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Background: Diabetic kidney disease (DKD) is a common pathway to End-stage renal disease (ESRD). Podocytes are crucial due to their dual barrier functions in kidney diseases. Their role in renal fibrosis and DKD regulatory mechanisms is increasingly studied. However, bibliometric research in this field has not been explored., Methods: 1,250 publications from Jan. 1, 2000, to Feb. 16, 2024, were retrieved from the WoSCC database and analyzed by the Web of Science results analysis tool, VOSviewer, and CiteSpace., Results: Our scrutiny reveals that authors Liu Youhua, Fogo Agnes B, and Zhao Yingyong have made substantial contributions to this domain. Notably, "Kidney International" has the highest volume of publications in this area. Furthermore, our analysis identifies ten co-citation clusters: DKD, IncRNA, reactive oxygen species, glomerulosclerosis, Poria cocos, glomerular diseases, fibroblasts, connective tissue growth factor, coagulation, and Wnt. Recent research accentuates keywords such as autophagy, TRPC6, ERS, epigenetics, and NLRP3 inflammasome as frequently occurring terms in this field. The prevailing research hotspot keywords include autophagy, biomarker, and exosomes., Conclusion: Through the utilization of bibliometric tools and knowledge graph analysis, we have undertaken a comprehensive review of the intricate nexus between podocytes in DKD and renal fibrosis. This study imparts valuable insights to scholars regarding the dynamic evolution of this association and delineates prospective research avenues in this pivotal realm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 An, Tan, Lu, Wen, Bao, Yao, Chen, Wang, Zhou, Yang and Hao.)

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels., Competing Interests: H. Qiu and R. L. Gao received institutional research grants from Biotyx Medical (Shenzhen) Co. Ltd., Shenzhen. China. G. Zhang, D. Y. Zhang, H. P. Qi, and Y. D. Lu are employees of Biotyx Medical (Shenzhen) Co. Ltd. Y. F. Zheng is an editor-in-chief for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All other authors have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial., Aim: To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage., Methods: The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg's test for publication bias was performed using Stata 13.0 software., Results: Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg's test revealed no significant publication bias., Conclusion: The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Room-temperature phosphorescence (RTP) two-dimensional (2D) organic-inorganic hybrid perovskites (OIHPs) that possess superior stability and efficient triplet energy transfer between inorganic parts and organic cations have been seen as promising materials in optoelectronic devices. However, the development of RTP 2D OIHP-based photomemory has not been explored yet. In this work, the spatially addressable RTP 2D OIHPs-based nonvolatile flash photomemory is first investigated to explore the function of triplet excitons in elevating the performance of photomemory. Thanks to the triplet excitons generated in RTP 2D OIHP, extremely low photo-programming time of 0.7 ms, multilevel behavior of minimum 7 bits (128 levels), remarkable photoresponsivity of 19.10 AW -1 and significantly low power consumption of 6.79 × 10 -8 J per bit can be achieved. The current study provides a new prospective in understanding triplet excitons function in nonvolatile photomemory., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The treatment of patients with femoral head fractures with regard to fixation versus excision is controversial. This study aimed to compare the results of fixation and excision in hip arthroscopy-assisted surgery. This retrospective study included adult patients with femoral head fractures who were treated with hip arthroscopy surgery from March 2016 to April 2020, with a minimum follow-up of 24 months. The patients were divided into two groups: Group 1 (fixation group) and Group 2 (excision group). To compare the therapeutic effects between the two groups, clinical and radiographic outcomes, operative time, pain score, length of hospital stay after surgery and related complications were investigated. There were 13 (mean duration, 47.5 months; range, 24-72 months) and 8 (mean duration, 48.6 months; range, 26-74 months) patients in the fixation and excision groups, respectively. The excision group had better functional results than the fixation group in terms of the median modified Harris hip score ( P  = 0.009). No significant differences were observed in operative time, pain score or hospital stay after surgery between the two groups. Further, no osteonecrosis of the femoral head or traumatic arthritis occurred in either group. A piece of fracture fragment >2 cm can be considered for hip arthroscopy-assisted internal fixation, whereas the others can be removed. The excision group had better outcomes than the fixation group. Hence, hip arthroscopy-assisted internal fixation or excision of bony fragments led to satisfactory short-term clinical and radiological results for the treatment of Pipkin Type I and II femoral head fractures., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Rationale: Granulomatous mastitis (GM) is a rare inflammatory disease and the presentation mimics infectious mastitis or breast cancer. The disease usually develops at the unilateral breast in women with breast-feeding history at their child-bearing age. Systemic steroids had been proposed as the first-line treatment, the combination of surgery was also recommended for complicated disease. However, recurrence might still happen in some rare cases. Few studies have addressed the management of such difficult situations., Patient Concerns: We report the case of a 33-year-old androgynous and nulliparous woman who initially presented left breast erythematous swelling and was treated as infectious mastitis with debridement and antibiotics., Diagnosis: After wider excision for pathology, the diagnosis of GM was confirmed., Interventions: Steroids combined with methotrexate were prescribed. However, the symptoms only subsided temporarily and progressed to the contralateral side within 3 months. She finally underwent double-incision mastectomy and free nipple grafting., Outcomes: The surgery was completed uneventfully, and she had a satisfactory result with no more recurrence at the 6-month follow-up., Lesson: This GM case with the refractory treatment courses brought out the importance of surgical resection and was the first case report of treating GM with top surgery in the literature. Total mastectomy facilitated a highest complete remission rate of GM and may be advantageous for selected patients, especially in cases where steroids are intolerable., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO)., Methods: A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk., Results: A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO ( HR =8.500, 95% CI : 3.024-23.887, P <0.001), 1-minute Apgar score ≤3 points ( HR =10.094, 95% CI : 2.577-39.534, P =0.001), a low value of minimum PaO 2 /FiO 2 within 12 hours after admission ( HR =0.067, 95% CI : 0.009-0.481, P =0.007), and a low value of minimum pH within 12 hours after admission ( HR =0.049, 95% CI : 0.004-0.545, P =0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO 2 /FiO 2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2., Conclusions: Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO 2 /FiO 2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

