Chronic fatigue syndrome (CFS) is a common problem in military maritime navigation, which greatly affects the safety of military missions. The use of animal models to carry out research on the mechanism of CFS and treatment measures is a common method. This paper systematically introduced the construction methods of CFS models such as single-factor and multi-factor models, summarized common evaluation indicators of CFS, including behavioral and biochemical indicators, and summed up key characteristics of CFS animal models in military oceanic navigation combined with common causes of CFS in military contexts, such as prolonged continuous work, high-intensity physical activity, sleep deprivation, psychological stress, and extreme environmental conditions. The key characteristics of the animal models included, but not limited to, chronic fatigue, sleep disorders, impaired cognitive function, psychological stress responses, and abnormal biochemical indicators. Furthermore, this article identified future research directions for CFS animal models in military oceanic navigation to enhance the application value of the models and provide robust support for the health protection and disease prevention of military personnel.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE To assess the correlation between the steady-state minimal concentration （cmin） and 24 h area under the drug concentration-time curve （AUC24）/minimal inhibitory concentration （MIC） ratio （AUC24/MIC） of vancomycin in pediatric patients， and analyze independent risk factors for treatment failure. METHODS Data of hospitalized children treated with vancomycin and receiving therapeutic drug monitoring in our hospital from January 2021 to July 2024 were retrospectively collected and divided into success group and failure group according to whether the treatment was successful or not. Spearman correlation analysis was used to analyze the correlation between cmin and AUC24/MIC of vancomycin， and one-way and multifactorial Logistic regression analyses were used to screen the independent risk factors for vancomycin treatment failure. RESULTS A total of 59 children were included， with 41 in the success group and 18 in the failure group. Compared with the failure group， AUC24/MIC of vancomycin was significantly higher in the success group （P＝0.038）， but there was no statistically significant difference in the cmin of the two groups （P＞0.05）； cmin of vancomycin was significantly positively correlated with AUC24/MIC （r＝0.499， P＜0.001）， but it has a certain efficacy in predicting the achievement of the AUC24/MIC standard （≥400） （area under the receiver operator characteristic curve＝0.696）， with an optimal cutoff value of 6.05 mg/L determined by the Youden index. The efficacy of AUC24/ MIC in predicting treatment failure was superior to cmin （areas under the receiver operator characteristic curve were 0.671 vs. 0.523， P were 0.038 vs. 0.684）， with higher sensitivity （83.3% vs. 66.7%）. Hypoproteinemia and AUC24/MIC≤369.1 were independent risk factors for vancomycin treatment failure （P＜0.05）. The incidence of nephrotoxicity was 3.4%. CONCLUSIONS There is a significant positive correlation between cmin and AUC24/MIC of vancomycin in pediatric patients； hypoproteinemia and AUC24/MIC≤369.1 are independent risk factors for vancomycin treatment failure in children.

Objective　To detect clustered regularly interspaced short palindromic repeats (CRISPR) in Listeria monocytogenes, and analyze the structure and homology of CRISPR loci. Methods Totally 34 strains of Listeria monocytogenes isolated in our laboratory were identified, PCR amplified and sequenced. The repeat sequence structure and spacer sequence homology in CRISPR loci were analyzed by bioinformatics software. Results A total of 7 CRISPR loci were detected in 34 strains. The mutation rate of the first 2 and last 2 bases of the Repeat sequence of CRISPR loci was higher, while the mutation rate of the middle part was lower. Seven CRISPR sites form eight CRISPR structural types, among which the Repeat sequences of CRISPR1 and CRISPR2 are relatively conserved, while the Repeat sequences of CRISPR1 and CRISPR5 can form dumbbell shaped secondary structures. The number of Spacer sequences contained in each CRISPR site ranges from 2 to 15, with an average of 2.43. The 136 Spacer sequences detected were not only homologous to Listeria plasmids and bacteriophages, but also homologous to uncultured virus sequences, staphylococcal bacteriophages, and Listeria innocua. The same CRISPR genotype did not show large-scale clustering, but some strains in the same year were in the same evolutionary cluster with close genetic relationships. Conclusion The CRISPR structure of Listeria monocytogenes in this study exhibits high specificity, and its homology with bacteriophages provides a theoretical basis for the application of bacteriophages in the control and prevention of Listeria monocytogenes.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.