Icariin is a pure compound derived from Epimedium brevicornu Maxim, and it helps the regulation of male reproduction. Nevertheless, the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified. Here, we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells (SSCs). Furthermore, surface plasmon resonance iron (SPRi) and molecular docking (MOE) assays revealed that phosphodiesterase 5A (PDE5A) was an important target of Icariin in mouse SSCs. Mechanically, Icariin decreased the expression level of PDE5A. Interestingly, hydrogen peroxides (H 2 O 2 ) enhanced the expression level of phosphorylation H2A.X (p-H2A.X), whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H 2 O 2 in mouse SSCs. Finally, our in vivo animal study indicated that Icariin protected male reproduction. Collectively, these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity. This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.
Male ; Animals ; Flavonoids/pharmacology* ; Mice ; Cyclic Nucleotide Phosphodiesterases, Type 5/drug effects* ; DNA Damage/drug effects* ; Cell Survival/drug effects* ; Cell Proliferation/drug effects* ; Spermatogonia/drug effects* ; Reproduction/drug effects* ; Adult Germline Stem Cells/metabolism* ; DNA Replication/drug effects*

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

A portable electrochemical sensing system for simultaneous detection of species relevant to carbon cycle(i.e.,Ca2+,CO32-and pH)in seawater was developed,in which a highly sensitive polymeric membrane ion-selective electrode array with NiCo2S4-based transduction layer was used as the core element.Such an electrochemical sensor array was developed via the combination of all-solid-state ion selective electrode technology and electrode integration technology based on screen printing.The proposed sensing system offered the linear response concentration ranges of 1.0×10-5-1.0×10-1 mol/L and 3.2×10-5-1.9×10-3 mol/L for Ca2+,CO32-and 5-9 for pH in 0.5 mol/L NaCl background,respectively,as well as a relative deviation of less than 2.0%for evaluation of detection accuracy(mean deviation compared to the readings of reference techniques).For successive measurements,the relative standard deviations(RSDs)of less than 2.5%were obtained.The proposed electrochemical sensing system was successfully used for seawater analysis,and the whole analysis process could be completed within 15 min.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Lung is the largest organ of the respiratory system. During hypoxia, pulmonary cells undergo rapid damage changes and activate the self-rescue pathways, thus leading to complex biomacromolecule modification. Death from mechanical asphyxia refers to death due to acute respiratory disorder caused by mechanical violence. Because of the absence of characteristic signs in corpse, the accurate identification of mechanical asphyxia has always been the difficulty in forensic pathology. This paper reviews the biomacromolecule changes under the pulmonary hypoxia condition and discusses the possibility of application of these changes to accurate identification of death from mechanical asphyxia, aiming to provide new ideas for related research.
Humans ; Asphyxia/pathology* ; Cause of Death ; Hypoxia/pathology* ; Lung/pathology* ; Forensic Pathology

OBJECTIVE: To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila (L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China. METHODS: Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing (SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci (MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue (lvh) and repeats in structural toxin (rtxA). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells. RESULTS: All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types (STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtxA loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells. CONCLUSION L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed.
Bacterial Proteins ; genetics ; Bacterial Toxins ; genetics ; China ; Genotyping Techniques ; Humans ; Legionella pneumophila ; genetics ; growth & development ; isolation & purification ; RNA, Ribosomal, 16S ; genetics ; Water Microbiology

