Implant surface culture may be a useful adjunct to standard tissue sampling culture for identification of pathogens accounting for fracture-device-related infection: a within-person randomized agreement study of 42 patients.

BACKGROUND AND PURPOSE: Identification of pathogens causing fracture-device-related infection (FDRI) is always a challenge as the positive rate of standard tissue sampling culture (TSC) remains unsatisfactory. This study evaluates the efficiency of implant surface culture (ISC) as an adjunct to standard TSC for identification of FDRI-associated microorganisms. PATIENTS AND METHODS: Between November 2020 and March 2022, patients diagnosed with FDRI defined by the International Fracture-Related Infection (FRI) Consensus Group, and indicated for implant removal, underwent both methods for bacteria detection. The test order of ISC and TSC was randomly selected for each patient included, as a within-person randomized design. For ISC, the recovered implants were gently covered with tryptic soy agar after rinsing with normal saline twice, and then incubated at 37℃ 5% CO2 for up to 14 days. For TSC, 5 specimens were sampled and sent to the Clinical Laboratory of Southern Medical University Nanfang Hospital, Guangzhou, for culture and identification. RESULTS: 42 consecutive patients were included, with a mean age of 46 years. The most frequent infection site and implant type were the tibia (21 cases) and plates with screws (30 cases), respectively. Altogether 21 patients were found with positive outcomes by both methods, and the identified pathogens were consistent. ISC found an additional 15 patients showing positive results, which were negative by TSC. Furthermore, the mean culture time of ISC was shorter than that of TSC (1.5 days vs. 3.2 days). INTERPRETATION: ISC may be a useful adjunct to TSC for detection of bacteria causing FDRI, with a relatively higher positive rate and a shorter culture time.

Asprin-loaded strontium-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite promotes regeneration of critical bone defects.

Our laboratory originally synthesized strontium(Sr)-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite (Sr-α-CSH/n-HA) and demonstrated its ability to repair critical bone defects. This study attempted to incorporate aspirin into it to produce a better bone graft material for critical bone defects. After 5% Sr-α-CSH was prepared by coprecipitation and hydrothermal methods, it was mixed with aspirin solution of different concentrations (50 µg/ml, 200 µg/ml, 800 µg/ml and 3200 µg/ml) at a fixed liquid-solid ratio (0.54 v/w) to obtain aspirin-loaded Sr-α-CSH/n-HA composite. In vitro experiments were performed on the composite extracts. The tibial defects (3 mm*5 mm) in SD rat model were filled with the composite for 4 weeks and 12 weeks to evaluate its osteogenic capacity in vivo. Our results showed its capability of proliferation, migration and osteogenesis of BMSCs in vitro got improved. In vivo treatment with 800 µg/ml aspirin-loaded Sr-α-CSH/n-HA composite led to significantly more new bone formation in the defects compared with Sr-α-CSH/n-HA composite and significantly promoted the expression of osteogenic-related genes and inhibited osteoclast activity. In general, our research suggests that aspirin-loaded Sr-α-CSH/n-HA composite may have a greater capacity of repairing tibial defects in SD rats than simple Sr-α-CSH/n-HA composite.

Stimulating factors for regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs), distributed in many tissues in the human body, are multipotent cells capable of differentiating in specific directions. It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors, including cell signaling pathways, cytokines, and other physical stimuli. Recent findings have revealed other underrated roles in the differentiation process of MSCs, such as material morphology and exosomes. Although relevant achievements have substantially advanced the applicability of MSCs, some of these regulatory mechanisms still need to be better understood. Moreover, limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy. This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.

The Role of Senescence-Associated Secretory Phenotype in Bone Loss.

As the population of most nations have a large proportion of older individuals, there is an increase in the prevalence of osteoporosis. Consequently, scientists have focused their attention on the pathogenic mechanisms of osteoporosis. Owing to an increase in studies on cellular senescence in recent years, research has begun to focus on the function of the senescent microenvironment in osteoporosis. With chronic inflammation, senescent cells in the bone marrow secrete a series of factors known as senescence-associated secretory phenotype (SASP) factors, acting on their own or surrounding healthy cells and consequently exacerbating ageing.The components of the SASP may differ depending on the cause of osteoporosis. This review aimed to summarize the relationship between SASP factors and osteoporosis and suggest new insights into the mechanistic investigation of osteoporosis.

