OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

OBJECTIVE: To comprehensively evaluate the effect of icariin in alleviating reproductive function damage (RFD) in male mice via in vitro and in vivo experiments. METHODS: We isolated Leydig cells from 60 KM male mice in vitro, and examined the toxic effect of icariin on the Leydig cells using Cell Counting Kit-8 (CCK-8). We equally randomized the mice into six groups: normal control, RFD model control (made by intraperitoneal injection of busulfan at 10 mg/kg combined with cyclophosphamide (CP) at 120 mg/kg), positive control, and low-, medium- and high-dose icariin. After modeling, we treated the mice in the positive control group with Wuziyanzong Pills and those in the low-, medium- and high-dose icariin groups by intragastrical administration of icariin at 20, 40 and 80 mg/kg-1, respectively, for 30 successive days. Then we obtained the weight and visceral coefficients of the reproductive organs, calculated the sperm count, observed the pathological changes in the testis tissue by HE staining, measured the serum testosterone (T) level by ELISA, determined the indexes of testicular oxidative stress and nitric oxide (NO) signaling pathway by colorimetric assay, and detected the expression levels of the pro-apoptotic genes Fas and Bax by qRT-PCR. RESULTS: CCK-8 assay confirmed that icariin had no toxic effect on the isolated Leydig cells of the mice, and could effectively reduce busulfan- and CP-induced cytotoxicity and promote the secretion of serum T. Icariin at 80 mg/kg significantly increased the visceral coefficient of the testis and promoted spermatogenesis (P<0.05), but had little effect on the visceral coefficient of the epididymis in the RFD model mice. Testicular histomorphometric observation revealed significantly improved testis structure, intact boundary membrane of seminiferous tubules and increased numbers of various types of spermatogenic cells of the model mice after treated with icariin. Compared with the mice in the model control group, those treated with high-dose icariin showed a significantly reduced content of malondialdehyde (MDA) (by 35.3%, P<0.01), elevated total antioxidant capacity (TAOC) and superoxide dismutase (T-SOD) activity (P<0.05), and decreased NO content and nitric oxide synthase (NOS) activity in the testis tissue (P<0.01). In addition, icariin exhibited an evident inhibitory effect on the expressions of the pro-apoptotic genes Bax and Fas. CONCLUSION Icariin can ameliorate oxidative stress-induced damage to the testicular function and protect spermatogenesis of male mice by elevating TAOC, decreasing NOS activity, inhibiting the NO level in the testis, and suppressing busulfan- and CP-induced apoptosis of testicular cells.
Animals ; Male ; Cyclophosphamide/adverse effects* ; Mice ; Busulfan/adverse effects* ; Flavonoids/pharmacology* ; Leydig Cells/drug effects* ; Oxidative Stress/drug effects* ; Testis/drug effects* ; Apoptosis/drug effects* ; Testosterone/blood*

BACKGROUND: The objective of this study was to investigate the potential link between myopia in adolescents and exposure to per- and polyfluoroalkyl substances (PFASs). METHODS: This investigation included 1971 subjects with accessible PFAS level data, myopia status, and associated variables from four cycles of the National Health and Nutritional Examination Survey (NHANES). The investigation focused on specific PFAS compounds found in the serum, including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), chosen for their frequent detection. Owing to the skewed nature of the PFAS level data, the PFAS levels were log-transformed (Ln-PFAS) prior to analysis. Logistic regression, restricted cubic spline modeling, subgroup analysis, and sensitivity analysis were used to examine the associations between exposure to PFASs and the onset of myopia. RESULTS: PFOA levels were significantly associated with myopia risk (OR: 1.33; 95% CI: 1.05-1.69; P = 0.019). More specifically, with respect to the first quartile, the second quartile (OR_Q2: 1.69; 95% CI: 1.16-2.46; P = 0.007), third quartile (OR_Q3: 1.45; 95% CI: 1.03-2.03; P = 0.035), and highest quartile (OR_Q4: 1.58; 95% CI: 1.12-2.21; P = 0.010) of participants presented with increased myopia risk. Mediation analysis revealed that PFOA and myopia risk were partially mediated by serum albumin (ALB), with a mediation percentage of 22.48% (P = 0.008). A nonlinear inverted U-shaped relationship was identified between the level of PFOA and myopia risk (P for nonlinearity = 0.005). CONCLUSION Our findings suggest a potential link between exposure to PFOA and the likelihood of myopia development in young individuals and a mediating effect of serum ALB on this relationship. Notably, PFOA was identified as a key PFAS significantly contributing to the observed link between PFAS exposure and myopia risk. The potential threat of PFOA to myopia should be examined further.
Humans ; Fluorocarbons/adverse effects* ; Myopia/blood* ; Adolescent ; Male ; Female ; Prevalence ; Environmental Exposure/adverse effects* ; Nutrition Surveys ; Environmental Pollutants/adverse effects* ; United States/epidemiology* ; Alkanesulfonic Acids/blood* ; Caprylates/blood* ; Serum Albumin/metabolism* ; Child ; Sulfonic Acids

Anniversaries and Special Events ; Alkanesulfonic Acids

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

OBJECTIVE: To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL). METHODS: CLAE regimen [cladribine 5 mg/(m²·d), d 1-5; cytarabine 1.5 g/(m²·d), d 1-5; etoposide 100 mg/(m²·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m²·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation. RESULTS: 2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD. CONCLUSION CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.
Male ; Humans ; Busulfan/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Treatment Outcome ; Leukemia, Myeloid, Acute/etiology* ; Acute Disease ; Graft vs Host Disease/prevention & control*

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Humans ; Adult ; Retrospective Studies ; Neoplasm Recurrence, Local ; Hematologic Neoplasms/therapy* ; Busulfan/therapeutic use* ; Graft vs Host Disease/prevention & control* ; Chronic Disease ; Unrelated Donors ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Transplantation Conditioning

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m² and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (β=-0.958), birth length (β=-0.073) and Apgar-5 score (β=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (β=-0.926; β=-0.552) and length (β=-0.074; β=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (β=0.111) and decreased Apgar-5 score (β=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Adult ; Birth Weight ; Prenatal Exposure Delayed Effects ; Alkanesulfonic Acids/analysis* ; Alkanesulfonates/analysis* ; Fluorocarbons/analysis* ; Ethers/analysis* ; Ethyl Ethers/analysis* ; Environmental Pollutants/analysis* ; Maternal Exposure

Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.
Male ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Graft vs Host Disease ; Transplantation Conditioning ; China ; Hematopoietic Stem Cell Transplantation ; Antilymphocyte Serum ; Busulfan ; Cyclophosphamide/therapeutic use* ; Immunosuppression Therapy