Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg-1)at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9％NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL-1;the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL-1;the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL-1;cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL-1;TXA2 content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL-1;PGI2 content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL-1;the relative expression levels of Notch1 protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1 protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P＜0.01,P＜0.001).Conclusion Lepirudine can inhibit thrombin activation in the treatment of acute pulmonary embolism by activating the Notch signaling pathway.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Traumatic spinal cord injury (SCI) refers to damage to the structure and function of spinal cord caused by external trauma. This damage results in the loss of sensation, movement, or autonomous functions, which can lead to partial or complete paralysis and impact the patients’ independence and quality of life. Studying drugs related to spinal cord injuries and their mechanisms of action will help enhance patients’ quality of life and alleviate social and economic burdens. Traumatic spinal cord injury can be categorized into primary and secondary injuries. It leads to ongoing neurodegeneration, inflammation, and scarring, necessitating continuous intervention to reduce the cascading effects of secondary injuries. Regenerative repair of SCI has been one of the most challenging problems in medicine. It is characterized by the involvement of microglia, phagocytes (including neutrophils and monocytes), and antigen-presenting cells of the central nervous system, such as dendritic cells. These inflammatory mediators contribute to axonal demyelination and degeneration, leading to severe nerve damage. Currently, there has been little progress in the clinical treatment of SCI. Current clinical modalities, such as surgical interventions and hormone shock therapies, have not yielded specific pharmacotherapeutic options, hindering significant functional recovery. The current treatment methods are ineffective in alleviating oxidative stress and neuroinflammatory responses caused by spinal cord injury. They also do not offer neural protection, resulting in ongoing neurofunctional degradation. Intravenous injection of methylprednisolone through the arm has been used as a treatment option for spinal cord injury. Recent studies have shown that the potential side effects of the drug, such as blood clots and pneumonia, outweigh its benefits. Methylprednisolone is no longer recommended for the routine treatment of spinal cord injury. In recent years, significant progress has been made in spinal cord injury intervention through the use of nanotechnology and biomaterials. Nanozymes can enhance the therapeutic efficacy of spinal cord injury by catalyzing the clearance of free radicals similar to enzymes and suppressing inflammatory responses. Nanozymes can reduce the degree of fibrosis, promote neuron survival and angiogenesis, and provide favorable conditions for tissue regeneration. Through in vitro and in vivo toxicology experiments, it was found that the nanozyme demonstrates good biocompatibility and safety. It did not cause any significant changes in body weight, hematological indicators, or histopathology. These findings indicate the potential for its clinical applications. Based on current research results and discoveries, nanozymes have broad application prospects in the biomedical field. There are numerous potential research directions and application areas that are worthy of further exploration and development. Although there have been preliminary studies on the catalytic performance of nanozymes, further research is needed to thoroughly investigate their catalytic mechanisms. Further exploration of the interaction between nanozymes and substrates, reaction kinetics, and factors affecting catalytic activity will help to better understand their mechanism of action in the field of biocatalysis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To analyze the diagnostic value of IgG anti-A/anti-B antibody titer in the serum of type O pregnant women after absorption of IgG anti-AB antibody for ABO hemolytic disease of fetus and newborn (ABO-HDFN).Methods:From February 2020 to September 2020,235 samples of neonatal hemolytic disease whose mother's blood type O from Beijing Blood Center were selected.The titer of IgG anti-A/anti-B antibody in mother's serum before and after absorption of IgG anti-AB antibody was detected by microcolumn gel card,and the incidence of ABO-HDFN was statistically analyzed.The titer level of IgG anti-A/anti-B antibody and the incidence of ABO-HDFN were compared before and after the absorption of IgG anti-AB antibody,and the diagnostic efficacy of the titer level of IgG anti-A/anti-B antibody in the serum of type O pregnant women after the absorption of IgG anti-A and B antibodies on the incidence of ABO-HDFN was analyzed using the receiver's work characteristic (ROC)curve.Results:Of the 235 neonatal hyperbilirubinemia samples with maternal blood type O,127 were blood type A,38 of which were diagnosed as ABO-HDFN;108 were blood type B,of which 31 were diagnosed as ABO-HDFN.Before and after absorption of IgG anti-AB antibody,there was a significant difference in the titer of IgG anti-A/anti-B antibody (P<0.05).Among the 69 confirmed cases,the incidence of ABO-HDFN increased with the increase of IgG anti-A/anti-B antibody with or without the IgG anti-AB antibody,but the anti-A/anti-B antibody titer≥1:512 before the absorption of IgG anti-AB antibody,while the anti-A/anti-B antibody titer decreased significantly,decreasing by three titers,all≤1∶512.The ROC curve shows that the titers of IgG anti-A/anti-B antibodies before and after absorption of IgG anti-AB antibodies can be used as the efficacy indicators for the diagnosis of ABO-HDFN.However,there was a significant difference in the potency of IgG anti-A/anti-B antibody titer for the diagnosis of ABO-HDFN before and after the absorption of IgG anti-AB antibody (P<0.05).The AUC values were greater than before absorption,indicating that the IgG anti-A/anti-B antibody after the absorption of IgG anti-AB antibody was better than before absorption (P<0.05).Conclusion:The higher the titer of IgG anti-A/anti-B antibody measured after absorbing IgG anti-AB antibody,the higher the incidence of ABO-HDFN. In addition,the efficacy of IgG anti-A/anti-B antibody titer to diagnose ABO-HDFN after absorption of IgG anti-AB antibody is higher than that before absorption.

