This study aims to investigate the protective effect and potential mechanism of Jingfang Granules(JF) on the mouse model of chronic fatigue syndrome(CFS). Mice were randomized into normal, model, and low-, medium-, and high-dose(0.9, 1.8, and 3.6 g·kg~(-1)·d~(-1), respectively) JF groups according to the body weight. In addition to the normal group, other groups of mice received exhaustive swimming training and tail suspension training every day for the modeling of CFS. The mice in each administration group were administrated with JF at the corresponding dose by gavage, and those in the other groups were administrated with an equal amount of purified water. The exhaustive swimming and tail suspension tests were conducted in each group. The UV-glutamate dehydrogenase method was used to determine the serum level of urea nitrogen(UREA), and the lactate dehydrogenase(LDH) assay kit was used to determine the LDH level. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum, muscle tissue, and brain tissue of mice in each group. Western blot was employed to determine the expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappa B(NF-κB) and their phosphorylated proteins in the muscle tissue of mice. The 16S rDNA sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) were adopted to detect the changes of intestinal flora and intestinal metabolites in mice. Compared with the model group, JF significantly prolonged the swimming exhaustion time and shortened the tail suspension time of the model mice, lowered the levels of LDH and UREA in the serum as well as the levels of IL-6 and TNF-α in the serum, muscle tissue, and brain tissue of CFS mice. In addition, JF down-regulated the expression of TLR4, MyD88, and p-NF-κB/NF-κB in the muscle tissue of CFS mice compared with the model group. The results of 16S rDNA sequencing demonstrated that JF ameliorated the intestinal flora disorder of CFS mice. The results of UPLC-MS/MS revealed that JF significantly affected the histidine metabolism pathway in the intestinal tract of CFS mice. Spearman analysis displayed that histamine, a metabolite involved in histidine metabolism, was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. The metabolite imidazole-4-acetaldehyde was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. In conclusion, JF can increase the swimming exhaustion time, reduce the immobility time of tail suspension, lower serum LDH and UREA levels, and alleviate inflammation response. It may exert the therapeutic effect by improving intestinal flora homeostasis and inhibiting histidine metabolism by down-regulating the expression of proteins in the TLR4/MyD88/NF-κB signaling pathway, thereby relieving the symptoms of CFS in mice.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Metabolomics ; Fatigue Syndrome, Chronic/genetics* ; NF-kappa B/genetics* ; Humans ; Interleukin-6/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Disease Models, Animal

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To investigate the development of intrapulmonary vascular volume (IPVV) in normal preschool children based on quantitative measurement on chest CT.Methods:The CT data of 407 normal preschool children (236 males and 171 females, aged 1-72 months, with a median of 36 months) who underwent chest CT examination from January 2014 to May 2017 in the "Digital Lung" imaging database were retrospectively collected. The pulmonary vessels were segmented by the "Digital Lung" automatic detection tool, and the IPVV of the whole lung, the right lung, the left lung and each lobe were obtained, and the IPVV upper/lower and IPVV left/right were calculated. According to the age, the subjects were divided into infant period (0-12 months), early childhood period (13-36 months) and preschool period (37-72 months), with 30 cases (17 males and 13 females), 175 cases (95 males and 80 females) and 202 cases (124 males and 78 females) respectively. Spearman correlation analysis was used to evaluate the correlation between IPVV and month age. One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences of IPVV, IPVV upper/lower and IPVV left/right between different months of age. Independent sample t test or Mann-Whitney U test was used to compare the differences of IPVV between different genders, and the normal reference range of IPVV in normal preschool children of different months of age was established. Results:The IPVV of the whole lung, right lung, left lung and each lung lobe were positively correlated with age, the correlation coefficient was 0. 638-0.820 in males and 0. 683-0.791 in females (all P<0.001). There was no significant difference in IPVV of whole lung, right lung, left lung and each lobe between male and female from 0 to 12 months (all P>0.05), but there was significant difference in IPVV of whole lung, right lung, left lung and each lobe between male and female from 13 to 36 months (all P<0.05). There were significant differences in IPVV of the whole lung, right lung, left lung and upper lobe of both lungs between boys and girls from 37 to 72 months (all P<0.05). IPVV upper/lower in the right lung (χ 2=14.00, 12.87, P=0.001, 0.002) and IPVV upper/lower in the left lung (χ 2=6.65, 22.84, P=0.036,<0.001) were significantly different in both boys and girls among 3 months of age. And with the increase of age, it showed a decreasing trend. There was no significant difference in IPVV upper/lower between boys and girls at the same age (all P>0.05).There was no significant difference in IPVV left/right among different months and between different sexes (all P>0.05). Finally, the normal reference value range of IPVV of different genders in infancy, early childhood and preschool age was calculated. Conclusions:The increase of pulmonary vessels in normal preschool children is positively correlated with age. There is no significant difference in IPVV between boys and girls in infant period, but IPVV in boys is larger than that in girls in early childhood period and preschool period. IPVV in the lower lung increased faster than that in the upper lung, but there was no significant difference between the left and right lungs.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.