Mechanisms of magnoliae cortex on treating sarcopenia explored by GEO gene sequencing data combined with network pharmacology and molecular docking.

BACKGROUND: Administration of Magnoliae Cortex (MC) could induce remission of cisplatin-induced sarcopenia in mice, however, whether it is effective on sarcopenia patients and the underlying mechanisms remain unclear. METHODS: Sarcopenia related differentially expressed genes were analysed based on three Gene Expression Omnibus (GEO) transcriptome profiling datasets, which was merged and de duplicated with disease databases to obtain sarcopenia related pathogenic genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were than performed to analyse the role of proteins encoded by sarcopenia related pathogenic genes and the signal regulatory pathways involved in. The main active components and target proteins of MC were obtained by searching traditional Chinese medicine network databases (TCMSP and BATMAN-TCM). MC and sarcopenia related pathogenic genes shared target proteins were identified by matching the two. A protein-protein interaction network was constructed subsequently, and the core proteins were filtered according to the topological structure. GO and KEGG analysis were performed again to analyse the key target proteins and pathways of MC in the treatment of sarcopenia, and build the herbs-components-targets network, as well as core targets-signal pathways network. Molecular docking technology was used to verify the main compounds-targets. RESULTS: Sarcopenia related gene products primarily involve in aging and inflammation related signal pathways. Seven main active components (Anonaine, Eucalyptol, Neohesperidin, Obovatol, Honokiol, Magnolol, and beta-Eudesmol) and 26 target proteins of MC-sarcopenia, of which 4 were core proteins (AKT1, EGFR, INS, and PIK3CA), were identified. The therapeutic effect of MC on sarcopenia may associate with PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, longevity regulating pathway, and other cellular and innate immune signaling pathways. CONCLUSION: MC contains potential anti-sarcopenia active compounds. These compounds play a role by regulating the proteins implicated in regulating aging and inflammation related signaling pathways, which are crucial in pathogenesis of sarcopenia. Our study provides new insights into the development of a natural therapy for the prevention and treatment of sarcopenia.

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling.

Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms. Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D-standard, -excess, -deficient, and -rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein. Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D-deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway. Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

Altered Gut Microbiota as an Auxiliary Diagnostic Indicator for Patients With Fracture-Related Infection.

Preoperative diagnosis of fracture-related infection (FRI) is difficult for patients without obvious signs of infection. However, specific profiles of gut microbiota may be used as a potential diagnostic tool for FRI as suggested by a previous study. The fecal microbiome was compared between 20 FRI patients (FRI group), 18 fracture healed patients (FH group), and 12 healthy controls (HC group) included after collection of fecal samples and evaluation. The α and ß diversity indices were used to characterize the fecal microbiome. Dysbiosis indexes were constructed based on the characteristic high-dimensional biomarkers identified in the fecal microbiota from the three groups by linear discriminant analysis and generalized linear model analysis to quantify the dysbiosis of fecal microbiota. The effectiveness of α and ß diversity indices and dysbiosis indexes was assessed in distinguishing the fecal microbiome among the three groups. The influences of serum inflammatory factors on gut microbiota were also addressed. The α diversity indices were significantly different between the three groups, the highest in HC group and the lowest in FRI group (P < 0.05). The ß diversity indices showed significant phylogenetic dissimilarity of gut microbiome composition among the three groups (P < 0.001). The dysbiosis indexes were significantly higher in FRI group than in FH and HC groups (P < 0.001). The area under Receiver operating characteristic curve showed the characteristics of gut microbiota and the gut microbiota was found as effective in distinguishing the three groups. The dysbiosis in the FRI patients was associated with systemic inflammatory factors. In addition, significant differences in the gut microbiota were not observed between the FRI patients versus without sinus tract or pus before operation. Since FRI patients, with or without sinus tract or pus, have a characteristic profile of gut microbiota, their gut microbiota may be used as an auxiliary diagnostic tool for suspected FRI.