Background: This study aimed to evaluate the effect of dipyridamole-thallium scanning (DTS) on the rates of 90-day cardiac complications and 1-year mortality in patients with a femoral neck fracture treated with hemiarthroplasty., Methods: Between 2008 and 2015, 844 consecutive patients who underwent cemented or cementless hemiarthroplasty were identified from the database of a single level-one medical center. One-hundred and thirteen patients (13%) underwent DTS prior to surgery, and 731 patients (87%) did not. Patient characteristics, comorbidities, surgical variables, and length of the delay until surgery were recorded. A propensity score-matched cohort was utilized to reduce recruitment bias in a 1:3 ratio of DTS group to control group, and multivariate logistic regression was performed to control confounding variables., Results: The incidence of 90-day cardiac complications was 19.5% in the DTS group and 15.6% in the control group (p = 0.343) among 452 patients after propensity score-matching. The 1-year mortality rate (10.6% vs 13.3%, p = 0.462) was similar in the two groups. In the propensity score-matched patients, utilization of DTS was not associated with a reduction in the rate of 90-day cardiac complications (matched cohort, adjusted odds ratio [aOR] = 1.32; 95% confidence interval [CI] 0.75-2.33, p = 0.332) or the 1-year mortality rate (aOR = 0.62; 95% CI 0.27-1.42, p = 0.259). Risk factors for cardiac complications included an American Society of Anesthesiologists grade ≥ 3 (OR 3.19, 95% CI 1.44-7.08, p = 0.004) and pre-existing cardiac comorbidities (OR 5.56, 95% CI 3.35-9.25, p < 0.001). Risk factors for 1-year mortality were a long time to surgery (aOR 1.15, 95% CI 1.06-1.25, p = 0.001), a greater age (aOR 1.05, 95% CI 1.00 to 1.10, p = 0.040), a low body mass index (BMI; aOR 0.89, 95% CI 0.81-0.98, p = 0.015), and the presence of renal disease (aOR 4.43, 95% CI 1.71-11.46, p = 0.002)., Discussion: Preoperative DTS was not associated with reductions in the rates of 90-day cardiac complications or 1-year mortality in patients with a femoral neck fracture undergoing hemiarthroplasty. The necessity for DTS should be re-evaluated in elderly patients with femoral neck fractures, given that this increases the length of the delay until surgery., Level of Evidence: Prognostic level III.

