Objective:To investigate the effect of low density lipoprotein cholesterol (LDL-C) on the progression of retinal arteriosclerosis by using a deep learning model.Methods:A cohort study was performed.Data of 1 928 individuals who underwent the medical examination at Beijing Yijiandian Clinic between January 2016 and August 2023 were reviewed, including baseline demographics, physical examination, serological test and fundus photography.Retinal arteriosclerosis was identified using a deep learning model.Five groups were divided according to LDL-C levels, including 389 subjects in group 1 (0.64-1.90 mmol/L), 387 subjects in group 2 (1.91-2.26 mmol/L), 384 subjects in group 3 (2.27-2.57 mmol/L), 385 subjects in group 4 (2.58-2.95 mmol/L), and 383 subjects in group 5 (2.96-6.06 mmol/L).The association between LDL-C levels and progression of retinal arteriosclerosis and the dose-response relationship were analyzed by logistic regression analysis and restricted cubic spline (RCS) regression model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2021PHB058-001).Written informed consent was obtained from each subject.Results:The incidence of retinal arteriosclerosis progression was 22.10% (426/1 928) during the mean follow-up (66.84±6.58) months.The proportions of fundus progression in groups 1, 2, 3, 4, and 5 were 15.68%(61/389), 21.71%(84/387), 21.35%(82/384), 25.71%(99/385), and 26.11%(100/383), respectively, with statistical significant differences among them ( χ2=15.97, P=0.003).Using group 1 as a reference, LDL-C 2.58-2.95 mmol/L was an independent risk factor for progression of retinal arteriosclerosis ( OR=1.52, 95% CI: 1.04-2.22), and RCS analysis showed an " L" shaped association.The effect of LDL-C on retinal arteriosclerosis showed a threshold effect, with the risk of retinal arteriosclerosis progression increasing with increasing LDL-C when LDL-C was <2.34 mmol/L ( OR=1.97, 95% CI: 1.10-3.62), and stabilizing when LDL-C was ≥2.34 mmol/L. Conclusions:LDL-C has a threshold effect on the impact of retinal arteriosclerosis progression, and the threshold is 2.34 mmol/L.

Objective: To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM). Methods: GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay. Results: Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation. Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.
Antineoplastic Agents, Alkylating/therapeutic use* ; Brain Neoplasms/metabolism* ; Cell Line, Tumor ; DNA/therapeutic use* ; Glioblastoma/metabolism* ; Humans ; Radiation, Ionizing ; Temozolomide/therapeutic use*

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

Objective To observe the acute toxicity and nephrotoxicity of antibacterial peptide R9 in mice.Methods Median lethal dose (LD50) test:Antimicrobial peptide R9 was intraperitoneally injected into mice.After 7 d of observation,the LD50 and 95 ％ confidence limits were calculated according to the Bliss method.Renal toxicity of R9 test:80 mice were randomly divided into 4 groups:the low,medium and high dose (6.7,10,15 mg · kg-1 R9) experimental groups and blank control group (distilled water) were injected intraperitoneally.The blood samples were collected on the 2nd day respectively from 10 mice,then blood indexes were tested.The serum were separated,then creatinine,blood urea nitrogen and total protein were measured.Kidneys and other organs were taken to calculate the organ coefficients.Results The LD50 of antimicrobial peptide R9 was 21.3 mg · kg-1,and its 95％ confidence limit was 19.1-23.5 mg · kg-1.On the second day after administration,WBC (4.07 × 109/L) and RBC (8.96 × 1012/L) in the high dose experimental group decreased compared with the blank control group,the differences were statistically significant difference (P ＜ 0.01,P ＜ 0.05).Creatinine (19.99 μmol · L-1) and urea nitrogen (8.07 mmol · L-1)increased with significant (P ＜0.05,P ＜ 0.01).The total protein (54.18 g · L-1) decreased with significant (P ＜0.05) and the kidney coefficient (13.40 mg· g-1) increased with significant (P ＜ 0.05).Conclusion A single intraperitoneal injection of antimicrobial peptide R9 can produce certain toxicity to mice,and the kidney was the main target organ.Nephrotoxicity was positively correlated with dose,and there was a trend of reversible improvement after withdrawal.

OBJECTIVETo investigate the effects of vitamin-mineral supplement on young males with physical overtraining.

METHODSTwo hundred and forty male Chinese field artillery personnel who undertook large scale and endurance military training and were on ordinary Chinese diet were randomized to receive a multivitamin/multimineral supplement or a placebo for 1 week. After a 1-week wash-out period, a cross-over with 1 week course of a placebo or multivitamin/multimineral supplement was conducted. Blood and urine samples were analyzed for adrenal, gonadal and thyroid hormones. In addition, cellular immune parameters (CD3+, CD3+CD4+, CD3+CD8+, CD4/CD8, CD3-CD56+, CD3-CD19+) were examined and psychological tests were performed before and after the training program and nutrition intervention.

