This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; metabolism ; urine ; Bile ; metabolism ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; blood ; metabolism ; urine ; Chromatography, Liquid ; Feces ; chemistry ; Male ; Organoselenium Compounds ; administration & dosage ; blood ; metabolism ; urine ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

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

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.

UNLABELLEDOBJECTIVE To verify the correlation between the points of eye acupuncture and zang-fu function so as to provide the theoretical evidence for the principle of point selection in eye acupuncture therapy.

METHODSSixty cases of cerebral infarction were treated with different points according to syndrome differentiation of Chinese medicine.

MAIN POINTSupper energizer area and lower energizer area. Supplementary points: liver area, kidney area and spleen area for hyperactivity of wind, phlegm and fire; liver area and spleen area for blockage of wind, phlegm and stasis; stomach area and large intestine area for excess fu syndrome due to phlegm heat; heart area and spleen area for qi deficiency and blood stasis; liver area and kidney area for yin deficiency and wind stirring. The single photon emission computed tomography (SPECT) was adopted to observe the changes in blood flow in local foci before and after treatment with eye acupuncture.

RESULTSAfter the treatment with eye acupuncture therapy, the intake ratio of region of interest (ROI) between the lesion area and corresponding area on the opposite side was 0.74 +/- 0.12 before eye acupuncture and was 0.91 +/- 0.08 after treatment, indicating significant statistical difference in comparison (P < 0.05). After eye acupuncture, cerebral blood flow increased apparently.

CONCLUSIONThe point selection according to syndrome differentiation in eye acupuncture therapy may increase local brain blood flow in the patients with cerebral infarction and improve the state of brain ischemia so that the correlation can be proved between the points of eye acupuncture and zang-fu function.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Brain ; diagnostic imaging ; Cerebral Infarction ; diagnostic imaging ; physiopathology ; therapy ; Cerebrovascular Circulation ; Eye ; Female ; Humans ; Male ; Middle Aged ; Tomography, Emission-Computed, Single-Photon

OBJECTIVE Corona-virus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 virus. The variant of corona-virus first identified in India, known as Delta, has become the dominant strain in China. Unfortunately, more conta-gious and unknown variants are coming, leading to a number of close contacts under quarantine. Chinese medicine (TCM) has been recommended to prevention and treatment due to the satisfactory therapeutic effects. However, the effect of TCM to decrease positive rate in close contacts remains unknown. METHODS We conducted an retrospective cohort study in Yangzhou, China to assess the effect of Chinese medicine on decreasing positive rate in close contacts under quarantine. The primary observation outcome was positive rate of Nucleic Acid Amplification Tests (NAATs). The secondary observation outcome was a composite of viral load of positive NAATs, severity levels of confirmed cases (asymptomatic, mild, moderate, or severe), daily body temperature, and levels of close contact (primary or secondary). RESULTS A total of 1286 subjects were collected, of which 1016 (79.00％) in TCM group and 270 (21.00％) in control group with 55 participants tested positive. The incidence of the primary outcome, positive rate of NAATs was significantly lower in the Chinese medicine group than in the control group, occurring in male and age≥60 years subjects. Multi-varia-ble logistic regression (excluding NO viral load) indicated that the risk of testing positive was reduced by 0.547 times in TCM groupcompared to control group. CT value of TCM group was higher than that of control group in all subjects and female subjects, and the re-sult showed statistically significant difference. CONCLUSIONS In our study involving close contacts under quarantine, Chinese medicine resulted in lower positive rate of NAATs and viral load than control.

Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and ¹H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and ¹H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and ¹H-NMR can be used together to identify unknown new psychoactive substances.
Chromatography, High Pressure Liquid ; Gas Chromatography-Mass Spectrometry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Tryptamines

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.