Vitamin D Receptor Genetic Variations May Associate with the Risk of Developing Late Fracture-Related Infection in the Chinese Han Population.

Variations in the vitamin D receptor (VDR) gene are related to several inflammatory disorders. However, the potential links between such alternations and the risk of developing late fracture-related infection (FRI) remain unclear. This study investigated associations between genetic variations in the VDR and susceptibility to late FRI in the Chinese Han population. Between January 2016 and December 2019, 336 patients with late FRI and 368 healthy controls were genotyped six VDR genetic variations, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820). Significant associations were observed between rs7975232 and FRI susceptibility in the recessive (P = 0.019, OR = 0.530, 95% CI 0.310-0.906) model. Patients with AA genotype had a relatively higher level of serological vitamin D (20.6 vs. 20.3 vs. 17.9 ng/ml) (P = 0.021) than those of AC and CC genotypes. Although no statistical differences were observed, potential correlations may exist between rs1544410 (dominant model: P = 0.079, OR = 0.634), rs2228570 (dominant model: P = 0.055, OR = 0.699), and rs4516035 (dominant model: P = 0.065, OR = 1.768) and the risk of FRI development. In the Chinese cohort, ApaI was associated with a decreased risk of developing FRI, and patients with the AA genotype had a higher vitamin D level. Further studies are required to assess the role of genetic variations in BsmI, FokI, and GATA in the pathogenesis of late FRI.

High-Fat Diet Increases Bone Loss by Inducing Ferroptosis in Osteoblasts.

Current research suggests that chronic high-fat dietary intake can lead to bone loss in adults; however, the mechanism by which high-fat diets affect the development of osteoporosis in individuals is unclear. As high-fat diets are strongly associated with ferroptosis, whether ferroptosis mediates high-fat diet-induced bone loss was the focus of our current study. By dividing the mice into a high-fat diet group, a high-fat diet + ferroptosis inhibitor group and a normal chow group, mice in the high-fat group were given a high-fat diet for 12 weeks. The mice in the high-fat diet + ferroptosis inhibitor group were given 1 mg/kg Fer-1 per day intraperitoneally at the start of the high-fat diet. Microscopic CT scans, histological tests, and biochemical indicators of ferroptosis were performed on bone tissue from all three groups at the end of the modelling period. Mc3t3-E1 cells were also used in vitro and divided into three groups: high-fat medium group, high-fat medium+ferroptosis inhibitor group, and control group. After 24 hours of incubation in high-fat medium, Mc3t3-E1 cells were assayed for ferroptosis marker proteins and biochemical parameters, and osteogenesis induction was performed simultaneously. Cellular alkaline phosphatase content and expression of osteogenesis-related proteins were measured at day 7 of osteogenesis induction. The results showed that a high-fat diet led to the development of femoral bone loss in mice and that this process could be inhibited by ferroptosis inhibitors. The high-fat diet mainly affected the number of osteoblasts produced in the bone marrow cavity. The high-fat environment in vitro inhibited osteoblast proliferation and osteogenic differentiation, and significant changes in ferroptosis-related biochemical parameters were observed. These findings have implications for the future clinical treatment of bone loss caused by high-fat diets.

Antimicrobial potency, prevention ability, and killing efficacy of daptomycin-loaded versus vancomycin-loaded ß-tricalcium phosphate/calcium sulfate for methicillin-resistant Staphylococcus aureus biofilms.