Purpose: Femoral head fracture dislocations are serious articular fractures that are associated with soft tissue injuries and are challenging to treat. Arthroscopic surgery may be a way to treat fracture reduction and fixation, thereby avoiding the need for extensive arthrotomy., Methods: We followed up a consecutive series of seven patients with femoral head fracture dislocation via a scope-assisted percutaneous headless screw fixation between 2016 and 2017. The clinical and radiological results were assessed., Results: The locations of the fracture were all involving infra-foveal area. The mean follow-up duration was 18 (range 12-24) months. The mean Harris hip score was 90.8 (range 88-93) at the latest follow-up. None of the patients showed early osteoarthritis, heterotopic ossification, or avascular necrosis. The average maximal displacement of the fracture site was improved from preoperative 6.79 mm (range 4.21-12.32) to postoperative 2.76 mm (range 0.97-3.97). Concomitant intra-articular hip lesions secondary to traumatic hip dislocation can also be treated., Conclusion: Managing the infra-foveal fracture of the femoral head using arthroscopic reduction and fixation with headless screws can be a safe and minimally invasive option. More patients and longer follow-up are needed for a definite conclusion.

Background: This study aimed to investigate the risk factors for mechanical failure of cement spacers and the impact on hip function after two-stage exchange arthroplasty for periprosthetic joint infection (PJI)., Methods: Thirty-one patients (19 males and 12 females) with hip PJIs underwent resection arthroplasty and implantation of cement spacers from January 2014 to December 2015. Patients who encountered spacer-associated mechanical complications in the interim period (14 of 31) were compared with those without complications (17 of 31). Complications were defined as spacer dislocation, spacer fracture, spacer fracture with dislocation, and femoral fracture during or following spacer implantation. Hip functional outcome was assessed using the Harris hip score (HHS). Treatment success was defined according to the following criteria: (1) no symptoms or signs indicative of infection; (2) no PJI-related mortality; and (3) no subsequent surgical intervention for infection after reimplantation surgery. Multivariate logistic regression and Kaplan-Meier survival curves were used for analysis., Results: Fourteen patients (14/31 = 45%) suffered at least one spacer-related complication within the interim period. The development of spacer complications was associated with a younger age (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.83-1.00, p = 0.045) and chronic PJI (OR 14.7, 95% CI 1.19-182, p = 0.036). Patients with spacer complications also had a lower median HHS (37 vs. 60, p < 0.001) before reimplantation in comparison to those without spacer complications. After reimplantation, the two groups had a similar median HHS (90 vs. 89, p = 0.945). Two patients did not undergo reimplantation due to extensive comorbidities, and subsequently retained the antibiotic spacer for definitive treatment. The 2-year treatment success rate was 84.6% in the spacer-complication group and 87.5% in the non-spacer-complication group (p = 0.81)., Conclusion: There was a high complication rate for articulating PMMA spacers during the interim period of two-stage revision total hip arthroplasty. A young age and chronic infection were the primary risk factors associated with mechanical complications. Patients at high risk of spacer-related mechanical complications should be advised accordingly by surgeons. Knowing the possible risk factors, surgeons should educate patients thoroughly to avoid spacer complications, thereby increasing patient satisfaction in the interim stage., Level of Evidence: Prognostic Level III.

