NDUFA8 is transcriptionally regulated by EP300/H3K27ac and promotes mitochondrial respiration to support proliferation and inhibit apoptosis in cervical cancer.

Cervical cancer, a common malignancy in women, poses a significant health burden worldwide. In this study, we aimed to investigate the expression, function, and potential mechanisms of NADH: ubiquinone oxidoreductase subunit A8 (NDUFA8) in cervical cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) database and immunohistochemical scoring were used to analyze NDUFA8 expression in cervical cancer tissues and normal tissues. Quantitative real-time PCR and Western blot analyses were performed to assess the expression level of NDUFA8 in cervical cancer cell lines. NDUFA8 knockdown or overexpression experiments were conducted to evaluate its impact on cell proliferation and apoptosis. The mitochondrial respiratory status was analyzed by measuring cellular oxygen consumption, adenosine triphosphate (ATP) levels, and the expression levels of Mitochondrial Complex I activity, and Mitochondrial Complex IV-associated proteins Cytochrome C Oxidase Subunit 5B (COX5B) and COX6C. NDUFA8 exhibited high expression levels in cervical cancer tissues, and these levels were correlated with reduced survival rates. A significant upregulation of NDUFA8 expression was observed in cervical cancer cell lines compared to normal cells. Silencing NDUFA8 hindered cell proliferation, promoted apoptosis, and concurrently suppressed cellular mitochondrial respiration, resulting in decreased levels of available ATP. Conversely, NDUFA8 overexpression induced the opposite effects. Herein, we also found that E1A Binding Protein P300 (EP300) overexpression facilitated Histone H3 Lysine 27 (H3K27) acetylation enrichment, enhancing the activity of the NDUFA8 promoter region. NDUFA8, which is highly expressed in cervical cancer, is regulated by transcriptional control via EP300/H3K27 acetylation. By promoting mitochondrial respiration, NDUFA8 contributes to cervical cancer cell proliferation and apoptosis. These findings provide novel insights into NDUFA8 as a therapeutic target in cervical cancer.

Suppression of MALAT1 promotes human synovial mesenchymal stem cells enhance chondrogenic differentiation and prevent osteoarthritis of the knee in a rat model via regulating miR-212-5p/MyD88 axis.

Osteoarthritis (OA) is one of the most common diseases of the skeleton. Long non-coding RNAs (lncRNAs) are emerging as key players in OA pathogenesis. This work sets out to determine the function of lncRNA MALAT1 in OA and the mechanisms by which it does so. Mesenchymal stem cells isolated from the human synovial membrane are called hSMSCs. The hSMSCs' surface markers were studied using flow cytometry. To determine whether or not hSMSC might differentiate, researchers used a number of different culture settings and labeling techniques. The expression levels of associated genes and proteins were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), and immunostaining. A dual luciferase reporter experiment and RNA immunoprecipitation (RIP) test demonstrated the direct association between miR-212-5p and MALAT1 or MyD88. MALAT1 was downregulated during the chondrogenic differentiation of hSMSCs, and underexpression of MALAT1 promotes chondrogenesis in hSMSCs. Using dual luciferase reporter and RIP assays facilitated the identification of MALAT1 as a competitive endogenous RNA (ceRNA) that sequesters miR-212-5p. Additionally, the expression of MYD88 was regulated by MALAT1 through direct binding with miR-212-5p. Significantly, the effects of MALAT1 on the chondrogenic differentiation of hSMSCs were counteracted by miR-212-5p/MYD88. Furthermore, our in vivo investigation revealed that the inhibition of MALAT1 mitigated osteoarthritis progression in rat models. In conclusion, the promotion of chondrogenic differentiation in hSMSCs and the protective effect on cartilage tissue in OA can be achieved by suppressing MALAT1, which regulates the miR-212-5p/MyD88 axis.

Endoplasmic reticulum stress: a novel targeted approach to repair bone defects by regulating osteogenesis and angiogenesis.

