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

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

Anniversaries and Special Events ; Alkanesulfonic Acids

Objective: To understand the social security situation of current cases of pneumoconiosis in non-coal mine industries in Jiangsu Province, and to provide reference for the treatment and security work of pneumoconiosis patients. Methods: From January to October 2020, a follow-up survey was conducted on 4038 cases of pneumoconiosis in non-coal mine industries of the province from October 1949 to December 2019. The age, type of pneumoconiosis, industry type, and social security status of the patients were collected. Namely, work-related injury insurance, employer compensation, basic medical insurance for urban and rural residents, major illness insurance, etc. SPSS 19.0 was used for statistical description and analysis. Results: The cases of pneumoconiosis in non-coal mine industries in Jiangsu Province ranged in age from 36 to 105 (70.78±8.43) years old, and had been exposed to dust for 1 to 55 (19.27±9.29) years. Silicosis was the main form (3875 cases, 95.96%), and non-metallic mining and dressing industry was the main form (2618 cases, 64.83%). A total of 3991 cases (98.84%) of pneumoconiosis patients enjoyed social security, most of them were urban and rural residents with basic medical insurance (3624 cases, 89.75%), but there were still 47 patients without any social security. 15 cases (0.37%) enjoyed the subsistence allowance, with the monthly allowance amount ranging from 104 to 3960 yuan, with the average amount of 954.87 yuan/month. Conclusion: In Jiangsu Province, the proportion of pneumoconiosis patients in non-coal mine industries enjoying social security is relatively high, but there are still patients who do not enjoy any social security, and the difference in the amount of subsistence allowance is slightly larger. It is necessary to further improve the medical security of pneumoconiosis patients and improve their quality of life.
Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Social Security ; Prevalence ; Quality of Life ; Pneumoconiosis/epidemiology* ; Silicosis/epidemiology* ; Etoposide ; Ifosfamide ; Mesna ; Coal Mining ; China/epidemiology*

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

OBJECTIVE: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities. METHODS: Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. RESULTS: PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC ₅₀: 9.03 ± 4.83 μmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 μmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 μmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 μmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 μmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 μmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity. CONCLUSION Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
Humans ; Pregnancy ; Female ; Rats ; Animals ; Placenta ; Progesterone/pharmacology* ; Aromatase/pharmacology* ; Cell Line, Tumor ; Fluorocarbons ; Alkanesulfonic Acids ; Structure-Activity Relationship ; Hydroxysteroid Dehydrogenases/pharmacology*

OBJECTIVE: To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China. METHODS: A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother. RESULTS: Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery. CONCLUSION MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.
Humans ; Child ; Male ; Female ; Infant ; Child, Preschool ; Graft vs Host Disease/etiology* ; China ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mucopolysaccharidoses/etiology* ; Busulfan ; Treatment Outcome