Background: Femoroacetabular impingement (FAI) is associated with decreased hip function and early hip osteoarthritis. Surgical treatment is often required to halt the process of mechanical degeneration. The study investigated the short-to-midterm results of using a modified anterolateral mini-open and arthroscopic osteochondroplasty in the treatment of cam-type FAI., Methods: Thirty-six patients (39 hips), with the mean age of 43.6 years, who had cam-type FAI, were operated by a mini-open and arthroscopy-assisted osteochondroplasty via the Watson-Jones interval between 2002 and 2016. Radiographic parameters and Harris hip scores were retrospectively analyzed after a mean follow-up of 44 months., Results: Of the 39 hips, the mean Harris hip score significantly improved from 61.1 preoperatively to 84.2 postoperatively (P < 0.01). There were nine hips (23%) undergoing total hip arthroplasty (THA) at a mean of 22 months (range, 3~64 months) due to progression of hip osteoarthritis. The 5-year survival for hip preserving was 74.9%. Cox proportional-hazards model showed that age ≥ 55 years (P = 0.03) and preoperative Tönnis stage II (P = 0.02) were independent risk factors for conversion to THA., Conclusions: The mini-open and arthroscopic approach allowed direct visualization and improved quality of the osteochondroplasty of FAI hip while avoiding the need for surgical dislocation. This technique could be a safe and viable option for symptomatic cam-type FAI patients to relieve symptoms and improve hip function.

Salmonellosis is a highly contagious bacterial disease that threatens both human and poultry health. Tests that can detect Salmonella in the field are urgently required to facilitate disease control and for epidemiological investigations. Here, we combined loop-mediated isothermal amplification (LAMP) with a chromatographic lateral flow dipstick (LFD) to rapidly and accurately detect Salmonella . LAMP primers were designed to target the Salmonella invA gene. LAMP conditions were optimized by adjusting the ratio of inner to outer primers, MgSO 4 concentration, dNTP mix concentration, amplification temperature, and amplification time. We evaluated the specificity of our novel LAMP-LFD method using six Salmonella species and six related non- Salmonella strains. All six of the Salmonella strains, but none of the non- Salmonella strains, were amplified. LAMP-LFD was sensitive enough to detect concentrations of Salmonella enterica subsp. enterica serovar Pullorum genomic DNA as low as 89 fg/µl, which is 1,000 times more sensitive than conventional PCR. When artificially contaminated feed samples were analyzed, LAMP-LFD was also more sensitive than PCR. Finally, LAMP-LFD gave no false positives across 350 chicken anal swabs. Therefore, our novel LAMP-LFD assay was highly sensitive, specific, convenient, and fast, making it a valuable tool for the early diagnosis and monitoring of Salmonella infection in chickens.

Background: Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT)., Methods: Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration. The association between PTH and body weight was investigated in 496 PHPT patients. The adipose browning activities of 20 PHPT and 60 control subjects were measured with PET/CT scanning., Findings: Elevated plasma PTH triggered adipose tissue browning, leading to increased energy expenditure, reduced fat content, and finally decreased body weight in PHPT mice. Higher circulating PTH levels were associated with lower body weight (β = -0.048, P = .0003) independent of renal function, serum calcium, phosphorus,and albumin levels in PHPT patients. PHPT patients exhibited both higher prevalence of detectable brown/beige adipose tissue (20% vs 3.3%, P = .03) and increased browning activities (SUV in cervical adipose was 0.77 vs 0.49,P = .02) compared with control subjects., Interpretation: Elevated serum PTH drove WAT browning program, which contributed in part to body weight loss in both PHPT mice and patients. These results give insights into the novel pathological effect of PTH and are of importance in understanding the metabolic changes of PHPT. FUND: This research is supported by the National Key Research and Development Program of China and National Natural Science Foundation of China., (Copyright © 2018. Published by Elsevier B.V.)

A novel and efficient method for the synthesis of nucleophilic 2-monoarylated indole-3-ones via palladium-catalyzed direct C(sp 3 )-H arylation of indole-3-ones with aryl halides has been developed. Various 2-monoarylated indole-3-ones were readily obtained with yields up to 95%. As a class of important nucleophilic intermediates, 2-monoarylated indole-3-ones can be used for the construction of C2-quaternary indolin-3-one skeletons., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

The putative tumor suppressor microRNA let-7c is extensively associated with the biological properties of cancer cells. However, the potential involvement of let-7c in the differentiation of mesenchymal stem cells has not been fully explored. In this study, we investigated the influence of hsa-let-7c (let-7c) on the proliferation and differentiation of human dental pulp-derived mesenchymal stem cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western blotting. In general, the proliferative capabilities and cell viability of DPMSCs were not significantly affected by the overexpression or deletion of let-7c. However, overexpression of let-7c significantly inhibited the expression of IGF-1 receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers (osteocalcin, osterix, runt-related transcription factor 2, dentin sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen, and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let-7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were significantly inhibited following the overexpression of let-7c in DPMSCs. Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK signaling pathways.

Objective: To investigate potential human leucocyte antigen (HLA)-A2-restricted epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide-specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC) cells., Methods: The potential HLA-A*0201-restricted GPC3 peptides were screened using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA-A*0201 complex assay. The peptide-specific CTLs were generated and their cytotoxicity against GPC3 + SMMC 7721 and HepG2 cells was detected using IFN-γ based enzyme-linked immunospot and lactate dehydrogenase release assays in vitro., Results: A total of six peptides were identified for bindings to HAL-A2 and the GPC3 522-530 and GPC3 229-237 peptides with HLA-A*0201 molecules displayed high binding affinity and stability. The CTLs induced by the GPC3 522-530 or positive control GPC3 144-152 peptide responded to the peptide by producing IFN-γ, which were abrogated by treatment with anti-HLA-A2 antibody. The GPC3 522-530-specific CTLs responded to and killed SMMC 7721 and HepG2 cells, instead of GPC3-silenced SMMC 7721 or HepG2 cells. GPC3 522-530-specific CTLs response to HCC cells was blocked by anti-HLA-A2 antibody., Conclusions: The GPC3 522-530 peptide contains antigen-determinant and its specific CTLs can effectively kill HCC in a HLA-A2-restricted and peptide-dependent manner. Our findings suggest that this peptide may be valuable for development of therapeutic vaccine., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Two-stage reimplantation arthroplasty is one of the standard treatments for chronic periprosthetic joint infection (PJI). Scanty data exist regarding the risk factors for failure after two-stage reimplantation for periprosthetic hip infection. The purpose of this study was to investigate and identify the risk factors associated with failure after two-stage reimplantation hip arthroplasty., Methods: Sixty-two patients with hip PJI treated with a two-stage reimplantation protocol at our institution from 2005 to 2012 were reviewed. Patients requiring medical treatment or reoperation for recurrent infection were defined as treatment failure. A multivariate Cox proportional hazards model was used to analyze the risk factors associated with treatment failure., Results: Of the 62 patients, 11 (17.7%) patients had developed reinfection after the two-stage reimplantation with a mean follow-up of 5.7 years. The implant survival was 82.2% (95% confidence interval [CI] 75.19-92.55) at 10 years. Multivariate analysis revealed BMI ≥30 kg/m 2 (hazard ratio [HR] 9.16; 95% CI 1.51-55.3; p = 0.0158), liver cirrhosis (HR 6.39; 95% CI 1.09-37.4; p = 0.0398), gram-negative organism (HR 5.68; 95% CI 1.18-27.4; p = 0.0303), and presence of sinus tract (HR 18.2; 95% CI 2.15-153; p = 0.0077) as the independent risk factors for treatment failure., Conclusions: We found obesity, liver cirrhosis, gram-negative organism, and the presence of sinus tract were significantly related to the risks of failure after reimplantation arthroplasties.

Introduction: There has been a debate on the use of ceramic-on-ceramic coupling with the retained femoral stem in isolated acetabular revision. The purpose of this study was to retrospectively review the results and complications of isolated revision of the acetabular component using alumina-on-alumina bearings., Methods: Between August 2010 and December 2013, 22 patients (23 hips) with a mean age of 60.74 years (40-73) underwent isolated revision of the acetabular component from metal-on-polyethylene to alumina-on-alumina bearings without using a metal sleeve on the undamaged trunnion. All patients completed clinical and radiographic evaluation., Results: At a mean follow-up of 3 years (2-5.5), all patients had a significant improvement in the clinical outcome, including Harris Hip Score (84.9 vs. 43, p < 0.001), West Ontario McMaster University Osteoarthritis Index Score (14.4 vs. 49.2, p < 0.001), and visual analogue pain score (1.42 vs. 6.63, p < 0.001). Complications included one aseptic loosening of the acetabular component and three noisy hips (click only). No fracture of the ceramic bearings, dislocation, infection, or squeaking noise were observed in any of the patients., Conclusion: Isolated revision of the acetabular component to alumina-on-alumina bearings on the undamaged trunnion may be considered if there is no available titanium sleeves. Our study showed a satisfactory early outcome with minimal complications. However, a longer term follow-up study is necessary.

This paper investigates the transportation and vehicular modes classification by using big data from smartphone sensors. The three types of sensors used in this paper include the accelerometer, magnetometer, and gyroscope. This study proposes improved features and uses three machine learning algorithms including decision trees, K-nearest neighbor, and support vector machine to classify the user's transportation and vehicular modes. In the experiments, we discussed and compared the performance from different perspectives including the accuracy for both modes, the executive time, and the model size. Results show that the proposed features enhance the accuracy, in which the support vector machine provides the best performance in classification accuracy whereas it consumes the largest prediction time. This paper also investigates the vehicle classification mode and compares the results with that of the transportation modes.

Background: Ceramic-on-ceramic (COC) total hip arthroplasty (THA) has gained popularity since improvements in wear characteristics and longevity. Whether large ceramic femoral heads (≥36 mm) have increased postoperative range of motion (ROM) and a lower dislocation rate is not clear. This study aimed to compare functional outcomes and early complications between large-head (≥36 mm) and smaller-head (≤32 mm) COC prostheses with a minimum follow-up of 12 months., Methods: A total of 95 consecutive uncemented COC THAs were performed in 90 patients between January 2012 and July 2013. Of these, 49 patients (smaller-head group) received third generation and 41 patients (large-head group) received fourth generation COC prostheses. Harris hip score (HHS), Western Ontario and McMaster Universities Arthritis index (WOMAC), and ROM of the hip pre- and post-operatively were compared, as well as the presence of early complications., Results: Postoperative HHSs (88.4 vs. 89.3, p = 0.34) and WOMAC scores (12.0 vs. 11.0, p = 0.111) were not different between the groups. Postoperative flexion ROM was lower in the smaller-head group (98.8° vs. 106.1°, p < 0.001), but there were no differences in extension, abduction, adduction, internal rotation, and external rotation. One patient in each group reported a grinding noise. There was one dislocation (1.9%) in the smaller-head group, and none in the large-head group (p = 0.371). No infections or loosening of the components occurred., Conclusions: Large-head COC articulation provided better flexion, but functional outcomes and early complications are similar to the smaller-head COC., (Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS) function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnT(R92Q) transgenic mice and thoracic aorta constriction (TAC)-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK) pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy., (© 2015. Published by The Company of Biologists Ltd.)

Objective: To analyze the clinical features and genotype in a 8-year-old boy with dyskeratosis congenita (DC)., Methods: We reviewed the clinical data of the case and amplified 7 DC-related genes (including DKC1,TERT,TERC,TINF2,NOP10, NHP2 and WRAP53) using polymerase chain reaction for DNA sequence analysis to identify the abnormal exons., Results: DNA sequence analysis showed a c.85-15T>C mutation in DKC1 gene of the patient. His mother was a carrier of the mutated gene and presented with partial clinical features such as abnormal nails., Conclusion: The mutation of c.85-15T>C in DKC1 gene was reported for the first time in China. The diagnosis of DC should be considered if a young patient presents with mucocutaneous abnormalities, bone marrow failure, cancer susceptibility and a family history of cancer. Early genetic tests can improve the diagnosis rates and reduce misdiagnosis and missed diagnosis.

Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival., Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group., Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups., Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.

Background: Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown., Methods: In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer., Results: In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p., Conclusions: Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho.

Typically, production of induced pluripotent stem cells requires direct contact with feeder cells. However, once the stem cells have reached the appropriate maturation point, it is difficult to separate them from feeder cells, which must be irradiated with γ-rays or treated with the antibiotic mitomycin-C. We used a microporous poly-membrane-based indirect contact co-culture system with mouse embryonic fibroblasts to induce mouse pluripotent stem cells without radiation or antibiotics. We found that induced pluripotent stem cells induced by this co-culture method had a reprogramming efficiency and time similar to those induced using traditional methods. Furthermore, strongly expressed pluripotent markers showed a normal karyotype and formation and contained all three germ layers in a teratoma.

Objective: To observe and compare the efficacy of intratympanic application of dexamethasone (DXM) for the treatment of refractory sudden sensorineural hearing loss (SSNHL), the DXM was given in three different ways: by tympanic membrane injection, by drip through a ventilation tube, and by perfusion through a round window catheter., Methods: We conducted a nonrandomized retrospective clinical trial involving 55 patients with refractory SSNHL. For 21 patients (the perfusion group), DXM (2.5 mg/0.5 ml) was perfused transtympanically through a round window catheter using an infusion pump for 1 h twice a day for 7 d giving a total amount of 35.0 mg. For 23 patients (the injection group), DXM (2.5 mg/time) was injected by tympanic membrane puncture at intervals of 2 d on a total of four occasions giving a total amount of 10.0 mg. For 11 patients (the drip group), DXM (2.5 mg/0.5 ml) was dripped via a ventilation tube placed by myringotomy, once on the first day and twice a day for the remaining 6 d giving a total amount of 32.5 mg. Thirty-two patients with refractory SSNHL who refused to undertake further treatments were defined as the control group. Hearing recovery and complications were compared among the groups. Hearing results were evaluated based on a four-frequency (0.5, 1.0, 2.0, 4.0 kHz) pure tone average (PTA)., Results: Post-treatment audiograms were obtained one month after treatments were completed. The improvements in average PTA for the perfusion, injection, and drip groups were 9.0, 8.6, and 1.7 dB, respectively. Hearing improvement was significantly greater in the perfusion and injection groups than in the control group (1.4 dB) (P<0.05). In the perfusion group, 8 out of 21 patients (38.1%) had a PTA improvement of 15‒56 dB (mean 29.8 dB); in the injection group, 8 out of 23 patients (34.8%) had a PTA improvement of 16‒54 dB (mean 24.9 dB); in the drip group, 1 of 11 patients (9.1%) had a PTA improvement of 26.0 dB; in the control group, 3 out of 32 patients (9.4%) had a PTA improvement of 15‒36 dB (mean 14.9 dB)., Conclusions: Topical intratympanic application of DXM is a safe and effective method for the treatment of SSNHL cases that are refractory to conventional therapies.

Aim: To investigate the effect of a new infant formula supplemented with a low level (0.24 g/100 mL) of galacto-oligosaccharide (GOS) on intestinal micro-flora (Bifidobacteria, Lactobacilli and E. coli) and fermentation characteristics in term infants, compared with human milk and a standard infant formula without GOS., Methods: Term infants (n = 371) were approached in this study in three hospitals of China. All infants started breast-feeding. Those who changed to formula-feeding within 4 wk after birth were randomly assigned to one of the two formula groups. Growth and stool characteristics, and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period. Fecal samples were collected from a subpopulation of recruited infants for analysis of intestinal bacteria (culture technique), acetic acid (gas chromatography) and pH (indicator strip)., Results: After 3 mo, the intestinal Bifidobacteria, Lactobacilli, acetic acid and stool frequency were significantly increased, and fecal pH was decreased in infants fed with the GOS-formula or human milk, compared with those fed with the formula without GOS. No significant differences were observed between the GOS formula and human milk groups. Supplementation with GOS did not influence the incidence of crying, regurgitation and vomiting., Conclusion: A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.

