The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

Objective: To establish a machine learning-based precision blood donor recruitment model at the county level and assess its generalizability and applicability. Methods: A retrospective study was conducted using blood donation and SMS recruitment data from the Taicang Branch of the Suzhou Blood Center between 2019 and 2024. Multiple machine learning algorithms were employed, including extreme gradient boosting, support vector machine, k-nearest neighbor, logistic regression, decision tree, random forest, and multilayer perceptron. These were combined with techniques such as synthetic minority oversampling, undersampling, and cost-sensitive learning (using MFE and MSFE loss functions). Model parameters were optimized through grid search to identify the best-performing model. Results: In a prospective comparative study against conventional methods, the machine learning models increased the recruitment success rate among high-willingness donors by an average of 129.15%, and the recruitment efficiency per SMS improved by 125.02% compared with the traditional method. Under full-scale SMS sending, the recruitment rate per SMS increased by 42.61%, and SMS sending efficiency improved by 31.77%, significantly enhancing recruitment performance. Conclusion: This study represents the first application of a machine learning-based precision donor recruitment model at the county-level in China. The precise recruitment framework not only improves recruitment efficiency and reduces recruitment costs but also demonstrates strong scalability and generalizability. It provides a scientific and feasible intelligent pathway to ensure the safety and sustainability of the blood supply.

Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Female ; Humans ; Anti-Mullerian Hormone ; Sexual Development ; Peptide Hormones

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation.Methods A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024.Additionally,a literature review was conducted.Results All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels,and one child was initially identified through neonatal genetic metabolic disease screening.According to the literature review,there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation(including the four children in this study).Among these,12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome,while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine(C5-OH)during neonatal genetic metabolic disease screening.Conclusions Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome,detectable as early as during neonatal genetic metabolic disease screening.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of coronary heart disease patients with angina pectoris after percutaneous coronary intervention(PCI). The basic elements of these RCTs, including sample size and estimation method, randomizing scheme, allocation concealment, blind method implementation, data integrity, statistical method, TCM syndrome, intervention measures, treatment course, follow-up time, and outcome indicators, were analyzed to provide reference for the design of future RCT and the clinical application of TCM in treating angina pectoris after PCI. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese Clinical Trial Registry were searched for the RCT about TCM treatment of coronary heart disease patients with angina pectoris after PCI according to pre-defined criteria, with the time interval from inception to January 31, 2024. A total of 188 RCTs were included, of which 184 were clinical research articles and 4 were clinical trial registration schemes. These RCTs involved a total of 15 521 patients, with an average sample size of 83 patients and a maximum sample size of 248 patients. Among them, 126 RCTs reported TCM syndromes, the top three of which were Qi deficiency and blood stasis(38.89%), phlegm combined with stasis(17.46%), and Qi stagnation and blood stasis(9.52%). The control group received guideline-directed medical therapy(GDMT) or GDMT combined with placebo, and the treatment group received GDMT combined with TCM. The treatment mainly lasted for 4-8 weeks, most of the RCTs did not set the follow-up period or the follow-up period was unknown. A total of 160 outcome indicators were used, with the total frequency of 1 348. According to functional attributes, the outcome indicators can be categorized into 6 groups: symptoms/signs(403, 29.90%), TCM syndromes/symptoms(182, 13.50%), physical and chemical examination(468, 34.72%), quality of life(89, 6.60%), long-term prognosis(5, 0.37%), and safety evaluation(201, 14.91%). The clinical trial design of TCM intervention in angina pectoris after PCI of coronary heart disease is becoming more and more rigorous, while it remains to be improved. It is expected that more clinical trial schemes with rigorous design and taking into account the TCM advantages can be adopted in the future to provide a basis for the TCM treatment of angina pectoris after PCI of coronary heart disease.
Humans ; Randomized Controlled Trials as Topic ; Angina Pectoris/drug therapy* ; Coronary Disease/drug therapy* ; Percutaneous Coronary Intervention ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Treatment Outcome ; Female

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*