OBJECTIVE: This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 μg/L maintained through sustainable universal salt iodization. METHODS: This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. RESULTS: The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5-198.1 μg/L) in the counties with an mUIC of 100-149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5-244.4 μg/L) in the counties with an mUIC of 150-249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken. CONCLUSION Compared with an mUIC of 150-249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China.
Female ; Humans ; Pregnancy ; Cross-Sectional Studies ; Iodine/urine* ; Pregnant Women ; Sodium Chloride, Dietary ; Thyroglobulin ; Thyroid Gland ; Thyrotropin ; East Asian People

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

Objective:To investigate the effect of early postoperative enteral nutrition(EN)on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer,in order to provide reference for postoperative rehabilitation of such patients.Methods:Patients who received laparoscopic assisted radical gastrectomy in Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2022 were included in the analysis.According to the different ways of postoperative nutritional treatment,patients were divided into the observation group(early postoperative EN group)and the control group(parenteral nutrition group),and indexes such as postoperative rehabilitation,abdominal drainage flow and the level of inflammatory mediators in drainage fluid were compared between the two groups.Results:A total of 81 patients were included,including 41 in the observation group and 40 in the control group.Interval of the first postoperative exhaust(t=3.806;P＜0.001)and resuming diet day(t=5.510;P＜0.001),and length of postoperative hospital stay(t=2.401;P=0.019)in the observation group were shorter than those in the control group.Levels of peripheral blood albumin(t=14.040;P＜0.001)and prealbumin(t=9.832;P＜0.001)of the observation group at postoperative day(POD)5 were significantly higher than those of the control group,but there was no significant difference in hemoglobin level(t=1.477;P=0.144).The level of CRP in peripheral blood of the observation group at POD 5(t=7.758;P＜0.001)and the incidence of postoperative SIRS[(12.2％,5/41)vs(32.5％,13/40),x2=4.830;P=0.028)]were significantly lower than those in the control group.The average drainage volume(t=6.858;P＜0.001),drainage removal time(t=5.016;P＜0.001),and TNF-α level(t=4.993;P＜0.001)and IL-6 level(t=20.640;P＜0.001)in postoperative drainage at POD 5 were significantly lower in the observation group than those in the control group.Conclusion:Early postoperative EN could accelerate the rehabilitation process after laparoscopic radical gastrectomy,improve postoperative nutritional status,and reduce abdominal inflammation.