Bone regeneration therapy is clinically important, and targeted regulation of endoplasmic reticulum (ER) stress is important in regenerative medicine. The processing of proteins in the ER controls cell fate. The accumulation of misfolded and unfolded proteins occurs in pathological states, triggering ER stress. ER stress restores homeostasis through three main mechanisms, including protein kinase-R-like ER kinase (PERK), inositol-requiring enzyme 1ɑ (IRE1ɑ) and activating transcription factor 6 (ATF6), collectively known as the unfolded protein response (UPR). However, the UPR has both adaptive and apoptotic effects. Modulation of ER stress has therapeutic potential for numerous diseases. Repair of bone defects involves both angiogenesis and bone regeneration. Here, we review the effects of ER stress on osteogenesis and angiogenesis, with emphasis on ER stress under high glucose (HG) and inflammatory conditions, and the use of ER stress inducers or inhibitors to regulate osteogenesis and angiogenesis. In addition, we highlight the ability for exosomes to regulate ER stress. Recent advances in the regulation of ER stress mediated osteogenesis and angiogenesis suggest novel therapeutic options for bone defects.

Evaluation of double-high insert mid-term outcomes in cruciate-retaining medial-pivotal total knee arthroplasty - a propensity score-matched analysis with averaged 8-year follow-up.

BACKGROUND: This study aimed to compare the mid-term clinical and radiographic outcomes between medial-pivotal (MP) insert and double-high (DH) insert used under the cruciate-retaining condition in ADVANCE® total knee arthroplasty (TKA). METHODS: The follow-up was conducted for 158 consecutive patients who underwent unilateral ADVANCE® TKA from January 2011 to April 2014. Eighty-four MP inserts and 74 DH inserts were used under cruciate-retaining conditions. A 1:1 propensity score matching (PSM) analysis was performed between MP inserts and DH inserts to compare the clinical and radiographic outcomes. RESULTS: After a 1:1 PSM, 120 patients (60 pairs) were matched between the MP and DH inserts groups. The baseline demographic parameters and clinical scores were comparable between the two groups. The postoperative clinical outcomes at an averaged 8-year follow-up of both groups were significantly improved. The range of motion (ROM) of the DH group was better than that of the MP group, and equivalent Knee Society Function Score (KSFS) between the two groups was found. However, the Knee Society Score (KSS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and Forgotten Joint Score (FJS) of the MP group were found to be significantly superior to those of the DH group. Comparable complication and revision rates were observed between the two groups. The radiographic results were also equally good between MP and DH groups. CONCLUSIONS: Although the mid-term clinical and radiographic outcomes of the DH inserts are fairly good, the clinical scores of the DH group were worse than those of the MP group.

Use of a new off-the-shelf 3D-printed trabecular titanium acetabular cup in Chinese patients undergoing hip revision surgery: Short- to mid-term clinical and radiological outcomes.

BACKGROUND: Revision total hip arthroplasty (THA) has been a challenge for surgeons. The purpose of this study was to explore the short-to mid-term clinical and radiological outcomes of Chinese patients who underwent revision THA using a new off-the-shelf three-dimensional (3D)-printed trabecular titanium (TT) acetabular cup by comparison with a conventional porous coated titanium acetabular cup, to provide a reference for the recommendation of this prostheses. METHODS: A retrospective analysis of 57 patients (57 hips) who received revision THA was performed from January 2016 to June 2019. A total of 23 patients received 3D-printed cups (observation group) and 34 patients received non-3D-printed cups (control group). Clinical scores including Visual Analogue Scale (VAS), Harris Hip Score (HHS) and Short Form 36 (SF-36), upward movement of the hip center of rotation(HCOR)and limb-length discrepancy (LLD), stabilization and bone ingrowth of cups were compared between two groups. The multivariate linear regression was used to determine the factors potentially influencing the HHS score. Postoperative complications in the two groups were also recorded. RESULTS: All 57 patients were routinely followed up. The average follow-up durations in the control and observation groups were 43.57 ± 13.68 (24-65) months and 41.82 ± 11.44 (24-64) months, respectively (p = 0.618). The postoperative clinical scores significantly improved in both groups compared to the preoperative scores (p < 0.001). The VAS score did not significantly differ between the groups at 3 (p = 0.946) or 12 (p = 0.681) months postoperatively, or at the last follow-up (p = 0.885). The HHS score did not significantly differ between the groups at 3 months (p = 0.378) postoperatively but differed at 12 months (p < 0.001) postoperatively and the last follow-up (p < 0.001). The SF-36 score did not significantly differ between the groups at 3 months (p = 0.289) postoperatively, but was significantly different at 12 months (p < 0.001) postoperatively and the last follow-up (p < 0.001). Compared with the control group, the postoperative recovery of HCOR and LLD was better in the observation group. All cups remained stable, with no loosening throughout the follow-up period. But the observation group had a significantly better rate of bone ingrowth compared to the control group (p = 0.037). Multivariate linear regression analysis showed that different cup types, upward movement of the HCOR, and LLD influenced the HHS score at the last follow-up (p < 0.001, p = 0.005, respectively). None of the patients exhibited severe postoperative complications. CONCLUSION: The new off-the-shelf 3D-printed TT acetabular cup demonstrated encouraging short-to mid-term clinical outcomes in Chinese patients. It can effectively relieve pain, improve hip function, provide satisfactory biological fixation and high survival rate. But further follow up is necessary to assess its long-term outcomes.

Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease, and is hard to be cured at present. Cytokine receptor-like factor 1 (CRLF1) has been identified as an upregulated gene in OA cartilage. However, the precise identities and functions of CRLF1 in OA progression have remained to be fully elucidated. METHODS: We used a murine model of injury-induced OA (destabilization of medial meniscus, DMM) and BMSCs to investigate the specific biological functions and mechanisms of CRLF1. RESULTS: We found that CRLF1 was significantly increased in the DMM surgery-induced OA model and was down-regulated during chondrogenic differentiation of BMSCs. Luciferase reporter assays showed that CRLF1 was a direct target of miR-320 in BMSCs. miR-320 can reverse the effect of CRLF1 on cell proliferation, apoptosis and chondrogenic differentiation of BMSCs. Furthermore, knockdown of CRLF1 or over-expression of miR-320 can inhibit the apoptosis of primary chondrocytes. CONCLUSION: Suppression of CRLF1 promotes the chondrogenic differentiation of BMSCs and protects cartilage tissue from damage in osteoarthritis via activation of miR-320.

Zoledronic acid and teriparatide have a complementary therapeutic effect on aseptic loosening in a rabbit model.

BACKGROUND: Revisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone. METHODS: We created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out. RESULTS: The results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration. CONCLUSION: This research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.

Mid-term clinical outcomes and survivorship of medial-pivot total knee arthroplasty-a mean five year follow-up based on one thousand, one hundred and twenty eight cases.

PURPOSE: The unique medial-pivot (MP) design of ADVANCE® system largely simulates the movement of a normal knee joint and a high mid- and long-term success rate has been reported in limited populations. The aims of this study are to investigate the mid-term clinical outcomes and survivorship based on a large cohort with 1128 cases. METHODS: One thousand seven patients received 1276 ADVANCE® MP TKAs from January 2011 to April 2016 in our institution were retrospectively investigated. The range of motion (ROM), the Knee Society Score (KSS), the Knee Society Function Score (KSFS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and the Forgotten Joint Score (FJS) were used to evaluate clinical outcomes and Kaplan-Meier survival curve was used to calculate the survivorship. RESULTS: In an averaged five year follow-up, the results of 879 patients (1128 knees) were successfully obtained and the clinical outcomes of 1107 knees were recorded. One hundred forty-eight knees (11.6%) were lost to follow-up. Excellent mid-term ROM, KSS, KSFS, and WOMAC score were recorded. A total of 53 complications were identified and most complications were related to the discordance of femoropatellar joint. Taking revision for any reason as end point, the overall survivorship was 99.2% at seven years. When taking all cases lost to follow-up as failures, the survivorship was 83.8% at five years and 50.6% at seven years. CONCLUSION: For MP designs, the intermediate clinical outcomes are good to excellent and the mid-term survivorship related to reasons other than infection is also satisfactory.

A prospective comparative study of staged total knee arthroplasty: ninety-day versus seven-day interval.

PURPOSE: The optimal interval between staged bilateral total knee arthroplasty (STBTKA) is unclear. Studies have reported STBTKA being performed at the same admission, with a seven day interval. The safety and outcomes of patients submitted to same-admission STBTKA (SA-STBTKA) are questionable and need further investigation. METHODS: A prospective non-randomized study was performed to compare the early postoperative outcomes, systemic complications, and surgical-related complications between the first and second knees, as well as between SA-STBTKA and STBTKA groups. From July 2018 to November 2019, a total of 430 patients were recruited. Analyzed parameters included the Knee Society score (KSS), Knee Society functional score (KSFS), range of motion (ROM), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score, WOMAC stiffness score, and WOMAC score for daily life difficulty. RESULTS: Pre-operatively, the demographic data and functional scores were not significantly different between the two groups. The KSS, WOMAC pain score, and WOMAC stiffness score of the second knee in the STBTKA group were significantly better than those of the first knee. A total of 426 patients completed the last follow-up one  year after surgery, and the post-operative functional scores were not significantly different between the two groups and between the two knees within the same group. Before the second operation, more systemic complications were identified in the SA-STBTKA group, while the rate of surgical complication was not significantly different when compared to STBTKA patients. CONCLUSIONS: With equivalent post-operative function and a higher frequency of minor complications, SA-STBTKA should be cautiously selected as a treatment option for bilateral osteoarthritis.

Carboxymethyl chitosan reduces inflammation and promotes osteogenesis in a rabbit knee replacement model.

BACKGROUND: The major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection. This study aimed to investigate the role of carboxymethyl chitosan (CMC) in knee arthroplasty. METHODS: A total of 20 New Zealand white rabbits that were divided into two groups (10 in the control group and 10 in the chitosan group) were included in the study. They underwent TKA surgery, and all were implanted with titanium rod prostheses; the prosthesis in the chitosan group was coated with CMC. After 12 weeks, all rabbits were euthanized, and the following analyses of some specific surface membrane tissues around the prosthesis were performed: X-ray analysis; micro-computed tomography scan; haematoxylin and eosin, Van Gieson, and Von Kossa staining; reverse transcription polymerase chain reaction; and Western Blotting. RESULTS: The result of CCK8 test showed CMC can promote cell proliferation and increase cell viability. Radiological result showed better amount of bone deposits and more bone formation in the chitosan group. HE staining result showed CMC reduces inflammation around the prosthesis. The VG and Von Kossa staining results showed CMC can promote bone deposition around prosthesis. And according to the results of PCR and WB, the OCN content was higher in the chitosan group, while the MMPs content was lower. The chitosan group has an increased OPG/RANKL ratio than the control group. CONCLUSION: CMC can effectively inhibit the inflammatory response around the prosthesis and osteoclast activation and promote osteogenesis by interfering with the osteoprotegerin/receptor activator of nuclear factor kappa-Β ligand/receptor activator of nuclear factor kappa-Β signalling pathway.

A posterior-only approach for ankylosing spondylitis (AS) with thoracolumbar pseudoarthrosis: a clinical retrospective study.

BACKGROUND: Surgical treatment has been recommended by most surgeons to treat pseudarthrosis in ankylosing spondylitis (AS). However, there is still some debate on the necessity of anterior fusion. There is very limited literature on the treatment and surgical outcomes of thoracolumbar pseudarthrosis in AS patients treated through a posterior-only approach. METHODS: From January 1, 2012 to December 31, 2017, a total of 42 cases diagnosed with thoracolumbar pseudarthrosis in AS patients with moderate kyphosis were included in this study. All of the patients received posterior-only kyphosis correction, internal fixation and fusion without anterior fusion, and underwent at least 2 years of follow-up. Clinical and radiographic results and complications were assessed. RESULTS: All of the patients were followed up for an average of 35.3 months (range, 24-48 months), and they achieved successful bone graft fusion at the pseudarthrosis sites. Satisfactory radiographic changes were achieved in these patients. The Cobb angles of global kyphosis (GK) were corrected from 53.2 ± 5.4 degrees preoperatively to 33.2 ± 4.3 degrees postoperatively, and to 36.1 ± 5.3 degrees at the latest follow-up. The Cobb angles of local kyphosis (LK) were corrected from 43.3 ± 4.6 degrees preoperatively to 26.8 ± 3.3 degrees postoperatively, and to 28.2 ± 3.6 degrees at the latest follow-up. The mean sagittal vertical axis (SVA) were corrected from 7.6 ± 4.2 cm preoperatively to 4.3 ± 2.1 cm postoperatively, and to 4.8 ± 2.3 cm at the latest follow-up. No serious neurological complication or deep wound infection was found in these 42 patients. CONCLUSION: Posterior-only kyphosis correction and fixation without anterior fusion can achieve excellent bone fusion and satisfactory improvement in AS patients with thoracolumbar pseudarthrosis. This method may be a good choice for treating thoracolumbar pseudarthrosis in AS patients with moderate kyphosis.

