OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

The analysis of nano-micro nuclear particles has attracted significant attention due to the crucial role of their elemental and isotopic characteristics in tracing the origins of particulate matter and assessing its potential risks to human health and the environment.However,challenges persist in obtaining accurate and consistent element profiles and ratios for small-sized nanoparticles due to their low level and the transient nature.In this study,a high-speed digital oscilloscope was integrated with multiple collector inductively coupled plasma mass spectrometry(MC-ICP-MS)to develop a high time-resolution"Event-triggered signal capture"(ETSC)system for single particle analysis.This innovative approach enabled the analysis of element/isotope within rare earth nanoparticles at ag-fg level.The ETSC accurately recorded the complete profile of single particle,event captured by the electron multiplier with nanosecond time resolution,allowing for high-sensitivity element analysis and high-precision isotope analysis of single particles.The results demonstrated that the ETSC system could achieve quantitative analysis of ag levels of ytterbium(Yb)in 50-nm rare earth-doped particles,with a detection limit as low as 38 ag for Yb.Moreover,the isotopic precision of single particle analysis for 173/171Yb could reach 0.047(standard deviation),and the standard error for isotopic analysis of multiple particles could achieve a level of 2‰-3‰(permil)for 173/171Yb.Finally,the capability of ETSC system to analyze environmental samples was demonstrated through the analysis of doped ytterbium oxide nanoparticles.All these findings demonstrated that the ETSC provided a unique method for elemental and isotopic analysis of single nuclear particles.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.
Humans ; Siblings ; Genetic Markers ; Computer Simulation ; Irritable Bowel Syndrome/genetics* ; Reproducibility of Results ; Genotype

To simultaneously determine the contents of p-coumaric acid, chlorogenic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid and ferulic acid in Imperatae Rhizoma concentrated granules, an ultra-high performance liquid chromatography (UPLC) with two internal references method (TIRM) was established and validated. Chromatographic separation was achieved on a ZORBAX RRHD Eclipse Plus C18 column (2.1 mm × 100 mm, 1.8 µm) using 1.7 mmol·L^-1 oxalic acid in water and methanol as mobile phase. The flow rate was 0.4 mL·min^-1 and the column temperature was set as 35 ℃. The relative correction factors (RCFs) of caffeic acid and ferulic acid using p-coumaric acid as internal reference were calculated and the RCFs of 4-caffeoylquinic acid and 5-caffeoylquinic acid were calculated using chlorogenic acid as the internal reference. The TIRM was fully validated for linearity, accuracy, repeatability, stability and recovery so that it could be compared with the external standard method (ESM). The RCFs of 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid, and ferulic acid were 1.069, 1.022, 1.368, and 1.493, respectively. The TIRM and ESM were used to determine the contents of six ingredients in Imperatae Rhizoma concentrated granules from different manufacturers and the variation between results was within acceptable limits. In conclusion, the newly established TIRM allowed simultaneous determination of six ingredients (p-coumaric acid, chlorogenic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid, ferulic acid) in Imperatae Rhizoma concentrated granules, providing support for the quality control of this traditional Chinese medicine.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

In this study, high-throughput sequencing technology was used to analyze the differentiallyexpressed microRNA (miRNA) of astrocyte-derived exosomes in control group and oxygen and glucosedeprivation/ reoxygenation (OGD/ R) group. Ultracentrifugation was used to extract exosomes from thesupernatant of astrocyte medium in the control group and OGD/ R group. Transmission electron microscopyshowed that exosomes had a typical vesicle shape with intact membrane and low electron content density. Nanoparticle tracking technology (NTA) detected astrocyte exosomes with a size of 100. 5 ± 31. 1 nm, accounting for 96. 8%. Western blot detection showed that the exosome contained exosome-specificproteins tumor-susceptibility protein (TSG101), heat shock protein 60 (Hsp60), ALG-2-interactingprotein X (ALIX). Compared with the control group, 41 miRNAs in the exosomes of the OGD / R groupwere significantly changed, of which 20 miRNAs were increased and 21 miRNAs were decreasedsignificantly (P < 0. 05). Gene ontology function (GO) analysis showed that significantly differentiallytarget genes were mainly involved in protein glycosylation, lipid metabolism, phosphorylation, Golgiapparatus, endoplasmic reticulum, endosome, cytoplasmic vesicles and cell protrusions, etc. KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential miRNAs weremainly related to metabolic pathways and signaling pathways such as butyrate metabolism, ß-alaninemetabolism, fatty acid degradation, mitophagy and P53 signaling pathway. Sequencing analysis of theexosomal miRNAs derived from control and OGD / R astrocytes and target gene function enrichmentanalysis can be useful for the mechanism study of astrocyte exosomes in response to oxygen and glucosedeprivation reperfusion.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy

Objective: To discuss the application principle in tuina manipulation for lumbar intervertebral disc herniation (LIDH) in Chinese literatures published in recent 30 years. Methods: The three major Chinese databases, Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP) and China National Knowledge Infrastructure (CNKI), were searched to collect the studies of tuina manipulations in treatment of LIDH published in recent 30 years. Clustering analysis was applied to analyze the top 20 tuina manipulations for LIDH. Results: The top 20 most frequently used manipulations for LIDH were Gun-rolling, Rou-kneading, Dian-digital pressing, oblique Ban-pulling, An-pressing, Tanbo-plucking, Bashen-pulling and extending, horizontal Tui-pushing, Na-grasping, Anrou-pressing and kneading, Dou-shaking, Yao-rocking, Ca-scrubbing, Pai-patting, post-extension Ban-pulling, Mo-rubbing, Zhen-vibrating, Nie-pinching, fist-back Ji-tapping, and dorsal Shen-extending methods. The involved manipulations can be divided into two categories by the treated body areas. One category is applied to the soft tissues, including Gun-rolling, Rou-kneading, Dian-digital pressing, An-pressing, Tanbo-plucking, horizontal Tui-pushing, Na-grasping, Anrou-pressing and kneading, Ca-scrubbing, Pai-patting, Mo-rubbing, Zhen-vibrating, Nie-pinching, and fist-back Ji-tapping methods. The other category is applied to bones and joints, including oblique Ban-pulling, Bashen-pulling and extending, Dou-shaking, Yao-rocking, post-extension Ban-pulling, and dorsal Shen-extending methods. Conclusion: Based on the treated body area, the tuina manipulations applied to treat LIDH are predominated by the ones performed on soft tissues, assisted by those on bones and joints. From the way of force exertion, the involved manipulations are majorly the swinging methods, followed by squeezing and pressing ones. The manipulations applied to bones and joints are predominated by the Ban-pulling ones, followed by the Bashen-pulling and extending ones.

Objective To establish the medical reference range of amino acid and acyl car-nitine tandem mass spectrometry in normal neonates in Gansu province,and provide the basis for the determination of amino acid and acyl carnitine test results in the screening of neonatal genetic metabolic diseases.Methods A non derivatization tandem mass spectro-metry kit was used to screen 77 957 samples of neonates in Gansu province.Statistical soft ware SPSS19.0 was used to analyze the 95％ reference range of 11 amino acids and 31 kinds of acylcarnitine indexes.Results The medical reference value(μmol/L) of the series mass spectra of newborn genetic metabolic diseases in Gansu province was established:ALA (216.17 ～ 727.58),ARG (1.80～33.03),CIT (4.87～30.67),GLY (183.43～841.46),LEU (79.85～289.45),MET (3.32～25.86),ORN (34.09～225.15),PHE (27.04～83.37),PRO (79.44～337.59),TYR (37.61～177.79),VAL (59.31～250.95),C0 (9.35～45.35),C2 (2.62～25.40),C3 (0.46～3.3),C3DC_C4OH (0.02～0.20),C4 (0.08～0.31),C4DC_C5OH (0.10～0.32),C5 (0.05～0.30),C5:1 (0.00～0.01),C5DC_C6OH (0.04～0.22),C6 (0.01～0.06),C6DC (0.03～0.13),C8 (0.02～0.08),C8:1 (0.05～0.31),C10 (0.02～0.12),C10:1 (0.03～0.10),C10:2 (0.01～0.10),C12 (0.02～0.13),C12:1 (0.02～0.10),C14 (0.07～0.30),C14:1 (0.03～0.13),C14:2 (0.01～0.03),C14OH (0.00～0.02),C16 (0.59～4.91),C16:1 (0.03～0.30),C16:1-OH (0.01～0.08),C16OH (0.01～0.03),C18 (0.29～1.30),C18:1 (0.57～2.32),C18:1-OH (0.01～0.05),C18:2 (0.08～0.51) and C18OH (0.00～0.02).Conclusion The establishment of the medical reference range of the normal neonatal dryblood spot amino acid and acyl carnitine tandem mass spectrometry in Gansu province can provide reference for the determination of the results of the cluster mass spectrometry in this region.