Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.

Objective:To explore the predictive value of multimodal ultrasound features combined with serum matrix metalloproteinase-9 (MMP-9) detection for tumor recurrence of breast cancer after breast-conserving surgery.Methods:A total of 194 patients with breast cancer who underwent breast-conserving surgery in Affiliated Hospital of Jining Medical College from Jan. 2017 to May. 2018 were selected. Routine ultrasound, automated breast volume imaging and contrast-enhanced ultrasound were performed before surgery. Logistic regression equation was used to analyze the risk factors affecting local tumor recurrence after breast-conserving surgery, and ROC curve was drawn to analyze the predictive value of multimodal ultrasound features combined with serum MMP-9 for local tumor recurrence after breast-conserving surgery.Results:After 5 years of follow-up, 29 out of 194 breast cancer patients who underwent breast-conserving surgery had local recurrence and metastasis. There were no significant differences in tumor diameter, spiculation sign, convergence sign, Alder blood flow grade, enhancement sequence, pattern and enhancement intensity between the two groups ( P>0.05 t=1.48, P=1.451; χ2=0.55, P=0.460; χ2=0.50, P=0.478; χ2=0.60, P=0.439; χ2=0.50, P=0.780; χ2=0.04, P=0.981; χ2=0.13, P=0.716). Logistic regression analysis showed that irregular tumor shape, small calcification,Peripheral radial enhancement, perfusion defect and abnormal elevation of serum MMP-9 were independent risk factors for local recurrence of breast cancer after breast-conserving surgery ( P=0.034, 95%CI=1.177~62.266; P=0.048, 95%CI=1.022~58.397; P=0.045, 95%CI=1.100~56.756; P=0.043, 95%CI=1.079~ 60.937; P=0.044, 95%CI=1.000~1.026). ROC curve showed that the AUC of multimodal ultrasound features combined with serum MMP-9 in predicting local tumor recurrence after breast-conserving surgery was 0.970, and the sensitivity and specificity were 98.63% and 91.67%, respectively. Conclusions:Multimodal ultrasound features combined with serum MMP-9 detection have high application value in the evaluation of local tumor recurrence after breast-conserving surgery, and provide a new idea for the clinical diagnosis and treatment of breast cancer.

Objective:To investigate the factors influencing recipient liver regeneration after full-size split liver transplantation (fSLT).Methods:The clinical data of patients undergoing split liver transplantation in the Affiliated Li Huili Hospital of Ningbo University from May 2019 to Sep 2023 were retrospectively collected. Graft volume (GV) and initial graft volume (IGV) at (30±7) days after operation were measured, and postoperative liver regeneration rate (LRR) was calculated. The patients undergoing fSLT were divided into high regeneration group and low regeneration group with LRR=30% as boundary. The differences of donor and recipient data and perioperative data between the two groups were compared.Results:A total of 52 patients were included. The low fSLT regeneration group (16 cases) was compared with the high fSLT regeneration group (36 cases), and in high fSLT regeneration group donor age was lower, the donor liver steatosis was less, GRWR was lower, the incidence of hepatitis B virus-related liver disease was lower, the postoperative diagnosis of malignant liver disease was lower, the intraoperative blood loss was less, and the postoperative platelet count was higher. The levels of liver enzyme and total bilirubin (TBiL) were higher than those in high regeneration group ( P<0.05). Conclusions:Donor age, donor liver steatosis, GRWR, hepatitis B virus associated liver disease, and recipient pathogenesis are important factors affecting liver regeneration after fSLT. Postoperative platelet and liver enzyme levels are important indicators for monitoring liver regeneration after fSLT.

Objective:To evaluate and summarize the best evidence related to the management of cancer-related fatigue in children with leukemia and provide an evidence-based basis for clinical practice.Methods:The search for the relevant guidelines and evidence synthesis from UpToDate, JBI, Cochrane Library, Registered Nurses′ Association of Ontario, Guidelines International Network, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, YiMaiTong Guideline Network, National Comprehensive Cancer Network, PubMed, CINAHL, EMbase, China National Knowledge Infrastructure, Wanfang, China Biology Medicine from January 1st, 2012 to May 1st, 2022. Two researchers evaluated the quality of the literature independently according to the unified standard and extracted the best evidence.Results:A total of 13 literatures were extracted, including three clinical practice guidelines, two evidence summaries and eight systematic reviews. Finally, 22 pieces of evidence were summarized, involving six aspects which were environmental management, cancer-related fatigue assessment, exercise management, adventure therapy, sleep management and psychosocial interventions.Conclusions:Best evidence for the management of cancer-related fatigue in children with leukemia, which should be used in conjunction with the environment, the child's age, physical ability, medical condition and psychological acceptability to develop an individualized symptom management plan to improve the quality of care and the child′s quality of life.