RESULTSAfter a large scale and endurance military training, the participants showed significantly increased thyroid function, decreased adrenal cortex, testosterone and immunological function, and significantly increased somatization, anger and tension. Compared to placebo, multivitamin/ multimineral intervention showed significant effects on functional recovery of the pituitary - adrenal axis, pituitary-gonadal axis, pituitary- thyroid axis and immune system as well as psychological parameters.

CONCLUSIONHigh-intensity military operations have significant impacts on the psychology, physical ability and neuroendocrine-immune system in young males. Appropriate supplementation of multivitamin/multimineral can facilitate the recovery of the psychology, physical ability and neuroendocrine-immune system in young males who take ordinary Chinese diet.

Adolescent ; Adult ; Affect ; drug effects ; CD4-CD8 Ratio ; Dietary Supplements ; Double-Blind Method ; Emotions ; drug effects ; Exercise ; Hormones ; blood ; Humans ; Killer Cells, Natural ; cytology ; Leukocyte Count ; Male ; Military Personnel ; Minerals ; administration & dosage ; Psychological Tests ; Stress, Psychological ; prevention & control ; Vitamins ; administration & dosage ; Young Adult

OBJECTIVETo screen the differentially expressing genes between silicotic lung tissue and normal lung tissue, to identify the differentially expressing genes of matrix metalloproteinase-12 (MMP-12) and Cathepsin E and to explore the roles of those genes in silicosis development.

METHODSThirty male SD rats were divided randomly into two groups: control group (6 rats) and exposure group (24 rats) which was exposed to SiO2 by intra-tracheal perfusion. On the 30 th, 60 th and 90 th days after exposure, 8 rats in model group and 2 rats in control group were executed and the lung tissues were obtained. The morphologic changes of lung tissues were observed with HE staining and VG staining under a light microscope. The gene microarrays were used to identify differentially expressing genes of lung tissues in rats exposed to SiO2 for 60 days. Two significantly up-regulated genes, MMP-12 and Cathepsin E, were validated using RT-PCR, immunohistochemistry and Western Blot assay.

RESULTSA total of 338 differentially expressing genes were identified from the 26 962 genes between silicotic rats and normal rats, including 267 up-regulated genes and 71 down-regulated genes. The results of RT-PCR showed that in the lung tissues of exposure group on the 30 th, 60 th and 90 th days, the mRNA expression levels of MMP-12 were 4.306, 5.338, 6.713 times higher than those in the control group, the mRNA expression levels of Cathepsin E were 1.434, 2.974, 3.889 times higher than those in the control group, respectively. The results of immunohistochemical showed that in the lung tissues of exposure group on the 30th, 60th and 90th days, the mRNA expression levels of MMP-12 were 1.435, 1.746, 2.069 times higher than those in the control group, the mRNA expression levels of Cathepsin E were 1.372, 1.663, 2.103 times higher than those in the control group, respectively. The results of immunohistochemical showed that in the lung tissues of exposure group on the 30th, 60th and 90th days, the expression levels of MMP-12 protein were 1.214, 1.531, 1.959 times higher than those in the control group, the expression levels of Cathepsin E protein were 1.262, 1.828, 1.907 times higher than those in the control group, respectively. Compared with the control group, the mRNA and protein expression levels of MMP-12 and Cathepsin E in lung tissues of exposure group were significantly up-regulated (P < 0.05).

CONCLUSIONThe differentially expressing genes in rat lung tissues screened by gene chip were validated, which suggested that a complex gene regulatory network may be contributed to occurrence of silicosis. MMP-12 and Cathepsin E genes may be involved in the development of silicotic pulmonary fibrosis by degrading the basement membrane of alveolar wall and participating in the immune response.

Animals ; Cathepsin E ; genetics ; metabolism ; Gene Expression ; Lung ; metabolism ; Male ; Matrix Metalloproteinase 12 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Silicosis ; genetics ; metabolism

BACKGROUNDOver one million soldiers were treated for battle- or training-fatigue during World War II. Of all ground combat troops, 37% were discharged for psychiatric reasons due to fatigue. The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel. The aim of this study was to investigate the characteristics of fatigue associated with military operations, and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies.

METHODSA total of 240 soldiers from the Field Artillery regiment were selected as subjects. Researchers and subjects received training before participating in the study. Data of the subjects' medical histories, physical examinations, scores on a fatigue assessment scale, and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)), pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4), triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)), and cellular immune parameters (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), B, and NK cells) were investigated before and after large-scale and high-intensity field exercises. Data were statistically analyzed with Student's t test using SPSS software (version 13.0), and P values < 0.05 were deemed to be significant.

RESULTSAfter the high-intensity military training, the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers. Additionally, the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores. After intensive military work, levels of plasma ACTH, F, and UFC of soldiers were decreased (P < 0.01). The level of testosterone decreased significantly after the maneuver ((23.51 ± 6.49) versus (18.89 ± 5.89) nmol/L; P < 0.001), whereas the thyroid function (TT3, FT4, and FT3) was markedly increased after the maneuver (P < 0.01). The number of CD3(+), CD4(+), CD4(+)/CD8(+) cells, and B lymphocytes were decreased (P < 0.05), and NK cells were increased (P < 0.001) after the maneuver.

