OBJECTIVE: To investigate the effect of irradiation dose rate of ⁶⁰Co γ-ray on hematopoietic and immune cells in total body irradiation (TBI) mice. METHODS: After TBI with 8 Gy ⁶⁰Co γ-ray at three irradiation dose rates of 0.027, 0.256 and 0.597 Gy/min, the survival and change of body weight of C57BL/6J mice were observed within 30 days. The peripheral blood parameters were examined at each time point within 30 days post-irradiation. The hematopoietic stem/progenitor cell counts of mice were examined on the 10^th and 30^th day post-irradiation by flow cytometry, as well as the proportions of immune cells in peripheral blood, bone marrow and spleen of mice on the 30^th day post-irradiation. RESULTS: After TBI with 8 Gy ⁶⁰Co γ-ray, the 30-day survival rate of high dose-rate group was 0, which was significantly lower than 90% of medium dose-rate group and 100% of low dose-rate group (both P < 0.001). The peripheral blood parameters of all three groups showed a sharp decline → low value → gradually recovering trend. The count of white blood cell, neutrophil, lymphocyte, red blood cell, platelet and hemoglobin level in the high dose-rate and medium dose-rate groups were significantly lower than those in the low dose-rate group on day 7-18 post-irradiation (all P < 0.05), but there were no significant differences between the high dose-rate and medium dose-rate groups (P >0.05). On the 10^th day after irradiation, the proportion and number of bone marrow hematopoietic stem/progenitor cells (including LK, LSK, LT-HSC, ST-HSC, and MPP cells) in the low dose-rate and medium dose-rate groups were significantly decreased compared to those in the normal group (all P < 0.05), but there were no significant differences between the two groups (P >0.05). On the 30^th day after irradiation, LSK, LT-HSC, ST-HSC and MPP cells in the low dose-rate group recovered to normal levels, while those in the medium dose-rate group were still significantly lower than those in the low dose-rate group (all P < 0.001). The results of bone marrow and peripheral immune cell tests on the 30^th day after irradiation showed that the ratios of T and B lymphocytes in the low dose-rate and medium dose-rate groups were reduced compared to that in the normal group (both P < 0.05), while the ratio of neutrophils was increased (P < 0.01). The trend of changes in the spleen and peripheral blood was consistent. CONCLUSION The degree of hematopoietic and immune cell damage in mice after TBI with 8 Gy ⁶⁰Co γ-ray is related to the dose rate, and low dose-rate irradiation can reduce the damage in the animal model. Therefore, choosing the appropriate dose rate of irradiation is a key factor in establishing an objective and reliable experimental animal model of irradiation.
Animals ; Mice ; Whole-Body Irradiation ; Gamma Rays ; Mice, Inbred C57BL ; Hematopoietic Stem Cells/radiation effects* ; Cobalt Radioisotopes ; Dose-Response Relationship, Radiation ; Male

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.
Mice ; Animals ; Heart Failure/metabolism* ; Stroke Volume ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Metabolomics ; Arachidonic Acids ; Proline

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4⁺T lymphocytes counts (CD4) counts levels of 200-349 cells/μl, 350-500 cells/μl and ≥501 cells/μl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/μl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.
Humans ; Middle Aged ; Retrospective Studies ; China/epidemiology* ; Acquired Immunodeficiency Syndrome/epidemiology* ; Anti-Retroviral Agents/therapeutic use* ; Asian People

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with ⁶⁰Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit⁺ HSC, and p16 and p38 mRNA expression of c-kit⁺ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit⁺ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit⁺ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.
Humans ; Mice ; Animals ; Thrombopoietin/metabolism* ; Hematopoietic Stem Cells ; Blood Platelets ; Recombinant Proteins/therapeutic use* ; Radiation Injuries ; RNA, Messenger/metabolism*

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of ellagic acid,gallic acid,dehydrodiisoeugenol,methyleugenol,agarotetrol,elemicin,chlorogenic acid,geniposide,rutin,ferulic acid,hydroysafflor-yellow A,deoxycholic acid,cholic acid,borneol and taurine in Zhuriheng Dropping Pills.METHODS The analysis of 50%methanol solution of this drug was performed on a 30℃thermostatic Thermo C18 column(2.1 mm×100 mm,1.9 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid(containing 10 mmol/L ammonium acetate)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Fifteen constituents showed good linear relationships within their own ranges(R2>0.990 0),whose average recoveries were 75.91%-112.13%with the RSDs of 3.06%-10.66%.CONCLUSION This simple,sensitive and efficient method can be used for the quality control of Zhuriheng Dropping Pills.

