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

Objective To analyze the high risk factors of obstetric brachial plexus palsy(OBPP),and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification.Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center.The shortcomings of hospitals in birth weight assessment,delivery mode selection,labor process observation and shoulder dystocia management,and the causal relation-ship between them and the damage consequences of the children were summarized.Results Fault medi-cal behavior was assessed as the primary cause in 2 cases,equal cause in 10 cases,secondary cause in 8 cases,minor cause in 1 case,no causal relationship in 1 case,and unclear causal force in 3 cases.Conclusion In the process of forensic identification of OBPP,whether medical behaviors fulfill diagno-sis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation,de-livery mode notification,standardized use of oxytocin,standard operation of shoulder dystocia,etc.Meanwhile,it is necessary to fully consider the objective risk of different risk factors and the diffi-culty of injury prevention,and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

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.

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

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*

BACKGROUND: The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9. METHODS: H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models. RESULTS: The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically. CONCLUSION The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Animals ; Antibodies, Monoclonal/therapeutic use* ; Antibodies, Neutralizing/therapeutic use* ; Antibodies, Viral ; Hemagglutinins ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; Influenza in Birds ; Influenza, Human/prevention & control* ; Mice

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid （AA）， ponatinib， and isoprenaline （ISO） were used to induce blood stasis models in zebrafish. A normal group， a model group， a positive drug group， and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated， the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib， the staining intensity of cardiac erythrocytes was reduced （P<0.01）， and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO （P<0.01）. The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model （P<0.01） and the myocardial apoptosis in the ISO-induced model （P<0.05）， while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model （P<0.01）， and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins （such as ginsenoside Re）， amino acids， and acetylenic alcohols. ConclusionAA， ponatinib， and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model， the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.