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 evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats. METHODS: Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed. RESULTS: BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05). CONCLUSION: BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats. UNLABELLED The graphical abstract is available on the website www.besjournal.com.
Rats ; Male ; Animals ; Leydig Cells/metabolism* ; Testosterone ; Glycogen Synthase Kinase 3 beta/pharmacology* ; Rats, Sprague-Dawley ; Sexual Maturation ; Testis ; Oxidative Stress ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

ObjectiveTo investigate the clinical efficacy of Niaoxue No.1 Prescription in treating Henoch-Schönlein purpura （HSP） nephritis with blood heat and stasis syndrome and its effect on urine erythrocyte， urine protein， blood neutrophils， and blood routine-derived indicators. MethodA multicenter， randomized controlled trial （RCT） was conducted involving 108 HSP nephritis patients from three hospitals. The patients were randomly divided into a control group （54 cases） and a treatment group （54 cases）. The treatment group received Niaoxue No.1 prescription once daily， while the control group was treated with captopril and ferulic acid tablets. Both groups underwent a 4-week course of treatment. The urine erythrocyte， urine microalbumin （mAlb）， urine sediment red blood cell count， traditional Chinese medicine （TCM） syndrome score， 24-hour urine protein， blood neutrophil count， neutrophil to lymphocyte ratio （NLR）， platelet to lymphocyte ratio （PLR）， lymphocyte to monocyte ratio （LMR）， D-dimer， and immunoglobulin A were detected. The recurrence rate of HSP nephritis was followed up for 6 months. ResultThe total effective rates were 88.9% （48/54） in the treatment group and 70.4% （38/54） in the control group， and the treatment group was superior to the control group （χ²=5.708， P<0.05）. Compared with the results before treatment， after 14 days of treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， and the improvement was more significant in the treatment group than the control group （P<0.05）. After 28 days of treatment， compared with the results before treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， urine sediment red blood cell count， D-dimer， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， with the treatment group showing a more significant reduction in urine mAlb than the control group （P<0.05）. On the 14^th and 28^th days of treatment， the neutrophil percentage and NLR were lower in the treatment group than in the control group （P<0.05）， while there was no statistically significant difference in PLR and LMR. The recurrence rate of nephritis in both groups showed no statistically significant difference after a 6-month follow-up. ConclusionNiaoxue No.1 Prescription in the treatment of HSP nephritis with blood heat and stasis syndrome can significantly improve clinical symptoms， shorten the course of the disease， and reduce urine erythrocyte， urine mAlb， 24-hour urine protein， blood neutrophils， and NLR， thereby effectively alleviating the inflammatory state and reducing kidney damage in children with HSP nephritis.

Objective:To report a family of Zellweger spectrum disorders (ZSD) caused by mutations in the PEX10 gene and to increase the level of awareness of the disease among clinicians. Methods:The clinical and genetic data of a brother-sister co-morbidity family with ZSD due to PEX10 gene mutation admitted to the Department of Neurology, Qilu Hospital of Shandong University in July 2022 were collected and a literature review was performed. Results:The proband was a 24-year-old female who was admitted to the Qilu Hospital of Shandong University due to unstable walking for 8 years and aggravated for 1 year with squatting effort. Cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography suggested peripheral neuropathy with motor and sensory involvement, and pure tone hearing threshold measurement showed neurogenic deafness. The 15-year-old brother of the proband presented with "unsteadiness in walking and difficulty in squatting for 2 years". His cranial MRI and electromyography were similar to those of the proband, and his laboratory results suggested abnormal liver function. The whole exon sequencing results of the proband suggested a compound heterozygous mutation in the PEX10 gene with c. 992G>A(p. R331Q) and c. 988T>C(p. C330R) mutations and both were likely pathogenic mutations and respectively from her parents. And her brother also carried the above variants. A total of 9 case reports in English literature (1 of which was published by domestic scholars) were retrieved from major domestic and international databases on PEX10 gene mutations causing ZSD, with a total of 15 patients, most of whom had childhood and adolescent onset. The most common initial symptom was slowly progressed ataxia. The majority of patients showed cerebellar atrophy on cranial MRI and peripheral neuropathy was found in the most patients.The 2 patients were suggested to have phytic acid-free food, at the same time, they bagan taking L-arginine and ursodeoxycholic acid. Fortunately,both the ataxia symptom and liver function of them were dramatically alleviated 3 months later. Conclusions:For the patients with unexplained ataxia with polyneuropathy and abnormal liver function,the possibility of ZSD should be considered. Phytic acid-free food, L-arginine and ursodeoxycholic acid supplement may be beneficial for the ZSD patients.