OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

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Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

  Objective  To evaluate the severity and features of pelvic coronal plane tilt in individuals with adolescent idiopathic scoliosis (AIS) who had lumbar curvature during the gait cycle.  Methods  AIS patients with lumbar curvature and patients with microcurvature (Cobb Angle less than 10 degrees) treated in Peking Union Medical College Hospital from September 2020 to February 2023 were retrospectively included. According to PUMC conservative classification system and Spinal Full-length Standing X-ray, AIS patients with lumbar curvature were enrolled. The bilateral iliac crest was used as the bony marker of the pelvic coronal surface, and the bilateral iliac crest height and its changes were measured during the standing position and walking cycle, so as to evaluate the degree of pelvic coronal tilt in AIS patients with lumbar curvature.  Results  A total of 209 AIS patients with lumbar curvature and 36 patients with microcurvature who met the inclusion and exclusion criteria were enrolled. The proportion of AIS patients with lumbar curvature who had a "congruent" relationship between the higher iliac crest and the convex side of the spine in standing position (iliac crest lower on the convex side than on the concave side) was significantly higher in AIS patients with lumbar curvature than patients with microcurvature(58.9% vs. 30.6%, P=0.002). AIS patients with lumbar curvature had statistically different bilateral iliac crest height change values throughout the gait cycle (including minimum, maximum, swing phase minimum, and swing phase maximum) (all P < 0.001), and the iliac crest height change values on the convex side were significantly higher than those on the concave side (all P < 0.05), whereas the patients with microcurvature did not have any statistically significant bilateral iliac crest height change values throughout the gait cycle (all P > 0.05).  Conclusion  The height of the iliac crest on the convex side of the lumbar spine is lower than that on the concave side in the standing position of AIS patients with lumbar curvature, and the value of the change of the iliac crest on the convex side of the pelvis is greater than that on the concave side in walking to maintain the balance of the body, which may provide a new direction for the intervention in the clinical rehabilitation treatment of AIS patients with lumbar curvature.

Objective To investigate the protective effects of melatonin(MT)on early embryo in vitro development of mice after exposure to benzophenone-3(BP-3).Methods Fertilized mouse oocytes at the synge-neic stage were cultured in KSOM culture medium,0.8 μmol/L BP-3 culture medium,and 1×10-7 mol/L MT + 0.8 μmol/L BP-3 mixed culture medium,respectively.The rescue effect of MT on the early embryos developmental potential of BP-3-exposed mice in vitro was explored by detecting the blastocyst rate,gene transcription level,protein expression level,and the degree of DNA damage in the three groups of embryos.Results MT improved the developmental potential of mouse embryos exposed to BP-3 in vitro.Compared with the control group,MT treatment significantly increased the protein expression of ATP5A and ATP5B and decreased the DNA damage(P<0.05).Furthermore,the transcription levels of antioxidant gene Gpx1 and pluripotency related genes Pou5f1 and Cdx2 were significantly up-regulated in MT-treated blastocysts,and the expression of pro-apoptotic gene Bax was decreased.Compared with the control group,BP-3 treatment enhanced the signal intensity of γ-H2AX in blastocysts(P<0.05),while adding MT could effectively alleviate DSBs(P<0.05).Conclusion The physiological concentration of BP-3 exposure has reproductive toxicity,but the addition of appropriate con-centration of MT could significantly improve the in vitro developmental potential and quality of BP-3-exposed early embryos.

Thoracic paravertebral nerve block(TPVB)is a regional anesthesia technique that pro-vides ipsilateral somatosensory,motor and sympathetic nerves block segmentally by injecting local anesthetics in the paravertebral space.In recent years,there has been an increasing number of studies on the use of TPVB technique for anesthesia and analgesia in pediatric thoracic and upper abdominal surgery,showing good perioperative analgesic efficacy.This article intends to provide a review of the current applica-tion and progress of TPVB technique for pediatric perioperative analgesia in terms of medication regimens,drug diffusion routes,block methods,clinical application,and complications.

OBJECTIVE:Clinically,chronic ankle instability has symptoms such as muscle weakness,loss of control and repeated sprains.These symptoms can be effectively improved by means of exercise intervention.Here,we conducted a comprehensive quantitative evaluation of the effects of exercise intervention on chronic ankle instability at home and abroad through Meta-analysis,and examined the moderating effects of different exercise interventions on chronic ankle instability in terms of effect size and exercise dose. METHODS:CNKI,WanFang,Web of Science,EBSCO-SPORTD and PubMed were searched and screened for relevant literature regarding randomized controlled trials of an exercise intervention program against chronic ankle instability.Included literature was analyzed by using Review Manager 5.3 and Stata-SE 15. RESULTS:A total of 52 documents were included with 1 880 patients with chronic ankle instability.Meta-analysis showed that exercise intervention could improve the functional score of patients with chronic ankle instability to a large amount.Neuromuscular control training,a 12-week intervention cycle,and two weekly interventions of>60 minutes are the best protocol for improving instability symptoms in patients with chronic ankle instability.Exercise intervention could improve the dynamic balance of patients with chronic ankle instability to reach the medium equivalent stress.The best exercise program to improve the dynamic balance ability is a combination of neuromuscular control training and hip strength training,with an exercise dose of 30-60 minutes,two or three times per week,for 8 weeks in total. CONCLUSION:Different exercise forms have a good effect on improving the unstable symptoms and dynamic balance ability of patients with chronic ankle instability,among which neuromuscular control training has a more comprehensive effect on improving chronic ankle instability.It is recommended that a multifunctional combination of training forms be used as a means of rehabilitation rather than a single form of exercise.

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 incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*