Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Myocardial ischemia-reperfusion injury （MIRI） is a common cardiac pathological process， resulting from the combined effects of multiple mechanisms involving metabolic changes and mitochondrial dysfunction. Mitochondrial quality control （MQC）， as a key regulatory mechanism， may serve as an important target for the prevention and treatment of MIRI. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the field of improving MIRI， with multiple targets， multiple pathways， and low toxic and side effects. It has gained widespread clinical recognition and application. Through systematically organizing and summarizing recent studies on the targeting of MQC by monomers， active fractions， herb pairs， compound formulas and related preparations of TCM to improve MIRI， this paper finds that monomers and active fractions of TCM （such as schisandrin B， isoliquiritigenin， calenduloside E， berberine， Lycium barbarum polysaccharides and so on） as well as TCM herb pairs， compound formulas， and related preparations （couplet medicinals of Fuzi-Ganjiang， Yixin formula， Shuangshen ningxin capsule， Baijin formula， Yiqi huoxue decoction and so on）， can alleviate MIRI by activating MQC to reduce oxidative stress-induced damage， promote mitochondrial biogenesis， maintain mitochondrial fission/fusion homeostasis， regulate mitochondrial autophagy， and restore mitochondrial calcium homeostasis.

A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT₄) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

Objective To observe whether the IL-23/Th17 inflammatory pathway is involved in the development of calcific aortic valve disease,and whether secukinumab can delay the progression of calcific aortic valve disease by inhibiting this pathway.Methods Forty-seven mice were divided into a blank control group,model group,and secukinumab group according to the random number table method.The blank control group was fed normal chow,while the model group and secukinumab group were fed pro-calcification chow for 16 weeks to establish a calcific aortic valve disease model.After intervention with secukinumab for 4 weeks,peak flow velocity changes in the aortic valves were detected under Doppler ultrasonography in all mice.Relevant indexes were determined by hematoxylin and eosin staining,Von Kossa staining,immunohistochemical staining,ELISA,and qPCR.Results Compared with the model group,the secukinumab group showed significantly reduced peak flow velocity(P＜0.05)and serum IL-6,IL-17,and IL-23 levels(P＜0.05)in the aortic valve.Compared with the secukinumab group,the model group's leaflet thickness was significantly increased,and there were more calcium deposits.Immunohistochemical result showed that macrophage infiltration(P＜0.05),IL-17A(P＜0.05)and IL-23(P＞0.05)levels in the valve leaflets were reduced in the secukinumab group compared with the model group.PCR result suggested that the expression of STAT3,BMP-2,and α-SMA mRNA was significantly lower in the secukinumab group than the model group(P＜0.05).Conclusions The IL-23/Th17 inflammatory pathway is involved in the pathogenesis of calcific aortic valve disease.The inflammation,fibrosis,osteogenic differentiation,and calcification of mouse valves were alleviated after intervention with secukinumab,which may delay disease progression by inhibiting the IL-23/Th17 inflammatory pathway.

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P＜0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P＜0.01,P＜0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P＜0.01,P＜0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P＜0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P＜0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P＜0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.

Objective:To improve the dosimetric accuracy of cell irradiation experiments by developing a method of accurately measuring the absorbed dose of ultra-thin solution in culture dishes under 200 kV medium-energy X-rays using EBT3 films.Methods:EBT3 film dose calibration was performed under Cyberknife 6 MV beam, and the beam quality (half-value layer) and effective energy of the 200 kV beam used in this study generated from Small Animal Radiation Research Platform through measurements and calculations were obtained to determine the EBT3 energy response correction factor. The 200 kV beam was utilized to irradiate three commonly used culture dishes filled with ultra-thin liquid placed on EBT3 films and the corrected EBT3 doses were taken as the liquid absorbed doses. The dose linearity of immersed films was also measured and analyzed. In addition, after modeling the irradiation environment, the independent Monte Carlo calculations of the liquid absorbed dose were performed by MCNP5 program. The calculation results were compared with the film measurement results to verify the accuracy of the measured doses.Results:The 200 kV beam had a half-value layer of 8.77 mm aluminum and effective energy of 57.4 keV, corresponding to an energy response correction factor of 0.889. The average liquid absorbed doses of large, medium and small culture dishes measured by EBT3 films under the specified parameters of 200 kV beam were (1.434±0.004) Gy, (1.467±0.011) Gy and (1.469±0.027) Gy after correction, respectively. The percentage errors from the corresponding Monte Carlo calculation doses were 0.07%, -0.70%, and 0.47%, respectively, where the relatively consistent results could be found. In addition, the dose linearity of immersed EBT3 films was also good, with coefficient of determination R2=0.9972. Conclusion:The method of measuring the dose of ultra-thin cell solution using EBT3 films proposed in this study is feasible, and the dose results obtained yield high accuracy under 200 kV beam.

OBJECTIVE: To explore the genetic basis for 4 patients with globozoospermia. METHODS: Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. RESULTS: All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region. CONCLUSION DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.
Male ; Humans ; Teratozoospermia/genetics* ; Homozygote ; Semen ; Sequence Deletion ; 3' Untranslated Regions ; Membrane Proteins

Marinesco-Sj?gren syndrome (MSS), also known as hereditary ataxia-dwarf-mental retardation syndrome, is a rare autosomal recessive ataxia syndrome. This article reviews the recent advance in clinic characteristics, pathogenic gene mutation sites, pathogenesis and clinic diagnosis and treatment of MSS, in order to improve clinicians' understanding of the disease and diagnosis and treatment level, and reduce the missed diagnosis and misdiagnosis of the disease.

Sialidosis is a rare lysosomal storage disease caused by NEU1 gene mutation at 6p21.33. It is characterized by myoclonic, ataxia, epilepsy, and decreased vision. A pair of twins with sialidosis type 1 are reported to enrich clinicians ′ understanding of the disease, so as to improve the diagnosis and treatment. The proband was a 16-year-old male. The main symptom was intermittent limb involuntary trembling for 2 years, with paroxysmal loss of consciousness. Fundus examination showed cherry-red spots. His twin brother had similar symptoms, but the overall performance was mild. Whole exome sequencing results showed that both patients carried compound heterozygous mutations of c.239C>T (p.P80L) and c.803A>G (p.Y268C) in NEU1 gene, which were from their normal phenotype mother and father.