Growing evidence has shown that the efficacy of systemic administration of daptomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-related infections is satisfactory. However, the clinical efficacy of the local administration of daptomycin for the management of osteoarticular infections remains unclear. This in vitro study compared the efficacy of daptomycin and vancomycin against MRSA biofilms. The elution kinetics of daptomycin and vancomycin, combined with gentamicin and loaded with either ß-tricalcium phosphate/calcium sulfate or calcium sulfate, in the presence of MRSA infection, was assessed. Their efficacy in preventing biofilm formation and killing pre-formed biofilms was assessed using colony-forming unit count and confocal laser scanning microscopy. In addition, the efficacy of daptomycin, vancomycin, and gentamicin in prophylaxis and eradication of MRSA biofilms was also evaluated. Daptomycin + gentamicin and vancomycin + gentamicin displayed similar antimicrobial potency against MRSA, by either ß-tricalcium phosphate/calcium sulfate or calcium sulfate. In the prevention assays, both daptomycin + gentamicin and vancomycin + gentamicin showed similar efficacy in preventing bacterial colony formation, with approximately 6 logs lower colony-forming units than those in the control group at both 1 and 3 days. The killing effect on pre-formed biofilms showed significant decreases of approximately 4 logs at 1 and 3 days following treatment with daptomycin + gentamicin and vancomycin + gentamicin. In addition, the confocal laser scanning microscopy results support the colony-forming unit data. Moreover, single use of vancomycin and gentamicin showed similar efficacies in preventing and killing MRSA biofilms, both of which were better than that of gentamicin. Our study demonstrated that vancomycin + gentamicin and daptomycin + gentamicin loaded with ß-tricalcium phosphate/calcium sulfate or calcium sulfate showed similar prophylactic and killing effects on MRSA biofilms, implying a potential indication of local administration daptomycin for the treatment of MRSA-associated osteoarticular infections, especially if vancomycin administration presents limitations.

Higher serum apolipoprotein B level will reduce the bone mineral density and increase the risk of osteopenia or osteoporosis in adults.

Objective: There is very limited evidence in the NHANES database linking serum apolipoprotein B and lumbar bone mineral density (BMD) in adults aged 20-59 years. There are few studies associating apolipoprotein B concentrations with BMD, and there is some debate about the association between obesity and BMD. Therefore, the purpose of this study was to determine the association between serum apolipoprotein B concentrations and lumbar spine BMD in adults aged 20-59 years and to predict its association with risk of osteopenia or osteoporosis. Methods: A cross-sectional study of the entire US ambulatory population was conducted using data from the National Health and Nutrition Examination Survey (NHANES) database. Weighted multiple regression equation models were used to assess the association between serum apolipoprotein B and lumbar BMD. A logistic weighted regression model was used to assess the association between serum apolipoprotein B concentrations and risk of osteopenia or osteoporosis. Subsequent stratified analyses were performed to refine the primary population of association. Results: Our study showed a significant negative association between serum apolipoprotein B concentration and lumbar BMD and a significant positive association with the risk of osteoporosis or osteopenia in the total population. After stratifying by sex, age and race, we concluded differently. The association of serum apolipoprotein B concentration with lumbar spine BMD and risk of osteopenia or osteoporosis was significant in male, but not in female. After stratification by age, the negative association between serum apolipoprotein B concentrations and lumbar BMD and the positive association with risk of osteopenia or osteoporosis was more significant in the 30-39 and 50-59 years age groups. When stratified by race, serum apolipoprotein B concentrations were significantly negatively associated with lumbar BMD and positively associated with risk of osteopenia or osteoporosis in Mexican American and non-Hispanic black populations. Thus, these findings suggest that these associations are influenced by sex, age, and race, respectively. Conclusion: Our results suggest that the association between serum apolipoprotein B levels and the risk of lumbar BMD and osteopenia or osteoporosis varies by sex, age, and race. In men, elevated serum apolipoprotein B levels were negative for bone quality. Elevated serum apolipoprotein B levels in the age groups 30-39 and 50-59 years also had a negative effect on bone quality. In the Mexican American and Non-Hispanic Black populations, elevated serum apolipoprotein B levels also had a significant negative effect on bone quality.

Interleukin-6 versus Common Inflammatory Biomarkers for Diagnosing Fracture-Related Infection: Utility and Potential Influencing Factors.

