiation source at5.7 accident in Nanjing.Methods Peripheral blood of the patient was collected on days 5,40 and 280 after exposure,respectively.The yields of dicentrics plus rings chromosomes (dic + r),cytokinesis-block micronuclei (CBMN) and nucleoplasmic bridge + fusion + horse shoe + circular(NPB + FHC) were analyzed.The dynamic reduction and dose estimation were both observed using the biomarkers mentioned above after exposure.Results Compared to the estimates on days 5 after exposure,the dose values estimated on days 40 and 280 decreased by 34％ and 49％ fordic + r method,48％ and 79％ for the CBMN assay,and 48％ and 75％ for NPN + FHC method,respectively.Conclusions Three biological dose estimation indexes show a progressive decrease in vivo,with the half-life of dic + r/cell being 40 days.The doses estimated using these three indexes on days 40 after exposure showed a relative deviation more than 20％ compared with those on days 5 after exposure.