The COVID-19 pandemic is still ongoing in the world, the risk of COVID-19 spread from other countries or in the country will exist for a long term in China. In the routine prevention and control phase, a number of local COVID-19 epidemics have occurred in China, most COVID-19 cases were sporadic ones, but a few case clusters or outbreaks were reported. Winter and spring were the seasons with high incidences of the epidemics; border and port cities had higher risk for outbreaks. Active surveillance in key populations was an effective way for the early detection of the epidemics. Through a series of comprehensive prevention and control measures, including mass nucleic acid screening, close contact tracing and isolation, classified management of areas and groups at risk, wider social distancing and strict travel management, the local COVID-19 epidemics have been quickly and effectively controlled. The experiences obtained in the control of the local epidemics would benefit the routine prevention and control of COVID-19 in China. The occurrence of a series of COVID-19 case clusters or outbreaks has revealed the weakness or deficiencies in the COVID-19 prevention and control in China, so this paper suggests some measures for the improvement of the future prevention and control of COVID-19.
COVID-19/prevention & control* ; China/epidemiology* ; Contact Tracing ; Epidemics/prevention & control* ; Humans ; Pandemics/prevention & control* ; SARS-CoV-2

Objective: The pattern of digestive tract reconstruction in radical gastrectomy for gastric cancer is still inconclusive. This study aims to compare mid-term and long-term quality of life after radical gastrectomy for distal gastric cancer between Billroth-I (B-I) and Billroth-II (B-II) reconstruction. Methods: A retrospective cohort study was conducted.Clinicopathological and follow-up data of 859 gastric cancer patients were colected cellected from the surgical case registry database of Gastrointestinal Surgery Center of Sichuan University West China Hospital, who underwent radical distal gastric cancer resection between January 2016 and December 2020. Inclusion criteria: (1) gastric cancer confirmed by preoperative gastroscopy and biopsy; (2) elective radical distal major gastrectomy performed according to the Japanese Society for Gastric Cancer treatment guidelines for gastric cancer; (3) TNM staging referenced to the American Cancer Society 8th edition criteria and exclusion of patients with stage IV by postoperative pathology; (4) combined organ resection only involving the gallbladder or appendix; (5) gastrointestinal tract reconstruction modality of B-I or B-II; (6) complete clinicopathological data; (7) survivor during the last follow-up period from December 15, 2021 to January 15, 2022. Exclusion criteria: (1) poor compliance to follow-up; (2) incomplete information on questionnaire evaluation; (3) survivors with tumors; (4) concurrent malignancies in other systems; (5) concurrent psychiatric and neurological disorders that seriously affected the objectivity of the questionnaire or interfered with patient's cognition. Telephone follow-up was conducted by a single investigator from December 2021 to January 2022, and the standardized questionnaire EORTC QLQ-C30 scale (symptom domains, functional domains and general health status) and EORTC QLQ-STO22 scale (5 symptoms of dysphagia, pain, reflux, restricted eating, anxiety; 4 single items of dry mouth, taste, body image, hair loss) were applied to evaluate postoperative quality of life. In 859 patients, 271 were females and 588 were males; the median age was 57.0 (49.5, 66.0) years. The included cases were divided into the postoperative follow-up first year group (202 cases), the second year group (236 cases), the third year group (148 cases), the fourth year group (129 cases) and the fifth year group (144 cases) according to the number of years of postoperative follow-up. Each group was then divided into B-I reconstruction group and B-II reconstruction group according to procedure of digestive tract reconstruction. Except for T-stage in the fourth year group, and age, tumor T-stage and tumor TNM-stage in the fifth year group, whose differences were statistically significant between the B-I and B-II reconstruction groups (all P<0.05), the differences between the B-I and B-II reconstruction groups in terms of demographics, body mass index (BMI), tumor TNM-stage and tumor pathological grading in postoperative follow-up each year group were not statistically significant (all P>0.05), suggesting that the baseline information between B-I reconstruction group and the B-II reconstruction group in postoperative each year group was comparable. Evaluation indicators of quality of life (EORTC QLQ-C30 and EORTC QLQ-STO22 scales) and nutrition-related laboratory tests (serum hemoglobin, albumin, total protein, triglycerides) between the B-I reconstruction group and B-II reconstruction group in each year group were compared. Non-normally distributed continuous variables were presented as median (Q(1),Q(3)), and compared by using the Wilcoxon rank sum test (paired=False). The χ(2) test or Fisher's exact test was used for comparison of categorical variables between groups. Results: There were no statistically significant differences in all indexes EORTC QLQ-30 scale between the B-I reconstruction group and the B-II reconstruction group among all postoperative follow-up year groups (all P>0.05). The EORTC QLQ-STO22 scale showed that significant differences in pain and eating scores between the B-I reconstruction group and the B-II reconstruction group were found in the second year group, and significant differences in eating, body and hair loss scores between the B-I reconstruction group and the B-II reconstruction group were found in the third year group (all P<0.05), while no significant differences of other item scores between the B-I reconstruction group and the B-II reconstruction group were found in postoperative follow-up of all year groups (P>0.05). Triglyceride level was higher in the B-II reconstruction group than that in the B-I reconstruction group (W=2 060.5, P=0.038), and the proportion of patients with hyperlipidemia (triglycerides >1.85 mmol/L) was also higher in the B-II reconstruction group (19/168, 11.3%) than that in the B-I reconstruction group (0/34) (χ(2)=0.047, P=0.030) in the first year group with significant difference. Albumin level was lower in the B-II reconstruction group than that in the B-I reconstruction group (W=482.5, P=0.036), and the proportion of patients with hypoproteinemia (albumin <40 g/L) was also higher in the B-II reconstruction group (19/125, 15.2%) than that in the B-I reconstruction group (0/19) in the fifth year group, but the difference was not statistically significant (χ(2)=0.341, P=0.164). Other nutrition-related clinical laboratory tests were not statistically different between the B-I reconstruction and the B-II reconstruction in each year group (all P>0.05). Conclusions: The effects of both B-I and B-II reconstruction methods on postoperative mid-term and long-term quality of life are comparable. The choice of reconstruction method after radical resection of distal gastric cancer can be based on a combination of patients' condition, sugenos' eoperience and operational convenience.
Aged ; Albumins ; Alopecia/surgery* ; Female ; Gastrectomy/methods* ; Gastric Bypass ; Humans ; Male ; Middle Aged ; Pain ; Quality of Life ; Registries ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome ; Triglycerides

