Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Polymyalgia rheumatica (PMR) is a syndrome characterized by pain and morning stiffness in the neck and shoulder and pelvic girdles, as well as raised acute-phase reactants, with or without systemic symptoms, such as fever. Giant cell arteritis (GCA) is a systemic vasculitis of unclear etiology that involves systemic arteries, principally affecting medium- and large-sized arteries with skipped, segmental alterations and granulomatous vasculitis seen on histopathology. In China, epidemiological data describing GCA are still limited; thus, the prevalence might be underestimated. The involvement of vessels in GCA can cause irreversible visual impairment or loss and stroke, which are serious complications. PMR is three times more prevalent than GCA, and other specific diseases should be excluded before the diagnosis is established. PMR symptoms can be present in 40%-60% of patients with GCA. Conversely, GCA can develop in 15% of patients with PMR. Chinese Rheumatology Association, based on the clinical diagnosis and treatment guidelines in 2005, utilizing the experience and guidelines of diagnosis and treatment at home and abroad, formulated this specification to standardize the diagnosis and treatment of GCA and PMR and improve the patient′s prognosis.

Objective:To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis.Methods:We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men,obtained differentially expressed piRNAs,and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility.Using histopathology,RNA-protein pull-down and Western blot,we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model.Results:RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary signifi-cance of hsa_piR_000478 in the diagnosis of the disease(AUC=0.7549).Transfection of hsa_piR_000478 and its homologous se-quence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility,increased the per-centage of morphologically abnormal sperm and destroyed the testicular structure.Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway,which elevated the level of cell glycolysis and interfered with normal spermatogenesis.Conclusion:hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility,and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.
Humans ; Hydrodynamics ; Computer Simulation ; Safety Management ; Occupational Diseases ; Technology

OBJECTIVE: To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology. METHODS: The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting. RESULTS: Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05). CONCLUSION Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Myocardial Infarction/drug therapy* ; Network Pharmacology

Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
Animals ; Cell Line ; Cyclic AMP/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cytokines/metabolism* ; Humans ; Inflammation ; Macrophages ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Signal Transduction/drug effects* ; Taurochenodeoxycholic Acid/pharmacology*

Objective: To provide the experimental basis for the coherence of the indirect bond position by comparing the position of the bracket on the digital occlusal model and the position of the transfer to the initial plaster model. Methods: Fifteen digitized models were selected for the brackets on the dental denture model, the brackets were transferred to the initial plaster model by indirect bond transfer trays, The line distance between each bracket position in digital dental model and initial plaster model was measured with OrthoRx software. Results : The difference between the position of the orthodontic brackets and the position of the initial plaster model was less than 0.20 mm, and the difference was statistically significant (P < 0.05). Conclusion The position of the bracket on the digital occlusal model is consistent with that of the original plaster model, which provides a theoretical basis for digital indirect bonding.

OBJECTIVETo evaluate the outcome after endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA) in single center.

METHODSA total of 711 AAA patients treated by EVAR in Department of Vascular Surgery, People's Liberation Army General Hospital and met the inclusion criteria from January 2004 to June 2014 were followed-up and analyzed. There were 612 male and 99 female patients, with a mean age of (69±13) years in this study group. The primary outcome of the study was all-cause mortality, secondary outcome included procedural data, intervention-related morbidity and secondary therapeutic procedures. The endpoint was death. Kaplan-Meier survival analysis were used to analyze long-term survival and cumulative probability of intervention related morbidity. Cox proportional hazards regression was used to analyze factors influenced the survival. Multivariable analysis were adjusted for covariates.

RESULTSThere were 74.8% of total patients followed up. The longest follow-up period was 10.4 years (mean 3.8 years). For the primary outcome of all-cause mortality, 140 deaths occurred. Intervention related morbidity was 9.3%, secondary therapeutic procedures was 5.3%.The Kaplan-Meier survival curve showed that cumulative survival is 78% (95% CI: 74% to 82%) in 5 years, 67% (95% CI: 61% to 74%) in 10 years and the cumulative probability of intervention related morbidity is 10.5% (95% CI: 7.3% to 13.7%) in 5 years, 19.3% (95% CI: 11.9% to 26.0%) in 10 years. Cox proportional hazards regression showed that age>75 years, American Society of Anesthesiologists classification III or IV, smoking, diabetes significantly increase the risk of long-term all-cause mortality, while hypertension significantly decreases the risk.

CONCLUSIONSLong-term outcome after EVAR of AAA in the study is similar to those advanced studies.The management of risk factors would improve the prognosis of these patients.

Aged ; Aged, 80 and over ; Aortic Aneurysm, Abdominal ; surgery ; Blood Vessel Prosthesis Implantation ; Endovascular Procedures ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Risk Factors ; Treatment Outcome

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.
Altitude ; Humans ; Hypoxia ; drug therapy ; Polycythemia ; drug therapy ; Stilbenes ; pharmacology

OBJECTIVETo study the effect of safflower injection on the proliferation and apoptosis of human leukemia cell line HEL and the relevant molecular mechanisms.

METHODSHEL cells were treated with different concentrations of safflower injection. HEL cells without safflower injection treatment were used as the control group. MTT method was used to detect the inhibitory rate of the HEL cells at 24, 48 and 72 hours after various concentrations of safflower injection treatment (10, 20, 30, 40 and 50 mg/mL). The cell cycle and apoptosis were detected using flow cytometry and the HOXB3-mRNA expression was measured by RT-PCR at 48 hours after safflower injection treatment (10, 20 and 30 mg/mL).

RESULTSCompared with the control group, various concentrations of safflower injection inhibited HEL cell proliferation in a dose-dependent manner (P<0.05). At 48 hours after various concentrations of safflower injection treatment, the number of treated cells in the G2/M phase increased, but that in the S phase decreased, and the apoptosis rate was significantly higher than that in the control group, with a dose-dependent manner (P<0.05). The expression of HOXB3-mRNA in safflower injection-treated cells decreased in a dose-dependent manner compared with the control group (P<0.05).

CONCLUSIONSSafflower injection can inhibit proliferation and induce apoptosis of HEL cells in vitro, and its underlying mechanisms may involve down-regulation of the HOXB3-mRNA expression.

Apoptosis ; drug effects ; Carthamus tinctorius ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Homeodomain Proteins ; genetics ; Humans ; Injections ; Leukemia ; drug therapy ; metabolism ; pathology