CONCLUSIONSFollowing high-intensity military operations, the psychological tolerance of soldiers was depressed. And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue. Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.

Adolescent ; Adrenal Glands ; secretion ; Adult ; Endocrine System ; metabolism ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Hydrocortisone ; blood ; Luteinizing Hormone ; blood ; Male ; Military Personnel ; Pituitary Gland ; secretion ; Pituitary Hormones ; blood ; Prolactin ; blood ; Testosterone ; blood ; Thyroid Hormones ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood ; Young Adult

Background Over one million soldiers were treated for battle- or training-fatigue during World War II.Of all groundcombat troops,37％ were discharged for psychiatric reasons due to fatigue.The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel.The aim of this study was to investigate the characteristics of fatigue associated with military operations,and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies.@@Methods A total of 240 soldiers from the Field Artillery regiment were selected as subjects.Researchers and subjects received training before participating in the study.Data of the subjects' medical histories,physical examinations,scores on a fatigue assessment scale,and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH),cortical hormone (F),and 24-hour urine-free cortisol (UFC)),pituitary-gonadal hormones (luteinizing hormone (LH),follicle-stimulating hormone (FSH),testosterone,estradiol (E2),and prolactin (PRL)),pituitary-thyroid hormones (thyroid-stimulating hormone (TSH),thyroxine (-I-r4),triiodothyronine (I-T3),free thyroxine (FT4),and free triiodothyronine (FT3)),and cellular immune parameters (CD3+,CD4+,CD8+,CD4+/CD8+,B,and NK cells) were investigated before and after large-scale and high-intensity field exercises.Data were statistically analyzed with Student's ttest using SPSS software (version 13.0),and Pvalues <0.05 were deemed to be significant.@@Results After the high-intensity military training,the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers.Additionally,the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores.After intensive military work,levels of plasma ACTH,F,and UFC of soldiers were decreased (P <0.01).The level of testosterone decreased significantly after the maneuver ((23.51±6.49) versus (18.89-5.89) nmol/L; P <0.001),whereas the thyroid function (Tr3,FT4,and FT3) was markedly increased after the maneuver (P <0.01).The number of CD3+,CD4+,CD4+/CDS+ cells,and B lymphocytes were decreased (P <0.05),and NK cells were increased (P<0.001) after the maneuver.@@Conclusions Following high-intensity military operations,the psychological tolerance of soldiers was depressed.And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue.Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.

Objective To study the related factors of central lymph node(CLN) metastasis in papillary thyroid carcinoma ( PTC ),the indications and the extent of central neck dissection ( CND ).Methods A total of 153 cases treated between Jan.2009 and Dec.2010 was analysed retrospectively.Of the cases 28 males and 125 cases females,with a mean age of (44 ± 14) years.T1,T2,and T3 diseases accounted for 51,10 and 81 cases,respectively; Ⅰ,Ⅱ,Ⅲ and Ⅳ diseases for 88,3,26 and 36 cases,respectively.Multifocal tumors were found in 63 cases.The related clinicopathologic factors were analyzed,including sex,age,tumor size,extrathyroidal extension,and multifocal tumor.Results All the cases had total/near total thyroidectomy and CND,of them 64 cases had unilateral neck dissection and 18 cases had bilateral neck dissection.CLN metastases existed in 68.6％ ( 105/153 ) cases,37.2％ (57/153) for unilateral and 31.4％ (48/153) for bilateral respectively.The rates of CLN metastasis were 86.6％ (71/82)in cN1 cases and 47.9％ (34/71) cN0 cases,respectively,and the rates of bilateral CLN metastases were 45.1％(37/82) in cN1 cases and 15.5％ (11/71) in cN0 cases. Multivariate analysis showed that extrathyroidal extension( P =0.002,OR =3.502) was an independent risk factor for CLN metastasis and that lateral neck lymph node metastasis( P =0.028,OR =3.080),surrounding tissue invasion ( P =0.014,OR =3.113 ),and maximum tumor diameter greater than 1 cm ( P =0.012,OR =3.732) were independent risk factors for bilateral CLN metastases.Conclusions It is indicated that ipsilateral CND should be obligatory for PTC. Intraoperative frozen section examination should be routine.Bilateral CND should be conducted when ipsilateral CLN metastases accompanied by one of following issues such as more invasive tumor(surrounding tissue invasion,T3 or T4 disease),maximum tumor diameter greater than 1 cm,and lateral neck lymph node metastasis.

Adult ; Child, Preschool ; Heart Ventricles ; pathology ; Humans ; Male ; Myocardium ; pathology ; Pre-Excitation Syndromes ; etiology ; pathology