OBJECTIVE: To study the effect of interleukin-6 (IL-6) gene deletion on radiation-induced hematopoietic injury in mice and relative mechanism. METHODS: Before and after whole body ⁶⁰Co γ-ray irradiation, it was analyzed and compared that the difference of peripheral hemogram, bone marrow hematopoietic stem and progenitor cells conts in IL-6 gene knockout (IL-6^-/-) and wild-type (IL-6^+/+) mice and serum IL-6 and G-CSF expression levels in above- mentioned mouse were detected. Moreover, 30 days survival rate of IL-6^-/- and IL-6^+/+ mice after 8.0 Gy γ-ray irradiation were analyzed. RESULTS: IL-6 levels in serum of IL-6^+/+ and IL-6^-/- mice were respectively (98.95±3.85) pg/ml and (18.36±5.61) pg/ml, which showed a significant statistical differences (P<0.001). There were no significant differences of peripheral blood cell counts and G-CSF level in serum between IL-6^+/+ and IL-6^-/- mice before irradiation (P>0.05). However, the number of leukocytes, neutrophils, lymphocytes, monocytes, platelets in peripheral blood and G-CSF level in serum of IL-6^-/- mice were significantly decreased at 6 h after 8.0 Gy γ-ray irradiation compared with that of IL-6^+/+ mice. On days 30 after 8.0 Gy γ-ray irradiation, the survival rate of IL-6^+/+ and IL-6^-/- mice was 62.5% and 12.5%, and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days, respectively. On days 14 after 6.5 Gy γ-ray irradiation, bone marrow nucleated cells in IL-6^+/+ and IL-6^-/- mice were respectively (10.0±1.2)×10⁶ and (8.3±2.2)×10⁶ per femur. Compared with IL-6^+/+ mice, the proportion of Lin^-Sca-1^-c-kit⁺ (LK) in bone marrow of IL-6^-/- mice had no significant change (P>0.05), but the proportion of Lin^-Sca-1⁺c-kit⁺ (LSK) was significantly decreased (P<0.05). CONCLUSION IL-6 plays an obvious role in regulating hematopoietic radiation injury, and IL-6 deficiency can inhibit the radiation-induced increase of endogenous G-CSF level in serum, aggravates the damage of mouse hematopoietic stem cells（HSC） and the reduction of mature blood cells in peripheral blood caused by ionizing irradiation, resulting in the shortening of the survival time and significant decrease of the survival rate of mice exposed to lethal dose radiation.
Animals ; Gene Deletion ; Granulocyte Colony-Stimulating Factor/pharmacology* ; Interleukin-6/metabolism* ; Mice ; Radiation Injuries ; Whole-Body Irradiation