Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

Intervertebral disc degeneration(IDD)is a prevalent clinical degenerative disease that currently can only be treated through conservative and surgical treatments,which only alleviate symptoms and are not significantly effective.In recent years,nanoparticles have been widely studied in the biomedical field due to their biodegradability,biocompatibility,extended body circulation,sustained and controlled release,and precise drug targeting.Nanoparticle drug delivery systems have the potential to deliver a range of therapeutic agents including proteins,drugs,genes,and cells,thereby promoting tissue and cell repair and regeneration,which offers hope for IDD treatment.However,there are still challenges in translating experimental data into practical therapies applicable to humans.This review summarizes recent research progress on drug delivery systems for IDD treatment based on nanoparticles and provides insights and prospects for the challenges faced by nanoparticles,aiming to provide a reference for the clinical translation of nanoparticle-based treatment for IDD.

G-protein coupled receptors (GPCRs) are an essential family of proteins on the cell membrane, widely distributed in various types of tissues and cells. Typical GPCRs are composed of characteristic 7 transmembraneα-helix domains, extracellular domain and intracellular domain. They play a key role in transmitting information inside and outside cells. These receptors can sense and respond to a variety of external signals, including odor molecules, hormones, neurotransmitters, chemokines, and so on, thereby regulating the physiological functions and metabolic activities of cells. When external signal molecules bind, these receptors undergo conformational changes, thereby activating signal transduction pathways inside cells. The most common downstream signal pathway is the activation of G proteins, but it may also activate the β-arrestin signaling pathway. This series of signal transduction processes ultimately regulates physiological processes such as cell metabolism, proliferation, and differentiation, and also plays an important role in the occurrence and development of diseases. Due to its importance in regulating cell functions and participating in the development of diseases, GPCRs have become important targets in the field of drug research and development. The mechanism of action of many drugs is achieved by intervening in the GPCR signaling pathway. As important form of function regulating, dimerization has attracted widespread attention in the research of GPCR field. In the early days, the formation of GPCR dimerization and its effect on receptor function were mainly studied by immunoprecipitation, immunofluorescence and radioligand binding experiments in overexpression systems. Nowadays, with the continuous development of biochemical and biophysical methods, more and more GPCR dimers have been identified. GPCR dimer refers to the process in which two GPCR subunits bind to each other to form a complex. The same GPCR subunits form homodimers, and different GPCR subunits form heterodimers through direct interaction. Dimerization changes the activity, affinity, internalization, localization and transport, and signal transduction characteristics of GPCR, thereby producing more complex and delicate regulation of cellular physiological processes. In recent years, the research on GPCR dimers has been continuously deepened, revealing its important role in a variety of physiological and pathological processes. In general, the structure of GPCR dimers is complex and diverse, and its formation and stability are affected by many factors, including the specificity of receptor interaction interface, the conformational changes of receptor, and the regulation of intracellular and extracellular environment. By understanding the mechanism of GPCR dimerization, we can better understand the behavior of these receptors in signal transduction and provide new ideas and opportunities for the development of novel drug targets. More and more studies have reported the dimerization of GPCR and its structure and function regulation mechanism. This article reviews the research progress on the structure and function of GPCR dimers, and summarizes some research methods and technologies, which provide a basis for understanding the discovery of GPCR dimers, dimerization methods, structure and function regulation mechanisms, and further targeting GPCR dimers. It provides a research basis for the development of polymer drugs.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To investigate the independent risk factors of comprehensive complication index(CCI)≥26.2 after radical resection of colon cancer,and use these factors to establish and verify a dynamic web-based nomogram model.Methods The clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected,and divided into main cohort(November 2020 to October 2021,n=438)and validation cohort(November 2021 to April 2022,n=196).CCI scores of all patients were obtained based on CCI calculator(http://www.assessurgery.com).Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI≥26.2,and a nomogram model was constructed.Receiver operator characteristic curve(ROC),C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model,and the decision curve analysis was conducted to assess the clinical benefits of the model.Internal validation of the model is performed in the validation cohort.Results A total of 438 patients were identified in present study,of which 63 cases(14.4%)had CCI≥26.2.Multivariate logistic regression analysis revealed that age≥60 years(OR=2.662,95%CI 1.341-5.285,P=0.005),low third lumbar spine skeletal muscle mass index(L3MI;OR=4.572,95%CI 2.435-8.583,P<0.001),NRS2002≥3(OR=4.281,95%CI 2.304-7.952,P<0.001),and preoperative bowel obstruction(OR=3.785,95%CI 1.971-7.268,P<0.001)were significant independent risk factors for postoperative CCI≥26.2.Based on these results,a static and web-based dynamic nomogram was established(https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/).The C-index and area under the curve(AUC)of the nomogram were 0.742 and 0.787,respectively.The calibration curve indicated a good consistency between the predicted probability and the actual probability.In the validation cohort,the nomogram also presented good discrimination(C-index=0.722,AUC=0.795)and predictive consistency.The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model.Conclusion This easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI≥26.2 after radical resection of colon cancer,which helps optimize the preoperative evaluation system,formulate precise individualized treatment strategies,and enhance recovery after surgery.

The transmission cycle of echinococcosis was established in 1853.More than 160 years have elapsed since Iceland initiated control measures to break the transmission cycle of echinococcosis in 1863.Control plans have been implemented in more than a dozen countries/territories,and lessons have been learned from failures as well as successes.In this review,we fo-cus on the failure experiences,which have also promoted successes in the control of cystic echinococcosis(caused by the para-site Echinococcus granulosus)in regions including Iceland,New Zealand,Uruguay,Wales(England),Turkana(Kenya),and Sardinia(Italy).The causes of the failures were analyzed,and the effects of health education,dog deworming,and con-trol measures for infected animal slaughter on echinococcosis control are comprehensively summarized.However,no suc-cessful experience has been reported in the control of alveolar echinococcosis(caused by the parasite Echinococcus multilocu-laris).On the basis of the biological characteristics of E.mul-tilocularis parasitization in dogs for a duration of 30 days and larvae parasitization in rodents,the fundamental measure for controlling alveolar echinococcosis is administration of monthly deworming treatments to dogs in high prevalence areas.

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*

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.
Child ; Male ; Humans ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Neoplasm Proteins/genetics* ; Optic Atrophy/genetics* ; Pelger-Huet Anomaly/genetics* ; Liver Failure, Acute/complications*

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment