Worldwide productivity and research trend of publications concerning extracellular vesicles role in fibrosis: A bibliometric study from 2013 to 2022.

Background: Fibrosis is a heavy burden on the global healthcare system. Recently, an increasing number of studies have demonstrated that Extracellular vesicles play an important role in intercellular communication under both physiological and pathological conditions. This study aimed to explore the role of extracellular vesicles' in fibrosis using bibliometric methods. Methods: Original articles and reviews related to extracellular vesicles and fibrosis were obtained from the Web of Science Core Collection database on November 9, 2022. VOSviewer was used to obtain general information, including co-institution, co-authorship, and co-occurrence visualization maps. The CiteSpace software was used to analyze citation bursts of keywords and references, a timeline view of the top clusters of keywords and cited articles, and the dual map. R package "bibliometrix" was used to analyze annual production, citation per year, collaboration network between countries/regions, thematic evolution map, and historiography network. Results: In total, 3376 articles related to extracellular vesicles and fibrosis published from 2013 to 2022 were included in this study, with China and the United States being the top contributors. Shanghai Jiao Tong University has the highest number of publications. The main collaborators were Giovanni Camussi, Stefania Bruno, Marta Tepparo, and Cristina Grange. Journals related to molecular, biology, genetics, health, immunology, and medicine tended to publish literature on extracellular vesicles and fibrosis. "Recovery," "heterogeneity," "degradation," "inflammation," and "mesenchymal stem cells" are the keywords in this research field. Literature on extracellular vesicles and fibrosis associated with several diseases, including "kidney disease," "rheumatoid arthritis," and "skin regeneration" may be the latest hot research field. Conclusions: This study provides a comprehensive perspective on extracellular vesicles and fibrosis through a bibliometric analysis of articles published between 2013 and 2022. We identified the most influential countries, institutions, authors, and journals. We provide information on recent research frontiers and trends for scholars interested in the field of extracellular vesicles and fibrosis. Their role in biological processes has great potential to initiate a new upsurge in future research.

METFORMIN MITIGATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY PROMOTING AMPK ACTIVATION AND INHIBITING HIF-1α-INDUCED AEROBIC GLYCOLYSIS.

ABSTRACT: Recent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)-induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. Cellular experiments demonstrated that lipopolysaccharide increased fibroblast activation through AMPK inactivation, HIF-1α induction, alongside an augmentation of aerobic glycolysis. By contrast, the effects were reversed by AMPK activation or HIF-1α inhibition. In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effects in vivo . Our research implies that targeting AMPK activation and HIF-1α-induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF.

Mutations in PLCZ1 induce male infertility associated with polyspermy and fertilization failure.

PURPOSE: To investigate the genetic causes of polyspermy and total fertilization failure (TFF) in two independent male patients suffering from male infertility. METHODS: Immunofluorescence (IF) staining was used to detect the localization of the PLCζ protein in sperm and the maternal pronucleus in the zygote. Genomic DNA samples were extracted from the peripheral blood of patients and their families. The ExAC database was used to identify the frequency of corresponding mutations. The PLCZ1 mutations were validated by Sanger sequencing. The pathogenicity of the identified mutations and their possible effects on the protein were assessed using in silico tools and molecular modeling. RESULTS: We identified a reported homozygous mutation c.588C > A (p.Cys196Ter) and a compound heterozygous mutation c.2 T > C(p.Met1Thr)/c.590G > A (p.Arg197His) with one novel mutation in PLCZ1. The IF results showed that these multipronuclear zygotes formed as a result of polyspermy. In silico analysis predicted that the mutations result in disease-causing proteins. IF staining revealed that PLCζ is abnormally localized in the sperm samples from the two affected patients. Assisted oocyte activation (AOA) successfully rescued polyspermy and TFF and achieved pregnancy in two patients with the PLCZ1 mutation. CONCLUSION: We identified a homozygous mutation in PLCZ1 (c.588C > A [p.Cys196Ter]) in a male patient with polyspermy after in vitro fertilization (IVF) as well as a compound heterozygous mutation c.2 T > C(p.Met1Thr)/c.590G > A (p.Arg197His) with one novel mutation in a male patient with fertilization failure after intracytoplasmic sperm injection (ICSI), and we provide evidence that the homozygous mutation can cause polyspermy and the compound heterozygous mutation can cause fertilization failure.

Peroxiredoxin 4 secreted by cumulus cells ameliorates the maturation of oocytes in vitro.

BACKGROUND: Peroxiredoxin 4 (Prdx4) in the endoplasmic reticulum (ER) is the only secretory member of the antioxidant Prdx family. Our previous studies demonstrated that Prdx4 in cumulus cells (CCs) ameliorated the maturation of oocytes in vitro and enhanced oocyte developmental competence by preventing CCs apoptosis caused by oxidative stress (OS) through gap junctions. In this study, we aimed to determine whether Prdx4 released by CCs can repair meiotic defects in mouse oocytes by co-culturing immature (germinal vesicle) oocytes with CCs from mature oocytes in the absence of gap junctions. RESULTS: The OS-induced meiotic defects in mouse oocytes were impeded by co-culture with CCs, as evidenced by the increased first polar body (PB1) extrusion rate and decreased ROS level. CCs increased Prdx4 expression and lowered IRE1α, Bip expression in H2O2-treated oocytes. After knockdown of Prdx4 expression in CCs, the rate of PB1 extrusion in the oocytes was significantly reduced to the level detected in H2O2 group, and ER stress was not alleviated. CO-IP and immunofluorescence co-localization experiments demonstrated that Prdx4 interacted with PDIA6 in the oocytes and the Pearson's R value was 0.69 calculated using ImageJ. CONCLUSIONS: Cumulus cells can promote the maturation of oocytes in vitro by secreting Prdx4 in a paracrine manner and serve as a promising therapeutic antioxidant for improving the quality of oocytes, especially aging oocytes, in clinical in vitro maturation (IVM).

[Analysis of three Chinese pedigrees affected with recurrent hydatidiform mole due to variants of NLRP7 gene].

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION: Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.

An In Situ Depolymerization and Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Polylactic Acid Microplastics in Environmental Samples.

Polylactic acid (PLA) is the most commonly used biodegradable plastic with rapid growth in recent years. This leads to predictable increased pollution of PLA microplastics (MPs) in the environment. However, quantification methods for the PLA MPs are still lacking. In this study, a method based on alkali-assisted thermal depolymerization and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was developed to quantify PLA MPs. After the background monomer compound was removed, PLA MPs were efficiently depolymerized to lactic acid and detected by LC-MS/MS with a limit of quantification of 18.7 ng/g. The ideal recovery of spiked PLA MPs of 93% was obtained, and the PLA MPs did not need to be separated or extracted in advance from the environmental samples. Using this method, PLA MPs were detected in all the sediment samples of a reservoir at a range of 53.5-491 ng/g dw, and the concentrations decreased with the sediment depth. In addition, after soaking in water at 95 °C for 30 min, approximately 12 µg of PLA MPs was released from a single teabag.

Nucleoporin37 may play a role in early embryo development in human and mice.

Maternal-effect genes (MEGs) play an important role in maintaining the survival and development of mammalian embryos at the cleavage stage after fertilization. Despite long-term efforts, the MEGs that regulate preimplantation embryo development remain largely unknown. Here, using whole-exome sequencing and homozygosity mapping, we identified a potential candidate gene associated with early embryo development: nucleoporin37 (NUP37), a nucleoporin gene that encodes a member of the nuclear pore complexes and regulates nuclear pore permeability and nucleocytoplasmic transport. Moreover, we determined the temporal and spatial expression patterns of Nup37 in mouse oocytes and early embryos, and explored the role of NUP37 in oocyte maturation and preimplantation embryo development. Immunoprecipitation assays confirmed that yes-associated protein-1 (YAP1) binds to TEA domain transcription factor 4 (TEAD4) and NUP37. Furthermore, Nup37 gene knockdown reduced the nuclear import of YAP1 and down-regulated the expression of YAP1-TEAD pathway downstream genes Rrm2 and Rpl13 in early embryos. Our study provides evidence that maternal NUP37 contributes to the nuclear import of YAP1 and then activates the YAP1-TEAD pathway, a signalling pathway essential for zygotic genome activation. Nup37 may be a key gene involved in preimplantation embryo development in mammals.

Earthworms' Degradable Bioplastic Diet of Polylactic Acid: Easy to Break Down and Slow to Excrete.

Microplastics (MPs) in soils may be ingested by terrestrial animals. While the application of bioplastics is increasing, the ingestion and excretion characteristics of bio-MPs by terrestrial animals are poorly understood as compared to fossil-MPs. Here, the approach-avoidance behavior of adult earthworms Eisenia fetida to MP-contaminated soil was assessed. Fossil-based poly(ethylene terephthalate) (PET) and bio-based poly(lactic acid) (PLA) MPs were found to be preferred by the earthworms, which might be due to the odor of polymer monomers. MPs in earthworm casts were analyzed by microscopy counting and liquid chromatography-tandem mass spectrometry. The amount of microscopically recognizable excreted PET and PLA was 553 and 261 items/g, respectively, while a higher proportion of smaller PLA particles also presented. Bio-based PLA is much easy to break down by earthworms than fossil-based PET. Submicron and nanocron PLA accounted for 57 and 13% of the excreted PLA on the 10th day of excretion. MP excretion was well described with the first-order kinetic model, and the elimination half-life was 9.3 (for PET) and 45 h (for PLA). A longer excretion period of PLA may be related to its potential to break down in the earthworms' digestive tract. This not only promotes the environmental degradation of PLA but also suggests the ecological risk caused by nanoparticles.

Comparison of Detection Methods of Microplastics in Landfill Mineralized Refuse and Selection of Degradation Degree Indexes.

A landfill is an important sink of plastic waste and potential sources of microplastics (MPs) when mineralized refuse is reused. However, limitations are still present in quantifying MPs in mineralized refuse and assessing their degradation degree. In this study, laser direct infrared spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify MPs of mineralized refuse from a landfill. Although 25-113 items/g MPs were detected in particles subjected to flotation, 37.9-674 µg/g polyethylene terephthalate (PET) and 0.0716-1.01 µg/g polycarbonate (PC) were detected in the residual solids by LC-MS/MS, indicating a great amount of plastic polymers still presented in the residue. This suggests that the commonly used flotation-counting method will lead to significant underestimation of MP pollution in mineralized refuse, which might be due to the aging and aggregation process caused by the long-term landfill process. The ratio of "bisphenol A/PC" and "plasticizer/MPs" was found to be positively correlated and negatively correlated with the landfill age, respectively. Therefore, in addition to the spectral index such as the carbonyl index, new indexes based on the concentrations of polymers, free monomers, and plasticizers were proposed to characterize the degradation degree of MPs in a landfill.

Jumbo cup in hip joint renovation may cause the center of rotation to increase.

BACKGROUND: Utilizing the large jumbo cup in revision total hip arthroplasty is an effective approach to cure many lacunar and segmental peripheral bone defects. However, with the use of the jumbo cup, the center of the hip joint may become elevated relative to the primary acetabulum, and the diameter of the large cup is greater. AIM: To study the height and the significance of the elevation of the hip joint center. METHODS: Eighty-eight patients matched the criteria for this condition and were included in the study. The center height of the hip joint was measured relative to the opposite normal hip joint. The diameter of the jumbo cup was measured and checked according to operation notes, and the diameter of the jumbo cup was measured with a prosthesis label. Then, the horizontal and vertical centers of rotation were measured on the surgical side and opposite side. The average center height of the hip joint on the renovated side and the opposite side and the position of the hip cup relative to the teardrop were compared using a paired t-test. RESULTS: Radiometric analysis showed that the average hip joint center was elevated by 7.6 mm. The rotational center height delta of the renovated hip was 7.6 ± 5.6 mm, and there was an obvious difference between the two groups (P = 0.00). The difference in horizontal distance was 0.5 ± 5.1 mm (-11.5 -14.0 mm), and there was no obvious difference between the two groups (P = 0.38). According to the foreign standard, the rotational center height delta of the renovated hip was 7.5 ± 6.2 mm, and there was a significant difference between the two groups (P = 0.00). There was no obvious difference between the domestic and foreign standards (P > 0.05) between the two groups. CONCLUSION: The application of the jumbo cup elevates the rotational center of the hip joint, but it is feasible and effective to use the jumbo cup.

Ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in mediastinal mass resection by median sternotomy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Ultrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection. METHODS: This randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18-65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h. RESULTS: There were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 µg vs. 67.67 ± 8.92 µg, P < 0.001). In addition, pain numerical rating scale (NRS) scores were significantly lower in the PSI group compared with control patients, both at rest and upon coughing within 24 postoperative hours. Postoperative adverse events were generally reduced in the PSI group compared with controls. CONCLUSIONS: USG bilateral parasternal intercostal nerve block effectively reduces postoperative pain and adjuvant analgesic requirement, with good patient satisfaction, therefore constituting a good option for mediastinal mass resection by median sternotomy.

[Revision reasons and prosthesis selection of Crowe â £ developmental dysplasia of hip after total hip arthroplasty].

OBJECTIVE: To investigate revision reasons and prosthesis selection of Crowe Ⅳ developmental dysplasia of the hip (DDH) after total hip arthroplasty (THA). METHODS: A clinical data of 14 patients (15 hips) with Crowe Ⅳ DDH, who underwent a revision hip arthroplasty between January 2008 and May 2018, was retrospectively reviewed. There were 1 male (1 hip) and 13 females (14 hips). The age ranged from 27 to 63 years (mean, 45.0 years). There were 7 cases of left hip, 6 cases of right hip, and 1 case of bilateral hips. The prosthetic interfaces of primary THA were metal-on-polyethylene (MOP) in 9 hips, ceramic-on-ceramic (COC) in 4 hips, ceramic-on-polyethylene (COP) in 1 hip, and ceramic-on-metal in 1 hip. The time from primary THA to revision was 3-204 months (mean, 65.0 months). The causes of revision included aseptic loosening in 7 hips, dislocation in 3 hips, periprosthetic joint infection in 2 hips, osteolysis in 1 hip, nonunion of osteotomy in 1 hip, and a small-angle of femoral anteversion in 1 hip. Preoperative Harris score was 54.1±17.8 and the range of motion (ROM) of flexion was (92.7±20.2)°. Preoperative X-ray films showed the acetabular bone defect in 11 hips and osteolysis of femoral side in 4 hips. During the revision, the prostheses with COP and COC interfaces were used in 5 hips and 10 hips, respectively. Both acetabular and femoral revisions were performed in 11 hips and only femoral revision was performed in 4 hips. RESULTS: The mean operation time was 3.7 hours (range, 1.5-6.0 hours). The mean intraoperative blood loss was 940.0 mL (range, 200-2 000 mL). All patients were followed up 16-142 months (mean, 73.9 months). Postoperative X-ray films showed no difference in inclination and anteversion between primary THA and revision ( P>0.05). The height of rotation center and offset after revision were higher than those after primary THA, and the difference in offset was significant ( P<0.05). At last follow-up, the Harris score and ROM of flexion were 85.0±7.3 and (115.0±17.0)°, respectively, which were significantly higher when compared with those before revision ( t=8.909, P=0.000; t=4.911, P=0.000). Three hips underwent a re-revision operation. All protheses were fixed well and no radiolucent line, loosening, or subsidence was observed at last follow-up. CONCLUSION: The most common reason for revision in patients with Crowe Ⅳ DDH after THA was aseptic loosening. Due to high activity demand of this population, the prosthesis with MOP interface should be prevented and the prosthesis with COC interface could be alternative. Metal block, cup-cage, and reinforcement ring were reasonable solutions for reconstruction of acetabulum with severe bone defects and have satisfactory effectiveness. S-ROM prosthesis should be the preferred stem for neither primary THA or revision.

Barrier function of zebrafish embryonic chorions against microplastics and nanoplastics and its impact on embryo development.

Embryonic stage is important for the development of aquatic animals, and embryonic chorion is an efficient barrier against exogenous pollutants. The efficient barrier function of zebrafish (Danio rerio) embryonic chorions against micro- and nano- polystyrene (PS) particles was observed. Embryonic chorions presented high affinity to PS particles. The covering layer of PS particles on the outer surface of chorions affected the patency of pores in chorions, and the nano- PS particles exerted a considerable effect. The accelerated heart rate and blood flow velocity in the embryos indicated that the PS particles adhering to embryonic chorions might cause an internal hypoxic microenvironment in the embryos. The coating of PS particles on embryonic chorions also resulted in delayed hatching of the embryos. The observed development toxicity induced by the nano- and micro-PS particles was confirmed via the expressions of metabolic pathways related to antioxidant system. The pathways of biosynthesis of unsaturated fatty acid, linoleic acid metabolism and alanine, and aspartate and glutamate metabolism extensively altered when the embryos were exposed to PS particles, especially to the nano- PS particles. Although micro- and nano- plastic particles can be efficiently blocked by embryonic chorions, they can still affect the early development of aquatic organisms.

Microplastics in Yellow River Delta wetland: Occurrence, characteristics, human influences, and marker.

Microplastics (MPs) are widespread in the environment including coastal wetlands. The influence of different types and intensities of human activities on the occurrence of MPs in coastal wetlands is still unknown. The aim of this study was to investigate the distribution of MPs and the contribution of human activities in different areas of Yellow River Delta wetland. MPs were widely detected in different areas of the wetland even in the protection area with little human activities. Direct human activities resulted in more severe MPs contamination in the protection area than the tourism area. In the soil of different areas, the MPs abundances ranged from 136 to 2060 items/kg. The concentrations of polyethylene terephthalate (PET) ranged from 536 to 660 µg/kg, and the concentrations of polycarbonate (PC) ranged from 83.9 to 196 µg/kg. The MP abundances of the three areas had significant correlations with PET concentrations. These results indicate that the direct influence of human activities has much greater contribution than indirect influence. These results also suggest that PET concentration can be used as a potential marker of MPs contamination in wetland soils.

[Short-term effectiveness of revision total knee arthroplasty with porous-coated metaphyseal Sleeve and MBT implant].

Objective: To evaluate short-term effectiveness of revision total knee arthroplasty (TKA) with porous-coated metaphyseal Sleeve and MBT implant. Methods: A clinical data of 23 patients (24 knees) who underwent revision TKA by using porous-coated metaphyseal Sleeve combined with MBT implant between March 2015 and April 2017 was retrospectively analyzed. There were 8 males (8 knees) and 15 females (16 knees). The age ranged from 48 to 85 years (mean, 65.4 years). The cause of revision TKA included infection in 14 knees, aseptic loosening in 8 knees, instability in 1 knee, and stiff knee in 1 knee. Bone defects were classified according to the Anderson Orthopaedic Research Institute (AORI) bone defect classification. The femoral defect was rated as type ⅡA in 5 knees, type ⅡB in 17 knees, and type Ⅲ in 2 knees; the tibial defect was rated as type ⅡA in 2 knees, type ⅡB in 20 knees, and type Ⅲ in 2 knees. The mean time between primary TKA and revision TKA was 30.6 months (range, 6-86 months). The preoperative range of motion (ROM) was (56.0±24.9)°. The preoperative Hospital for Special Surgery (HSS) total score was 41.9±14.2; and the pain and function scores were 8.5±5.2 and 33.4±13.5, respectively. Results: All patients were followed up 12-39 months (mean, 25.6 months). The mean operation time was 2.2 hours (range, 1.6-2.9 hours). The mean intraoperative blood loss was 580 mL (range, 400-1 000 mL). There were 2 knees (8.3%) of intraoperative fracture associated with Sleeve insertion and 1 knee (4.2%) of acute postoperative infection at 25 days after revision TKA. All incisions healed by first intention. No deep venous thrombosis of lower extremity occurred. X-ray film showed that all implants were stable. At last follow-up, slight discomfort after exercise occurred in 4 knees (16.7%); end-of-stem pain in the tibia occurred in 1 knee (4.2%). The ROM was (114.6±5.1)°, which had significant improvement compared with the preoperative result ( t=11.698， P=0.000). The HSS total score (89.0±10.9), pain score (26.9±6.6), and function score (62.1±5.8) also had significant improvement compared with the preoperative results ( t=15.616, P=0.000; t=12.522, P=0.000; t=10.076, P=0.000). Conclusion: The porous-coated metaphyseal Sleeve combined with MBT implant in revision TKA has a significant improvement in short-term effectiveness and no signs of implant loosening.

Dietary education with customised dishware and food supplements can reduce frailty and improve mental well-being in elderly people: A single-blind randomized controlled study.

BACKGROUND AND OBJECTIVES: The elderly population is increasing rapidly worldwide, and frailty is a common geriatric syndrome. Comprehensive dietary management strategies may have beneficial effects on frailty prevention and reversal. This 3-month single-blind, paralleled, randomized controlled trial compared the effects of micronutrients and/or protein supplements, and a personalised diet on frailty status in elderly individuals. METHODS AND STUDY DESIGN: Between 2014 and 2015, 40 prefrail or frail subjects aged >=65 years were recruited at Miaoli General Hospital, Taiwan. Of these, 37 completed the study, and 36 were included in the analysis. Participants were randomly assigned to one of four treatment groups: (1) the control (2) multiple micronutrient supplements, (3) multiple micronutrients plus isolated soy protein supplement, and (4) individualised nutrition education with customised dishware and food supplements (mixed nuts and skimmed milk powder). Dietary intake, protein biomarkers, frailty score, and geriatric depression score were assessed. RESULTS: Individualised nutrition education with customised dishware and food supplements significantly increased the participants' intake of vegetables, dairy, and nuts, in addition to increasing the concentration of urinary urea nitrogen. It yielded a significant reduction in frailty score (p<0.05) and a borderline reduction (p=0.063) in geriatric depression score. No significant beneficial changes were observed for the other two intervention groups. CONCLUSIONS: Our study indicated that a dietary approach with easy-to-comprehend dishware and food supplements to optimize the distribution of the consumption of six food groups improved frailty status and, potentially, psychological well-being in elderly people.