Currently, the utility of white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), for diagnosis of fracture-related infection (FRI), is still controversial, and potential efficiency of interleukin-6 (IL-6) as a novel cytokine in assisted diagnosis of FRI remains unclear. This study is aimed at investigating the utility and potential influencing factors of IL-6 and the common biomarkers for diagnosing FRI. Preoperative serological levels of IL-6 and the three biomarkers were compared between 407 FRI patients and 195 fracture-healed (FH) patients. Diagnostic efficiency of the indicators was evaluated using the areas under the receiver operating characteristic (ROC) curves, and their potential influencing factors were also analyzed. Outcomes showed that the median levels of all of the four biomarkers were significantly higher among the FRI patients than those among the FH patients (P < 0.01). The areas below the ROC curves of ESR, CRP, and IL-6 were 76.5%, 76.4%, and 71.8%, respectively, with WBC of only 56.9%. Compared with ESR and CRP, IL-6 displayed a lower sensitivity (ESR vs. CRP vs. IL - 6 = 72.7% vs. 65.6% vs. 57.5%) but a higher specificity (ESR vs. CRP vs. IL - 6 = 70.3% vs. 75.4% vs. 83.6%). Serological IL-6 level was influenced by pathogen culture result and pathogen number; nonetheless, bacteria type appeared to have no influence on the levels of the four biomarkers. In short, this study displayed similar value of IL-6 with that of ESR and CRP in assisted diagnosis of FRI. Whether IL-6 can be regarded as a promising diagnostic indicator requires more studies.

Inhibition of SDF-1/CXCR4 Axis to Alleviate Abnormal Bone Formation and Angiogenesis Could Improve the Subchondral Bone Microenvironment in Osteoarthritis.

The pathogenesis of the osteoarthritis (OA) is complex. Abnormal subchondral bone metabolism is an important cause of this disease. Further understanding on the pathology of the subchondral bone in OA may provide a new therapy. This research is about to investigate the role of SDF-1 in the subchondral bone during the pathological process of OA. In vitro, Transwell was used to test the migratory ability of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Western blot presented the protein level after SDF-1 treatment in BMSCs and HUVESs. Alizarin red was used to assess the ability of osteogenic differentiation. To inhibit SDF-1 signaling pathway in vivo, AMD3100 (SDF-1 receptor blocker) was continuously delivered via miniosmotic pump for 4 weeks in mice after performing anterior cruciate ligament transaction surgery. Micro-CT, histology staining, immunofluorescence, immunohistochemistry, and TRAP staining were used to assess the role of SDF-1 on osteogenesis and angiogenesis in the subchondral bone. Our results showed that SDF-1 could recruit BMSCs, activate the p-ERK pathway, and enhance osteogenic differentiation. SDF-1 promoted the ability of proliferation, migration and tube formation of HUVECs by activating the ERK and AKT signaling pathways. In an animal study, inhibition of SDF-1/CXCR4 axis could significantly reduce subchondral osteogenesis differentiation and H-type vessel formation. Furthermore, the AMD3100-treated group showed less cartilage destruction and bone resorption. Our research shows that SDF-1 alters the microenvironment of the subchondral bone by promoting osteoid islet formation and abnormal H-type angiogenesis in the subchondral bone, resulting in articular cartilage degeneration.

Association of Antibiotic Alterations in Gut Microbiota With Decreased Osseointegration of an Intramedullary Nail in Mice With and Without Osteomyelitis.