OBJECTIVE: To explore the expression level of PLK1 in mantle cell lymphoma(MCL), and the effect of silencing PLK1 gene by RNA interference on the cell proliferation, apoptosis, and cell cycle. METHODS: S-P immunohistochemistry technique was used to detect the expression of PLK1 in tissues of 42 patients with MCL and 30 patients with reactive proliferative lymphodenitis(RPL), their expression levels were compared and analyzed. The Jeko-1 cells were transfected with lentivirus contaiming PLK-1 shRNA, then the mRNA and protein expression of PLK-1 was detected by real-time guantitative PCR and Western blot nespectively, and the silencing efficacy of PLK-1 shRNA was identificd. The cell proliferation was detected by CCK method, the cell apoptosis was detected by Annexin V/PI double staining, the cell cycle was detected by PI single staining, the changes of apoptosis-related proteins BAX, BCL-2 and Caspase 3 were detected by Western blot. RESULTS: The positive expression rate of PLK-1 in tissue of MCL patients was 66.67%(28/42), which was significanfly higher than 20%(6/30) in tissue of RPL patients (P＜0.05). The PLK-1 positive expression correlated with B symptom, IPI score, Ann-Arbor stage(P＜0.05). After infection of Jeko-1 cells with lentivirus containing PLK-1 shRNA for 72 hours, the mRNA and protein expressions of PLK-1 were significantly down-regulated(P＜0.05), the proliferation rate of cells in group of PLK-1 shRNA was significanly lower than that in control and Neg shRNA groups(P＜0.05); the apoptosis rate of cells in PLK-1 shRNA group was (27.42±3.44)%, which was significantly higher than that in control group (1.23±0.42)% and Neg shRNA group (2.07±0.58) % (P＜0.05). The cell cycle analysis showed that the cell ratio in G/M phase of PLK-1 shRNA group was (27.21±3.59) %, which was higher than that in control group (13.28±2.63)% and Neg shRNA group (14.34±2.37) %. The detection of apoptosis-related proteins showed that the expression of BAX was up-regulated, the expression of BCL-2 was down-regnlated and the expression of caspase 3 was up-regulated. CONCLUSION The PLK-l overexpression appears in tissue of MCL patients. The silencing PLK-1 gene can inhibit the proliferation of Jeko-1 cells, induce the apopotosis of Jeko-1 cells and arrestes cell cycle in G/M phase.
Apoptosis ; Cell Cycle Proteins ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma, Mantle-Cell ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Proto-Oncogene Proteins ; genetics ; RNA, Small Interfering

Objective To investigate the changing curve of mean lung density (MLD)in normal preschool children based on CT quantitative measurement.Methods Chest CT data of 409 preschool children were reviewed retrospectively from the "digital lung"database.A computerized algorithm based on the "digital lung"was applied to all examinations in a batch manner.The MLD values of total lung,right lung,left lung and each lobe were obtained automatically.Results There was no correlation between the gender and MLD,however a moderately negative correlation was found between the age of month and MLD (P＜0.05).No significant difference of MLD was found between genders of the same age of month group,except in left lower lobe of 49-60 months of age (P=0.043). The MLD was decreased gradually with age (P＜0.05).Conclusion There is not a statistical difference in MLD between the preschool boys and preschool girls of the same age of month.With the growth of preschool children,the MLD is gradually decreased.

OBJECTIVETo establish a method to determine lead and Isotope Ratios in whole blood by inductively coupled plasma mass spectrometry (ICP-MS).

METHODSThe whole blood samples was removed protein by 5% nitric acid , Online join thallium (Tl) as internal standard substance, used lyophilized bovine blood lead and cadmium standard material (GBW09139h and GBW09140h) for quality control of blood lead concentrations. Lead isotope standard substances (GBW04426) is used to determine the correction factor, lead isotope ratios will lead isotope standard reference material NIST SRM981 by icp-ms with samples for testing.

RESULTSOptimize the detection method, detection of blood lead and lead isotope, and the method of linear range r >0.9999, GBW09139h and GBW09140h test results are within the scope of quality control. NIST SRM981 isotope determination precision RSD<1%, NIST SRM981 test results and the certificate of value close to.

CONCLUSIONThe method is simple and convenient data is reliable, can meet the total lead (pb) in blood and former isotope simultaneous determination.

Animals ; Cattle ; Lead ; analysis ; blood ; Lead Radioisotopes ; analysis ; blood ; Mass Spectrometry ; methods

This study was aimed to investigate the effects of sodium valproate (VPA) on the proliferation and regulation of histone acetylation of multiple myeloma cell line U266. U266 cells were treated with VPA. Cell proliferation was determined by CCK-8 assay, and cell cycle were analyzed by flow cytometry (FCM). The expression level of HDAC1 mRNA was detected by RT-PCR, and the protein levels of HDAC1 and histone H3, H4 acetylation was detected by Western blot. The results showed that the VPA inhibited the proliferation of U266 cells in concentration-and time-dependent manners.After exposure to different concentrations of VPA for 48 hours, the proportion of G(0)/G(1) cells increased, while the proportion of S phase cells decreased. The cell cycle was arrested obviously in G(0)/G(1) phase (p < 0.05). The expression of HDAC1 mRNA was inhibited, and the protein level of HDAC1 was down-regulated, while the histone H3/H4 acetylation was up-regulated in U266 cells. It is concluded that the VPA can inhibit cell proliferation of U266 and induce G(0)/G(1) phase arrest. The increase of histone H3/H4 acetylation resulting from inhibiting HDAC1 by VPA might be considered as a possible mechanism.
Acetylation ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histone Deacetylase 1 ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Histones ; metabolism ; Humans ; Multiple Myeloma ; metabolism ; Valproic Acid ; pharmacology