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.

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: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.

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 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.

  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 effects and mechanisms of melatonin(MT)on improving oocyte quality in mice exposed to benzophenone-3(BP-3).Methods In this study,6～12-week-old female ICR mice were cultured in vitro in M16 culture,0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT+0.8 μmol/L BP-3 mixed culture.Female ICR mice were randomly segregated into three groups:control,BP-3,and BMT.The control group received 0.5 mL of purified water,the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution,and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks,to facilitate in vivo experimentation.Subsequently,the oocyte maturity rate,transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1,Opa1,Fis1 and Drp1,mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice.Results Compared to the control group,MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes,while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1.Additionally,the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group,yet their mitochondrial membrane potential was notably elevated.Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction,but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.

Objective To investigate the effects and mechanisms of melatonin(MT)on improving oocyte quality in mice exposed to benzophenone-3(BP-3).Methods In this study,6～12-week-old female ICR mice were cultured in vitro in M16 culture,0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT+0.8 μmol/L BP-3 mixed culture.Female ICR mice were randomly segregated into three groups:control,BP-3,and BMT.The control group received 0.5 mL of purified water,the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution,and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks,to facilitate in vivo experimentation.Subsequently,the oocyte maturity rate,transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1,Opa1,Fis1 and Drp1,mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice.Results Compared to the control group,MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes,while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1.Additionally,the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group,yet their mitochondrial membrane potential was notably elevated.Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction,but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.