Treatment of osteomyelitis requires prolonged antibiotic therapy which significantly alters the gut microbiota. While the influences on bone mass and microstructure have been extensively studied, it is poorly understood what impact the changes in gut microbiota may have on the host response to osseointegration around an intramedullary nail implanted. Here, we explored the influence of gut microbiota on the bone osseointegration process around an implant under two conditions: implantation of an intramedullary nail in the bone marrow cavity and chronic osteomyelitis (CO) induced by Staphylococcus aureus infection. Body weight, hepatorenal functions, serum levels of proinflammatory cytokines were monitored. The composition of gut microbiota was assessed via 16S rRNA sequencing, and the bone condition was analyzed via micro-computed tomography, hematoxylin and eosin staining, Safranin O-fast green and Goldner's trichrome staining. Osteoblastogenesis and osteoclastogenesis were assessed by detecting tartrate-resistant acid phosphatase and osterix expression. We found that perturbation of gut microbiota (increase in Proteobacteria and decrease in Bacteroidetes) associated with delayed osseointegration and increased levels of proinflammatory cytokines in the serum (p<0.05), lower bone mass (p<0.05), deficient endochondral ossification and bone formation, reduced osteoblastogenesis (p<0.05) and enhanced osteoclastogenesis (p<0.001). Survival rates (p=0.002) and bacterial loads (p=0.0363) in bone differed significantly between the CO and antibiotic-treated CO mice, but cytokines levels, bone mineral density, and bone formation did not differ, likely because of the severely damaged bone structure. In summary, antibiotic treatment perturbed the gut microbiota and significantly interfered with the bone osseointegration around the nail by increasing proinflammatory cytokine levels in circulation, inhibiting osteoblastogenesis, enhancing osteoclastogenesis, and thus leading to higher pathogen colonization as well as higher mortality postinfection. This report of ours is the first to demonstrate antibiotic-induced alterations in the gut microbiota affect bone osseointegration, helping us understand the role of gut microbiota disorders in osteoblastogenesis and osteoclastogenesis following implant insertion with or without infection.

Fascia Iliaca Compartment Block for Perioperative Pain Management of Geriatric Patients with Hip Fractures: A Systematic Review of Randomized Controlled Trials.

Background: With continuous increase of the aging population, the number of geriatric patients with fragility hip fractures is rising sharply, and timely surgery remains the mainstay of treatment. However, adequate and effective pain control is the precondition of satisfactory efficacy. This systematic review aimed to summarize the use of fascia iliaca compartment block (FICB) as an analgesic strategy for perioperative pain management in geriatric patients with hip fractures. Methods: PubMed and Embase databases were searched for English published randomized controlled trials (RCTs) reporting application of FICB for pain control of the older adults with hip fractures between January 1st, 2000, and May 31st, 2020. The modified Jadad scale was used to evaluate quality of the RCTs included. Primary outcomes of the eligible RCTs were presented and discussed. Results: A total of 27 RCTs with 2478 cases were included finally. The present outcomes suggested, after admission or in the emergency department (ED), FICB can provide patients with equal or even better pain relief compared with the conventional analgesia methods, which can also reduce additional analgesic consumptions. While, before positioning for spinal anesthesia (SA), FICB is able to offer superior pain control, facilitating SA performance, after surgery FICB can effectively alleviate pain with decreased use of additional analgesics, promoting earlier mobilization and preventing complications. Conclusions: FICB is a safe, reliable, and easy-to-conduct technique, which is able to provide adequate pain relief during perioperative management of geriatric patients with hip fractures.

Impact of UGT2B7 and ABCC2 genetic polymorphisms on mycophenolic acid metabolism in Chinese renal transplant recipients.

AIM: To evaluate genetic variants affecting mycophenolic acid (MPA) metabolism in Chinese renal transplant recipients. METHODS: Total 11 SNPs of UGT1A9, UGT1A8, UGT2B7, ABCC2, ABCG2 and SLCO1B3 were genotyped in 408 Chinese renal transplant recipients. Associations between SNPs and MPA concentration/dose ratio (C0/D) were analyzed using different genetic models. Multivariate linear regression was used to analyze associations between log (C0/D) and clinical factors. Results: After adjustment by clinical factors, UGT2B7 rs7662029 was associated with log (C0/D) using a dominant (p = 0.041) and an additive (p = 0.038) model, ABCC2 rs717620 was associated with log (C0/D) using a recessive model (p = 0.019). Using additive model, SNP-SNP interactions were identified (p = 0.002) between ABCC2 rs717620 and UGT1A9 rs2741049, with interactions (p = 0.002) between ABCC2 rs717620 and UGT1A8 rs1042597. Age, albumin and serum creatinine were associated with log (C0/D). CONCLUSION: rs7662029 and rs717620 may affect MPA pharmacokinetics. SNP-SNP interactions and clinical factors may have significant effects on MPA metabolism.