ObjectiveTo observe the morphological changes of bone in the progress of chronic fluorosis.MethodsWistar rats were randomly divided into three groups,30 rats in each group:normal control group,experimental group Ⅰ and experimental group Ⅱ according to body weight.Rats in normal control group drank distilled water freely.Experimental group Ⅰ and group Ⅱ drunk distilled water with sodium fluoride preparation of fluorine containing ion 100,150 mg/L solution for six months,respectively.Bone mineral density was detected by X-ray,bone morphological changes were observed under light microscope and bone histomorphometric parameters were calculated using image analysis software.ResultsThe bone mineral density values were different statistically between the three groups after feeding for 2 and 4 months(F =19.79,3.28,all P ＜ 0.05).However no significant difference was found after feeding for 6 months(F =1.80,P ＞ 0.05).The bone mineral density of experimental group Ⅰ (0.20 ± 0.03,0.21 ± 0.03) was significantly higher than that of the normal control group(0.17 ± 0.03,0.20 ± 0.04) after feeding for 2 and 4 months.The bone mineral density of experimental group Ⅱ (0.21 ± 0.02) was lower than that of normal control group(0.22 ± 0.03) after feeding for 6 months.The bone lamella in experimental group Ⅰ was arranged disorderly,the number of osteocytes increased with their nucleus atrophy and the osteoblasts were more than that of control grouo which arranged in layers observed under light microscooy.In exoerimental group Ⅱ,the bone lamella was bent deformation,the number of osteocytes had decreased with their nucleus shrinking or even disappeared and the number of osteoclasts had increased significantly observed under light microscopy.In experimental group Ⅰ,the mean trabecular density [(0.33 ± 0.03)％] increased and the mean trabecular separation,thickness [( 163.57 ± 1.99),(59.26 ± 7.18 ) μm] decreased compared with that of normal control group [(0.31 ± 0.02)％,(186.60 ± 2.90)μm,(86.42 ± 1.48)μm,all P ＜ 0.05].In experimental group Ⅱ,the mean trabecular density[(0.26 ± 0.02)％] decreased,the mean trabecular thickness[(71.42 ± 10.77)μm] reduced compared with that of normal control group[(0.31 ± 0.02)％,(86.42 ± 1.48)μm].ConclusionsExcess fluoride can damage bone tissue.Low doses of fluoride can stimulate osteoblast activity and enhance osteogenesis.The activity of osteoblasts is great than that of osteoclasts.High doses of fluoride can stimulate both osteoblasts and osteoclasts activity,but mainly the activity of osteoclasts,and bone resorption increases.

ObjectiveTo detect the concentration and distribution of fluoride ions in osteoblasts exposed to fluoride in vitro culture,and to provide basic information for studying the effect of fluoride on osteoblast injury.MethodsIn vitro cultured osteoblasts were exposed to 0,5,10,20,40 mg/L fluoride for 3,10,30 d (n =6),respectively.Concentration and distribution of fluoride ions in the cytoplasm and the nucleus of these osteoblasts were determined by nuclear magnetic resonance spectroscopy.Results(①) After cultured for 3 d,fluoride ion content of the bone cytoplasm exposed to different concentrations of fluoride 0,5,10,20,40 mg/L were (0.83 ±0.65),(0.54 ± 0.23),(0.65 ± 0.77),(0.59 ± 0.87),(3.64 ± 1.21 )mg/L,respectively,and the values of exposed to 40 mg/L fluoride group was significantly higher than that of exposed to 0,5 mg/L groups (all P ＜ 0.05).(②)after cultured for 10 d,the composition of the fluoride ion in cytoplasm of exposed to fluoride 10,20,40 mg/L groups were (4.03 ± 1.23),(3.66 ± 0.98),(6.26 ± 2.10)mg/L,respectively,which were higher than that of exposed to 0,5 mg/L groups [(0.78 ± 0.75),(2.69 ± 0.89)mg/L,respectively,all P ＜ 0.05].Of fluoride 20,40 mg/L groups,the composition of the fluoride ion in nucleus were (1.63 ± 1.19),(2.17 ± 1.21 )mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.65 ± 0.46),(1.57 ± 0.33) mg/L,all P ＜ 0.05].(③)After cultured for 30 d,of the exposed to fluoride 10,20,40 mg/L groups,the composition of the fluoride ion in cytoplasm were (3.99 ± 0.84),(4.33 ± 1.67),(5.80 ± 1.38)mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.88 ± 0.44),(2.84 ± 0.43)mg/L,all P ＜ 0.05].The composition of the fluoride ion in nucleus of the fluoride 20,40 mg/Lgroups were (3.33 ± 1.46),(3.53 ± 1.22)mg/L,respectively,which were significantly higher than that of 0,5mg/L groups [(0.70 ± 0.66),(1.99 ± 0.76)mg/L,all P ＜ 0.05].ConclusionsWhen osteoblasts are exposed to fluoride environment,fluoride ions enter into the osteoblasts quickly,and quickly accumulate in the nucleus,showing a special affinity between fluoride and bone tissue.Intracellular fluoride ions increase with the increase of contact time and exposure dose.