Role of Brd4 in the production of inflammatory cytokines in mouse macrophages treated with titanium particles.

Brd4 protein is an important epigenetic regulator involved in the process of inflammatory cytokine production in many diseases. However, whether and how Brd4 participates in the process of wear-particle-induced inflammation remain unclear. This study aimed to investigate the potential role of Brd4 in titanium (Ti) particle-induced inflammatory cytokine production in mouse macrophage RAW264.7 cells. Our experiment detected Brd4 expressed in both normal synovium and periprosthetic osteolysis interface membrane, but the expression increased in the interface membrane as compared with that in normal synovium. Treatment with Ti particles significantly increased TNF-α, IL-6, and IL-1ß production in RAW264.7 cells, which was inhibited by JQ1 or Brd4-siRNA. Ti particles enhanced the expression of Brd4, which was abrogated by JQ1. Ti particles enhanced NF-κB p65 and IKK phosphorylation and attenuated IκBα protein expression, which were abrogated by JQ1. Co-immunoprecipitation analysis indicated that Ti particles promoted the binding of Brd4 to acetylated NF-κB p65 (lysine-310), which was also abrogated in JQ1-treated RAW264.7 cells. In conclusion, Brd4 expression increases in interface membrane and Brd4 participates in the production of pro-inflammatory cytokines induced by Ti particles via promoting the activation of NF-κB signaling and binding to acetylated NF-κB p65 (lysine-310) in mouse macrophages.

Genome-wide identification, evolution, and expression analysis of the KT/HAK/KUP family in pear.

The K+ transporter/high-affinity K+/K+ uptake (KT/HAK/KUP) family, as one of the largest K+ transporter families in higher plants, plays an essential role in plant growth, mineral element absorption, salt stress tolerance, and other physiological processes. However, little is known about this family in pear (Pyrus). Here, we identified 20 K+ transporter genes in pear (P. bretschneideri) using genome-wide analysis. Their gene structure, chromosomal distribution, conserved motifs, phylogenetics, duplication events, and expression patterns were also examined. The results of phylogenetic analysis showed that PbrKT/HAK/KUP genes were clustered into three major groups (Groups I-III). Among the 20 PbrKT/HAK/KUP genes, 18 were mapped to nine chromosomes and two to scaffolds. Four WGD/segmental gene pairs were identified, indicating that WGD/segmental duplication may have contributed to the expansion of the KT/HAK/KUP family in pear. Among the four pairs of WGD/segmentally duplicated genes, both members of three pairs had been subjected to purifying selection, whereas the fourth pair had been subjected to positive selection. Furthermore, phenotypic experiments showed that the growth of pear seedlings was affected by potassium deficiency treatment. Expression patterns of 20 PbrKT/HAK/KUP genes in roots were further assayed with qRT-PCR. PbrHAK1 and PbrHAK12/16 were significantly expressed in response to K+ deficiency, suggesting that these genes are crucial for K+ uptake in pear, especially under the condition of K+ starvation. Our results provide a foundation for further study on the function of KT/HAK/KUP genes in pear.

The gene PbTMT4 from pear (Pyrus bretschneideri) mediates vacuolar sugar transport and strongly affects sugar accumulation in fruit.