Background: Activating on mammalian and human body LDR is thought to induce adaptive response, enhance immune function and increase anti-tumor ability. This study was designed to assess the effect of low-dose radiation on tumor growth and on erythrocyte immune function and superoxide dismutase (SOD) activity in tumor-bearing mice., Methods: Male Kunming mice were subcutaneously implanted with S180 sarcoma cells in the right inguen to create an experimental in situ animal model. Six hours before implantation, the mice were given 75 mGy X-ray radiation, over the body. Tumor size was observed 5 days later while tumor volume was calculated every other day, allowing for the creation of a graph depicting tumor growth. Fifteen days after implantation, the mice were killed to measure tumor weight and observe the necrotic areas and the location of tumor-infiltrating lymphocytes (TILs). Erythrocyte immune function and SOD activity were also determined., Results: Mice pre-exposed to low-dose radiation had a lower tumor formation rate than did those receiving no radiation (P < 0.05). Tumor growth was significantly lower in the mice pre-exposed to low-dose radiation; after 15 days, the average tumor weight in the mice pre-exposed to low-dose radiation was also lower (P < 0.05). Areas of tumor necrosis and infiltration of TILs were larger in the low-dose radiation group than in the non-radiation group. Erythrocyte immune function and SOD activity were higher in the low-dose radiation group than in the non-radiation group (P < 0.05)., Conclusion: Low-dose radiation can markedly increase the anti-tumor ability of an organism and improve erythrocyte immune function and red blood cell SOD activity as well, suggesting that low-dose radiation might be useful in the clinical treatment of cancer.

Objective: To investigate the curative effect of transtympanic perfusion of gentamicin on unilateral Ménière's disease., Methods: Twenty-three patients with unilateral Ménière's disease, 14 males and 9 females, aged 24 - 61, all with vertigo, tinnitus and ear fullness sensation to different degrees, were treated with transtympanic perfusion of gentamicin via the tympanostomy tube, 12 mg per 3 hours and 5 times a day. Pure tone audiometry and caloric test were performed every day before treatment. When destruction type of nystagmus was observed by Frenzel's glasses and the treated ear showed no response to caloric test, the treatment was ceased. After the treatment the patients were followed up for 9 - 11 years (10.2 years on average)., Results: The average amount of gentamicin used was 216 mg. The treatment lasted for 1.5 to 5 days (3.6 days on average). Vertigo disappeared in 21 patients (91%) and remained unchanged in 2. Hearing was improved or remained unchanged in 17 patients (73%) and became worse in 6. Tinnitus decreased or disappeared in 15 patients (66%), and increased in 2 patients. Ear fullness sensation decreased or disappeared in 21 patients (91%). and remained unchanged in 2. Twenty-one patients were completely recovered and returned to work (91%)., Conclusion: Relieving intractable vertigo and preserving hearing, transtympanic perfusion of gentamicin is effective on unilateral Ménière's disease.

Before exploratory tympanotomy, it is difficult to diagnose an idiopathic perilymph fistula (PLF) because of its variable presentations. An animal model tube-PLF on guinea pigs was established to evaluate the change of the sensitivity of the cochlea function and the value of the postural audiometry in PLF. A fine polyethylene tube (O.D. 0.6mm) was inserted into the scala tympani of the basal turn through the incised round window membrane in 10 experimental guinea pigs, and another 5 as controls. The hearing threshold (HT), action potential (AP) latency for stimulus of 105 dB SPL, difference of HT and AP latency from the test ear down to up were measured by electrocochleography (ECoG) immediately after operation and one week later. The HT, AP latency and postural audiometry showed no significant changes immediately but a significant difference one week later in HT (P less than 0.01) and postural audiometry, the AP latency also presented a significant delay (P less than 0.01). The results showed that the tube-PLF model may be a valuable method for studying chronic PLF.