Success Rate of Fungal Peri-Prosthetic Joint Infection Treated by 2-Stage Revision and Potential Risk Factors of Treatment Failure: A Retrospective Study.

BACKGROUND The aim of this study was to investigate the success rate of fungal peri-prosthetic joint infection treated by 2-stage revision and related factors of treatment failure to offer a better treatment protocol. MATERIAL AND METHODS We reviewed 18 joints (13 knees and 5 hips) of 17 patients (10 women and 7 men) diagnosed with fungal peri-prosthetic joint infection from January 2000 to June 2015 at our institute. The mean follow-up was 65.1 months (range, 25-129 months). All joints were treated with complete debridement, implantation of antifungal-loaded cement spacers, at least 6 weeks of parenteral antifungal agents, and delayed reimplantation. RESULTS Notably, 15 joints were infected with Candida, and molds were isolated in 3 joints. The median duration of resection arthroplasty and reimplantation was 33.9 weeks (range, 12-132 weeks). Thirteen (10 knees and 3 hips, 72.2%) of the 18 joints (13 knees and 5 hips) had no recurrent or persistent infection, while the remaining 5 joints (3 knees and 2 hips, 27.8%) failed to control infection after reimplantation of prosthesis or spacer. The long interval between prosthesis resection and reimplantation (69 weeks vs. 23.1 weeks, p=0.240) and mixed bacterial infection (80% vs. 46.2%, p=0.314) were associated with higher failure rate. CONCLUSIONS Debridement with the retention of the prosthesis is not an ideal treatment protocol for fungal peri-prosthetic joint infection; thus, a two-stage revision could be valid. We suggest that 6 weeks of parenteral antifungal agents are necessary, and 6 subsequent weeks of oral antifungal treatment is also important. We do not recommend that the two-stage revision be performed on patients who have more than 2 host risk factors.

[A study of total hip arthroplasty with subtrochanteric osteotomy in Crowe type â £ developmental dysplasia of hip].

Objective: To evaluate the effectiveness of total hip arthroplasty (THA) combined with subtrochanteric osteotomy in the treatment of Crowe type Ⅳdevelopmental dysplasia of the hip (DDH). Methods: Between April 2008 and June 2016, 71 patients with unilateral Crowe type Ⅳ DDH were treated with THA. Of 71 cases, 44 were performed with subtrochanteric osteotomy (osteotomy group) and 27 were performed without subtrochanteric osteotomy (non-osteotomy group). There was no significant difference in gender, age, body mass, height, body mass index, affected side, and preoperative Harris score between 2 groups ( P>0.05). The complications were recorded and the effectiveness was assessed by Harris score. Besides, the femoral dislocation height and the settling depth of sleeve were measured in the pelvic anteroposterior X-ray film pre- and post-operatively. Results: Osteotomy group was followed up 12-90 months (mean. 34.77 months), and non-osteotomy group was followed up 12-79 months (mean, 34.33 months). There was no significant difference in follow-up time between 2 groups ( t=-0.088, P=0.930). There was 11 cases of intraoperative or postoperative complications in osteotomy group, and 3 cases of postoperative complications in non-osteotomy group. Among the osteotomy group, 1 case had nonunion due to infection and received revision after 20 months. No loosening or dislocation of the implant occurred in both 2 groups. Significant differences were found in femoral dislocation height and settling depth of sleeve between 2 groups ( t=-8.452, P=0.000; t=6.783, P=0.000). Moreover，the osteotomy length was not correlated with the settling depth of sleeve ( r=-0.038, P=0.806). At last follow-up, there was no significant difference in Harris score between 2 groups ( t=-1.160, P=0.254). Conclusion: THA combined with subtrochanteric osteotomy can provide a favorable outcome for treating Crowe type Ⅳ DDH. Furthermore, patients with higher femoral dislocation and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance.

Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer's disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.