Tonoplast monosaccharide transporters (TMTs) play important roles in vacuolar sugar accumulation in plants. In this study, six TMT genes (PbTMT1-6) were identified in the Pyrus bretschneideri genome database, and their expression profiles were correlated with soluble sugar contents during the pear (P. bretschneideri cv. Ya Li) fruit development process. Subsequently, PbTMT4 was identified as a strong contributor to fructose, glucose and sucrose accumulation in fructescence of pears. Heterologous expression of PbTMT4, in the hexose transporter-deficient yeast strain EBY.VW4000, facilitated growth in media containing low levels of glucose, fructose, sucrose or sorbitol. In addition, PbTMT4-transformed tomato plants flowered and bore fruit significantly earlier than wild-type (WT) plants, and glucose and fructose levels in mature tomatoes were increased by about 32 and 21% compared with those in WT plants. However, no obvious alterations in sucrose content, plant height and weight per fruit were observed. Finally, subcellular localization experiments in transformed Arabidopsis plants showed that PbTMT4 is localized to tonoplast vesicles of protoplasts. These preliminary results suggest that PbTMT4 participates in vacuolar accumulation of sugars, and thus affects plant growth and development.

Clinical efficacy and pharmaco-economic analysis of xiaozhong zhitong decoction on preventing deep venous thrombosis in major orthopaedic operation.

The clinical efficacy and pharmacoeconomics of Xiaozhong Zhitong Decoction on preventing deep venous thrombosis in major orthopaedic operation are observed and analyzed. The 160 patients who are implemented major orthopaedic operation in our hospital are selected as the subjects, which are randomly divided into research group applying Xiaozhong Zhitong decoction and reference group using low molecular heparin with same cases in each group for observing their treatment efficacy and analyzing pharmacoeconomics. Through observing and comparing the rate of deep venous thrombosis in two groups, the results show that study group is significantly lower than reference group with p<0.05. The incidence of adverse reactions in study group is significantly lower than that of reference group with P<0.05; after observing the postoperative quality of life and analyzing cost-effectiveness in two groups, it shows that study group has more significant advantage than reference group with p<0.05. The Xiaozhong Zhitong decoction has a better clinical effect on preventing deep venous thrombosis in major orthopaedic operation with higher safety and reliability and has a better cost effect ratio at the same time.

A Novel Method for Pathway Identification Based on Attractor and Crosstalk in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND Juvenile idiopathic arthritis (JIA) is one of the most common inflammatory disorders of unknown etiology. We introduced a novel method to identify dysregulated pathways associated with polyarticular JIA (pJIA). MATERIAL AND METHODS Gene expression profiling of 61 children with pJIA and 59 healthy controls were collected from E-GEOD-13849; 300 pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) database and 787,896 protein-protein interaction sets were gathered from the Retrieval of Interacting Genes. Attractor and crosstalk were designed to complement each other to increase the integrity of pathways assessment. Then, impact factor was used to assess the interactions inter-pathways, and RP-value was used to evaluate the comprehensive influential ability of attractors. RESULTS There were seven attractors with p<0.01 and 14 pathways with RP<0.01. Finally, two significantly dysfunctional pathways were found, which were related to pJIA progression: p53 signaling pathway (KEGG ID: 04115) and non-alcoholic fatty liver disease (NAFLD) (KEGG ID: 04932). CONCLUSIONS A novel approach that identified the dysregulated pathways in pJIA was constructed based on attractor and crosstalk. The new process is expected to be efficient in the upcoming era of medicine.

Comparison of hIGF-1 gene transfection to the hBMSCs and human meniscal fibrochondrocytes.

