Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Pulmonary administration can directly deliver drugs to the lungs， making it the preferred mode of administration for pulmonary disease. Active ingredients of traditional Chinese medicine （TCM）， such as quercetin and paclitaxel have demonstrated promising therapeutic effects on lung diseases. However， they face challenges such as poor water solubility and high lung clearance rates. Loading the active ingredients of TCM onto nano-drug delivery systems can enhance their water solubility， stability， permeability and retention in the lungs. Based on this， this study reviewed the research progress on inhalation nano-drug delivery systems for the active ingredients of TCM in the treatment of lung diseases. It was found that there are nano-drug delivery systems for TCM active ingredients based on chitosan， lipids （including liposomes， solid lipid nanoparticles， and nanostructured lipid carriers）， and targeting ligands （including targeting folate receptor， targeting transferrin receptor， and exosomes）. These inhalation nano-drug delivery systems comprehensively consider key factors such as particle size， surface charge， and hydrophobicity， which can prevent the drugs from being cleared by mucus， cilium and macrophages， thus exhibiting great potential for application.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Female ; Humans ; Antibodies, Antineutrophil Cytoplasmic ; Organizing Pneumonia ; Autoantibodies ; Glomerulonephritis ; Anti-Glomerular Basement Membrane Disease ; Pneumonia ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications*

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

Objective: To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods: The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results: A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m² (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions: Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.
Humans ; Female ; Adolescent ; Middle Aged ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Hepatitis B virus ; Risk Factors ; Tobacco Smoke Pollution ; Exercise ; Hypertension

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
B-Lymphocytes ; Graft vs Host Disease ; HLA Antigens/genetics* ; Haplotypes ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Leukemia, B-Cell/complications* ; Leukemia, Lymphocytic, Chronic, B-Cell/complications* ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Retrospective Studies ; Siblings

OBJECTIVES: The prevalence of intrauterine adhesion (IUA) increased gradually, which seriously affected female reproductive health and fertility. This study aims to analyze the clinical features of pre-, intra-, and post hysteroscopic adhesiolysis (HA) and to identify the main risk factors for non-live birth and other factors affecting pregnancy outcome in patients with IUA. METHODS: A total of 486 IUA patients with reproductive needs, who underwent HA in the third Xiangya Hospital of Central South University from January 2017 to May 2018, were retrospectively included. The follow-up period was 2-3 years after operation. Univariate analysis and multivariate logistic regression analysis were used to explore the relationship between clinical features and live birth rate in patients with IUA. Pre-operative clinical indicators included age, gravidity, parity, abortion, IUA recurrence, menstrual patterns, and disease course. Intraoperative clinical features assessed in the last operation were uterine cavity length, IUA appearance, IUA area, number of visible uterine cornua, number of visible tubal ostia, and American Fertility Society (AFS) scores. The relationship between clinical indicators and postoperative live birth rate was investigated by univariate analysis and multivariate logistic regression analysis. Pregnancy pattern was the main variable. RESULTS: Among the 486 IUA patients included in this study, there were 256 (52.67%) live births and 230 (47.33%) non-live births. Univariate analysis and multivariate logistic regression showed that the live birth rate of in vitro fertilization and embryo transfer (IVF-ET) after HA was higher than that of spontaneous pregnancy (OR=0.557, 95% CI 0.361 to 0.861, P=0.008). When the bilaterally fallopian tube ostia were invisible in the last operation (OR=0.322, 95% CI 0.104 to 0.997, P=0.049), patients were more likely to have live birth. The older the patient was, the lower the live birth rate was (OR=1.081, 95% CI 1.034 to 1.131, P<0.001). The live birth rate would be low when the last AFS score was moderate (OR=2.973, 95% CI to 1.541 to 5.738, P<0.010). CONCLUSIONS Based on the outcome of the first pregnancy after HA, IUA patients' pregnancy patterns, age, number of visible tubal ostia, and AFS scores noted by a second-look hysteroscopy, are the factors influencing the prognosis for the live birth rate in IUA patients. IVF-ET may improve live birth rate for patients with IUA after HA.
Humans ; Female ; Pregnancy ; Birth Rate ; Retrospective Studies ; Embryo Transfer

Animals ; Aspartate Aminotransferases ; Drugs, Chinese Herbal/pharmacology* ; Male ; Myocardial Ischemia/drug therapy* ; Myocardium ; Rats ; Rats, Sprague-Dawley ; Triglycerides