BACKGROUND: Treatment strategies for meniscal injury are shifting from meniscectomy to repair, especially cell-based therapy. Delivering selected genes to donor cells can modify differentiation and proliferation. Efficiency of gene transfection and expression may relate to cell type. MATERIAL AND METHODS: Full-length hIGF-1 cDNA was cloned into eukaryotic expression vector by PCR. Human BMSCs and meniscal fibrochondrocytes were isolated and cultured in vitro and hIGF-1 gene was transfected by FuGene 6. Expression of EGFP and hIGF-1 were determined. Biological activity of the hIGF-1 in medium was assessed by MTT chromatometry. Real-time quantitative PCR and Western blot were used to assess the expression of exogenous genes. Efficacy of gene transfection was detected by immunohistochemistry staining and flow cytometry. RESULTS: Sequences of hIGF-1 were verified by sequence analysis. Expression of EGFP increased gradually and reached peak intensity 48 h after transfection. Transfection efficiency of BMSCs was higher than meniscal fibrochondrocytes. The population doubling time was decreased in both cell types. Peak concentration of hIGF-1 in the medium of BMSCs and meniscal cells was 32.5±4.8 ng/ml and 24.5±4.6 ng/ml, respectively. Secreted hIGF-1 possessed the ability to enhance proliferation of the cell line. Results of qPCR and Western blot confirmed the expression of hIGF-1. Type II collagen appeared within the cells, and percentage of cells in S stage was increased in both cell types after transfection. CONCLUSIONS: hIGF-1 cDNA can be transfected into BMSCs and meniscal fibrochondrocytes, resulting in gene expression. Expression efficiency in BMSCs was higher than that in fibrochondrocytes.

[Efficacy of photodynamic antimicrobial therapy for wound flora and wound healing of pressure sore with pathogen infection].

OBJECTIVE: To explore the efficacy of photodynamic antimicrobial therapy in the treatment of pressure sore with pathogen infection. METHODS: A total of 42 pressure sore patients with pathogen infection were divided randomly into experimental and control groups (n = 21 each). Fufanghuangbai liquid was used for external application with control group. In the experimental group, wound was treated with Fufanghuangbai liquid wet dressing and irradiated by semiconductor laser 30 min late. The distance from semiconductor laser probe to wound site was 10-15 cm, 20 min twice daily, continuous exposure to 7 days for 1 course. The results of bacterial culture and epidermal growth factor (EGF) expression of wound granulation tissue were observed before and after treatment. And the changes of healing rate of pressure sore were measured at post-treatment in each group. RESULTS: The positive rates of bacterial culture, rates of change around wound inflammation, healing rate of days 7 and 14, the high expression of EGF on healing wound granulation tissue was 9.75%, (32.2% ± 5.8%), (89.1% ± 5.6%), (12.4% ± 2.9%), (34.7% ± 3.6%), 14/21 in the treatment group versus 51.2%, (17.8% ± 2.0%), (57.3% ± 2.6%), (5.1% ± 1.1%), (10.5% ± 2.4%), 2/21 in the control group respectively. The inter-group differences were statistically significant (P < 0.05). CONCLUSION: Photodynamic antimicrobial therapy is an effective method for pressure sore with pathogen infection. Wound healing is promoted through an up-regulation of EGF.

Ceramic fragmentation after total hip arthroplasty: two case reports and literature review.

Background: Ceramic fragmentation is a rare but serious complication after total hip arthroplasty (THA). We reviewed the PubMed literature from 1990 to 2023 and found only 31 case reports of ceramic fragmentation after THA. Our case reports help to expand understanding of this rare complication. We shared our surgical experience and identified an ideal material for revision surgery, which can serve as a useful reference for other orthopedic surgeons to perform ceramic fragmentation revision surgery in the future. We also analyzed the possible causes, diagnosis, and treatment opinions of ceramic fragmentation. Case presentation: This study presents two cases of ceramic fragmentation after THA. One patient had ceramic head fragmentation 10 years after the primary THA, and one patient had ceramic liner fragmentation 5 years after the primary THA. Both patients presented with pain, and one patient also reported a clicking sound in the hip. The two patients described here had BMIs of 23.7 and 23.1, respectively. Both patients' ceramic fragmentation were due to aseptic loosening, not periprosthetic joint infections, as confirmed by negative microbiological cultures. Radiographic examinations of both patients revealed radio-opaque wear debris around the hip joint prostheses and we describe the surgical protocols and intraoperative findings in both cases in detail. Conclusion: Our cases and the literature suggest that ceramic fragmentation can occur at any time after THA. The most immediate symptoms are pain and noise, but some patients may be asymptomatic. Ceramic on polyethylene bearings is recommended for revision surgery whenever possible; metal bearings should be avoided.